Sonography in Obstetrics & Gynecology: Principles and Practice [7 ed.] 0071760881, 9780071760881

Table of contents :
SONOGRAPHY IN OBSTETRICS AND GYNECOLOGY: Principles & Practice
Seventh Edition
Arthur C . Fleischer, M D
Professor of Radiology and Radiologic Sciences Professor of Obstetrics and Gy
Chief, Diagnostic Sonography
V anderbilt University Medical Center Nashville, T ennessee
W esley Lee, MD
Division of Fetal Imaging
W illiam Beaumont Hospital
R o y al Oak, Michigan
Clinical Professor of Obstetrics and Gynecology Oakland University William Be
R ochester, Michigan
Eugene C . T o y , MD
V ice Chair of Academic Affairs and Residency Program Director
Department of Obstetrics and Gynecology
T he Methodist Hospital-Houston
Associate Clinical Professor
W eill Cornell College of Medicine
Associate Clinical Professor and Clerkship Director Department of Obstetrics
F r ank A. Manning, M D
Professor
Department of Obstetrics and Gynecology Montefiore Medical Center
Bronx, New York
R oberto J. R omero, MD
Chief, P erinatology Research Branch
EDITORS
E ugene C. Toy, MD, i s Vice- Chair of
F rank A . Manning, MD, is a tenured
E ditors
CONTENTS
Contributors ix Preface xv Acknowledgments xvii
I. GENERAL OBSTETRIC SONOGRAPHY
1. Ultrasound Bioeffects and Safety: What the Practitioner Should Know 2
2. Normal Pelvic Anatomy as Depicted with Transvaginal Sonography 21
3. Transvaginal Sonography of Early Intrauterine Pregnancy 39
4. Transvaginal Sonography of Ectopic Pregnancy 71
5. Fetal Biometry 99
6. Prenatal Diagnosis of Congenital Heart Disease 121
7. Placenta, Cord, and Membranes 155
8. Prenatal Diagnosis of Placenta Accreta 187
9. Fetal Growth Restriction 195
10. Doppler Velocimetry of the Uteroplacental Circulation 223
11. Doppler Interrogation of the Fetal Circulation 257
12. Color Doppler Sonography in Obstetrics 309
13. Sonography in Multiple Gestation 337
II. FETAL ANOMALIES AND DISORDERS
14. Fetal Anomalies: Overview 376
15. Prenatal Diagnosis of Cerebrospinal Anomalies 413
16. Fetal Neck and Chest Anomalies 441
17. Fetal Gastrointestinal Anomalies 461
18. The Fetal Genitourinary System 509
19. Fetal Skeletal Anomalies 523
20. Fetal Syndromes 593
21. Ultrasound Detection of Chromosomal Anomalies 651
III. RISK ASSESSMENT AND THERAPY
22. First Trimester Screening 682
23. Fetal Biophysical Profile Score: Theoretical Considerations and Practical
24. Chorionic Villus Sampling 715
25. Amniocentesis 733
26. Fetal Blood Sampling 775
27. Fetal Therapy: Maternal Fetal Surgery and Percutaneous Ultrasound Guided
IV. M A TERNAL DISORDERS
28. Sonographic Examination of the Uterine Cervix 816
29. Sonography of Trophoblastic Diseases 849
30. Postpartum Ultrasound 859
V . GYNECOLOGIC SONOGRAPHY
31. Sonographic Evaluation of Pelvic Masses with Transabdominal and/or Transv
32. Color Doppler Sonography of Pelvic Masses 897
33. Sonographic Evaluation of Uterine Disorders 933
34. Transvaginal Sonography of Endometrial Disorders 961
35. Sonographic Techniques for Early Detection of Ovarian and Endometrial Ca
36. Acute Pelvic Pain: Transvaginal and Doppler Evaluation 1001
37. Transvaginal Sonography in Gynecologic Infertility 1011
C ontents
viii
38. Sonohysterography and Sonohysterosalpingography 1043
39. Guided Procedures Using Transvaginal, Transperineal, and Transrectal Son
40. Pelvic Floor Ultrasound 1087
41. Breast Sonography 1111
42. Breast Ultrasound 1119
VI. COMPLIMENTARY IMAGING MODALITIES
43. Volume Sonography: Core Concepts for Clinical Practice 1134
44. Obstetrical Applications for 3D Ultrasonography 1171
45. Fetal Cardiac Evaluation Using 3D and 4D Ultrasonography 1205
46. Magnetic Resonance Imaging in Obstetrics 1235
47. Three-Dimensional Volumetric Sonography in Gynecology 1263
48. MRI of the Female Pelvis: Problem Solving Sonographic Uncertainties 1295
Index 1319
CONTRIBUTORS
Jacques S. Abramowicz, MD
R o chelle F. Andreotti, MD
Ahmet A. Baschat, MD
George Bega, MD
Beryl R. Benacerraf, M D
Carol B. Benson, MD
F ionnuala M. Breathnach, MD, MRCOG, MRCPI
Daniel M. Breitkopf, M D
Mieke Cannie, MD, PhD
P eter S. Cartwright, MD
T innakorn Chaiworapongsa, MD
W erther Adrian Clavelli, MD
Christine H. C omstock, MD
David O. C osgrove, MA, MSc, FRCP, FRCR
Marta Crispens, MD
Antonella Cromi, MD, PhD
Laura Cruciani, MD
V alentina De Robertis
Greggory R. DeVore, MD
Michael P. Diamond, MD
Hans Peter Dietz, MD, PhD
P eter M. Doubilet, MD, PhD
David A. F ishman, MD
Arthur C . Fleischer, M D
Maria-Teresa Gervasi, MD
F abio Ghezzi, MD
Luís F. Gonçalves, MD
F r ancesca Gotsch, MD
Christopher Harman, MD
Sonia S. Hassan, MD
J ill Herzog, RDMS
T amarya L. Hoyt, MD
John G. H uff, MD
James C . H uhta, MD
Jacques Jani, MD, PhD, F A CR
Marcia C . Javitt, MD, F A CR
Philippe Jeanty, MD, PhD
Cristiano Jodicke, M D
Howard W. Jones, III, MD
xii
Sun Kwon Kim, MD, PhD
Juan Pedro Kusanovic, M D
Debbie J. Lee, BS
W esley Lee, MD
Jodi P. Lerner, M D
Andréj Lyshchik, MD, PhD
F ergal D. Malone, MD
F r ank A. Manning, M D
Joan M. Mastrobattista, MD
Alexandra Matias, MD PhD
Ana Monteagudo, M D
Juliana Moyses L Abdalla
Ana Luisa Neves, MD
Melinda S. New, MD
Giovanna Ogge’, MD
xiii
P ercy Pacora, MD
Dario Paladini, MD
Anna K. P arsons, MD
Gianluigi Pilu, MD
Dolores Pretorius, MD
Elizabeth E. Puscheck, MD
Mark Redman, MD
Georgios Rembouskos, MD
Silvia Susana Romaris, MD
R oberto J. R omero, MD
A. Cristina Rossi , M D
Gabriella Sglavo, M D
Eyal Sheiner, M D
Gabriele Siesto, M D
xiv
Sandra R. Silva, MD
W illiam E. Svensson, FRCR, FRCSI, LRCPI, LRCSI, LM
Eugene C . T o y , MD
Ilan E. T imor-Tritsch, MD
Diane M. T wickler, M D , F A CR
E di Vaisbuch, MD
Jaime M. V asquez, MD
P aolo Volpe, MD
R onald.J. W apner, M D
Phillip K. W illiams, RDMS
Douglas Wilson, MD
Lami Yeo, MD
PREFACE
A CKNOWLEDGMENTS
GENERAL OBSTETRIC SONOGRAPHY
ULTRASOUND BIOEFFECTS AND SAFETY: WHAT THE PRACTITIONER SHOULD KNOW
J acques S. Abramowicz
E yal Sheiner
INTRODUCTION
B ASIC PHYSICS OF ULTRASOUND
T he Ultrasound Wave
T issue Characteristics
Instrument Outputs
distance. A very important control is receiver gain.
THERMAL EFFECTS
MECHANICAL EFFECTS
THE OUTPUT DISPLAY STANDARD
T able 1-2
RISK ASSESSMENT
HISTORICAL RESEARCH
Animal Research
H uman Research and Epidemiology
Clinical Exposimetry
Nonmedical Ultrasound
Official Positions
RECOMMENDATIONS
FUTURE DIRECTIONS
KEY POINTS
REFERENCES
H ighlighted References
NORMAL PELVIC ANATOMY AS DEPICTED WITH TRANSVAGINAL SONOGRAPHY
SCANNING TECHNIQUE AND INSTRUMENTATION (Figures 2-1 to 2-3)
UTERUS (Figures 2-4 to 2-7)
O V ARIES (Figure 2-8)
O THER PELVIC STRUCTURES (Figures 2-9 and 2-10)
REFERENCES
SUMMARY
Appendix 2-1
AIUM Practice Guidelines for the Performance of Ultrasound Examination of the
I. INTRODUCTION
II. INDICATIONS
III. QUALIFICATIONS AND RESPONSIBILITIES OF PERSONNEL
IV. SPECIFICATIONS OF THE EXAMINATION
A. General Pelvic Preparation
B. Uterus
C. A dnexa (Ovaries and Fallopian Tubes)
D . Cul-de-Sac
V . DOCUMENTATION
VI. EQUIPMENT SPECIFICATIONS
VII. QUALITY CONTROL AND IMPROVEMENT, SAFETY, INFECTION CONTROL, AND PATIE
Appendix 2-2
Guidelines for Cleaning and Preparing Endocavitary Ultrasound T r ansducers B
TRANSVAGINAL SONOGRAPHY OF EARLY INTRAUTERINE PREGNANCY
O VERVIEW
CLINICAL INDICATIONS
INSTRUMENTATION AND SCANNING TECHNIQUE
Normal First-Trimester Pregnancy
T able 3-1B
T able 3-1C
T able 3-1A
T able 3-1D
4 to 6 Weeks
7 to 8 Weeks
9 to 11 Weeks
COMPLICATED EARLY INTRAUTERINE PREGNANCY
CAVEATS
O THER APPLICATIONS
SUMMARY
K E Y P O I N T S
Appendix 3-1
Ultrasound Examination of the Female Pelvis in the First
10 Weeks (Embryonic Period) of Pregnancy
INTRODUCTION
SPECIFICATIONS OF THE EXAMINATION
1. Indications
Comment
2. Imaging Parameters
Overall Comment
Comment
3. Equipment Specifications
Comment
4. F etal Safety
TRANSVAGINAL SONOGRAPHY OF ECTOPIC PREGNANCY
A rthur C. Fleischer
M ichael P. Diamond
Peter S. Cartwright
M elinda New
INTRODUCTION
INCIDENCE
P A THOGENESIS
CLINICAL ASPECTS
hCG ASSAY
SONOGRAPHIC EVALUATION
SCANNING TECHNIQUE
SONOGRAPHIC FINDINGS
Uterine
A dnexal
P e r itoneal
RARE TYPES OF ECTOPIC PREGNANCY
O THER ADNEXAL MASSES
TREATMENT IMPLICATIONS
MEDICOLEGAL CONSIDERATIONS
SUMMARY
REFERENCES
FETAL BIOMETRY
E u gene C . Toy
Philippe Jeanty
INTRODUCTION
IMPORTANCE OF A CRITICAL APPROACH
WHY FETAL BIOMETRY?
Selection of Patients
T ypes of Studies: Cross-Sectional or Longitudinal?
PRINCIPLES OF FETAL BIOMETRY
How Are Normal Values Derived?
T able 5-2
Prediction from Equations
How to Compute the Confidence Limits
ESTIMATION OF GESTATIONAL AGE
Definition
P arameters Proposed for Gestational Age Assessment
Gestational Sac
Crown-Rump Length
Biparietal Diameter
H ead Perimeter or Head Circumference
F emur and Humerus Lengths
Other Parameters
Ossification Center
Selection of an Appropriate Table
HOW TO REPORT THE RESULTS
THE ABDOMINAL PERIMETER
W hen Different Parameters Have Discrepancies in Estimates
O THER AVAILABLE NOMOGRAMS
CLINICAL CORRELATES
Answers
Appendix 5-1 Biometry Tables
T able A5-1
T able A5-2
T able 5-4
T able A5-5
T able A5-7
T able A5-8
PRENATAL DIAGNOSIS OF CONGENITAL HEART DISEASE
J ames Huhta
A na Luisa Neves
INTRODUCTION
CARDIAC ANATOMY AND FETAL CIRCULATION
FETAL HEART SCAN
F etal Heart Screening
T able 6-1
Maternal Autoimmune Disease
T e ratogen Exposure 30
F etal Echocardiogram
Indications for Fetal Echocardiogram
M AT E R N A L I NDIC A TIONS Maternal Metabolic Disorders
Obstetrical Ultrasound Examination Suggesting F etal Heart Disease
Obstetrical Ultrasound Scan Suggesting Extracardiac Disease in the Fetus
Maternal Congenital (or Familial) Heart Disease
P a ternal congenital heart disease
M endelian syndromes
Responsible Personnel for Fetal Echocardiogram
F etal Heart Echocardiographic Technique
Rhythm Abnormalities
Significance and Effectiveness of Prenatal Cardiac Diagnosis
Limitations of Fetal Echocardiography
Safety Issues
CONGENITAL HEART DISEASES
Left Heart Defects
H ypoplastic Left Heart Syndrome
Coarctation of the Aorta
Right Heart Defects
Pulmonary Valve Stenosis
Pulmonary Atresia With Intact Ventricular Septum
Ebstein’s Anomaly of the Tricuspid Valve or Tricuspid Dysplasia
Septal Defects
V entricular Septal Defects
A t rial Septal Defects
A t rioventricular Septal Defect
C onotruncal Defects
T etralogy of Fallot
Other Defects
H eterotaxy Syndromes
Common Arterial Trunk
D-Transposition of the Great Arteries
OUTCOMES OF CONGENITAL HEART DISEASE
HYDROPS FETALIS
Cardiac Failure in the Fetus
Prognosis of Fetal Heart Failure— Markers of Fetal Mortality
T he Cardiovascular Profile Score
P a r t 1 GENERAL OBSTETRIC SONOGRAPHY
T r eatment
EMERGING CONCEPTS
T ei Ind e x
V olume Sonography of the Fetal Heart
CLINICAL CORRELATES
T issue Doppler Imaging in the Fetus
CONCLUSIONS
K E Y P O I N T S
REFERENCES
H ighlighted References
PLACENTA, CORD, AND MEMBRANES
J oan M. Mastrobattista
E u gene C . Toy
INTRODUCTION
DEVELOPMENT OF THE PLACENTA: EMBRYOLOGY
Decidual Change
F e rtilization and Implantation
Placenta and Fetal Membranes
PLACENTAL IDENTIFICATION
Placental Calcification
MACROSCOPIC LESIONS OF THE PLACENTA: NORMAL
Subchorionic Fibrin Deposition
Intervillous Thrombosis
P e r ivillous Fibrin Deposition
Maternal Lakes
Infarcts
MACROSCOPIC LESIONS OF THE PLACENTA: ABNORMAL (TABLE 7-1)
Gestational Trophoblastic Disease
Primary Neoplasm
T able 7-1
Secondary Neoplasms
THE RETROPLACENTAL AREA
C ontractions
Leiomyomas
THE MEMBRANES
Placenta Extrachorialis
T he Umbilical Cord Insertion
V ARIATIONS IN SHAPE
Succenturiate Lobes
Placenta Membranacea
ANTEPARTUM HEMORRHAGE
R etroplacental/Submembranous Hematoma
Abruptio Placentae
Placenta Previa
UMBILICAL CORD
F ormation of the Umbilical Cord
Structure and Function of the Umbilical Cord
SONOGRAPHIC ANATOMY OF THE NORMAL CORD
CORD ABNORMALITIES
A bnormalities of Cord Length
A bnormalities of Cord Position
Single Umbilical Arter y
T rue Cord Cysts
Other
ABNORMAL CONDITIONS ASSOCIATED WITH MEMBRANES, SEPTA, OR SYNECHIAE
MULTIPLE PREGNANCIES
SUMMARY
K E Y P O I N T S
REFERENCES
PRENATAL DIAGNOSIS OF PLACENTA ACCRETA
Christine H. Comstock
RISK FACTORS
INTRODUCTION
P A THOLOGY
Before the beginning of a scan, ask all patients about previous uterine surge
DETECTION IN THE FIRST TRIMESTER
SECOND AND THIRD TRIMESTERS
V ascular Spaces
Clear Zone
Uterine-Bladder Serosa
Diagnosis in the Patient Without Uterine Scarring
Diagnosis of Placenta Percreta
USE OF COLOR DOPPLER
MAGNETIC RESONANCE IMAGING
Answer
KEY POINTS
CLINICAL CORRELATE
REFERENCES
FETAL GROWTH RESTRICTION
Christopher Harman
Ahmet A. Baschat
IMPACT OF FGR
NORMAL FETAL GROWTH
FGR TERMINOLOGY
CAUSES OF FGR
MATERNAL CAUSES V ascular Disease
T hrombophilias
Maternal Hypoxemia
Inadequate Substrate
Drugs
Demographics
FETAL FACTORS
THE SMALL FETUS
PLACENTA-BASED FGR Placental Development
IMPACTS OF PLACENTAL DEFICIENCY
T able 9-4
P A TTERNS OF FGR
Early Severe FGR—Easy to Diagnose, Hard to Manage
Late FGR—Hard to Diagnose, Easy to Manage
ULTRASOUND IN FGR
Biometry
BPD
Head Circumference
Abdominal Circumference
HC/AC Ratio
Skeletal Measurements
F etal Proportions
Estimated Fetal Weight
Measurement Definition of FGR
DETAILED ANATOMIC REVIEW
AMNIOTIC FLUID VOLUME
FETAL HEART RATE MONITORING
T able 9-5
C omputerized Heart Rate Analysis
C ontraction Stress Testing
DOPPLER
Multivessel Surveillance
Normal Progression
FGR Hemodynamics
FETAL BEHAVIOR
Biophysical Profile Scoring
INTEGRATED FETAL TESTING
T able 9-8
WHEN SHOULD THE FGR FETUS BE DELIVERED?
T able 9-10
P atterns of Deterioration in FGR Fetuses
ANCILLARY MEASURES T herapeutic Amnioinfusion
Antenatal Steroid Administration
Maternal Oxygenation
Maternal Volume Expansion
Maternal Hyperalimentation
OUTCOME—IMMEDIATE AND LONG TERM
Neonatal Outcomes
Long-Term Outcomes
REFERENCES
H ighlighted References
DOPPLER VELOCIMETRY OF THE UTEROPLACENTAL CIRCULATION
Lami Yeo
Luís F. Gonçalves
Roberto J. Romero
Maria-Teresa Gervasi
Percy Pacora
INTRODUCTION
ANATOMY AND DEVELOPMENT OF THE UTEROPLACENTAL CIRCULATION
INSTRUMENTATION AND EXAMINATION TECHNIQUE
DOPPLER VELOCITY WAVEFORMS OF THE NORMAL UTEROPLACENTAL CIRCULATION
Nonpregnant Uterus
F i r st Trimester
Second and Third Trimesters
Puerperium
T able 10-2
Influence of Sampling Site and Placental Implantation on Doppler Flow Velocit
ABNORMAL DOPPLER VELOCITY WAVEFORMS OF THE UTERINE ARTERY
Elevated Doppler Indices in the Uterine Arteries as a Measure of Impedance to
Computer Models of the Uteroplacental Circulation
Embolization of the Uteroplacental Circulation of Pregnant Ewes
Correlation of Placental Bed Biopsies and Uterine Artery Doppler Velocity Wav
Prediction of Preeclampsia and SGA Fetuses
T able 10-3
T able 10-5
T able 10-6
T able 10-7
T able 10-8
Prediction of Superimposed Preeclampsia in P atients With Chronic Hypertens
Risk of Stillbirth
UTERINE ARTERY DOPPLER IN PREGNANCIES ALREADY COMPLICATED BY PREECLAMPSIA
UTERINE ARTERY DOPPLER IN PREGNANCIES COMPLICATED BY FETAL GROWTH RESTRICTIO
RANDOMIZED CONTROLLED TRIALS
COMBINATION OF UTERINE ARTERY DOPPLER VELOCIMETRY WITH O THER TESTS
Uterine Artery Doppler Velocimetry C ombined With 24-Hour Automated Blood P
Uterine Artery Doppler Velocimetry in Patients W ith Elevated Maternal Serum
Uterine Artery Doppler in Pregnancies With Elevated Free β -hCG
C ombination of MSAFP, Maternal Serum hCG, and Uric Acid Levels
C ombination of Inhibin A and Uterine Artery Doppler
Pregnancy-associated plasma protein A, F r ee
β -hCG, A ctivin A, Inhibin A, and Uterine Artery Doppler
Placental Growth Factor, Soluble Fms-Like Tyrosine Kinase, and Uterine Arte
Homocysteine and Uterine Artery Doppler
PRETERM LABOR
DIABETES MELLITUS
FIRST TRIMESTER UTERINE ARTERY DOPPLER VELOCIMETRY
Association With Miscarriage
Uterine Artery Doppler in the First Trimester as a Screen for Preeclampsia
F irst Trimester Uterine Artery Doppler
Changes in Uterine Artery Doppler From First to Second Trimesters
Uterine Artery Doppler in the First Trimester as a Screen for Fetal Growth Re
Uterine Artery Doppler and First Trimester Biochemical Serum Markers
P APP-A and First Trimester Uterine Artery Doppler
Combination of PAPP-A and Free β -hCG With Second T rimester Uterine Artery
Combination of Placental Protein 13 With First T rimester Uterine Artery Dopp
F irst Trimester PAPP-A, PP-13, and Second T rimester Uterine Artery Doppler
Placental Growth Factor and First Trimester U terine Artery Doppler
EMERGING CONCEPTS
REFERENCES
K E Y P O I N T S
H ighlighted References
DOPPLER INTERROGATION OF THE FETAL CIRCULATION
F r ancesca Gotsch
Laura Cruciani
F abio Ghezzi
Giovanna Ogge’
Lami Yeo
Roberto J. Romero
INTRODUCTION
UMBILICAL ARTERY
Anatomy of the Umbilical Arteries
Physiology of the Umbilical Arteries
Sampling Techniques
Morphology of the Umbilical Artery Waveform and Changes with Gestational Age
T he Physiologic Significance of an Abnormal Umbilical Artery Waveform
T able 11-1
Clinical Correlations of Abnormal Umbilical Artery Doppler Velocimetry
Small for Gestational Age
Congenital/Chromosomal Anomalies
Placental Abruption
P e rsistent Discordant Flow Velocity Waveforms in the 2 Umbilical Arteries
Umbilical Artery Doppler Velocimetry during Labor
UMBILICAL VEIN
Anatomy of the Umbilical Vein
Sampling Techniques
Morphology of the Umbilical Vein Waveform and Changes with Gestational Age
Definition of Umbilical Vein Pulsations
Umbilical Vein Pulsations in Normal Pregnancies
P athophysiology of Umbilical Vein Pulsations
Clinical Correlations of Umbilical Vein Pulsations
U mbilical Vein Pulsations in SGA Fetuses
DOPPLER INTERROGATION OF THE CEREBRAL CIRCULATION
Middle Cerebral Artery
Anatomy of the Middle Cerebral Arter y
Sampling Techniques
Morphology of the Middle Cerebral Artery Waveform and Changes with Gestationa
Indices
Clinical Correlations of an Abnormal Middle Cerebral Artery Doppler Velocimet
T able 11-4
ANTERIOR CEREBRAL ARTERY
Anatomy of the Anterior Cerebral Arter y
Sampling Techniques
Indices
Clinical Correlations of an Abnormal Anterior Cerebral Artery Doppler Velocim
DUCTUS VENOSUS
Anatomy of the Ductus Venosus
Physiology of the Ductus Venosus
Shunting
Sampling Techniques
Morphology of the Ductus Venosus Waveform and Changes with Gestational Age
Doppler Indices
Clinical Correlations of an Abnormal Ductus V enosus Doppler Velocimetry
INFERIOR VENA CAVA
Anatomy of the Inferior Vena Cava
Sampling Techniques
Indices
Morphology of the Inferior Vena Cava Waveform and Changes with Gestational Ag
Clinical Correlations of an Abnormal Inferior V ena Cava Doppler Velocimetry
HEPATIC VEINS
Anatomy of the Hepatic Veins
Sampling Technique
Indices
Morphology of the Hepatic Veins Waveform and Changes with Gestational Age
Clinical Correlations
PULMONARY VEINS
Anatomy of the Pulmonary Veins
Sampling Techniques
T he Physiology of the Pulmonary Veins
Morphology of the Pulmonary Veins Waveform and Changes with Gestational Age
Indices
T he Physiologic Significance of an Abnormal Pulmonary Vein Waveform
A ORTIC ISTHMUS
Anatomy of the Aortic Isthmus
Hemodynamics in the Aortic Isthmus
Sampling Techniques
Morphology of the Aortic Isthmus Waveform and Changes with Gestational Age
Doppler Indices
T he Physiologic Significance of an Abnormal A o rtic Isthmus Waveform
T able 11-7
Clinical Correlations of an Abnormal Aortic Isthmus Doppler Velocimetry
DESCENDING AORTA
Sampling Techniques
Morphology of the Descending Aorta Waveform and Changes With Gestational Age
Indices
Clinical Correlations of an Abnormal Descending A o rta Doppler Velocimetry
T able 11-9
R E N A L A R T E R I E S
Anatomy of the Renal Arteries
Sampling Techniques
Morphology of the Renal Arteries Waveform and Changes with Gestational Age
ADRENAL ARTERY
Anatomy of the Adrenal Arteries
Sampling Techniques
T able 11-10
Physiology of the Adrenal Artery
Morphology of the Adrenal Artery Waveform and Changes with Gestational Age
Indices
Clinical Correlations of an Abnormal Adrenal Artery Doppler Velocimetry
SUPERIOR MESENTERIC ARTERY
Anatomy of the Superior Mesenteric Artery
Sampling Techniques
Indices
Morphology of the Superior Mesenteric Artery W a v e f orm and Changes with G
Clinical Correlations of an Abnormal Superior Mesenteric Artery Doppler Velo
CELIAC ARTERY
Anatomy of the Celiac Artery
Sampling Techniques
Morphology of the Celiac Artery Waveform and Changes with Gestational Age
Indices
Implications
SPLENIC ARTERY
T able 11-11
Anatomy of the Splenic Artery
Sampling Techniques
Indices
Morphology of the Splenic Artery Waveform and Changes with Gestational Age
Clinical Significance
PELVIC AND LOWER EXTREMITIES CIRCULATION: EXTERNAL ILIAC ARTERIES AND FEM
Anatomy
Sampling Techniques
F emoral and External Iliac Artery Flow V elocity Waveforms
Clinical Implications
CORONARY CIRCULATION
Anatomy of the Coronary Circulation
Physiology of the Coronary Circulation
Sampling Techniques
Normal Coronary Arteries Waveform and Changes with Gestational Age
Clinical Implications
FUTURE DIRECTIONS
K E Y P O I N T S
REFERENCES
COLOR DOPPLER SONOGRAPHY IN OBSTETRICS
Dario Paladini
Gabriella Sglavo
P aolo Volpe
B ASIC CONSIDERATIONS
CDUS/PDUS TO DEMONSTRATE NORMAL/ ABNORMAL FETAL CARDIOVASCULAR ANATOMY
F etal Heart
C entral Venous S ystem
T he Aortic Arch
T he Normal Cerebral Circulation
C e r ebral Arteriovenous Malformations
Other Conditions Associated with Arteriovenous Shunt
CDUS/PDUS TO HELP IDENTIFY DISPLACED FETAL ORGANS AND ABNORMAL FETAL MASSE
CDUS/PDUS TO GUIDE PULSED-WAVE DOPPLER SAMPLING OF MATERNAL AND FETAL VESSEL
Uterine Artery in Screening Protocols for Intrauterine Growth Restriction/Pre
Ductus Venosus in the Staging of Vascular C ompromise in Fetuses with IUGR
Middle Cerebral Artery for Noninvasive Diagnosis and Monitoring of Fetal Anem
CDUS/PDUS TO STUDY PLACENTAL MEMBRANES AND UMBILICAL CORD
Placenta and Membranes
Umbilical Cord
CLINICAL CORRELATES
CONCLUSIONS
2. H ow are neuromuscular disorders ruled out?
Middle cerebral artery for fetal anemia
Uterine artery Doppler in screening for preeclamp sia or IUGR
Ductus venosus for IUGR assessment
REFERENCES
KEY POINTS
1. A ctivate color/power Doppler sonography only after
H ighlighted References
SONOGRAPHY IN MULTIPLE GESTATION
Alexandra Matias
Philippe Jeanty
E u gene C . Toy
EMBRYOLOGY
INTRODUCTION
TIMING OF SEPARATION
HETEROTOPIC GESTATION
Differential Diagnosis
MOLAR GESTATION WITH A CONCURRENT PREGNANCY
CHORIONICITY AND PERINATAL PROGNOSIS
THE NAMING OF TWINS
MONOAMNIOTIC TWINS
Definition
Sonographic Features
Differential Diagnosis
Associated Syndromes
CONJOINED TWINS
Definition
Sonographic Features
Classification
T able 13-2
Differential Diagnosis
Associated Syndromes
Prognosis
Management
UNIQUE MONOZYGOTIC MONOCHORIONIC SYNDROMES
Affecting structurally normal babies
Being associated with important perinatal morbid ity and mortality
Diagnosis of Twin-to-Twin Transfusion S yndrome
1 . Discordance in amniotic fluid volume (oligo polyhydramnios sequence)
2. Discordance in fetal size
3. A bnormal Doppler findings
4. F etal echocardiography
5. Signs of hydrops in the recipient twin
6. Other ultrasonographic findings
Ti m i n g
Prognosis
Management
Differential Diagnosis
Associated Complications
Prediction of Twin-to-Twin Transfusion Syndrome
N uchal Translucency
Ductus Venosus Flowmetr y
Growth Discordance in the First Trimester of Pregnancy
Arterio-Arterial Anastomoses
Intertwin Membrane Folding
T win “Embolization” S yndrome
Differential Diagnosis
T win Reversed Arterial Perfusion Syndrome (or Acardiac Twin)
Management
Differential Diagnosis
Associated Syndromes
F etus In Fetu
Synonyms
E tiology
P a thogenesis
Localization
V ascularization
Age at Detection
W eight
Presenting Symptoms in Children
N umber
Z y gosity
Macroscopic Appearance
What Is Included
Differential Diagnosis
Associated Anomalies
E volution
Prognosis
Recurrence Risk
Management
V ANISHING TWIN
Sonographic Features
Associated Syndromes
FETUS PAPYRACEOUS
PRENATAL SCREENING AND DIAGNOSIS: DOES CHORIONICITY MATTER?
Differential Diagnosis
INVASIVE TECHNIQUES IN TWINS
Diagnostic Amniocentesis
DISCORDANCE OF FETAL GROWTH: WHAT IS ADAPTATION, PROMOTION, AND GROWTH RE
VELAMENTOUS INSERTION OF THE PLACENTA
CONGENITAL ANOMALIES
MULTIFETAL PREGNANCY REDUCTION
PRETERM DELIVERY: DOES CERVICAL LENGTH MATTER?
KEY POINTS
REFERENCES
FETAL ANOMALIES AND DISORDERS
FETAL ANOMALIES: O VERVIEW
Lami Yeo
Roberto J. Romero
S u n Kwon Kim
Luís F. Gonçalves
INTRODUCTION
FUNDAMENTAL CONCEPTS
Malformation
Deformation
Disruption
T able 14-1
T he Fetus with Multiple Anomalies
P olytopic Field Defect
Dysplasia
Sequence
Syndrome
Association
CLASSIFICATION OF ANOMALIES
Ultrasonographic Markers
INCIDENCE OF CONGENITAL ANOMALIES
T able 14-7
T able 14-8
MORBIDITY, MORTALITY, AND BURDEN OF CONGENITAL ANOMALIES TO SOCIETY
T able 14-10
CAUSES AND RECURRENCE RISK OF CONGENITAL ANOMALIES
ULTRASOUND DIAGNOSIS OF CONGENITAL ANOMALIES
A CCURACY OF PRENATAL ULTRASOUND IN THE DETECTION OF CONGENITAL ANOMALIES S
T able 14-13
Chapter 14 F etal Anomalies: Overview
T able 14-14
T able 14-16
F i r st Trimester Ultrasound
Legal Implications of Accuracy Studies
MANAGEMENT PRINCIPLES IN THE DETECTION OF CONGENITAL ANOMALIES
P erformance of Prenatal Diagnosis
W orkup of an Abnormal Finding
Pregnancy Termination
Site, Mode, and Timing of Delivery
SHOULD EVERY PREGNANT PATIENT HAVE AN ULTRASOUND EXAMINATION?
W h y the Discrepancy Between the Results of the T w o Studies (RADIUS Compar
Detection of Congenital Anomalies
T able 14-19
Correction of Dating Errors
Detection of Multiple Pregnancies
Detection of Growth Disorders
Cost of a Routine Screening Program
IMPACT OF PRENATAL DIAGNOSIS ON
THE BIRTH PREVALENCE AND OUTCOME
OF FETUSES WITH CONGENITAL ANOMALIES
EMERGING CONCEPTS
KEY POINTS
REFERENCES
H ighlighted References
PRENATAL DIAGNOSIS OF CEREBROSPINAL ANOMALIES
Gianluigi Pilu
NORMAL SONOGRAPHIC ANATOMY OF THE FETAL CENTRAL NERVOUS SYSTEM
INTRODUCTION
VENTRICULOMEGALY
NEURAL TUBE DEFECTS
T able 15-1
MIDLINE ANOMALIES
DESTRUCTIVE CEREBRAL LESIONS
DISORDERS OF NERVE CELL PROLIFERATION
T able 15-4
T able 15-6
ANOMALIES OF NEURONAL MIGRATION
V ASCULAR ABNORMALITIES
INTRACRANIAL CYSTS
CONCLUSIONS
H ighlighted References
FETAL NECK AND CHEST ANOMALIES
M ieke Cannie
J acques Jani
FETAL NECK ANOMALIES
Anterocervical Pathologies
Enlargement of the Thyroid Gland or Goiter
Cervical Teratoma
P osterocervical Pathology
Second Trimester Nuchal Fold Thickness
Encephalocele
C ystic Hygroma or Lymphangioma
FETAL CHEST ANOMALIES
P athologies of the Fetal Lungs
Congenital Cystic Adenomatoid Malformation
Sequestration
Bronchogenic Cyst
Congenital High Airway Obstruction
Pleural Effusion
C ongenital Diaphragmatic Hernia
Overview
Diagnosis
Prediction of Postnatal Outcome by Two- and T hree-Dimensional Ultrasonograph
T able 16-1
Prediction of Postnatal Outcome by MRI
F etal Surgery for CDH
EMERGING CONCEPTS
What are other important considerations in this case?
H ighlighted References
FETAL GASTROINTESTINAL ANOMALIES
P aolo Volpe
Dario Paladini
V alentina De Robertis
Cristina Rossi
Georgios Rembouskos
EMBRYOLOGIC DEVELOPMENT OF THE GASTROINTESTINAL SYSTEM
T he Primitive Gut
Physiologic Herniation of the Midgut and Its Subsequent Reduction
Liver, Choledocal System, P ancreas, and Spleen
F etal Thorax
NORMAL ULTRASONOGRAPHIC APPEARANCE OF THE GIT AND SECTIONAL APPROACH: FROM
F etal Head
F etal Abdomen
Emerging Concepts
INTRAABDOMINAL MASSES AND DIFFERENTIAL DIAGNOSIS
Splenic Cyst
E tiology
Differential Diagnosis
Prognosis and Management
Choledochal Cyst
E tiology
Ancillary Ultrasound Signs
Differential Diagnosis
Caroli Disease
T able 17-2
Prognosis and Management
P ancreatic Cyst
Sonographic Appearance
Associated Anomalies
Prognosis and Management
Answer
5. Fetal sex : Female.
STENOSIS AND ATRESIAS
Esophageal Atresia
Definition and Incidence
E tiology
Ancillary Ultrasound Signs
Associated Anomalies
Recurrent Risk
Management
Emerging Concepts and Future Directions
Duodenal Atresia
Definition and Incidence
E tiology
Ancillary Ultrasound Signs
Associated Anomalies
K E Y P O I N T S
K E Y P O I N T S
Management
E tiology
Ancillary Ultrasound Signs
Associated Anomalies
Jejunoileal Stenosis and Atresia
Definition and Incidence
Management
Emerging Concepts
K E Y P O I N T S
Ancillary Ultrasound Signs
Anal Atresia and Other Anorectal Abnormalities
Definition and Incidence
E tiology
Associated Anomalies
Management
K E Y P O I N T S
HYPERECHOGENIC BOWEL
Definition and Incidence
Etiology
Ancillary Ultrasound Signs
Associated Anomalies
Management
Emerging Concepts
Ancillary Ultrasound Signs
K E Y P O I N T S
MECONIUM ILEUS
Definition and Incidence
Etiology
Associated Anomalies
Management
ENTERIC DUPLICATION CYST
Definition and Incidence
Etiology
Ancillary Ultrasound Signs
Differential Diagnosis
Associated Anomalies
Management
K E Y P O I N T S
Associated Anomalies
HEPATIC AND SPLENIC ABNORMALITIES
Hepatic Echogenicities
Definition and Incidence
E tiology
Ancillary Ultrasound Signs
Management
Hepatomegaly and Splenomegaly
Definition and Incidence
E tiology
Ancillary Ultrasound Signs
Management
KEY POINTS
CLINICAL CORRELATE
C omment
F inal Consideration
GALL BLADDER AGENESIS
Definition and Incidence
Ancillary Ultrasound Signs
Associated Anomalies
Management
UMBILICAL, PORTAL, AND HEPATIC VENOUS SYSTEMS
Umbilical and Portal Venous Systems Malformations
Definition and Anatomy
E tiology
Ancillary Ultrasound Signs
Associated Anomalies
Management
Emerging Concepts and Future Directions
Umbilical Vein Varix
Definition and Incidence
E tiology
Ancillary Ultrasound Signs
Associated Anomalies
Management
P e r sistent Right Umbilical Vein
Definition and Incidence
E tiology
Ancillary Ultrasound Signs
Associated Anomalies
ABDOMINAL WALL DEFECTS
Gastroschisis
Definitions
T able 17-3
KEY POINTS
Incidence
Embryogenetic Mechanism
Risk of Recurrence
Causative Factors
Ancillary Ultrasound Signs
Complications
Associated Anomalies
Management
Exomphalos (Omphalocele)
Definition and Incidence
Embryogenetic Mechanism
Risk of Recurrence
Causative Factors
Ancillary Ultrasound Signs
Complications
Associated Anomalies
T able 17-4
Management
KEY POINTS
REFERENCES
THE FETAL GENITOURINARY SYSTEM
Carol B. Benson
Peter M. Doubilet
RENAL AGENESIS
RENAL ECTOPIA
HYDRONEPHROSIS
URETEROPELVIC JUNCTION OBSTRUCTION
VESICOURETERAL REFLUX
PRIMARY MEGAURETER
BLADDER OUTLET OBSTRUCTION
RENAL DUPLICATION
MULTICYSTIC DYSPLASTIC KIDNEY
HEREDITARY POLYCYSTIC KIDNEY DISEASE
A utosomal Recessive Polycystic Kidney Disease
A utosomal Dominant Polycystic Kidney Disease
RENAL MASSES AND CYSTS
ABNORMALITIES OF THE URINARY BLADDER
Megacystis
Exstrophy
ABNORMALITIES OF THE REPRODUCTIVE SYSTEM AND EXTERNAL GENITALIA
Ovarian Cysts and Masses
Hydrometrocolpos
Hydrocele
Cryptorchidism
Ambiguous Genitalia
T esticular Feminization
K E Y P O I N T S
FETAL SKELETAL ANOMALIES
Lami Yeo
Roberto J. Romero
F r ancesca Gotsch
E d i Vaisbuch
Gianluigi Pilu
MOLECULAR GENETIC BASIS OF THE CHONDRODYSPLASIAS
ABNORMAL MESENCHYMAL DIFFERENTIATION
Bone Morphogenetic Proteins
Mutation in Transcription Factor Genes
INTRODUCTION
SOX and TBX Genes
ABNORMAL CHONDROCYTES MATURATION
F ibroblast Growth Factor Receptors
H omeotic Genes
P arathyroid Hormone Related Protein Receptor
DEFECTS OF EXTRACELLULAR MATRIX COMPONENTS
C ollagen
Cartilage Oligomeric Matrix Protein
DISORDERS OF PROTEOGLYCAN SULFATATION
BIRTH PREVALENCE AND CONTRIBUTION T O PERINATAL MORTALITY
CLASSIFICATION OF SKELETAL DYSPLASIAS
T able 19-3
T able 19-4
T able 19-4
T able 19-4
T able 19-4
T able 19-4
TERMINOLOGY FREQUENTLY USED IN THE DESCRIPTION OF BONE DYSPLASIAS
BIOMETRY OF THE FETAL SKELETON
IN THE DIAGNOSIS OF BONE DYSPLASIAS
T able 19-6
T able 19-8
R OLE OF ULTRASONOGRAPHY IN THE DETECTION OF SKELETAL DYSPLASIAS
CLINICAL PRESENTATION
APPROACH TO THE DIAGNOSIS OF SKELETAL DYSPLASIAS
Evaluation of Long Bones
T able 19-9
Evaluation of Thoracic Dimensions
Evaluation of Hands and Feet
Evaluation of the Fetal Cranium
Evaluation of the Fetal Face
T able 19-10
T able 19-11
T able 19-12
Evaluation of the Fetal Spine
Ve r t e b r a l B o d i e s
Spinal Curvature
Evaluation of the Internal Organs
Evaluation of the Neonate
INCREASED NUCHAL TRANSLUCENCY AND SKELETAL DYSPLASIAS
OSTEOCHONDRODYSPLASIAS
A CHONDROPLASIA, THANATOPHORIC D Y SPLASIA, AND HYPOCHONDROPLASIA
A chondroplasia
T he most common nonlethal skeletal dysplasia is
T able 19-19
SADDAN (Severe Achondroplasia with Developmental Delay and Acanthosis Nigrica
T hanatophoric Dysplasia
Hypochondroplasia
FIBROCHONDROGENESIS, A TELOSTEOGENESIS
F ibrochondrogenesis
A telosteogenesis
A CHONDROGENESIS
OSTEOGENESIS IMPERFECTA AND HYPOPHOSPHATASIA
Osteogenesis Imperfecta
Hypophosphatasia
DIASTROPHIC DYSPLASIA
KNIEST SYNDROME
D Y SSEGMENTAL DYSPLASIA
CAMPOMELIC DYSPLASIA
SKELETAL DYSPLASIAS CHARACTERIZED BY A HYPOPLASTIC THORAX
Asphyxiating Thoracic Dysplasia (Jeune Syndrome)
Short Rib–Polydactyly Syndromes
Chondroectodermal Dysplasia
T able 19-21
LIMB DEFICIENCY OR CONGENITAL AMPUTATIONS
T able 19-22
SYNDROMES WITH ABSENT LIMBS AND FACIAL ANOMALIES
Limb Reduction Defects Associated With Other Anomalies
PHOCOMELIA
In phocomelia , the e x tremities resemble those of a seal
F ocal Proximal Femoral Deficiency, or Congenital Short Femur
Split Hand and Foot Deformities
CLUB HAND DEFORMITIES
Radial Clubhand
POLYDACTYLY
ARTHROGRYPOSIS
T able 19-26
EMERGING CONCEPTS
KEY POINTS
REFERENCES
H ighlighted References
FETAL SYNDROMES
J uliana Moyses L Abdalla
Sandra R. Silva
Philippe Jeanty
INTRODUCTION
A CHONDROGENESIS
A CHONDROPLASIA
AICARDI SYNDROME
ALAGILLE SYNDROME
AMNIOTIC BAND SYNDROME
ANTLEY-BIXLER SYNDROME
APERT SYNDROME
ARNOLD-CHIARI MALFORMATION
ARTHROGRYPOSIS MULTIPLEX CONGENITA
ASPHYXIATING THORACIC D Y SPLASIA
ASPLENIA-POLYSPLENIA SYNDROMES
BECKWITH-WIEDEMANN SYNDROME
CAMPOMELIC DYSPLASIA
CAUDAL REGRESSION SYNDROME
CORNELIA DE LANGE SYNDROME
FETAL ALCOHOL SYNDROME
FETAL CYTOMEGALOVIRUS INFECTION
FETAL RUBELLA SYNDROME
FETAL TOXOPLASMOSIS SYNDROME
FETAL VARICELLA ZOSTER
FRASER SYNDROME
FRYNS SYNDROME
GOLDENHAR SYNDROME
HEREDITARY LYMPHEDEMA I
HOLT-ORAM SYNDROME
D EFINITION : The Holt-Oram syndrome consists of an upper-limb malformation
HYDROLETHALUS SYNDROME 1
HYPOPLASTIC LEFT HEART SYNDROME
KLIPPEL-FEIL SYNDROME
KLIPPEL-TRENAUNAY-WEBER SYNDROME
LARSEN SYNDROME
LETHAL MULTIPLE PTERYGIUM SYNDROME
MECKEL SYNDROME
MONOSOMY X (TURNER) SYNDROME
NOONAN SYNDROME
P ALLISTER-KILLIAN SYNDROME
PENA-SHOKEIR SYNDROME
PENTALOGY OF CANTRELL
PFEIFFER SYNDROME
PRADER-WILLI SYNDROME
PRUNE BELLY SYNDROME
R OBERTS SYNDROME
PIERRE ROBIN SYNDROME
SEPTOOPTIC DYSPLASIA
TUBEROUS SCLEROSIS
V A CTERL ASSOCIATION
W ALKER-WARBURG SYNDROME
REFERENCES
ULTRASOUND DETECTION OF CHROMOSOMAL ANOMALIES ∗
Philippe Jeanty
W erther Adrian Clavelli
S ilvia Susana Romaris
COMPLEMENTARY INVESTIGATIONS
T r iple Screen
REVIEW OF THE GENETIC CONCEPTS AND TERMINOLOGY
Mitosis
Meiosis
Chromosomal Anomalies
Aneuploidy
Inversion
Isochromosomes
U niparental Disomy
Deletions
Duplications
Ring Chromosome
Reciprocal Translocation
Robertsonian Translocation
Dominant and Recessive Alleles
A utosomal Dominant
A utosomal Recessive
X-Linked Transmission
ULTRASOUND FINDINGS DURING THE FIRST TRIMESTER
Nuchal Edema
T ight Amnion
T w o-Vessel Cord
Y olk Sac Anomalies
Major Structural Anomalies
Shapeless Embryo
SECOND-TRIMESTER FINDINGS
C entral Nervous System
Head and Neck
Cardiovascular Anomalies
Echogenic Focus in the Heart
Chest
T w o-Vessel Cord
C o r d Cysts
Swiss-Cheese Placenta
Gastrointestinal Findings
Duodenal Atresia
Esophageal Atresia or Tracheoesophageal Fistulas
Omphalocele
T o Karyotype or not to Kar yotype?
Bowel Obstructions
Urinary Tract Anomalies
Genital Findings
Skeletal Findings
Limb Shortening
Simian Crease
F indings Related to Anomalies of the Skull and Skull Shape
Eleven Pairs of Ribs
Iliac Wing Angle
Growth Restriction
Definition
Prevalence
E tiology
SCORING SYSTEMS
DIFFERENTIAL DIAGNOSES
TRISOMY 21
Synonyms
P a thogenesis
Differential Diagnosis
Associated Anomalies
Prognosis
Recurrence Risk
Management
TRISOMY 18
Synonyms
Definition
Prevalence
E tiology
P a thogenesis
Prognosis
Recurrence Risk
Management
Associated Anomalies
TRISOMY 13
Synonyms
Definition
E tiology
P a thogenesis
Differential Diagnosis
Prognosis
Recurrence Risk
Management
Associated Anomalies
TRISOMY 8
Synonyms
Definition
Prevalence
E tiology
P a thogenesis
Differential Diagnosis
Prognosis
Recurrence Risk
Associated Anomalies
TRISOMY 9
Synonyms
Definition
Prevalence
E tiology
P a thogenesis
Differential Diagnosis
Prognosis
Recurrence Risk
Management
Associated Anomalies
4p-SYNDROME
Synonyms
Definition
Prevalence
E tiology
P a thogenesis
Prognosis
Recurrence risk
Management
Associated Anomalies
TRIPLOIDY
Synonyms
Definition
Prevalence
E tiology
P a thogenesis
Differential Diagnosis
Prognosis
Recurrence Risk
Management
Associated Anomalies
MONOSOMY X
Synonyms
Definition
Prevalence
E tiology
P a thogenesis
Differential Diagnosis
Prognosis
Recurrence Risk
Management
Associated Anomalies
REFERENCES
RISK ASSESSMENT AND THERAPY
Chapter 22
FIRST TRIMESTER SCREENING
F ionnuala M. Breathnach
F ergal D. Malone
INTRODUCTION
EVOLUTION OF FIRST TRIMESTER SCREENING
NUCHAL TRANSLUCENCY: TECHNIQUE AND CHALLENGES
T able 22-1
SEPTATED CYSTIC HYGROMA: A DISTINCT ENTITY?
COMBINED/INTEGRATED/SEQUENTIAL AND CONTINGENT SCREENING APPROACHES
ANCILLARY FIRST TRIMESTER MARKERS FOR ANEUPLOIDY
F etal Nasal Bone in the First Trimester
F i r st Trimester Doppler Assessment of the Ductus Venosus
F i r st Trimester Tricuspid R egurgitation
QUALITY ASSURANCE
SCREENING FOR ANEUPLOIDIES O THER THAN TRISOMY 21
T able 22-3
FIRST TRIMESTER SCREENING FOR ANATOMIC DEFECTS
T able 22-5
T able 22-7
SCREENING IN MULTIPLE GESTATION
T able 22-8
FUTURE DIRECTIONS
CONCLUSIONS
CLINICAL CORRELATES
KEY POINTS
REFERENCES
H ighlighted References
FETAL BIOPHYSICAL PROFILE SCORE: THEORETICAL CONSIDERATIONS AND PRACTICAL AP
F r ank A. Manning
FETAL ADAPTIVE RESPONSES TO ACUTE AND CHRONIC HYPOXEMIA OR ACIDEMIA
FETAL BIOPHYSICAL PROFILE SCORE: METHOD AND MODIFICATION
FETAL BIOPHYSICAL PROFILE SCORING: CLINICAL APPLICATION, PREDICTIVE A CCURA
Clinical Application
P e r inatal Outcome: Mortality and Morbidity
T able 23-2
BIOPHYSICAL PROFILE SCORE AND FETAL CORD BLOOD ACID–BASE AND pH VALUES
FETAL BIOPHYSICAL PROFILE SCORING: OUTCOME IN SELECTED HIGH-RISK SUBGROUPS
BIOPHYSICAL PROFILE SCORE: RELATION TO NEUROLOGIC CONDITIONS OF CHILDHOOD
EMERGING CONCEPTS
CLINICAL CORRELATE
K E Y P O I N T S
REFERENCES
H ighlighted Reference
CHORIONIC VILLUS SAMPLING
Ronald J. Wapner
E u gene C . Toy
CONCEPTS AND INDICATIONS FOR CHORIONIC VILLUS SAMPLING
INTRODUCTION
HISTORY OF CHORIONIC VILLUS SAMPLING
CHORIONIC VILLUS SAMPLING: THE PROCEDURE
Procedure-Related Anatomy (Figure 24-1)
Sampling Techniques
T able 24-2
T r anscervical Sampling
T r ansabdominal Chorionic Villus Sampling
C onfirmation of Adequate Tissue R etrieval
RISKS ASSOCIATED WITH CHORIONIC VILLUS SAMPLING
Bleeding
Infection
Ruptured Membranes
Elevated MSAFP
Rh Isoimmunization
Pregnancy Loss
PREGNANCY LOSS: TRANSCERVICAL VERSUS TRANSABDOMINAL CHORIONIC VILLUS SAMPLI
RISK OF FETAL ABNORMALITIES AFTER CHORIONIC VILLUS SAMPLING
T able 24-3
PERINATAL RISKS AND IMPACT ON
LONG- TERM DEVELOPMENT OF THE INFANT
LABORATORY ASPECTS OF CHORIONIC VILLUS SAMPLING
MATERNAL CELL CONTAMINATION
CONFINED PLACENTAL MOSAICISM
BIOCHEMICAL AND DNA PROCEDURES
CHORIONIC VILLUS SAMPLING IN MULTIPLE GESTATIONS
CHORIONIC VILLUS SAMPLING AND MULTIFETAL PREGNANCY REDUCTION
SUMMARY
KEY POINTS
AMNIOCENTESIS
J uan Pedro Kusanovic
Cristiano Jodicke
Lami Yeo
Roberto J. Romero
L u ís F. Gonçalves
Maria-Teresa Gervasi
Mark Redman
F abio Ghezzi
1. Amniocentesis with a filtration technique:
HISTORICAL ASPECTS
INDICATIONS
Ultrasound
Operative Technique
TECHNICAL ASPECTS OF THE PROCEDURE
Gestational Age
Needle Selection
V olume of Amniotic Fluid
INTRAOPERATIVE COMPLICATIONS
Membrane Tenting
Multiple Needle Insertions
Bloody Taps
F etomaternal Transfusion
Discolored Amniotic Fluid
AMNIOCENTESIS RISKS
Maternal Risks
F etal Risks
Fetal Loss
Infection
F etal Injuries Associated with Amniocentesis
Other Complications
Leakage of Amniotic Fluid
Long-Term Outcome
Isoimmunization
EARLY AMNIOCENTESIS
T able 25-5
MOLECULAR DIAGNOSTIC TECHNIQUES
AMNIOCENTESIS IN MULTIPLE GESTATIONS
AMNIOCENTESIS FOR THE DIAGNOSIS OF MICROBIAL INVASION OF THE AMNIOTIC CAVITY
Definition
T able 25-6
F r equency
Diagnosis of Microbial Invasion of the Amniotic Cavity Using Conventional Cul
T able 25-7
T able 25-8
T able 25-10
Diagnosis of Microbial Invasion of the Amniotic Cavity Using Molecular Microb
Importance of the Diagnosis
Amniotic Fluid Collection
T able 25-11
Chapter 25 Amniocentesis
T ests for Diagnosis of Microbial Invasion of the Amniotic Cavity
Amniotic Fluid Gram Stain
T able 25-12
A cridine Orange Stain
Limulus Amebocyte Lysate Assay
Glucose Concentration in Amniotic Fluid
T able 25-13
White Blood Cell Count in Amniotic Fluid
T able 25-15
Amniotic Fluid Interleukin-6 Concentrations
Matrix Metalloproteinase-8 in Amniotic Fluid
C omparison between Amniotic Fluid Tests
Bedside Rapid Test for Diagnosis of Microbial Invasion of the Amniotic Cavity
T able 25-18
REFERENCES
KEY POINTS
H ighlighted References
Chapter 26 F etal Blood Sampling
FETAL BLOOD SAMPLING
F abio Ghezzi
A n tonella Cromi
F r ancesca Gotsch
Gabriele Siesto
Edi Vaisbuch
Roberto J. Romero
Definitions
2. P e r cutaneous umbilical blood sampling (PUBS):
TECHNIQUES OF FETAL BLOOD SAMPLING
C o r docentesis
Intrahepatic Vein Blood Sampling
Cardiocentesis
Quality Control of the Specimen
Duration of the Procedure
T r aining
Normal Values f or F etal Blood
COMPLICATIONS
Maternal Complications
F etal Losses
T able 26-4
Chapter 26 F etal Blood Sampling
Hemorrhage
C o r d Hematoma
Bradycardia
F etomaternal Hemorrhage
Abruptio Placentae
Preterm Delivery
F etal Resuscitation
T able 26-5
INDICATIONS
C ytogenetic Diagnosis
C ongenital Infections
F etal Anemia
Primary Immunodeficiency Diseases
C oagulopathies
T able 26-6
Platelet Disorders
T hrombocytopenias
T hrombocytopathies
Hemoglobinopathies
T able 26-7
Intrauterine Growth Restriction
T h yroid Disease
FETAL BLOOD SAMPLING IN MULTIPLE GESTATIONS
FETAL THERAPY
EMERGING CONCEPTS
KEY POINTS
FETAL THERAPY: M A TERNAL FETAL SURGERY AND PERCUTANEOUS ULTRASOUND GUIDE
R. Douglas Wilson
Definitions
2. C ongenital anomalies/birth defect terminology:
8. T horacocentesis/vesicocentesis/fetal cyst aspiration:
INTRODUCTION
SECTION I: MATERNAL FETAL SURGERY
T able 27-2
Summary
SECTION II: PERCUTANEOUS ULTRASOUND GUIDED FETAL THERAPY PROCEDURES
F etal Thoracic P athology (pleural effusion; macrocystic CCAM)
Lower Urinary Tract Obstruction (LUTO)
T able 27-4
T able 27-5
T able 27-6
T able 27-7
Monochorionic Twin P athology: T win-to-Twin T r ansfusion Syndrome (TTTS)
Monochorionic Twin Pathology and Selective T ermination for TTTS, TRAP, Dis
F etal Ovarian Cyst
Placental Chorioangioma Management With Ultrasound-Guided Techniques
Multifetal Reduction (MFR) and Selective T ermination
Other Case Reports of Ultrasound-Guided Fetal T herapy Techniques
KEY POINTS
FUTURE CONSIDERATIONS
MATERNAL DISORDERS
SONOGRAPHIC EXAMINATION OF THE UTERINE CERVIX
Sonia S. Hassan
T i nnakorn Chaiworapongsa
E d i Vaisbuch
Maria-Teresa Gervasi
Roberto J. Romero
Definitions
INTRODUCTION
PHYSIOLOGY OF CERVICAL CHANGE IN PREGNANCY
C ervical Ripening
C ervical Dilation
SONOGRAPHIC EVALUATION OF THE UTERINE CERVIX
T e chnique and Pitfalls
T echnique
THE COMMON TERMINAL PATHWAY OF PARTURITION
CERVICAL SONOGRAPHY FOR PREDICTION OF PRETERM BIRTH
C ervical Examination in Asymptomatic Patients
Cervical Length in the Prediction of Preterm Deliver y in Asymptomatic Patien
T able 28-1
T able 28-3
Longitudinal Study of Cervical Ultrasound in Asymptomatic Patients
C ervical Length in Predicting Preterm Delivery in High-Risk Singleton Gestat
Short Cervix and the Risk of Preterm Premature Rupture of Membranes and Subse
C ervical Length in Twin Pregnancies
Sonographic Evaluation of Cervical Length in Triplet Pregnancies
C ervical Examination in Patients Presenting with Preterm Labor
WHY DO PATIENTS HAVE A SHORT CERVIX?
T he Syndromic Nature of a Sonographic Short Cervix
A Sonographic Short Cervix as the Only Clinical Manifestation of Intra-amniot
ADDITIONAL P ARAMETERS TO ASSESS THE RISK OF PRETERM BIRTH DURING TRANSVAGI
C ervical Funneling
Amniotic Fluid “Sludge”
T able 28-9
IS THERE AN EFFECTIVE TREATMENT FOR A SONOGRAPHIC SHORT CERVIX?
C ervical Cerclage in Patients with a Sonographic Short Cervix
Randomized Clinical Trials of Cervical Cerclage before the Cervical Ultrasoun
Cervical Cerclage after Cer vical Ultrasound Assessment
T able 28-11
Progesterone Use in Patients with a Sonographic Short Cervix
SHORT SONOGRAPHIC CERVICAL LENGTH: A POWERFUL PREDICTOR OF PRETERM DELIVERY
THREE-DIMENSIONAL ULTRASOUND IMAGING OF THE CERVIX
NONINVASIVE ASSESSMENT OF COLLAGEN CONTENT
FUTURE CHALLENGES
KEY POINTS
SONOGRAPHY OF TROPHOBLASTIC DISEASES
A rthur C. Fleischer
H oward W. Jones III
E u gene C . Toy
CLASSIFICATION SCHEMES
H istopathologic
INTRODUCTION
T able 29-1
Clinical Aspects
MOLAR PREGNANCIES
P athogenesis
Clinical Aspects
Sonographic Features
Sonographic Differential Diagnosis
INVASIVE MOLE, CHORIOCARCINOMA, AND PSTT
P athogenesis and Clinical Aspects
SUMMARY
CLINICAL CORRELATE
KEY POINTS
REFERENCES
POSTPARTUM ULTRASOUND
E u gene C . Toy
THE GYNECOLOGIC ORGANS
Normal Anatomy
T he Uterus
INTRODUCTION
T he Broad Ligament
V ulva, Vagina, and Pararectal Space
T he Ovaries
T he Cul-de-sac
P athology
P ostpartum Hemorrhage
P ostpartum Infection
Cesarean Deliver y
T able 30-1
THE GENITOURINARY SYSTEM
THE HEPATOBILIARY SYSTEM
KEY POINTS
V ASCULAR RISKS AND COMPLICATIONS
SUMMARY
H ighlighted References
GYNECOLOGIC SONOGRAPHY
SONOGRAPHIC EVALUATION OF PELVIC MASSES WITH TRANSABDOMINAL AND/OR TRANSVAGINAL SONOGRAPHY
Definitions
INTRODUCTION
SONOGRAPHIC PARAMETERS
T he Presence or Absence of a Pelvic Mass
Size and Location
Internal Consistency
Detection of Associated Lesions
Sonographic Guidance for Aspiration or Biopsy
TRANSVAGINAL SONOGRAPHY OF PELVIC MASSES
SONOGRAPHIC DIFFERENTIAL DIAGNOSIS OF PELVIC MASSES
T able 31-1
C ystic Masses
Physiologic Ovarian Cysts
H ydrosalpinx/Tubo-ovarian Abscesses
Endometriosis (Endometriomas)
C ystadenomas
Other Less Common Cystic Masses
C omplex Masses
Dermoid Cysts
Ectopic Pregnancy
C ystadenoma/Cystadenocarcinoma
To r s e d O v a r y
Solid Pelvic Masses
U terine Leiomyomata
Ovarian Masses
Other Solid Masses
Benign versus Malignant Determination Based on Sonographic Morphology
P e r sistent Versus Regressing Masses
SUMMARY
REFERENCES
H ighlighted References
COLOR DOPPLER SONOGRAPHY OF PELVIC MASSES
INTRODUCTION
NORMAL O V ARIAN ANATOMY AND FLOW
MORPHOLOGY OF ADNEXAL MASSES
PRINCIPLES OF COLOR DOPPLER SONOGRAPHY
COLOR DOPPLER SONOGRAPHY OF ADNEXAL MASSES
General Principles
A dnexal Torsion
T he Postmenopausal Ovary
EARLY VERSUS LATE STAGES OF OVARIAN CARCINOMA
T able 32-1
THE ROLE OF COLOR DOPPLER SONOGRAPHY IN CLINICAL MANAGEMENT
NEW DEVELOPMENTS
T able 32-4
SUMMARY/EMERGING CONCEPTS
CLINICAL CORRELATE
KEY POINTS
REFERENCES
Part 5 GYNECOLOGIC SONOGRAPHY
SONOGRAPHIC EVALUATION OF UTERINE DISORDERS
A rthur C. Fleischer
Rochelle F. Andreotti
SCANNING TECHNIQUE
SONOGRAPHIC FEATURES OF THE NORMAL UTERUS
CONGENITAL MALFORMATIONS AND RELATED DISORDERS
F usion Anomalies—Bicornuate versus Septated Uterus
Hydrometrocolpos and Hematometrocolpos
T -Shaped Uterus
INFLAMMATORY DISORDERS
UTERINE LEIOMYOMATA
Clinical Aspects
Sonographic Features
Sonographic Mimics of Fibroids
ADENOMYOSIS
CERVICAL MASSES
CARCINOMA OF THE OVIDUCT
ENDOMETRIAL DISORDERS
POSTHYSTERECTOMY EVALUATION
INTRAUTERINE CONTRACEPTIVE DEVICE LOCALIZATION
UTERINE ARTERY (FIBROID) EMBOLIZATION
TRANSRECTAL AND TRANSPERINEAL SONOGRAPHIC GUIDANCE FOR INTRAOPERATIVE PROCED
SUMMARY/EMERGING CONCEPTS
KEY POINTS
REFERENCES
TRANSVAGINAL SONOGRAPHY OF ENDOMETRIAL DISORDERS
Definitions
INTRODUCTION
CLINICAL ASPECTS
INSTRUMENTATION AND SCANNING TECHNIQUE
NORMAL (FIGURES 34-1, 34-2, AND 34-3)
POSTMENOPAUSAL BLEEDING
(FIGURES 34-4, 34-5, 34-6, 34-7, AND 34-8)
D Y SFUNCTIONAL UTERINE BLEEDING (FIGURE 34-5)
SERIAL MONITORING (FIGURES 34-4, 34-5, AND 34-6)
CANCER (FIGURE 34-8)
COLOR DOPPLER SONOGRAPHY (FIGURE 34-13)
MISCELLANEOUS CONDITIONS (FIGURES 34-6 AND 34-7)
SUMMARY
CLINICAL CORRELATE
H ighlighted References
SONOGRAPHIC TECHNIQUES
FOR EARLY DETECTION OF OVARIAN AND ENDOMETRIAL CANCERS
A rthur C. Fleischer
Debbie J. Lee
A n d réj Lyshchik
H oward W. Jones, III
Marta Crispens
Phillip K. Williams
David A. Fishman
Definitions
O VERVIEW
INTRODUCTION
SONOGRAPHY’S ROLE IN MULTIMODAL SCREENING FOR ENDOMETRIAL AND O V ARIAN CANC
T able 35-1
FUNDAMENTAL CONCEPTS OF SCREENING AND EARLY DETECTION OF OVARIAN AND ENDOMET
RISK F A CTORS AND LABORATORY TESTS
TRANSVAGINAL SONOGRAPHY
COLOR DOPPLER SONOGRAPHY
SONOGRAPHIC ASSESSMENT OF V ASCULARITY WITH 2D- AND 3D-CDS
CONTRAST-ENHANCED TRANSVAGINAL SONOGRAPHY OF OVARIAN MASSES
ENDOMETRIAL CANCER
SUMMARY/EMERGING CONCEPTS
CLINICAL CORRELATE
KEY POINTS
REFERENCES
H ighlighted References
A CUTE PELVIC PAIN: TRANSVAGINAL AND DOPPLER EVALUATION
Rochelle F. Andreotti
INTRODUCTION
GYNECOLOGIC CAUSES OF ACUTE PELVIC PAIN
A dnexal Torsion
Ovarian Functional Cyst
P elvic Inflammatory Disease
NONGYNECOLOGICAL CAUSES OF ACUTE PELVIC PAIN
KEY POINTS
REFERENCES
TRANSVAGINAL SONOGRAPHY IN GYNECOLOGIC INFERTILITY
E l izabeth E. Puscheck
M ichael P. Diamond
A rthur C. Fleischer
J aime M. Vasquez
A nna K. Parsons
J ill Herzog
Definitions
INTRODUCTION
INSTRUMENTATION
CLINICAL ASPECTS AND INDICATIONS
Spontaneous Cycles
ENDOMETRIAL ASSESSMENT
B ASELINE SONOGRAPHY FOR INFERTILITY
Ovarian Reserve Assessment
Applications of Color Doppler Sonography
Infertility Assessment with Sonohysterography (Figure 37-6)
T ubal Patency Assessment
SONOGRAPHIC EVALUATION OF TUBAL P A TENCY (SONOSALPINGOGRAPHY)
T e chnique
Normal and Abnormal Anatomy
C omparison With Hysterosalpingography
Sonosalpingography Findings
Sonographic Assessment of the Intrauterine Lumen
THE ROLE OF TVS IN INFERTILITY TREATMENTS
FOLLICULAR MONITORING
F ollicular Monitoring by Type of Ovulation Induction
IN VITRO FERTILIZATION
O VULATION INDUCTION FOR IVF
GUIDED FOLLICULAR ASPIRATION
GUIDED EMBRYO TRANSFER AND TUBAL CANNULATION
R ecovery after Ovulation Induction/IVF and Complications
SUMMARY
KEY POINTS
REFERENCES
Appendix 37-1
Ultrasound Examination of the Female Pelvis for Infertility and Reproductive
P ART I: EQUIPMENT AND DOCUMENTATION GUIDELINES
Equipment
Care of the Equipment
Documentation
P A R T II: GUIDELINES FOR PERFORMANCE OF THE ULTRASOUND EXAMINATION OF
General Pelvic Preparation
Uterus
A dnexa (Ovaries and Fallopian Tubes)
Cul-de-Sac
Limited Examination
Ultrasound-Guided Procedures
Qualifications and Responsibilities of the Physician
SONOHYSTEROGRAPHY AND SONOHYSTEROSALPINGOGRAPHY
Daniel M. Breitkopf
SONOHYSTEROGRAPHY
H istoric Development Using Transabdominal T e chnique
Limitations of Transvaginal Sonography
T r ansvaginal Sonohysterography
Indications for Sonohysterography
C o ntraindications to Sonohysterography
Equipment
T e chnique
Directed Biopsies
Use of 3D Imaging in Sonohysterography
EVALUATION OF TUBAL PATENCY
BY SONOHYSTEROSALPINGOGRAPHY T r aditional Hysterosalpingography
Sonographic Hysterosalpingography
Enhanced Saline
Stabilized Bubble Contrast Agents
T hree-Dimensional SonoHSG
SonoHSG and Transcervical Sterilization
P ossible Complications of Uterine Infusion
A V OIDING COMPLICATIONS/IMAGING TIPS AND TRICKS
SONOHYSTEROGRAPHIC IMAGING OF SPECIFIC CONDITIONS
Normal (Figure 38-9)
P o l yps (Figures 38-10 through 38-13)
T amoxifen Changes (Figures 38-14 and 38-15)
Leiomyomas (Figures 38-16 and 38-17)
S ynechiae (Figure 38-19)
Uterine Anomalies (Figures 38-20 and 38-21)
C esarean Scars (Figures 38-22 and 38-23)
Endometrial Carcinoma and Hyperplasia (Figures 38-24 through 38-26)
FUTURE DIRECTIONS
REFERENCES
CLINICAL CORRELATE
W hat Should Be the Next Steps in the Management of This Patient?
H ighlighted References
GUIDED PROCEDURES USING TRANSVAGINAL, TRANSPERINEAL, AND TRANSRECTAL SONOG
Jodi P. Lerner
A na Monteagudo
Ilan E. Timor-Tritsch
A rthur C. Fleischer
Definitions
INTRODUCTION
GENERAL CONCEPTS
B A CKGROUND
TRANSVAGINAL PUNCTURE PROCEDURES
T r ansvaginal Puncture/Catheterization Procedures in Assisted R eproduction
Oocyte Retrieval
TECHNIQUE
Intrauterine Transfer of Fertilized Oocytes
T ubal Catheterization and/or Embryo Transfer
Puncture of Ovarian Cysts
Multifetal Pregnancy Reduction
T r eatment of Ectopic Pregnancy
T ubal Pregnancy (Salpingocentesis)
Cornual Pregnancy
Cervical Pregnancy
C esarean Section Scar Pregnancy
P elvic Drainage Procedures
Culdocentesis
C oelocentesis
GUIDANCE WITH TRANSRECTAL AND TRANSPERINEAL SONOGRAPHY
SUMMARY
PELVIC FLOOR ULTRASOUND
H a ns Peter Dietz
METHODOLOGY AND INSTRUMENTATION
T w o-Dimensional Imaging
INTRODUCTION
T hree-Dimensional/Four-Dimensional Imaging
Display Modes
F o ur-Dimensional Imaging
FUNCTIONAL ASSESSMENT
V alsalva
P elvic Floor Muscle Contraction
Rest
First Valsalva
Optimal Valsalva
ANTERIOR COMPARTMENT
Bladder Neck Mobility
F unneling and Stress Incontinence
U rethral Mobility
C olor Doppler Imaging of Stress Incontinence
C ystocele
Urethral and Paraurethral Pathology
Detrusor Wall Thickness
Other Bladder Pathology
CENTRAL COMPARTMENT Uterine Descent
V ault Prolapse
POSTERIOR COMPARTMENT
R ectocele
POSTOPERATIVE FINDINGS
Anterior Colporrhaphy/Vaginal Paravaginal Repair
Burch/Marshall-Marchetti-Krantz (MMK) Colposuspension
F ascial/Synthetic Traditional Slings
Injectables
Suburethral Slings
Modern Mesh Implants
THE LEVATOR HIATUS AND MUSCLE
EMERGING CONCEPTS
KEY POINTS
REFERENCES
B ASIC BREAST SONOGRAPHY
J ohn G. Huff
T amarya L. Hoyt
INTRODUCTION
INDICATIONS
Diagnostic
Screening
Intervention
INSTRUMENTATION
SCAN TECHNIQUE AND REPORTING
NORMAL ANATOMY
P A THOLOGIC FINDINGS
F ibrocystic Condition
Solid Masses
Other Findings
Implants
AMERICAN INSTITUTE OF ULTRASOUND IN MEDICINE GUIDELINES
SUMMARY
KEY POINTS
REFERENCES
ADVANCED BREAST ULTRASOUND
David O. Cosgrove
W illiam E. Svensson
INTRODUCTION
NORMAL FINDINGS
P A THOLOGIC FEATURES
CYSTS
BENIGN BREAST CHANGE (ANDI)
FIBROADENOMAS
CARCINOMAS
CALCIFICATIONS
PROSTHETIC IMPLANTS
TRAUMA AND INFLAMMATION
THE MALE BREAST
THE CLINICAL ROLE OF ULTRASOUND
NEW DEVELOPMENTS
KEY POINTS
REFERENCES
COMPLEMENTARY IMAGING MODALITIES
V OLUME SONOGRAPHY: CORE CONCEPTS FOR CLINICAL PRACTICE
George Bega
INTRODUCTION
RATIONALE FOR VOLUME SONOGRAPHY
V OLUME ACQUISITION
Gray-Scale Scanning and Acquisition Guidelines
3D/4D Color/Power Doppler Sonography, B-Flow, and STIC Acquisition Guideline
A cquiring Volumes with B-Flow
Spatio-temporal Image Correlation
T able 43-2
V OLUME DISPLAY AND NAVIGATION
POST-PROCESSING: QUALITATIVE TOOLS
POST-PROCESSING: QUANTITATIVE TOOLS
Extraction of Standard Anatomical Planes and Quantification of Their Relation
V olume Quantification of Organ Systems
Blood Flow Quantification and Tissue P erfusion Studies
DOCUMENTATION, STORAGE, AND NETWORKING
ARTIFACTS, PITFALLS, AND LIMITATIONS
TRAINING AND RESEARCH
EMERGING CONCEPTS
A cquisition
V isualization
Qualitative and Quantitative Post-processing
Documentation
CLINICAL CORRELATE
What are the most important 2D/3D/4D ultra sound considerations in imaging th
KEY POINTS
REFERENCES
H ighlighted References
OBSTETRICAL APPLICATIONS FOR 3D ULTRASONOGRAPHY
We s l e y L e e
Dolores Pretorius
IMPORTANT CONCEPTS FOR VOLUME SONOGRAPHY
Use 2D Ultrasonography for an Initial Diagnostic Impression
Match the 3DUS Technique With a Specific Clinical Question That Is Being Aske
Do Not Underestimate the Diagnostic V alue of 3D Multiplanar Imaging
Good Two-Dimensional Imaging Is Likely to Translate to Satisfactory Three-Di
EARLY PREGNANCY EVALUATION USING 3DUS
Early Fetal Anatomic Evaluation
Genetic Risk Assessment
N uchal Translucency
N asal Bone Assessment
F rontomaxillary Facial Angle
F etal Iliac Angle
Embryonic Volume
SELECTED 3DUS APPLICATIONS FOR LATER PREGNANCY
F ace
T able 44-1
Eyes
Ears
M etopic Sutures
Cleft Lip and Palate
J a w Abnormalities
Brain
Spina Bifida
Skeletal Dysplasias
TISSUE VASCULARIZATION ASSESSMENT T issue Perfusion Using 3D Vascular Flow In
1. VI vascularization index (standardized range 0 to 100)
2. FI flow index (standardized range 0 to 100)
3. VFI vascularization flow index (VI *FI)/100
FETAL GROWTH AND WEIGHT ESTIMATION
O THER CONSIDERATIONS Safety Issues
P arental Bonding
M edicolegal Issues
Ultrasound for Entertainment
EMERGING CONCEPTS
CONCLUSIONS
KEY POINTS
H ighlighted References
FETAL CARDIAC EVALUATION USING 3D AND 4D ULTRASONOGRAPHY
Greggory R. DeVore
B ASIC IMAGING PRINCIPLES OF THREE DIMENSIONAL ULTRASONOGRAPHY Mechanical Ar
THREE-DIMENSIONAL STATIC VOLUME SWEEP
B ASIC IMAGING PRINCIPLES OF FOUR DIMENSIONAL ULTRASONOGRAPHY
Mechanical Volume Transducer
Spatiotemporal Image Correlation
4D Volume Display
Matrix Array Transducer
CLINICAL APPLICATIONS FOR 3D AND 4D FETAL ECHOCARDIOGRAPHY WHEN PERFORMING A
T omographic Ultrasound Imaging 109
A utomated Multiplanar Imaging
Spin Technique
CLINICAL APPLICATIONS OF 3D AND 4D FETAL ECHOCARDIOGRAPHY WHEN PERFORMING T
T omographic Ultrasound Imaging
T ransverse Sweep: 4-Chamber View and Aortic Outflow Tract (Planes 1 and 2)
Sagittal Sweep: The Long-Axis View of the Right V entricular Outflow Tract (P
Sagittal Sweep: Short-Axis View at the Level of the Great Vessels, Ductal Arc
Multiplanar View
Sagittal Sweep: Caval Long-Axis View (Plane 7)
THREE-DIMENSIONAL RENDERING OF CARDIAC ANATOMY
Mechanical Array Transducer
Matrix Array Transducer
P A THOLOGY
KEY POINTS
Chapter 45 F etal Cardiac Evaluation Using 3D and 4D Ultrasonography
What approaches could the examiner use to fur ther elucidate cardiac anatomy?
1. T hree-dimensional multiplanar imaging
REFERENCES
H ighlighted References
Chapter 46 Magnetic Resonance Imaging in Obstetrics
MAGNETIC RESONANCE IMAGING IN OBSTETRICS
Diane M. Twickler
SAFETY
TECHNIQUE
FETAL CENTRAL NERVOUS SYSTEM
FETAL THORAX
FETAL ABDOMEN
FETAL SURGERY CONSIDERATIONS
PLACENTA
MR VOLUMETRY
MR FETAL SURVEY
MATERNAL CONSIDERATIONS
MR Pelvimetry
Maternal Complications of Pregnancy
P elvic Floor
C ervix
EMERGING CONCEPTS
CLINICAL CORRELATE
Important MR considerations:
KEY POINTS
THREE-DIMENSIONAL VOLUMETRIC SONOGRAPHY IN GYNECOLOGY
Beryl R. Benacerraf
A rthur C. Fleischer
INTRODUCTION
TECHNIQUE (FIGURES 47-1 THROUGH 47-7)
CORONAL VIEW OF THE PELVIS
T he Uterus (see Figures 47-1 and 47-2)
Uterine Anomalies (Figures 47-8 through 47-20)
Uterine Polyps and Fibroids (Figures 47-21 through 47-29)
T he Uterus and IUD Location (Figures 47-29 through 47-37)
USING THE CORONAL VIEW OF THE UTERUS
THE CORONAL VIEW IN THE ADNEXA (FIGURES 47-38 THROUGH 47-40)
SONOHYSTEROGRAPHY WITH 3D (SEE FIGURES 47-21 THROUGH 47-23)
IMAGING OF THE PELVIC FLOOR WITH 3D
SURFACE RENDERING WITHIN A VOLUME (SEE FIGURES 47-21, 47-22, 47-24,
AND 47-25, 47-41 THROUGH 48)
INVERSION ULTRASOUND (FIGURES 47-49 THROUGH 47-51)
V OLUME MEASUREMENT
DOPPLER SONOGRAPHY IN 3D
(SEE FIGURES 47-6, 47-26, AND 47-27; FIGURES 47-51, AND 47-52)
ARTIFACTS (FIGURE 47-53)
T OMOGRAPHIC ULTRASOUND IMAGING (FIGURE 47-54)
EMERGING FRONTIERS
KEY POINTS
REFERENCES
MRI OF THE FEMALE PELVIS: PROBLEM SOLVING SONOGRAPHIC UNCERTAINTIES
Marcia C . Javitt
A rthur C. Fleischer
MRI TECHNIQUE
BENIGN CONDITIONS OF THE UTERUS Müllerian Anomalies
Leiomyomas
A denomyosis
BENIGN CONDITIONS OF THE OVARIES AND ADNEXA
Endometriosis
Dermoid Cysts
Ovarian Fibromas
F allopian Tube Abnormalities
TUMOR STAGING
C ervical Cancer
Endometrial Cancer
Ovarian Cancer
R ecurrent Gynecologic Malignancy
ENDOMETRIAL DISORDERS
EVALUATION OF DISTORTED PELVIC ANATOMY
UROGYNECOLOGY
NEW ADVANCES H igh Field Systems
P arallel Imaging
New MRI Contrast Materials
Diffusion-Weighted MR Imaging
MR Spectroscopy
SUMMARY
KEY POINTS
INDEX

Citation preview

SONOGRAPHY IN OBSTETRICS AND GYNECOLOGY: Principles & Practice Seventh Edition

Edited by

Wesley Lee, MD

Arthur C. Fleischer, MD

Division of Fetal Imaging William Beaumont Hospital Royal Oak, Michigan Clinical Professor of Obstetrics and Gynecology Oakland University William Beaumont School of Medicine Rochester, Michigan

Professor of Radiology and Radiologic Sciences Professor of Obstetrics and Gynecology Chief, Diagnostic Sonography Vanderbilt University Medical Center Nashville, Tennessee

Eugene C. Toy, MD Vice Chair of Academic Affairs and Residency Program Director Department of Obstetrics and Gynecology The Methodist Hospital-Houston Associate Clinical Professor Weill Cornell College of Medicine Associate Clinical Professor and Clerkship Director Department of Obstetrics and Gynecology University of Texas Medical School at Houston Houston, Texas

Frank A. Manning, MD Professor Department of Obstetrics and Gynecology Montefiore Medical Center Bronx, New York

Roberto J. Romero, MD Chief, Perinatology Research Branch Program Director for Obstetrics and Perinatology Intramural Division, NICHD, NIH, DHHS Bethesda, Maryland and Detroit, Michigan Professor of Molecular Obstetrics and Genetics Center for Molecular Medicine and Genetics Wayne State University School of Medicine Detroit, Michigan

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Copyright © 2011 by The McGraw-Hill Companies, Inc. All rights reserved. Except as permitted under the United States Copyright Act of 1976, no part of this publication may be reproduced or distributed in any form or by any means, or stored in a database or retrieval system, without the prior written permission of the publisher. ISBN: 978-0-07-176088-1 MHID: 00-7-176088-1 The material in this eBook also appears in the print version of this title: ISBN: 978-0-07-154772-7, MHID: 0-07-154772-X. All trademarks are trademarks of their respective owners. Rather than put a trademark symbol after every occurrence of a trademarked name, we use names in an editorial fashion only, and to the benefit of the trademark owner, with no intention of infringement of the trademark. Where such designations appear in this book, they have been printed with initial caps. McGraw-Hill eBooks are available at special quantity discounts to use as premiums and sales promotions, or for use in corporate training programs. To contact a representative please e-mail us at [email protected]. TERMS OF USE This is a copyrighted work and The McGraw-Hill Companies, Inc. (“McGrawHill”) and its licensors reserve all rights in and to the work. Use of this work is subject to these terms. Except as permitted under the Copyright Act of 1976 and the right to store and retrieve one copy of the work, you may not decompile, disassemble, reverse engineer, reproduce, modify, create derivative works based upon, transmit, distribute, disseminate, sell, publish or sublicense the work or any part of it without McGraw-Hill’s prior consent. You may use the work for your own noncommercial and personal use; any other use of the work is strictly prohibited. Your right to use the work may be terminated if you fail to comply with these terms. THE WORK IS PROVIDED “AS IS.” McGRAW-HILL AND ITS LICENSORS MAKE NO GUARANTEES OR WARRANTIES AS TO THE ACCURACY, ADEQUACY OR COMPLETENESS OF OR RESULTS TO BE OBTAINED FROM USING THE WORK, INCLUDING ANY INFORMATION THAT CAN BE ACCESSED THROUGH THE WORK VIA HYPERLINK OR OTHERWISE, AND EXPRESSLY DISCLAIM ANY WARRANTY, EXPRESS OR IMPLIED, INCLUDING BUT NOT LIMITED TO IMPLIED WARRANTIES OF MERCHANTABILITY OR FITNESS FOR A PARTICULAR PURPOSE. McGraw-Hill and its licensors do not warrant or guarantee that the functions contained in the work will meet your requirements or that its operation will be uninterrupted or error free. Neither McGraw-Hill nor its licensors shall be liable to you or anyone else for any inaccuracy, error or omission, regardless of cause, in the work or for any damages resulting therefrom. McGraw-Hill has no responsibility for the content of any information accessed through the work. Under no circumstances shall McGraw-Hill and/or its licensors be liable for any indirect, incidental, special, punitive, consequential or similar damages that result from the use of or inability to use the work, even if any of them has been advised of the possibility of such damages. This limitation of liability shall apply to any claim or cause whatsoever whether such claim or cause arises in contract, tort or otherwise.

EDITORS Arthur C. Fleischer, MD, is Professor of Radiology, Professor of Obstetrics and Gynecology, and Chief of the Section of Sonography at Vanderbilt University Medical Center, Nashville, Tennessee. He has written over 20 books and authored over 200 scientific papers involving sonography. His major emphasis has been on furthering clinical applications of sonography, particularly in gynecology and oncology. Dr. Fleischer is most proud of the many individuals he has mentored. He has received several awards for teaching excellence for medical students and graduates, including the Distinguished Alumnus Award for Professional Achievement from his alma mater, Medical College of Georgia; the Larry Mack Award from the Society of Radiologists in Ultrasound; and the William Fry Award from the American Institute of Ultrasound in Medicine. An avid space buff, he and his wife, Lynn, have three grown children. Eugene C. Toy, MD, is Vice-Chair of Academic Affairs in the Department of Obstetrics and Gynecology at Methodist Hospital-Houston, and the John Dunn, Sr., Academic Chief of Obstetrics and Gynecology at St. Joseph Medical Center-Houston. He is the Chair of the Graduate Medical Education Committee and Director of the Methodist Hospital-Houston Obstetrics/Gynecology Residency Program. Dr. Toy is Associate Clinical Professor of Obstetrics and Gynecology at the University of Texas Medical School at Houston where he is the assistant course director and clerkship director of the obstetrics/ gynecology medical student rotation. He has an appointment as an Associate Professor Clinical, Department of Obstetrics and Gynecology at Weill Cornell Medical College. He is the Director of Ultrasound at three different clinics in Houston, and practices the full scope of obstetrics and gynecology. Dr. Toy is recognized for his teaching and has received numerous medical school as well as national awards. As an author, Dr. Toy is the creator of the popular Case Files series, which has 17 titles and has been translated into 14 different languages. He has authored or coauthored over 100 peer-reviewed articles or book chapters. He is currently president of the Texas Association of Obstetricians and Gynecologists and is active in the American Congress of Obstetrics and Gynecology. He is board certified by the American Board of Obstetricians and Gynecologists, and is a Fellow of the American College of Obstetrics and Gynecologists. He is likewise board

certified by the American Board of Family Physicians. As an avid runner, Dr. Toy has completed seven marathons including the Boston Marathon. He and his wife Terri have four lovely children. Wesley Lee, MD, is a Clinical Professor of Obstetrics and Gynecology at Oakland University William Beaumont School of Medicine, Rochester, Michigan. Dr. Lee works in the Division of Fetal Imaging at William Beaumont Hospital in Royal Oak, Michigan. He has authored many scientific articles and book chapters pertaining to maternal-fetal medicine, prenatal detection of congenital anomalies, 3D/4D fetal ultrasonography, and fetal magnetic resonance imaging. He is an Associate Investigator with the Perinatology Research Branch of the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) and also serves as a Scientific Advisor to the World Health Organization. Dr. Lee chaired task forces for the development of fetal cardiac screening guidelines (AIUM, ISUOG) and practice guidelines for fetal echocardiography (AIUM, ACOG, SMFM, ACR). He received the AIUM Presidential Recognition Award in 2001 and other major accomplishments include an NIH Small Business Innovations Research Grant award that led to the development of an educational CD-ROM for the ACOG (Fetal Ultrasound Simulator). Other activities have included Chair, Clinical Standards Committee at the International Society of Ultrasound in Obstetrics and Gynecology; Editorial Board for Ultrasound in Obstetrics and Gynecology; and Deputy Editor of the Journal of Ultrasound in Medicine. He and his wife, Pam, have two grown children, Malinda and Allison. Frank A. Manning, MD, is a tenured Professor of Obstetrics and Gynecology and Associate Director of the Division of Maternal Fetal Medicine at New York Medical College. He has coauthored more than 150 peer-reviewed scientific articles, several invited articles, and seven books, as well as an independently authored textbook in maternal fetal medicine. He is best known as the originator of the fetal biophysical profile score but is also recognized for his original work in the clinical applications of ultrasound in fetal medicine, including developing the standard method for amniotic fluid volume measurement and interpretation, and for in-utero fetal therapy comprising intravascular transfusions and fetal surgery. He

Editors has lectured widely and has been the recipient of numerous national and international degrees, awards, and gold medals for his contributions to ultrasound and fetal medicine. He is an honorary member of 70 national and international OB/GYN and medical societies. He and his wife, Ann, have three daughters. Roberto J. Romero, MD, is currently Chief of the Perinatology Research Branch and Program Director for Obstetrics and Perinatology in the Division of Intramural Research of the NICHD/NIH; Professor of Molecular Obstetrics and Genetics at Wayne State University School of Medicine in Detroit, Michigan; and Professor of Epidemiology at Michigan State University. Dr. Romero trained in obstetrics and gynecology at Yale University where he later became Director of Perinatal Research. Dr. Romero’s work has focused on the early diagnosis of ectopic pregnancy, the prenatal diagnosis of congenital anomalies, and the study of the mechanisms of disease responsible for pregnancy complications and fetal injury, with particular emphasis on preterm labor. Dr. Romero is the author of over 750 peer-reviewed publications and several books, including a medical best seller: Prenatal Diagnosis of Congenital Anomalies. He has done original

vi research in defining fetal anatomy with ultrasound (2D and 3D) and longitudinal studies of fetal growth (with 2D and 3D ultrasound), and has made pioneering contributions to fetal treatment (endoscopic treatment of TRAP sequence). His team has made major contributions in the prenatal diagnosis of congenital heart disease and the use of Doppler to assess the fetal circulation and predict the development of pregnancy complications. A member of the Institute of Medicine of the National Academies of the United States, Dr. Romero participates in numerous national committees such as the International Academy of Perinatal Medicine and the United Cerebral Palsy Research and Education Foundation. He also serves as editor of the journal Ultrasound in Obstetrics and Gynecology, and is an associate editor of the American Journal of Obstetrics and Gynecology, Journal of MaternalFetal and Neonatal Medicine, and the Journal of Perinatal Medicine. Dr. Romero is the recipient of the Ian Donald Gold Medal for contributions to Ultrasound in Obstetrics and Gynecology, awarded in Stockholm, Sweden in 2004 and countless others awards, as well as several Doctorate Honoris Causa from universities around the world (Semmelweis University, Budapest, Hungary; University of Athens, Greece; University of San Marcos, Lima, Peru; Pontificia Catolica University, Santiago, Chile; University of El Cuzco, Peru; and University of Zulia, Venezuela).

CONTENTS Contributors ix Preface xv Acknowledgments xvii I. GENERAL OBSTETRIC SONOGRAPHY 1. Ultrasound Bioeffects and Safety: What the Practitioner Should Know 2 2. Normal Pelvic Anatomy as Depicted with Transvaginal Sonography 21 3. Transvaginal Sonography of Early Intrauterine Pregnancy 39 4. Transvaginal Sonography of Ectopic Pregnancy 71 5. Fetal Biometry 99 6. Prenatal Diagnosis of Congenital Heart Disease 121 7. Placenta, Cord, and Membranes 155 8. Prenatal Diagnosis of Placenta Accreta 187 9. Fetal Growth Restriction 195 10. Doppler Velocimetry of the Uteroplacental Circulation 223 11. Doppler Interrogation of the Fetal Circulation 257 12. Color Doppler Sonography in Obstetrics 309 13. Sonography in Multiple Gestation 337

II. FETAL ANOMALIES AND DISORDERS 14. Fetal Anomalies: Overview 376 15. Prenatal Diagnosis of Cerebrospinal Anomalies 413 16. Fetal Neck and Chest Anomalies 441 17. Fetal Gastrointestinal Anomalies 461 18. The Fetal Genitourinary System 509 19. Fetal Skeletal Anomalies 523 20. Fetal Syndromes 593 21. Ultrasound Detection of Chromosomal Anomalies 651

III. RISK ASSESSMENT AND THERAPY 22. First Trimester Screening 682 23. Fetal Biophysical Profile Score: Theoretical Considerations and Practical Application 705 24. Chorionic Villus Sampling 715 25. Amniocentesis 733 26. Fetal Blood Sampling 775 27. Fetal Therapy: Maternal Fetal Surgery and Percutaneous Ultrasound Guided Fetal Therapy Techniques for Congenital Anomalies 793 IV. MATERNAL DISORDERS 28. Sonographic Examination of the Uterine Cervix 816 29. Sonography of Trophoblastic Diseases 849 30. Postpartum Ultrasound 859 V. GYNECOLOGIC SONOGRAPHY 31. Sonographic Evaluation of Pelvic Masses with Transabdominal and/or Transvaginal Sonography 870 32. Color Doppler Sonography of Pelvic Masses 897 33. Sonographic Evaluation of Uterine Disorders 933 34. Transvaginal Sonography of Endometrial Disorders 961 35. Sonographic Techniques for Early Detection of Ovarian and Endometrial Cancers 979 36. Acute Pelvic Pain: Transvaginal and Doppler Evaluation 1001 37. Transvaginal Sonography in Gynecologic Infertility 1011

Contents

38. Sonohysterography and Sonohysterosalpingography 1043 39. Guided Procedures Using Transvaginal, Transperineal, and Transrectal Sonography 1063 40. Pelvic Floor Ultrasound 1087 41. Breast Sonography 1111 42. Breast Ultrasound 1119 VI. COMPLIMENTARY IMAGING MODALITIES 43. Volume Sonography: Core Concepts for Clinical Practice 1134

viii

44. Obstetrical Applications for 3D Ultrasonography 1171 45. Fetal Cardiac Evaluation Using 3D and 4D Ultrasonography 1205 46. Magnetic Resonance Imaging in Obstetrics 1235 47. Three-Dimensional Volumetric Sonography in Gynecology 1263 48. MRI of the Female Pelvis: Problem Solving Sonographic Uncertainties 1295 Index 1319

CONTRIBUTORS Jacques S. Abramowicz, MD

Fionnuala M. Breathnach, MD, MRCOG, MRCPI

Director, Ob/Gyn Ultrasound Co-Director, Rush Fetal and Neonatal Medicine Program Department of Obstetrics and Gynecology Rush University Medical Center Chicago, Illinois (Chapter 1)

Clinical Fellow Division of Maternal Fetal Medicine Columbia University Medical Center New York (Chapter 22)

Daniel M. Breitkopf, MD Rochelle F. Andreotti, MD Professor of Clinical Radiology Associate Professor of Obstetrics and Gynecology Vanderbilt University Medical Center Nashville, Tennessee (Chapters 33, 36)

Ahmet A. Baschat, MD Professor and Head Section of Fetal Therapy Department of Obstetrics, Gynecology, and Reproductive Sciences University of Maryland-Baltimore Baltimore, Maryland (Chapter 9)

George Bega, MD Assistant Professor of Obstetrics and Gynecology Thomas Jefferson University Philadelphia, Pennsylvania (Chapter 43)

Beryl R. Benacerraf, MD Clinical Professor of Radiology and Obstetrics and Gynecology Harvard Medical School Boston, Massachusetts (Chapter 47)

Carol B. Benson, MD Professor of Radiology Harvard Medical School Brigham and Women’s Hospital Boston, Massachusetts (Chapter 18)

Currently: Senior Associate Consultant Department of Obstetrics and Gynecology Mayo Clinic Rochester, Minnesota Formerly: Associate Professor Department of Obstetrics and Gynecology University of Texas Medical Branch Galveston, Texas (Chapter 38)

Mieke Cannie, MD, PhD Department of Radiology, University Hospital Brugmann Department of Radiology, Free University of Brussels Brussels, Belgium (Chapter 16)

Peter S. Cartwright, MD Associate Clinical Professor Department of Obstetrics and Gynecology Duke University School of Medicine Durham, North Carolina (Chapter 4)

Tinnakorn Chaiworapongsa, MD Maternal-Fetal Medicine Fellow Perinatology Research Branch Intramural Division, NICHD, NIH, DHHS Bethesda, Maryland, and Detroit, Michigan and Department of Obstetrics and Gynecology Wayne State University Detroit, Michigan (Chapter 28)

x

Contributors

Werther Adrian Clavelli, MD

Greggory R. DeVore, MD

11 de Septiembre 1745 Piso 7 Department A Codigo Postal 1426 Republica Capital Federal Buenos Aires, Argentina (Chapter 21)

Director, Fetal Diagnostic Center Pasadena, California (Chapter 45)

Christine H. Comstock, MD Director, Fetal Imaging William Beaumont Hospital Clinical Professor, Oakland University William Beaumont School of Medicine Royal Oak, Michigan (Chapter 8)

David O. Cosgrove, MA, MSc, FRCP, FRCR Emeritus Professor of Clinical Ultrasound Imperial College of Science, Technology, and Medicine Consultant Hammersmith Hospital London (Chapter 42)

Marta Crispens, MD Assistant Professor Department of Obstetrics and Gynecology Vanderbilt University Medical Center Nashville, Tennessee (Chapter 35)

Michael P. Diamond, MD Director, Reproductive Endocrinology and Infertility Wayne State University/Hutzel Hospital Detroit, Michigan (Chapters 4, 37)

Hans Peter Dietz, MD, PhD Professor and Head of Discipline Obstetrics, Gynecology, and Neonatology Sydney Medical School - Nepean University of Sydney Nepean Hospital Penrith, Australia (Chapter 40)

Peter M. Doubilet, MD, PhD Professor of Radiology Harvard Medical School Brigham and Women’s Hospital Boston, Massachusetts (Chapter 18)

David A. Fishman, MD Professor of Obstetrics, Gynecology, and Reproductive Science The Mount Sinai Medical Center New York, New York (Chapter 35)

Antonella Cromi, MD, PhD Assistant Professor Department of Obstetrics and Gynecology University of Insubria Varese, Italy (Chapter 26)

Laura Cruciani, MD Research Associate Perinatology Research Branch Intramural Division, NICHD, NIH, DHHS Bethesda, Maryland, and Detroit, Michigan (Chapter 11)

Valentina De Robertis Fetal Medicine Unit “Di Venere” and “M. Sarcone” Hospitals Bari, Italy (Chapter 17)

Arthur C. Fleischer, MD Professor of Radiology and Radiologic Sciences Professor of Obstetrics and Gynecology Chief, Diagnostic Sonography Vanderbilt University Medical Center Nashville, Tennessee (Chapters 2, 3, 4, 29, 31, 32, 33, 34, 35, 37, 39, 47, 48)

Maria-Teresa Gervasi, MD Chief, Obstetric Unit Department of Obstetrics and Gynecology, Azienda Ospedaliera of Padova Padova, Italy (Chapters 10, 25, 28)

Fabio Ghezzi, MD Associate Professor Department of Obstetrics and Gynecology University of Insubria Varese, Italy (Chapters 11, 25, 26)

Contributors

xi

Luís F. Gonçalves, MD

John G. Huff, MD

Perinatology Research Branch Intramural Division, NICHD, NIH, DHHS Bethesda, Maryland, and Detroit, Michigan and Department of Diagnostic Radiology Wayne State University Detroit, Michigan (Chapters 10, 14, 25)

Associate Professor of Clinical Radiology and Radiological Sciences Vanderbilt University Medical Center Nashville, Tennessee (Chapter 41)

Francesca Gotsch, MD Research Fellow Perinatology Research Branch Intramural Division, NICHD, NIH, DHHS Bethesda, Maryland, and Detroit, Michigan (Chapters 11, 19, 26)

Christopher Harman, MD Professor and Vice Chair Head, Division of Maternal and Fetal Medicine Department of Obstetrics, Gynecology, and Reproductive Sciences University of Maryland, Baltimore, School of Medicine Baltimore, Maryland (Chapter 9)

James C. Huhta, MD Perinatal Cardiology Congenital Heart Institute of Florida Tampa Bay, Florida (Chapter 6)

Jacques Jani, MD, PhD, FACR Chairman, Department of Obstetrics and Gynecology Fetal Medicine and Minimal Invasive Fetal Surgery University Hospital Brugmann Brussels, Belgium (Chapter 16)

Marcia C. Javitt, MD, FACR Section Head of Body MRI Section Head of Genitourinary Radiology Walter Reed Army Medical Center Washington DC (Chapter 48)

Sonia S. Hassan, MD Director, Center for Advanced Obstetrical Care and Research Perinatology Research Branch Intramural Division, NICHD, NIH, DHHS Bethesda, Maryland, and Detroit, Michigan and Associate Professor Director, Maternal-Fetal Medicine Fellowship Division of Maternal-Fetal Medicine Department of Obstetrics and Gynecology Wayne State University Detroit, Michigan (Chapter 28)

Jill Herzog, RDMS Program Director, School of Diagnostic Sonography Department of Radiology Vanderbilt University Nashville, Tennessee (Chapter 37)

Tamarya L. Hoyt, MD Assistant Professor of Radiology Department of Radiology Vanderbilt University Medical Center Nashville, Tennessee (Chapter 41)

Philippe Jeanty, MD, PhD Chief Fetustician Inner Vision Women’s Ultrasound Nashville, Tennessee (Chapters 5, 13, 20, 21)

Cristiano Jodicke, MD Maternal-Fetal Medicine Fellow Perinatology Research Branch Intramural Division, NICHD, NIH, DHHS Bethesda, Maryland, and Detroit, Michigan and Department of Obstetrics and Gynecology Wayne State University Detroit, Michigan (Chapter 25)

Howard W. Jones, III, MD Professor of Obstetrics and Gynecology Director, Division of Gynecologic Oncology Department of Obstetrics and Gynecology Vanderbilt University Medical Center Nashville, Tennessee (Chapters 29, 35)

Contributors

xii

Sun Kwon Kim, MD, PhD

Frank A. Manning, MD

Research Associate Perinatology Research Branch Intramural Division, NICHD, NIH, DHHS Bethesda, Maryland, and Detroit, Michigan (Chapter 14)

Professor Department of Obstetrics and Gynecology New York Medical College Valhalla, New York (Chapter 23)

Juan Pedro Kusanovic, MD

Joan M. Mastrobattista, MD

Assistant Professor Perinatology Research Branch Intramural Division, NICHD, NIH, DHHS Bethesda, Maryland, and Detroit, Michigan and Department of Obstetrics and Gynecology Wayne State University Detroit, Michigan (Chapter 25)

Director, Prenatal Diagnosis Professor Department of Obstetrics, Gynecology, and Reproductive Sciences The University of Texas Medical School at Houston Houston, Texas (Chapter 7)

Debbie J. Lee, BS Department of Radiology Vanderbilt University Medical Center Nashville, Tennessee (Chapter 35)

Wesley Lee, MD

Alexandra Matias, MD PhD Assistant Professor, Porto Medical School Senior Consultant, Hospital de S. João Porto, Portugal (Chapter 13)

Ana Monteagudo, MD Associate Professor Department of Obstetrics and Gynecology New York University Medical Center New York (Chapter 39)

Division of Fetal Imaging William Beaumont Hospital Royal Oak, Michigan Clinical Professor of Obstetrics and Gynecology and Oakland University William Beaumont School of Medicine Rochester, Michigan (Chapter 44)

Juliana Moyses L Abdalla

Jodi P. Lerner, MD

Ana Luisa Neves, MD

Associate Clinical Professor of Obstetrics and Gynecology Department of Obstetrics and Gynecology Columbia University College of Physicians and Surgeons New York (Chapter 39)

Pediatric Cardiology Hospital de S. João Porto, Portugal (Chapter 6)

Andréj Lyshchik, MD, PhD

Fetal Medicine, Hospital Mater Dei Belo Horizonte, MG Brazil (Chapter 20)

Melinda S. New, MD

Department of Radiology Vanderbilt University Medical Center Nashville, Tennessee (Chapter 35)

Assistant Professor Department of Obstetrics and Gynecology Vanderbilt University Medical Center Nashville, Tennessee (Chapter 4)

Fergal D. Malone, MD

Giovanna Ogge’, MD

Professor and Chairman Department of Obstetrics and Gynecology Royal College of Surgeons in Ireland The Rotunda Hospital Dublin, Ireland (Chapter 22)

Research Associate Perinatology Research Branch Intramural Division, NICHD, NIH, DHHS Bethesda, Maryland, and Detroit, Michigan (Chapter 11)

Contributors

xiii

Percy Pacora, MD

Georgios Rembouskos, MD

Visiting Professor Perinatology Research Branch Intramural Division, NICHD, NIH, DHHS Bethesda, Maryland, and Detroit, Michigan and Department of Obstetrics and Gynecology Wayne State University Detroit, Michigan (Chapter 10)

Fetal Medicine Unit “Di Venere” and “M. Sarcone” Hospitals Bari, Italy (Chapter 17)

Dario Paladini, MD Associate Professor in Obstetrics and Gynecology Fetal Medicine and Cardiology Unit Department of Obstetrics and Gynecology University Federico II, Naples, Italy (Chapters 12, 17)

Anna K. Parsons, MD Associate Professor of Obstetrics and Gynecology Director of Reproductive Ultrasound University of South Florida College of Medicine Department of Obstetrics and Gynecology Tampa, Florida (Chapter 37)

Silvia Susana Romaris, MD 11 de Septiembre 1745 Piso 7 Department A Codigo Postal 1426 Republica Capital Federal Buenos Aires, Argentina (Chapter 21)

Roberto J. Romero, MD Chief, Perinatology Research Branch Program Director for Obstetrics and Perinatology Intramural Division, NICHD, NIH, DHHS Bethesda, Maryland, and Detroit, Michigan Professor of Molecular Obstetrics and Genetics Center for Molecular Medicine and Genetics Wayne State University School of Medicine Detroit, Michigan Professor of Epidemiology, Michigan State University East Lansing, Michigan (Chapters 10, 11, 14, 19, 25, 26, 28)

Gianluigi Pilu, MD Consultant in Obstetrics and Gynecology Azienda Ospedaliera di Bologna Policlinico S. Orsola-Malpighi Bologna, Italy (Chapters 15, 19)

A. Cristina Rossi , MD

Dolores Pretorius, MD

Gabriella Sglavo, MD

Professor Department of Radiology University of California San Diego La Jolla, California (Chapter 44)

Fetal Medicine and Cardiology Unit Department of Obstetrics and Gynecology University Federico II, Naples, Italy (Chapter 12)

Elizabeth E. Puscheck, MD

Eyal Sheiner, MD

Associate Professor Department of Obstetrics and Gynecology Wayne State University Detroit, Michigan (Chapter 37)

Department of Obstetrics and Gynecology Soroka University Medical Center Ben Gurion University of the Negev Beer Sheva, Israel (Chapter 1)

Mark Redman, MD

Gabriele Siesto, MD

Clinical Assistant Professor Department of Obstetrics and Gynecology Wayne State University Detroit, Michigan (Chapter 25)

Department of Obstetrics and Gynecology University of Insubria Varese, Italy (Chapter 26)

Fetal Medicine Unit “Di Venere” and “M. Sarcone” Hospitals Bari, Italy (Chapter 17)

xiv

Contributors

Sandra R. Silva, MD

Jaime M. Vasquez, MD

Assistant Doctor Maternal Fetal Medicine Fetus—Centro de Diagnóstico Pré-natal e Medicina Fetal São Paulo, Brazil (Chapter 20)

Director Center for Reproductive Health Nashville, Tennessee (Chapter 37)

Paolo Volpe, MD William E. Svensson, FRCR, FRCSI, LRCPI, LRCSI, LM Reader in Breast Imaging at Imperial College Consultant Radiologist and Nuclear Medicine Specialist Nuclear Medicine Imaging Department Charing Cross Hospital London (Chapter 42)

Eugene C. Toy, MD Vice Chair of Academic Affairs and Residency Program Director Department of Obstetrics and Gynecology The Methodist Hospital-Houston Associate Clinical Professor Weill Cornell College of Medicine Associate Clinical Professor and Clerkship Director Department of Obstetrics and Gynecology University of Texas Medical School at Houston Houston, Texas (Chapters 5, 7, 13, 24, 29, 30)

Fetal Medicine Unit, “Di Venere” and “M. Sarcone” Hospitals Bari, Italy (Chapters 12, 17)

Ronald.J. Wapner, MD Director Division of Maternal and Fetal Medicine Department of Obstetrics and Gynecology Thomas Jefferson University Philadelphia, Pennsylvania (Chapter 24)

Phillip K. Williams, RDMS Supervisor, Diagnostic Sonography Department of Radiology Vanderbilt University Medical Center Nashville, Tennessee (Chapter 35)

Douglas Wilson, MD

Professor of Obstetrics and Gynecology Director, OB/GYN Ultrasound Unit New York University Medical Center New York (Chapter 39)

Professor and Head Department of Obstetrics and Gynecology Alberta Health Services, Calgary University of Calgary Calgary, Alberta, Canada (Chapter 27)

Diane M. Twickler, MD, FACR

Lami Yeo, MD

Professor, Radiology and Obstetrics/Gynecology Program Director, Diagnostic Radiology Residency Holder of Fred Bonte Professorship in Radiology University of Texas Southwestern Medical Center Dallas, Texas (Chapter 46)

Director Fetal and Maternal Imaging Perinatology Research Branch Intramural Division, NICHD, NIH, DHHS Bethesda, Maryland, and Detroit, Michigan and Associate Professor Department of Obstetrics and Gynecology Wayne State University School of Medicine Detroit, Michigan (Chapters 10, 11, 14, 19, 25)

Ilan E. Timor-Tritsch, MD

Edi Vaisbuch, MD Assistant Professor Perinatology Research Branch Intramural Division, NICHD, NIH, DHHS Bethesda, Maryland, and Detroit, Michigan and Department of Obstetrics and Gynecology Wayne State University Detroit, Michigan (Chapters 19, 28)

PREFACE Since the publication of the sixth edition, there have been major new developments and improved understanding of a variety of obstetric and gynecologic disorders. Concomitantly, there have been significant improvements and innovations in sonographic imaging. A few examples of this include 3D/“live 3D” imaging, more sensitive Doppler techniques, and evaluation of the pelvic floor with 3D/4D sonography. The editors have endeavored to revise and enhance this “mega-project” to include both a standard textbook and an associated Website containing dynamic studies and upto-date information on an extensive list of topics. I hope that

the readers/Web users will gain much insight into the sonographic application in obstetrics and gynecology by using this educational material. In each chapter, we have endeavored to optimize the potential for learning by including key definitions and a clinical correlate, and by highlighting important references. While using this textbook and Website, please continue to question and think creatively, and ultimately contribute to improving women’s health. Arthur C. Fleischer, MD Nashville, Tennessee May, 2010

ACKNOWLEDGMENTS This endeavor was generously guided and supported by Steven Gabbe, MD, whose well-respected text has an accompanying Website. I personally am grateful to Dean Gabbe for his thoughtful advice and support throughout the duration of this project, from it’s inception to completion. In addition to Dr. Gabbe, I would like to dedicate this work to my parents, Lucille and Gene Fleischer, who have always supported my creative endeavors, and my family, Lynn, Braden, Jared, and Amy, for humoring me during this process by turning off lights that I tend to leave on during my late night/early morning vigils. Many individuals helped and were crucial in achieving a final product. Marsha Loeb and Alyssa Fried, editors for McGraw-Hill Publishers, and Vera Merriweather and Areka Young were so helpful, as well as, John Bobbitt, our departmental audio-visual expert. Rajni Pisharody and the Glyph International staff are thanked for their efforts in turning the manuscript and images into a beautiful final product. Arthur C. Fleischer, MD We are grateful to Dr. Alan Kaplan at Methodist Hospital-Houston and Patricia Fernandez, RDMS at Southwest Community Health Center, Houston, for assisting in this book. Eugene C. Toy, MD

Sincere appreciation is extended to my teachers and mentors—particularly Drs. Christine Comstock and Roberto Romero—who continue to guide my journey and contributions in fetal imaging. Of course, a special “thank you” is also reserved for my lovely wife, Pam, for all of her unconditional support along the way. Wesley Lee, MD I’m grateful to Annie and the girls who keep me motivated and grounded, and to residents and fellows past and present who provide all the inspiration. Frank A. Manning, MD I’m grateful to my wife, Ginny, my parents, Asdrubal and Zoila, my brothers and sisters, and my grandmother, Angela Galue, who have made it all possible; also to the exceptional and talented professionals and friends with whom I have worked at the Perinatology Research Branch of NICHD/NIH, Wayne State University, Yale University, AIUM, and ISUOG. Roberto J. Romero, MD

PA RT

1

GENERAL OBSTETRIC SONOGRAPHY

2

Part 1 GENERAL OBSTETRIC SONOGRAPHY

Chapter 1

ULTRASOUND BIOEFFECTS AND SAFETY: WHAT THE PRACTITIONER SHOULD KNOW Jacques S. Abramowicz

Definitions1 1. Acoustic streaming: movement of tissue or fluid, resulting from the passage of alternating positive and negative pressures of the ultrasound wave. Can also result from movements of bubbles, as a result of changes in pressure. 2. ALARA principle: stands for As Low As Reasonably Achievable, a way to obtain the best, clinically relevant image while keeping ultrasound intensity and exposure as low as possible. 3. Cavitation: bubble activity, secondary to ultrasound insonation. The positive aspect of the ultrasound pressure wave causes compression of the bubble while the negative part, also called rarefactional, causes production of the bubbles or expansion of existing ones. Cavitation can be stable or inertial. ● Stable cavitation: bubble activity where bubble does not collapse (see inertial cavitation, below) but is moving back and forth in the tissue or fluid, thus potentially causing the surrounding medium to flow (ie, stream, hence the term streaming). ● Inertial (previously known as transient) cavitation: bubbles that are compressed and expanded but with each compressing (positive) component, causing the volume to diminish ever more, until collapse occurs. This collapse can generate tremendously elevated temperature and pressure for an extremely short time and over an extremely short space (called an adiabatic reaction). This can result in production of several more bubbles, local cell damage, and/or generation of free radicals. 4. Derating: action of multiplying a value measured in water with standard methods by a correction factor to account for the attenuation of the ultrasound field by the tissue traversed by the beam (usually 0.3 dB/cm/MHz). 5. Dwell time: the time during which the ultrasound beam impinges on a specific organ, body part, or entire organism. 6. Mechanical index (MI): expresses the potential for non-thermal (also known as mechanical) effects in tissues traversed by the ultrasound wave. Depends on the pressure and the frequency (= P/√f).

●

Eyal Sheiner

7. Output Display Standard (ODS): actual name— Standard for Real-Time Display of Thermal and Mechanical Acoustic Indices on Diagnostic Ultrasound Equipment. Introduced to make end users aware, in real-time, of the potential effects of ultrasound in tissues. See also mechanical index and thermal index. 8. Radiation force: force resulting from absorption of some of the energy of the acoustic wave by tissue and transformation into heat. 9. Scanned mode: refers to the ultrasound beam moving through the field, with energy distributed over a large volume, such as in B-mode and color flow Doppler. 10. Thermal index (TI): expresses the potential for temperature increase in tissues traversed by the ultrasound wave. It is given by the ratio of the power emitted by the transducer to the ultrasonic power required to raise tissue temperature by 1°C for the specific exposure conditions. This is a relative indication and does not necessarily correspond to the actual temperature increase. One of three thermal indices is displayed, based on whether soft tissue (TIS, mostly first and early second trimesters), bone (TIB, late second and third trimesters), or adult cranium (TIC) is being scanned. 11. Unscanned mode: the ultrasound beam is stationary with power concentrated along a single line, such as in M-mode and spectral Doppler.

INTRODUCTION “Is this safe for my baby?” Ultrasound practitioners hear this question almost every day in clinical practice. The answer generally given is: “Of course. Ultrasound is not x-rays, it is not invasive, it has been used for close to fifty years and is perfectly safe.” While this answer may, in fact, contain some correct facts (ultrasound is not x-rays), the concept of perfect safety is not scientifically valid, and furthermore, the level of knowledge regarding potential effects of ultrasound in tissues is, by and large, very low among clinicians. Ultrasound in obstetrics is convenient, painless, and results are available immediately. The belief exists that is does not pose any risk to the pregnant patient or her fetus. However, ultrasound is a form of energy and, as such, has effects in

Chapter 1

Ultrasound Bioeffects and Safety: What the Practitioner Should Know

biological tissues (bioeffects). The physical mechanisms responsible for these effects are thermal or nonthermal (mechanical). The nonthermal mechanisms can further be separated into acoustic cavitation (inertial and noninertial) and noncavitational mechanisms, ie, acoustic radiation force (time-averaged force exerted by the ultrasound beam), acoustic radiation torque (producing in the insonated tissue a tendency to rotate or spin), and acoustic streaming (circulatory flow). It is the role of science to show whether any of these bioeffects may be harmful. The question has been debated since the introduction of ultrasound in clinical obstetrics, particularly as it relates to the fetal nervous system2,3 and continues to be discussed currently.4-9 This chapter presents basic notions of acoustics and physics as they relate to ultrasound, examines some literature on bioeffects and the safety of ultrasound, reviews statements of various ultrasound organizations, and affords a practical approach to limit the potential risks to the fetus of exposure to diagnostic ultrasound (DUS).

6

BASIC PHYSICS OF ULTRASOUND

0

A detailed description of ultrasound physics can be found in various publications.10-12 However, certain properties of ultrasound are very important when trying to understand safety and bioeffects. Equally important are tissue characteristics, such as attenuation coefficient. A basic knowledge of instrument controls (“knobology”) is essential not only for appropriate clinical usage, but it is imperative to avoid potential harm.

The Ultrasound Wave Sound is a mechanical vibratory form of energy. It propagates through a medium by means of the motions of the particles in the medium, under the influence of the alternating positive and negative components of the wave. Megapascal (MPa) is the unit for pressure. Ultrasound instrumentation can generate peak pressures of 5 MPa and above. This is in comparison to the atmospheric pressure, which is 0.1 MPa. Several other characteristics define the ultrasound beam. The ultrasonic wave progresses in the insonated tissue at a velocity that is related to the sound characteristics as well as the tissue characteristics. For practical purposes, the average speed of sound propagation in biological tissues is estimated at 1540 ms/sec. Frequency is the number of cycles per second, measured in hertz (Hz). The limits of human hearing spans from approximately 20 to 20,000 Hz. Diagnostic ultrasound is, generally, 2 to 10 million Hz (megahertz, MHz). Wavelength is the distance between 2 corresponding points on a particular wave. It is inversely proportional to the frequency. Equipment resolution (the shortest distance between 2 objects or parts of an object to be represented by 2 separate echoes) depends on the wavelength: axial resolution ranges between 2 and 4 wavelengths. Hence, the shorter the wavelength (ie, the higher the frequency), the better the resolution (the distance between 2 points is smaller). The trade-off is that the higher the frequency (better resolution), the lower the penetration of the beam through a given tissue (Figure 1-1).

3

Resolution Penetration 5

4

3

2

1

Figure 1-1. Resolution (solid line) and penetration (dotted line) as a function of increasing frequency, represented by the x-axis. Units on the y-axis are not actual but representative of increasing values. The red arrow represents the goal of improving penetration at high frequencies.

Diagnostic ultrasound is pulsed, ie, pulses of acoustic energy separated by “silent” gaps. The number of pulses occurring in 1 second is the pulse repetition frequency (PRF) and is controlled by the instrument in B-mode. In Doppler mode, it can be changed by the end user. Another important parameter is the duty factor: this is the fraction of time that the pulsed ultrasound is on. With an increase in PRF, the duty factor increases. The pulse amplitude reflects pressure and is the maximum variation from the baseline, expressed in megapascals (MPa). Since the ultrasound wave is sinusoidal, there are periods of positive and negative pressure. When the ultrasound wave exerts pressure on the resisting insonated tissue, work is produced. The ability of the wave to do work is its energy (in joules). The rate at which the energy is transformed from one form to another is the power (in watts or milliwatts). Intensity represents the rate at which energy passes through area unit. Average intensity of a beam is expressed by the beam power (in milliwatts, mW), divided by the cross-sectional area of the beam (in cm2) and is, therefore, expressed in mW/cm2. As stated earlier, DUS is performed with a pulsed wave. The intensity is proportional to the square of the instantaneous ultrasound wave pressure. There are pulses of energy intermingled with periods where no energy is emitted. Depending on the time and location of the measurement, several parameters can be described in relation to time or space: temporal peak intensity (the greatest intensity), average intensity over time, ie, including “silent” time between pulses (temporal-average intensity), maximal intensity at a particular location (spatial-peak intensity), as well as average-spatial intensity. By combining time and space, 6 intensities can be described: spatial average–temporal average (ISATA), spatial average–pulse average (ISAPA), spatial average–temporal

Part 1 GENERAL OBSTETRIC SONOGRAPHY

4

VALUES OF ISPTA BY MODALITY AND YEAR OF DEFINITION

Table 1-1 Modality/ Application

1976 Values

1986 Values

1992 Values

Fetal imaging

46

94

720

Cardiac

430

430

720

Peripheral vessel

720

720

720

Ophthalmic

17

17

17

Note: All are derated values in mW/cm2. Sources: Modified from Nyborg WL. Biological effects of ultrasound: development of safety guidelines. Part II: general review. Ultrasound Med Biol 2001;27:301-33; Abramowicz JS. Prenatal exposure to ultrasound waves: is there a risk? Ultrasound Obstet Gynecol 2007;29:363-7; Gressens P, Huppi PS. Are prenatal ultrasounds safe for the developing brain? Pediatr Res 2007;61:265-6.

peak (ISATP), spatial peak–temporal average (ISPTA), spatial peak–pulse average (ISPPA), and spatial peak–temporal peak (ISPTP). The most practical, and commonly referred to, is the ISPTA. The maximal permitted value varies by clinical application. This had been determined in 1976 by the US Food and Drug Administration (FDA),13 but was modified in 1986.14 The most recent definition dates from 1992.15 These values are shown in Table 1-1. One can observe from the table that, for fetal imaging, the ISPTA has been allowed to increase by a factor of almost 16-fold from 1976 and almost 8-fold from 1986 to 1992, yet, all epidemiological information available regarding fetal effects predates 1992. A remarkable fact is that intensity for ophthalmic examination has not changed from the original 17 mW/cm2, a value approximately 42.5 times lower than the present allowed value for fetal scanning.

Tissue Characteristics When the ultrasound wave travels through a medium, its intensity diminishes with distance.16 In completely homogeneous, idealized materials, the signal amplitude would be reduced only because the wave is spreading. Biologic tissues, however, are different and induce further weakening by absorption and scattering (an effect called attenuation) and by reflection. Many models have been described to help calculate attenuation, particularly in obstetrical scanning,17 but the most commonly used model uses an average attenuation of 0.3 dB/cm/MHz.18 It is important to note that the attenuation increases logarithmically with frequency and distance traveled. Technically, many measurements of acoustic power are performed in water, which has almost no attenuation. To apply these calculations to tissues, values are multiplied by this factor, an action called derating.19 Absorption is the sound energy being converted to other forms of energy, and scattering is the sound being reflected in directions other than its original direction of propagation. Since attenuation is proportional to the square of sound frequency, it

becomes evident why higher frequency transducers have less penetration (but better resolution; see Figure 1-1). One needs, therefore, to be closer to the organ of interest, such as through transesophageal or, in obstetrics and gynecology, transvaginal scanning. Another possibility is increasing the power of the instrument, resulting in improved resolution, as depicted by the red arrow in Figure 1-1. This is seemingly simple, but instrument outputs are regulated in the United States (see The Output Display Standard section). Another important parameter is acoustic impedance, which can be described as the opposition to transmission of the ultrasound wave. It is proportional to the velocity of sound in the tissue (estimated at 1540 ms/sec) and to the tissue density.

Instrument Outputs Although some publications of various instrument outputs are available,20-22 these are generally quickly outdated, since manufacturers introduce new commercial machines to the market (or modify existing ones) at a rate too fast for immediate objective evaluation. From a clinical standpoint, there is no easy way to verify the actual output of the instrument in use. In addition to different instruments, each attached transducer will generate a specific output, further complicated by the different modes that may be applied.23 When comparing modes, the ISPTA increases from B-mode (34 mW/cm2, average) to M-mode to color Doppler to spectral Doppler (1180 mW/cm2). Average values of the temporal averaged intensity are 1 W/cm2 in Doppler mode but can reach 10 W/cm2.23 Therefore, caution should be exercised when applying Doppler mode, particularly in the first trimester. Color Doppler, while having higher intensities than B-mode, is still much lower than spectral Doppler. This is mainly due to the mode of operation—sequences of pulses, scanned through the area of interest (“box”). Most measurements are obtained from manufacturers’ manuals, having been derived in laboratory conditions. Real-life conditions may be different.24 Furthermore, machine controls can alter the output. If one keeps in mind that, for instance, the degree of temperature elevation is proportional to the product of the amplitude of the sound wave by the pulse length and the PRF, it becomes immediately evident why any change (augmentation) in these properties can add to the risk of elevating the temperature, a potential mechanism for bioeffects (see Thermal Effects). The 3 important parameters under enduser control are the scanning (or operating) mode, including transducer choice; the system setup and output control; and the dwell time. 1. Scanning mode: B-mode carries the lowest risk, and spectral Doppler carries the highest (with M-mode and color Doppler in between). High pulse repetition frequencies are used in pulsed Doppler techniques, generating greater temporal average intensities and powers than B- or M-mode, and hence greater heating potential. An additional risk is that since, in spectral Doppler, the beam needs to be held in relatively constant position over the vessel of interest, there may be a further increase in temporal average intensity.

Chapter 1

Ultrasound Bioeffects and Safety: What the Practitioner Should Know

Naturally, transducer choice is of great consequence since it will determine frequency, penetration, resolution, and field of view. 2. System setup: starting or default output power and, particularly, mode (B-mode, Doppler etc.) control changes. A subtler element is fine tuning performed by the examiner to optimize the image and influence output but with no visible effect (except if one follows thermal index [TI] and/or mechanical index [MI] displays). Controls that regularize output include focal depth (usually with greatest power at deeper focus but occasionally, on some machines, with highest power in the near field); increasing frame rate; and limiting the field of view, for instance, by high-resolution magnification or certain zooms (Figure 1-2). In Doppler mode, changing sample volume and/or velocity range (all done to optimize received signals) changes output. Video Clip 1 demonstrates change in output (as observable by change in TI) when changing the focal

5

distance. A very important control is receiver gain. It often has similar effects to the above controls on the recorded image but none on the output of the outgoing beam, and is therefore completely safe to manipulate. In other words, the receiver gain should be maximized before output is increased. In addition, over the years, output of instruments has increased.22 3. Dwell time is directly under the control of the examiner. Interestingly, dwell time is not taken into account in the calculation of the safety indices nor, in general, until now, reported in clinical or experimental studies. However, one needs to remember that it takes only 1 pulse to induce cavitation, and about a minute to raise temperature to its peak. Directly related with dwell time is examiner experience: knowledge of anatomy, bioeffects, instrument controls, and scanning techniques. It can be safely assumed that the more experienced the examiner, the less scanning time will be needed. A standardized method of providing the end user a parameter related to acoustic output and expressing potential for bioeffects is clearly needed; hence, the generation of the Output Display Standard, based on the 2 most likely interactions of ultrasound with tissues: thermal and nonthermal or mechanical.25

THERMAL EFFECTS

Figure 1-2. Acoustic output changes (as reflected by changes in TI). A: Non-zoomed image. Please note TI = 0.2. B: Zoomed image. Please note TI = 1.0 (arrow).

Normal core human body temperature is generally accepted to be 37°C with a diurnal variation of ±0.5°C to 1.0°C, although 36.8°C ± 0.4°C (95% confidence interval) may be closer to the actual mean for large populations.26 During the entire gestation, temperature of the human embryo/fetus is higher than maternal core body temperature27 and gradually rises until the final trimester (near term). The fetal temperature generally exceeds that of the mother by 0.5°C.28 Thermally induced teratogenesis has been demonstrated in many animal studies, as well as several controlled human studies.29 While elevated maternal temperature in early gestation has been associated with an increased incidence of congenital anomalies,30 the majority of these studies do not involve ultrasound-induced temperature elevation. Edwards and others have demonstrated that hyperthermia is teratogenic for numerous animal species, including humans,31 and suggested a 1.5°C temperature elevation above the normal value as a universal threshold.32 Some scientists believe that there are, indeed, temperature thresholds for hyperthermia-induced birth defects, hence the ALARA (as low as reasonably achievable) principle. However, there is some evidence that any positive temperature differential for any period of time has some effect. In other words, that there may be no thermal threshold for hyperthermia-induced birth defects.33 From careful thermal dose determinations derived from published literature in this area, it may be that hyperthermia-induced birth defects are induced in accordance with an Arrhenius relation for chemical rate effects, and thus have no threshold.34 Any temperature increment for any period of time has some effect.

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Part 1 GENERAL OBSTETRIC SONOGRAPHY

Likewise, the higher the temperature differential or the longer the temperature increment, the greater the likelihood of producing an effect. Gestational age is a vital factor: milder exposure during the preimplantation period can have similar consequences to more severe exposures during embryonic and fetal development and can result in prenatal death and abortion or a wide range of structural and functional defects. The organ at greatest risk is the central nervous system (CNS) due to a lack of compensatory growth of undamaged neuroblasts. In experimental animals the most common defects are of the neural tube, microphthalmia, cataract, and microencephaly, with associated functional and behavioral problems.31 Defects of craniofacial development including clefts,35 the axial and appendicular skeleton,36 the body wall, teeth, and heart37 are also commonly found. Hyperthermia in utero (due to maternal influenza) has recently been described as a risk factor for subsequent childhood psychological/behavioral disturbances38 and, more particularly, schizophrenia.39 Nearly all these defects have been found in human epidemiological studies following maternal fever or hyperthermia during pregnancy. It should be emphasized that these investigations have not involved ultrasound-induced hyperthermia effects. Yet, there are data on the effects of hyperthermia and measurements of in vivo temperature induced by pulsed ultrasound, but not in human beings.40-43 These data have been widely reviewed.31,34,44-46 However, there is a serious lack of data that examine the effects of ultrasound while rigorously excluding other confounding factors. Two widely accepted facts are that ultrasound has the potential to elevate the temperature of the tissues being scanned,47-50 and elevated maternal temperature, whether from illness or exposure to heat, can produce teratologic effects.30,31,34,51-53 The major question is whether DUS can induce a harmful rise in temperature in the fetus.54-56 Some believe that this temperature rise is, in fact, a major mechanism for ultrasound bioeffects.29,34 Temperature elevation in the insonated tissue can be calculated and estimated fairly accurately if the field is sufficiently well characterized.57,58 For prolonged exposures, temperature elevations of up to 5°C have been obtained.54 Temperature change in insonated tissues depends on the balance between heat production and heat loss. A particular tissue property that strongly influences the amount of heat transported is local perfusion, which very clearly diminishes the risk, if present. Similar experimental conditions caused a 30% to 40% lower maximal temperature increase in live versus dead sheep fetuses exposed in the near field,42 while in guinea pig fetuses exposed at the focus the difference was approximately 10%.43 These findings were estimated to be secondary to vascular perfusion in live animals. A significant cooling effect of vascular perfusion was observed only when the guinea pig fetuses reached the stage of late gestation near term, when the cerebral vessels were well developed. In the midterm, there was no significant difference when guinea pig fetal brains were exposed, alive (perfused) or postmortem (nonperfused), in the focal region of the ultrasound beam.43 In early pregnancy, under 6 weeks gestation, there appears to be minimal maternal-fetal circulation, that is,

minimal fetal perfusion, which may potentially reduce heat dispersion.59 The lack of perfusion is one reason why the spatial peak-temporal average intensity (ISPTA) for ophthalmic applications has been kept very low, in fact much lower than peripheral, vascular, cardiovascular, and even obstetric scanning, despite the general increase in acoustic power that was allowed after 1992 (see Table 1-1). There are some similarities in physical characteristics between the early, first-trimester embryo and the eye. Neither is perfused; they can be of similar size; and protein is present (in an increasing proportion in the fetus). At about weeks 4 to 5, the gestational sac is about the size of the eye (2.5 cm in diameter), and by week 8 it is around 8 cm in diameter. This may allow whole-body fetal scanning (and possibly temperature increase), a concept that is generally ignored in the literature dealing with thermal effects of ultrasound. So is, often, the issue of transducer heating, which may be particularly relevant in the first trimester, if performing endovaginal scanning.60,61 There are additional concerns in early gestation because of the lack of or the minimal perfusion. Only at about weeks 10 to 11 does the embryonic circulation actually linkup with the maternal circulation.62 There may thus be some underestimation of the actual DUS-induced temperature in early gestation, mainly because of the absence of perfusion. The perfusion issue is in addition to modifications of tissue temperature due to ambient maternal and fetal temperatures. Furthermore, motions (even very small) of the examiner’s hand as well as the patient’s breathing and body movements (in the case of obstetric ultrasound, both the mother and the fetus) tend to spread through the region being heated. However, for spectral (pulsed) Doppler studies, it is necessary to have the transducer as steady as possible. This is because, in general, blood vessels are small in comparison to the general organ or body size being scanned with B-mode imaging, and hand movements while performing Doppler studies will have more undesired effects on the resulting image. As described earlier, the intensity (ISPTA) and acoustic power associated with Doppler ultrasound are the highest of all the general-use categories. Ziskin63 reported that among 15,973 Doppler ultrasound examinations, the average duration was 27 minutes (and the longest 4 hours!). There is a mathematical/physical relation between temperature elevation and several beam characteristics. The elevation is proportional to the product of the wave amplitude, length of the pulse, and PRF. Hence, manipulating any of these via instrument controls will alter the insitu conditions. It is clear that temperature increases of 1°C are easily reached in routine scanning.64 Elevation of up to 1.5°C were obtained in the first trimester and up to 4°C in the second and third trimesters, particularly with the use of pulsed Doppler.65 There is a large body of literature on heat shock proteins (HSPs), the production of which is triggered by a core temperature increase and the function of which is to protect against hazardous effects of elevated temperature as well as to induce some thermotolerance, ie, the ability to withstand higher elevations than in the past, with no harmful results.66 While their production is activated by whole-body temperature elevation, and may be speculated in ultrasound-induced thermal effects, it has

Chapter 1

Ultrasound Bioeffects and Safety: What the Practitioner Should Know

not been shown to actually occur during experimental (or clinical) insonation.

MECHANICAL EFFECTS Ultrasound bioeffects also occur through mechanical mechanisms.67,68 These are interactions between the ultrasound wave and the tissue that do not cause a significant degree of temperature increase (less than 1°C above physiologic temperature). These include acoustic cavitation as well as radiation torque and force, and acoustic streaming secondary to propagation of the ultrasound waves. While included in this category, some effects are, in fact, the result of the mechanical interaction but are actually physical (shock wave) or chemical (release of free radicals) effects. Table 1-29 summarizes nonthermal effects described in the literature in laboratory or animal experiments—and not in humans—which may be pertinent to fetal ultrasound. Investigations with laboratory animals clearly indicate that nonthermal interactions of ultrasound fields with tissues can produce biological effects in vivo.68 It is interesting to note that chemical effects of ultrasound were described more than 80 years ago!69 Cavitation seems to be the major factor in mechanical effects70 as it has been demonstrated to occur in living tissues under ultrasound insonation.71,72 Two types of cavitation can be described— stable and inertial (previously defined as transient)—both of which need the presence of gas bubbles to occur. Stable cavitation indicates vibrations or small backward and forward movements with possible resulting microstreaming. Inertial cavitation indicates expansion and reduction in volume, secondary to alternating positive and negative pressures generated by the ultrasound wave. Expansion in growth is less with each cycle until collapse occurs with

Table 1-2

MAJOR NONTHERMAL EFFECTS OF ULTRASOUND OBSERVED IN THE LABORATORY AND IN ANIMALS AND WITH THE POTENTIAL TO AFFECT THE FETUS

Free-radical generation Increase in cell membrane permeability Erythrocyte agglutination Growth restriction (transient decrease) DNA single-strand break Increased sister chromatid exchange Increased mutation frequency Capillary petechiae Vasoconstriction Lung microvascular hemorrhage Intestine microvascular hemorrhage Neuronal migration delay Auditory tract stimulation Tactile radiation pressure perception effect Cardiac, premature contractions Source: Modified from Stratmeyer ME, Greenleaf JF, Dalecki D, Salvesen KA. Fetal ultrasound: mechanical effects. J Ultrasound Med 2008;27:597-605.

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production of very high pressure (hundreds of atmospheres) and very elevated temperature (thousands of degrees), but on such a small area (less than 100 nanometers) and for such a brief time (few tens of nanoseconds) that it will not be felt and is very hard to measure (adiabatic reaction—occurring without the gain or loss of heat) but can produce microstreaming—a phenomenon that has been described also with no clear involvement of bubbles,73-75 or even release of free radicals.76,77 Acoustic streaming is easily demonstrated by watching ultrasound-induced movements of solid-mattercontaining fluids in insonated cavities (see Video 2). Radiation torque refers to the induction, in objects found in the acoustic field, of rotation or of the tendency to rotate. Biological effects of ultrasound in animals such as local intestinal,78 renal,79 and pulmonary80 hemorrhages have been attributed to mechanical effects, although cavitation could not always be implicated. Furthermore, since gas bubbles do not seem to be present in fetal lungs or bowels (where effects have been described in neonates or adult animals), the risk from mechanical effect secondary to cavitation appears to be minimal.81 There are several other effects that do not appear to involve cavitation such as tactile sensation of the ultrasound wave, auditory response, cell aggregation, and cell membrane alteration. Hemolysis has also been reported.82 It seems, however, that the presence of some cavitation nuclei is necessary for hemolysis to occur. At present, there is no clear clinical indication for the use of ultrasound contrast agents (a source of cavitation nuclei, when injected into the body before ultrasound examination) in fetal ultrasound, and to date, no studies have specifically investigated the interaction of ultrasound and microbubble contrast agents in fetal tissues in vivo. Nevertheless, it should be noted that in the presence of such contrast agents, fetal red blood cells are more susceptible to lysis from ultrasound exposure in vitro.83 Additionally, fetal stimulation caused by pulsed ultrasound insonation has been described, with no apparent relation to cavitation.84 This effect may be secondary to radiation forces associated with ultrasound exposures. These forces were suspected at the earliest stages of ultrasound research85 and are known to possibly stimulate auditory,86 sensory,87 and cardiac tissues.88 No harmful effects of DUS, secondary to nonthermal mechanisms, have been reported in human fetuses. A very intriguing nonthermal effect of ultrasound is acceleration of bone fractures healing in animals and humans.89 Because of these known effects of ultrasound in living tissues and the fact that pressures involved with Doppler propagation are much higher than B-mode, caution is further recommended, based on scientific evidence of potential effect, particularly in the first trimester.90

THE OUTPUT DISPLAY STANDARD In 1992, the FDA yielded to pressure from ultrasound clinical users as well as manufacturers to increase the power output of instruments. The rationale for this request was that higher outputs would generate better images, and thus improve diagnostic accuracy. To allow clinical users of ultrasound to use their instruments at higher powers than

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Part 1 GENERAL OBSTETRIC SONOGRAPHY

originally intended and to reflect the 2 major potential biological consequences of ultrasound (mechanical and thermal, see pp. 5-7), the American Institute of Ultrasound in Medicine (AIUM), the National Electrical Manufacturers’ Association (NEMA), and the FDA (with representatives from the Canadian Health Protection Branch, the National Council on Radiation Protection and Measurements,91 and 14 other medical organizations29) developed a standard related to the potential for ultrasound bioeffects. The full name was the Standard for Real-Time Display of Thermal and Mechanical Indices on Diagnostic Ultrasound Equipment, generally known as the Output Display Standard or ODS.15 The importance of this document and what it describes is that it represents historically the first attempt at providing to the end user quantitative safetyrelated information. One important result is that the end users are able to see how manipulation of the instrument controls during an examination causes alterations in the output and thus on the exposure. As a consequence, for fetal imaging the output, as expressed by the ISPTA, went from a previous value of 92 mW/cm2 to 720 mW/cm2 (see Table 1-1). To allow the output to reach such levels, the manufacturers were requested to display, on screen and in realtime, 2 types of indices with the intent of making the user aware of the potential for bioeffects, as described earlier. These indices are the thermal index (TI), to provide some indication of potential temperature increase, and the mechanical index (MI), to provide indication of potential for nonthermal (ie, mechanical) effects15,29,92 (Figure 1-3). The TI is the ratio of total acoustic power to the acoustic power estimated to be required to increase tissue temperature by a maximum of 1°C. It is an estimate of the maximal temperature rise at a given exposure. There are 3 variants: for soft tissue (TIS), to be used mostly in early pregnancy when ossification is low; for bones (TIB), to be used when the ultrasound beam impinges on bone at or near the beam focus, such as late second and third trimesters of pregnancy; and for transcranial studies (TIC) when the transducer is essentially against bone, mostly for

examinations in adult patients. These indices were required to be displayed if equal to or over 0.4. It needs to be made very clear that TI does not represent an actual or an assumed temperature increase. It bears some correlation with temperature rise in degrees Celsius but in no way allows an estimate or a guess as to what that temperature change actually is in the tissue.92 The MI represents the potential for nonthermal damage in tissues but is not based on actual in-situ measurements. It is a theoretical formulation of the ratio of the pressure to the square root of the ultrasound frequency (hence, the higher the frequency, the lesser risk of mechanical effect). Both the TI and MI can and should be followed as an indication of change in output during the clinical examination. A clear extension of the above statements is that education of the end user is a major part in the implementation of the indices. Attempts have been made to educate the end users,93 but, unfortunately, this aspect of the ODS does not seem to have succeeded as end users’ knowledge of bioeffects, safety, and output indices is found lacking.94,95 Furthermore, several assumptions were made, which prompts some questions on the clinical value of these indices. Maybe the most significant (from a clinical aspect) is the choice of the homogeneous attenuation path model (defined as the H3 model), with an attenuation coefficient of 0.3 dB/cm/MHz. The reason to employ models of that nature is the impossibility, for obvious reasons, to perform certain measurements in pregnant women. This coefficient may be an overestimation of the attenuation in many clinical scenarios, a situation that would underestimate the actual exposure. In National Council on Radiation Protection and Measurements (NCRP) report number 140,29 there is an entire chapter (Chapter 9) indicating conditions where both indices may be inaccurate, eg, long fluid path (full bladder, amniotic fluid, ascites, or hydrocephalus) or path through increased amounts of soft tissue such as obese patients. Because of these uncertainties, the accuracy of the TI and MI may be within a factor of 2 or even 6.96 For example, an on-screen TI of 1 may correspond to an actual value of 0.5 or 2 if the error factor is 2, but possibly 0.33 or 6, if the error factor is 6 (as previously stated, these are not actual temperature indications). A further disturbing and confusing element is that outputs reported by manufacturers are not necessarily equivalent to those calculated in the laboratory.97

RISK ASSESSMENT

Figure 1-3. Onscreen TI (= 0.3, red arrow) and MI (= 1, yellow arrow).

Risk means the chance or the possibility of loss or bad consequence. It refers to the possibility, with a certain degree of probability, of damage to health, environment, and objects, in combination with the nature and magnitude of the damage.98 These are the 3 important characteristics of risk: probability of occurrence, and nature and magnitude of harm. It has been, specifically, applied to the use of medical instruments.99 A complicating factor that makes definition and classification difficult is that the concept of risk means various things to different people. Age, background, education, morals, religion, and many other traits will direct this evaluation and not only the absolute possible result of the activity, putting the participant at risk.

Chapter 1

Ultrasound Bioeffects and Safety: What the Practitioner Should Know

For instance, in bungee jumping, rupture of the elastic cord and subsequent death may be, indisputably, the worst possible outcome but different people evaluate this and make decisions that are not necessarily based on this absolute result. Furthermore, the reason to take a possible risk has to be investigated. Two approaches are possible in risk evaluation: how much harm is acceptable to obtain the desired results (risk-benefit ratio) or how much harm can be avoided by withholding the action or modifying it (the precautionary principle). The risk-benefit principle is what is almost universally used in medicine to justify a medical diagnostic procedure (such as ultrasound) or a therapeutic intervention. If the benefit to be obtained from the procedure in terms of diagnosis (ultrasound) or intervention (a newly discovered and not yet commercialized cancer or AIDS drug, for instance) is deemed to be sufficient, then even if this diagnostic or interventional procedure carries some risks (recognized or presumed to be possible), the benefit overrides these risks, assuming the subject understands those risks and is willing to take them. The precautionary principle (PP) is a diametrically opposed ethical, political, and economic approach stating that if a certain action may cause severe damage to the public, in the absence of a scientific consensus that harm would not ensue, the burden of proof falls on those who would advocate taking that action.100 This principle is much less familiar to the medical field, although “first do no harm” is its direct application, but it may be extremely relevant when considering safety and risks of a procedure, such as prenatal ultrasound. The concept originated in the 19th century when John Snow, a London, UK, physician, determined that cholera was due to the extensive, common use of an unclean water supply and recommended closing of this source of water, although it was the sole one in a large vicinity.101 This may have been the first epidemiological analysis of a disease. Although the beginning of the PP was medical, it became a social idea in Germany in the 1930s as Vorsorge, “forecaring.” This later became the Vorsorgeprinzip, the forecaring or precautionary principle, in West German environmental law in the 1970s.102 The idea was adopted by decision and policy makers but, remarkably, much more extensively in Europe than in the United States. Some key concepts in the original formulation were environmental harm to a population and responsibility: “When an activity raises threats of harm to human health or the environment, precautionary measures should be taken even if some cause and effect relationships are not fully established scientifically. In this context the proponent of an activity, rather than the public, should bear the burden of proof” (the Wingspread Statement on the Precautionary Principle103). From environmental research it spread to toxicology and was first applied only recently in the United States to a clinical medical field.104 However, several medical mishaps clearly belong to the history of the development of the PP—from the diethylstilbestrol debacle105 to the thalidomide tragedy.106 While referring mostly to environmental issues, such as global warming, the PP can certainly be extended to other medical activities (such as diagnostic ultrasound) and be applied to individuals (such as fetuses). The simple enunciation of the principle,

9

particularly in reference to diagnostic ultrasound in general and entertainment ultrasound in particular, is that even if a particular action or procedure has not been proved to be harmful, it’s better to avoid it so as not to take the risk until safety is established through clear, scientific evidence, popularly expressed as “better safe than sorry.”107 This is also the basis of the Hippocratic Oath, which includes the recommendation to first do no harm. A major difference with the risk-benefit principle is that proponents of the PP believe that public action is necessary if there is any evidence of likely or substantial harm, however limited but plausible, and the burden of proof is shifted from showing the presence of risk to demonstrating its absence.108 As such, epidemiologic research on chronic diseases and the use of surrogates for human studies (eg, animal research or tissue cultures) have been shown to be uncertain.109 There are several variations of the PP, but all have some common key elements: 1. There must be scientific uncertainty about nature of harm, probability, magnitude, and causality (fulfilled by DUS). 2. Mere speculation is not enough to invoke the PP. Scientific analysis must have triggered the process (also fulfilled by DUS). 3. Per definition, the PP deals with procedures with probability of unclear outcome, in that it is different from prevention or from risk-benefit assessment where some clear knowledge or precise suspicion exists, and where decision may be made to go ahead despite this risk by, for instance, taking additional measures to attempt and limit the danger. Clearly, the ALARA principle is the exact application of this element110,111 (fulfilled by DUS). 4. In general, the PP applies to unacceptable (“serious,” “irreversible,” “global”) high levels of risk to large populations, present or future, local or distant112 (may not be the case for DUS). 5. One needs to intervene (not observe or procrastinate) before damage has been demonstrated (eg, “do not perform DUS”). 6. The intervention must be proportional to the possible risk: indicating DUS may be acceptable but not nonclinical use of DUS. A level of “zero risk” is probably never attainable. Those who support the PP make the following very strong argument for precaution: serious damage may be caused if one uses a risk-based approach. A well-known example is what constitutes toxic levels of lead in paint. As early as 1897, it was known that lead may be toxic, but at first the upper limit of safety for children was assumed to be 60 μg/dL of blood, and this had terrible results. The “safe” level was reduced over the years to 40, then 20, then 10, which it is today, although some scientists feel that even 2 μ/dL may pose some risk.113 The basic conclusion of risk analysis with the PP is that measures against a possible risk should be taken (such as exposure avoidance) even if the available evidence is weak (or maybe absent) regarding the existence of that risk as a scientifically established fact.114 In many European countries this “stop first then

10

Part 1 GENERAL OBSTETRIC SONOGRAPHY

study” approach (a clear application of the PP) has been adopted (particularly for chemicals). The exact opposite is often true in the United States where something, once introduced, has to be proven harmful by science before being removed or forbidden. A major goal of the PP is to help delineate (preferably quantitatively) the possibility that some exposure is hazardous, even in cases where this is not established beyond reasonable doubt.115 The classical statistical approach to hypothesis testing is unhelpful, because lack of significance can be due to either uninformative data or genuine lack of effect (type II error).116 There are many critics of the PP because of the risk of exaggeration in caution and slowing down of scientific progress.117,118 A major issue is that the PP relies very heavily on a single conjecture: prevention is better than cure. There is no scientific evidence for this. Furthermore, it may be true that often it is better to be “safe than sorry” and the primum non nocere (first do no harm) principle is a direct application of this, but preventative measures can be long lasting and possibly incapacitating, whereas cures can be targeted and effective.117 What is more, no moral opinion is formed of people when treating them, but if the main focus is upon precaution, then it can be deemed morally wrong not to take preventative measures. The whole precaution approach is imbued with what may appear to many as an excessively moralistic tone.119 Furthermore, the probability of a problem occurring that one tries to avoid has to be high (which does not apply, as far as we know, to ultrasound) and preventative measures have to be effective. Hence this approach may be adopted with some restrictions and this is, in fact, exactly what ALARA recommends.111 Most scientists and professional organizations have recommended such a practice in clinical obstetrical ultrasound.120-122

HISTORICAL RESEARCH The first descriptions of ultrasound as an imaging mode date from the 19th century.123 The French engineer Paul Langevin designed an ultrasound machine, using Pierre Curie’s principle of the piezoelectric effect. During World War I, he attempted to use this instrument to detect submarines through echo location (hence the later coined term SONAR: SOund Navigation And Ranging). He also demonstrated that the waves produced by his machine could kill small animals in an insonated water bath, and could cause pain to his assistants when they were required to plunge their hands in the water bath in the path of the beam. Other bioeffects observed included the searing of skin when touching a resonant quartz bar, and explosive atomization (!) of fluid drops from the end of the rod. Since that time, the question of effects and safety has been on the minds of researchers85 and has given rise to literature too extensive to review in detail.2,3,6,46,120,124-136 Initially, cell suspensions and cell and tissue cultures were employed and many reports described clear effects of the ultrasound waves on these, mostly secondary to cavitational and other nonthermal mechanisms, such as cell aggregation,137 membrane damage,138 and cell lysis,139 among others. Plants were another extensively studied organism for effects of ultrasound,140 particularly the Elodea leaf, since

internal gas channels are present.141 Insects have been exposed to ultrasound with significant effects, such as death of eggs and larvae as well as abnormal development, presumably secondary to the presence of gas-filled channels.142 Additionally, alterations at the chromosomal and even DNA levels have been described.143 The above effects have been reviewed extensively elsewhere,5,29 and while of major scientific and historical importance, are not of major relevance to clinical exposure of human fetuses.

Animal Research Effects of ultrasound were demonstrated in animals more than 80 years ago.85 Since then, multiple studies have been performed with ultrasound on a wide variety of species. Studies of gross effects on the brain and liver of cats were first performed with well-defined lesions and demyelination in the brain144 and tissue damage in the liver,145 resulting from ultrasound exposure of a few seconds at 1 and 3 MHz, respectively. Other observed effects include limb paralysis as a result of spinal cord injury in the rat,146,147 as well as lesions in the liver, kidney, and testicles of rabbits.148 While some effects are likely due to mechanical influences, very high temperature elevations (much higher than anything reachable with diagnostic ultrasound) have also been observed and may be more directly involved with the tissue damage. Effects in muscles have been obtained, but with outputs much higher than those usually generated in clinical studies,149 and so have intestinal78 and lung150 hemorrhages, also at acoustic pressures well above those generated by ultrasound fields. These are helpful in understanding the mechanisms involved with possible bioeffects of DUS. It should also be noted that some similar effects have also been demonstrated with acoustic fields much closer to clinically pertinent ones, in particular lung and intestinal hemorrhage.78 Several major clinical end-points for bioeffects that could have direct relevance to human studies include fetal growth and birth weight, effects on brain and CNS function, and change in hematological function, and will be considered in more detail. Decreased birth weight after prenatal exposure to ultrasound has been reported in the monkey151,152 and the mouse,153,154 but not convincingly in the rat.155 Therefore, clear species differences seem to exist,156 making it difficult to generalize, and even more difficult to extrapolate to humans. Tarantal and Hendrickx151 evaluated 30 pregnancies in monkeys, half of which were exposed to ultrasound. The scanned fetuses had lower birth weights and were shorter than the control group. No significant differences were noted between the groups with regard to the rate of abortions, major malformations, or stillbirths. Moreover, all showed catch-up growth when examined at 3 months of age.151 It should be noted that in-situ intensities were higher than what is considered routine in clinical obstetrical imaging in humans. Hande and Devi157 evaluated the effect of prenatal exposure to diagnostic ultrasound on the development of mice. Swiss albino mice were exposed to diagnostic ultrasound for 10 minutes on day 3.5 (preimplantation period), 6.5 (early organogenesis period), or 11.5 (late organogenesis period) of gestation. Shamexposed controls were maintained for comparison. Fetuses

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Ultrasound Bioeffects and Safety: What the Practitioner Should Know

were dissected out on the 18th day of gestation, and changes in total mortality, body weight, body length, head length, brain weight, sex ratio, and microphthalmia were recorded. Exposure on day 3.5 of gestation resulted in a small increase in the resorption rate and a significant reduction in fetal body weight. Low fetal weight and an increase in the incidence of intrauterine growth-restriction were produced by exposure on day 6.5 postcoitus.157 Others have also demonstrated restricted growth in newborns after in-utero exposure to DUS.158 Subtler findings have also been described. Pregnant Swiss albino mice were exposed to diagnostic ultrasound (3.5 MHz, 65 mW, ISPTP = 1 W/cm2, ISATA = 240 W/cm2) for 10, 20, or 30 minutes on day 14.5 (fetal period) of gestation.159 Shamexposed controls were studied for comparison. There were significant alterations in behavior in the exposed groups as revealed by decreased locomotor and exploratory activity, and an increase in the number of trials needed for learning. No changes were observed in physiological reflexes and postnatal survival. The authors concluded that ultrasound exposure during the early fetal period can impair brain function in the adult mouse.159 Likewise, Hande et al160 found that anxiolytic activity and latency in learning were more noticeable in ultrasound-treated animals. The authors exposed pregnant Swiss mice to diagnostic levels of ultrasound (3.5 MHz, maximum acoustic output: ISPTP = 1 W/cm2 and ISATA = 240 mW/cm2, acoustic power = 65 mW) for 10 minutes on postcoital day 11.5 or 14.5. At 3 and 6 months postpartum, offspring were subjected to behavioral tests. The effect was more pronounced in the 14.5 days postcoital group than in the 11.5 days group. They concluded that exposure to diagnostic ultrasound during late organogenesis period or early fetal period in mice may cause changes in postnatal behavior.160 Temperature elevations were induced by ultrasound in guinea pig fetal brains.43 In fact, mean temperature increases of 4.9°C close to parietal bone and 1.2°C in the midbrain were recorded after 2-minute exposures, albeit at exposure conditions higher than what is usually employed in clinical examinations.43 This greatest temperature rise recorded close to the skull correlated with both gestational age and progression in bone development.40 The skull bone becomes progressively thicker and denser between 30 and 60 days’ gestational age (normal gestation for guinea pigs is 66 to 68 days). After only 2 minutes of insonation with an ISPTA of 2.9 W/cm2 (about 4 times higher than currently permitted by the FDA for diagnostic use), mean maximum temperature increases varied from 1.2°C at 30 days to 5.2°C at 60 days. It is important to note that most of the heating (80% of the mean maximum temperature increase) occurred within 40 seconds. The rate of heating is relevant to the safety of clinical examinations in which the dwell time may be an important factor. Because maximal ultrasound-induced temperature increase occurs in the fetal brain near bone, worst-case heating will occur later in pregnancy, when the ultrasound beam impinges on bone, and less will occur earlier in pregnancy, when bone is less mineralized. However, milder insults early in gestation may be as significant (or more) than more severe ones in later stages. Neurons of the cerebral neocortex in mammals, including humans, are generated during fetal life in the

11

brain proliferative zones and then migrate to their final destinations by following an inside-to-outside sequence. Recently, Ang et al161 evaluated the effect of ultrasound waves on neuronal positioning within the embryonic cerebral cortex in mice. Neurons generated at embryonic day 16 and destined for the superficial cortical layers were chemically labeled in over 335 animals. A small but statistically significant number of neurons failed to acquire their proper position and remained scattered within inappropriate cortical layers and/or in the subjacent white matter when exposed to ultrasound for a total of 30 minutes or longer during the period of their migration. The magnitude of dispersion of labeled neurons was variable but systematically increased with duration of exposure to ultrasound (although not linearly, with some extended exposure yielding less effect than lower ones). These investigators concluded that further research in larger and slower-developing brains of nonhuman primates and continued scrutiny of unnecessarily long prenatal ultrasound exposure is warranted. It is unclear whether a relatively small misplacement in a relatively small number of cells that retain their origin cell class is of any clinical significance. It is also important to note that there are several major differences between the experimental setup of Ang et al161 and the clinical use of ultrasound in humans.6 The most noticeable difference was the length of exposure of up to 7 hours in the setup of Ang et al. No real mechanistic explanation was given for the findings, and furthermore, there was no real dose effect with high effects at the penultimate high dose, but less so at the highest dose. Moreover, scans were performed over a small period of several days. The experimental setup was such that embryos received whole-brain exposure to the beam, which is rare in humans. In addition, brains of mice are much smaller than those in humans, and develop over days. This should not completely deter from the study, but encourages caution. It should be noted that some have described a complete lack of effects of prenatal ultrasound exposure on postnatal development and growth162 or behavior.163 Another recently published study is worth considering.164 Chick brains were exposed, in ovo, on day 19 of a 21-day incubation period to B-mode (5 or 10 min), or to pulsed Doppler (1, 2, 3, 4, or 5 min) ultrasound. After hatching, learning and memory function were assessed at day 2 post-hatch. B-mode exposure did not affect memory function. However, significant memory impairment occurred following 4 and 5 min of pulsed Doppler exposure. Short-, intermediate-, and long-term memory was equally impaired, suggesting an inability to learn. Chicks were also unable to learn with a second training session. In this study, exposure to pulsed Doppler ultrasound adversely affected cognitive function in chicks. Although some methodological issues exist and extrapolation to humans is unwarranted, these findings justify further investigations. The hematological system is the second major system to be investigated for ultrasound effects. The following have been assessed: hemolysis, coagulation factors and platelets, and leukocyte production and function.165 Increased hemolysis has been demonstrated for ultrasound in (human) fetal cells as compared to adult cells, but only

12

Part 1 GENERAL OBSTETRIC SONOGRAPHY

in the presence of ultrasound contrast agents, with human cells being less fragile than certain tested animals.83,166 Other alterations have been described in the hemolytic system167 but appear to be of minimal, if any, clinical significance.

Human Research and Epidemiology In 2005, the American Institute of Ultrasound in Medicine (AIUM) published the following statement: “Based on the epidemiological data available and on current knowledge of interactive mechanisms, there is insufficient justification to warrant a conclusion of a causal relationship between diagnostic ultrasound and recognized adverse effects in humans. Some studies have reported effects of exposure to diagnostic ultrasound during pregnancy, such as low birth weight, delayed speech, dyslexia, and non–right-handedness. Other studies have not demonstrated such effects. The epidemiological evidence is based on exposure conditions prior to 1992, the year in which acoustic limits of ultrasound machines were substantially increased for fetal/obstetrical applications.”168 Applied to ultrasound, epidemiology is the study of effects on human populations as a result of ultrasound scanning and, in the case of obstetrical ultrasound, this should include the pregnant patient as well as her infant. Laboratory animal experiments under similar diagnostic exposure levels have shown some effects from ultrasound, under certain conditions. Effects have also been reported in humans, but a definitive statement regarding risk should, ideally, include direct analysis of the effects in human populations. Several epidemiological studies have been published. 4,46,169 For an extensive discussion, including elements of statistics, see Chapter 12 in NCRP report number 140,29 an extensive review by Newnham,132 and AIUM document, Conclusions Regarding Epidemiology for Obstetric Ultrasound.170,171. Relevant details will be summarized. Several biological end points have been analyzed in the human fetus/neonate in an attempt to determine whether prenatal exposure to diagnostic ultrasound had observable effects: intrauterine growth restriction (IUGR) and low birth weight, delayed speech, dyslexia, neurological and mental development or behavioral issues, and, more recently, non–right-handedness. Occasional studies report an association between diagnostic ultrasound and some specific abnormalities such as lower birth weight,169 delayed speech,172 dyslexia,173 and non–right-handedness.174,175 With the exception of low birth weight (also demonstrated in monkeys,166 ) these findings have never been duplicated, and the majority of studies have been negative for any association. Moore et al176 examined a large number of infants (over 2000, half of them exposed to ultrasound) and found a small but statistically significant lower mean birth weight of exposed versus non-exposed infants. However, information was collected several years after exposure, no indications for the examination are known, and no exposure information is available. This is very often the major problem in analyzing these reports. In a later study, the authors concluded that the relationship of ultrasound exposure and reduced birth weight may be due to shared common risk factors, which lead to both exposure and a

reduction in birth weight. 177 Another retrospective study, with Moore as a coauthor, reported a 2.0 greater risk of low birth weight after 4 or more exposures to diagnostic ultrasound.133 These results were not reproduced in other retrospective studies.176 In a large study (originally 10,000 pregnancies exposed to ultrasound matched with 500 controls) with a 6-year follow-up, Lyons et al178 did not find differences in birth weight (nor increased congenital malformations, chromosomal abnormalities, infant neoplasms, speech or hearing impairment, or developmental problems). Newnham et al171 performed a randomized control trial including more than 2800 parturients. Of these, about half received 5 ultrasound imaging and Doppler flow studies at 18, 24, 28, 34, and 38 weeks gestation, and half received a single ultrasound imaging at 18 weeks. They found an increased risk of IUGR when exposed to frequent Doppler examinations, possibly via some effects on bone growth. However, when children from the last mentioned study were examined at 1 year of age, there were no differences between the study and control groups. In addition, after examining their original subjects after 8 years, no evidence of long-term adverse impact in neurological outcome was noted by the same group.179 Similarly, no harmful effect of a single or 2 prenatal scans on growth were found in several randomized studies.180,181 In fact, in some studies, birth weight was slightly higher in the scanned group, but not significantly so, except in one.182 In conclusion, decreased birth weight has been extensively analyzed after DUS exposure in utero, and it does not appear that such exposure is associated with reduced birth weight, although Doppler exposure may have some risks.136 In a few studies that appear to favor such an effect, a major problem is that there is an important confounding factor: many studies include pregnancies at risk for IUGR due to existing maternal or fetal conditions. A second major potential effect extensively evaluated is delayed speech. In an attempt to determine if there is an association between prenatal ultrasound exposure and delayed speech in children, Campbell et al172 studied 72 children with delayed speech and found a higher rate of ultrasound exposure in utero than the 144 control subjects. Some issues render these results less valid: there was neither a dose-response effect nor any relationship to time of exposure, and many of the records were more than 5 years old. Another study of over 1100 children exposed to ultrasound in utero and over 1000 controls found no significant differences in delayed speech, limited vocabulary, or stuttering.183 Dyslexia is another widely studied subject. In one study over 4000 children, aged 7 to 12, exposed to ultrasound in utero were used as a study group and compared to matched controls to evaluate the appearance of adverse effects.173 Seventeen outcomes measures were examined, at birth (APGAR scores, gestational age, head circumference, birth weight, length, congenital abnormalities, neonatal infection, and congenital infection) or in early infancy (hearing, visual acuity and color vision, cognitive function, and behavior). No significant differences were found, except for a significantly greater proportion of dyslexia in those children exposed to ultrasound. However, the authors indicated that this could be an incidental

Chapter 1

Ultrasound Bioeffects and Safety: What the Practitioner Should Know

finding, given the design of the study and the presence of several confounding factors that could have contributed to the possible dyslexia finding. On the other hand, it should be noted that exposure conditions were probably much lower than modern ultrasound systems, given that the fetal examinations were performed from 1968 to 1972. Subsequently, a long-term follow-up study was performed on over 2100 children.180,184 End points included evaluation for dyslexia along with additional hypotheses including an examination of non–right-handedness (see below) said to be associated with dyslexia. These studies185-187 included the specific examination of more than 600 children with various tests for dyslexia such as spelling and reading. No statistically significant differences were found between ultrasound-exposed children and controls for reading, spelling, arithmetic, or overall performance as reported by teachers. Specific dyslexia tests showed similar rates of occurrence among scanned children and controls in reading, spelling, and intelligence scores, and no discrepancy between intelligence and reading or spelling. Since the original finding of dyslexia was not confirmed in subsequent randomized controlled trials, it is considered unlikely that routine ultrasound screening exams can cause dyslexia. However, these studies did raise the issue of laterality (in terms of handedness), which is discussed below. The issue of non–right-handedness as a result of prenatal exposure has caused much ink to be used in extensive discussions and reports. The first report of a possible link between prenatal exposure to ultrasound and subsequent non–right-handedness in insonated children was published in 1993 by Salvesen et al,185 but according to the authors, “only barely significant at the 5% level.” In a later analysis of the data, they described that the association was restricted to males.186 A second group of researchers (with Salvesen, the main author of the first study, included but with a new population, in Sweden as opposed to Norway) published similar findings of a statistically significant association between ultrasound exposure in utero and non–right-handedness in males.174 Salvesen then published a meta-analysis of these 2 studies and of previously unreported results.173 No difference was found in general, but a small increase in non–right-handedness was present when analyzing boys separately. No valid mechanistic explanation is given in the studies to explain the findings. In conclusion, although there may be a small increase in the incidence of non–right-handedness in male infants, there is not enough evidence to infer a direct effect on brain structure or function or even that non–right-handedness is an adverse effect. Other end points that have been considered but not found to be associated with ultrasound exposure include congenital malformations and malignancies.189 There has been no epidemiological study published on populations scanned after 1992, when regulations were altered and acoustic output of diagnostic instruments were permitted to reach levels many times higher than previously allowed (from 94 to 720 mW/cm2 ISPTA for fetal applications). There are no epidemiological studies related to the output display standard (thermal and mechanical indices) and clinical outcomes. The safety of new technolo-

13

gies such as harmonic imaging and three-dimensional (3D) ultrasound, as well as that of probe self-heating, needs to be investigated.

Clinical Exposimetry Unfortunately there is no way to perform actual sonographic exposure measurements in the human fetus. Pressure, intensity, and power are not measured in situ, but are estimated from laboratory obtained measurements. Several tissue models have been developed to help with this estimation, depending mostly on approximate attenuation coefficients for various tissues or beam paths.29,47 A large range of variation is expected secondary to individual patient characteristics, such as weight and thickness of tissues.190 Because of these possible variations, the reasonable worst-case scenario is usually considered. There are scarce data on instruments’ acoustic output (nor patient acoustic exposure) for routine clinical ultrasound examinations. Acoustic output was recorded in several prospective observational studies investigating first-trimester ultrasound,191 Doppler studies, 192 and 3D/four-dimensional (4D) studies.193 Basically, first-trimester ultrasound was associated with very low TI values (with a mean of 0.2 ± 0.1).190 The TI was significantly higher in the pulsed wave Doppler (mean 1.5 ± 0.5, range 0.9-2.8) and color flow imaging studies (mean 0.8 ± 0.1, range 0.6-1.2) as compared to Bmode ultrasound (mean 0.3 ± 0.1, range 0.1-0.7; P < .01).190 In the same study, TI was above 1.5 in 43% of the Doppler studies.192 Mean TI during the 3D (0.27 ± 0.1) and 4D examinations (0.24 ± 0.1) was comparable to the TI during the B-mode scanning (0.28 ± 0.1; P = .343).193 Figures 1-3 through 1-7 are examples of actual screen shots during clinical exams, for B-mode, color Doppler, M-mode, spectral Doppler, and 3D acquisition, respectively. Figure 1-8 demonstrates that extremely elevated TIs are easily reachable with spectral Doppler, although in manufacturer’s fetal setting. The other side of the equation is, “What are we looking for?” Ultrasound is neither radiation nor thalidomide,

Figure 1-4. TI and MI during color Doppler exam. Please note TI = 0.6 (arrow).

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Part 1 GENERAL OBSTETRIC SONOGRAPHY

Figure 1-5. TI and MI during M-mode examination. Please note TI = 0.8

Figure 1-6. TI and MI during spectral Doppler examination. Please note

(arrow).

TI = 2.4 (arrow).

and it is certain that ultrasound does not kill fetuses, does not cause limb amputations, and does not cause gross structural anomalies.194 But are we looking where we should, and have we studied enough cases in a scientific fashion, looking at subtle changes? The answer is clearly, “No.” We have been looking for macroscopic, gross findings and have not found any, but is it possible that harmful effects of ultrasound have been missed because the wrong time frame reference was used? Two possible factors are described for such errors.195 If one uses a term human

pregnancy (280 days [40 weeks]) to life expectancy of 70 years (25,550 days) ratio, then 7 in-utero days are comparable to about 631 ex-utero days. Therefore, it is conceivable that a much shorter time interval (1 day) should be used to group fetuses to evaluate effects, not intervals of 1 or more weeks as is usually done. Furthermore, there is also a potential “dilution error.” Assuming an event has a background rate of 10% in the general population but occurs in 100% of fetuses exposed on day 35, if a large number (for instance, 1000) of fetuses exposed on that

Figure 1-7. TI and MI during multiplanar acquisition in 3D scanning. Please note TI = 0.4 (arrow).

Chapter 1

Ultrasound Bioeffects and Safety: What the Practitioner Should Know

Figure 1-8. Second-trimester spectral Doppler. Please note TI = 3.3 (arrow). This is with the instrument on “fetal” setting.

particular day are examined, the incidence will be 100%, ie, 90% increase over the control population (background rate of 10%). But if we assume 1000 fetuses are exposed per day for 12 weeks, this represents 84,000 scans, and only 11.1% will be affected (all 1000 scanned on day 30 and 10% [the background rate] of all 83,000 others [8300], or 9300 total), an increase of only 1.1% (1.07 to be precise) over the background rate of 8400 (10% of 84,000), which is very difficult to extract and observe, but still present in 100% of the fetuses exposed at the critical time (day 35 in the above example). The actual numbers are probably even more complicated since more than 1000 fetuses are scanned every day, the background rate of major anomalies is 3% to 4% in the general population and much lower for nongross macroscopic findings, and furthermore, the hit rate of any teratological agent is rarely 100%. This points to the need for extensive, well-planned research—a goal very difficult to accomplish, given that the majority of pregnant women who receive prenatal care will have 1 or several DUS scans during their pregnancy.

Nonmedical Ultrasound Nonmedical ultrasound refers to the performance of obstetrical ultrasound with no medical indication but to provide the mother/parents-to-be with images or video clips of the fetus (on hard copy, tape, CD, or DVD), also called “scanning for pleasure.”196 There are several reasons why most official organizations are opposed to this practice, such as issues of training of the providers, quality and nature of the scans, feedback to the “customers,” and risks that these customers will not have a regular, clinical exam. But perhaps the most obvious reason for the resistance to these scans is the safety issue. For instance, the FDA is strongly opposed, stating, “ . . . ultrasound energy delivered to the fetus cannot be regarded as completely innocuous. Laboratory studies have shown that diagnostic levels of ultrasound can produce physical effects in tissue, such as mechanical vibrations and rise in temperature. Although

15

there is no evidence that these physical effects can harm the fetus, public health experts, clinicians and industry agree that casual exposure to ultrasound, especially during pregnancy, should be avoided.”197 The FDA goes further and indicates, “Persons who promote, sell or lease ultrasound equipment for making ‘keepsake’ fetal videos should know that the FDA views this as an unapproved use of a medical device. In addition, those who subject individuals to ultrasound exposure using a diagnostic ultrasound device (a prescription device) without a physician’s order may be in violation of state or local laws or regulations regarding use of a prescription medical device.”197,198 Equally opposed to the nonclinical use of DUS are the American Institute of Ultrasound in Medicine (AIUM), the American College of Obstetrics and Gynecology (ACOG), and the European Committee for Medical Ultrasound Safety (ECMUS). The AIUM’s most recent statement is, “The AIUM advocates the responsible use of diagnostic ultrasound . . . [and] strongly discourages the non-medical use of ultrasound. . . . The use of either two-dimensional (2D) or three-dimensional (3D) ultrasound to only view the fetus, obtain a picture of the fetus or determine the fetal gender without a medical indication is inappropriate and contrary to responsible medical practice. Although there are no confirmed biological effects on patients caused by exposures from present diagnostic ultrasound instruments, the possibility exists that such biological effects may be identified in the future. Thus ultrasound should be used in a prudent manner to provide medical benefit to the patient.”199 Similarly, the ECMUS’s statement includes the following: “The embryonic period is known to be particularly sensitive to any external influences. Until further scientific information is available, investigations should be carried out with careful control of output levels and exposure times. With increasing mineralization of the fetal bone as the fetus develops the possibility of heating fetal bone increases.”200 More recently the World Federation of Ultrasound in Medicine and Biology (WFUMB) and the International Society of Ultrasound in Obstetrics and Gynecology (ISUOG) issued a joint statement with identical conclusions: “The WFUMB and ISUOG disapprove of the use of ultrasound for the sole purpose of providing souvenir images of the fetus. . . . Furthermore, ultrasound should be employed only by health professionals who are well trained and updated in ultrasound clinical usage and bioeffects.”201

Official Positions Many national and international organizations or societies have issued official statements regarding the epidemiology, bioeffects, and safety of ultrasound, as well as the nonmedical usage of ultrasound such as the AIUM, WFUMB, British Medical Ultrasound Society (BMUS), and European Committee of Medical Ultrasound Safety (ECMUS). They all state, in one way or another, that ultrasound appears safe if performed for clinical indications by appropriately trained personal, but that prudence is recommended because of the possibility of yet unknown deleterious effects. For instance, the AIUM has several statements available on its Web site for epidemiology,167 prudent

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Part 1 GENERAL OBSTETRIC SONOGRAPHY

use,199 and keepsake fetal imaging.201 The Keepsake Fetal Imaging statement contains a clear “safety clause” particularly addressing pulsed Doppler: “Although the general use of ultrasound for medical diagnosis is considered safe, ultrasound energy has the potential to produce biological effects. Ultrasound bioeffects may result from scanning for a prolonged period, inappropriate use of color or pulsed Doppler ultrasound without a medical indication, or excessive thermal or mechanical index settings.”201

Table 1-3

MAXIMAL ALLOWED EXPOSURE TIME AS A FUNCTION OF TI

TI

Maximum Exposure Time (min)

0.7

60

1.0

30

1.5

15

RECOMMENDATIONS

2.0

4

The sonographer and sonologist are interested in knowing how to keep the examination safe. One needs to provide recommendations based on scientific evidence. This is a difficult task. In terms of clinical exposure, what should be recommended? A general recommendation is that DUS should be used only when indicated, and minimal exposure should be used to obtain the diagnostic images. Furthermore, exposure time should be kept as short as possible.112 Several organizations have actually published recommendations, based more or less on scientific data. The most rigorous is the BMUS. Their 1999 statement declares, “For equipment for which the safety indices are displayed over their full range of values, the TI should always be less than 0.5 and the MI should always be less than 0.3*.” When the safety indices are not displayed, Tmax should be less than 1°C and MImax should be less than 0.3. Frequent exposure of the same subject is to be avoided.”200 They have very strict recommendations for maximum allowed exposure time, depending on the TI (Table 1-3). In 2009 they updated their recommendations and these are, at the moment, the most detailed guidelines for safe use of DUS in medicine in general and obstetrics in particular (http://www.bmus.org/policies-guides/pg-safety03.asp). The WFUMB offers some scientific rationalization, stating that diagnostic exposure resulting in a temperature rise of no more than 1.5°C above normal physiological levels (37°C) may be used clinically without reservation on thermal grounds. Furthermore, diagnostic exposure that elevates embryonic and fetal in situ temperature above 41°C (4°C above normal temperature) for 5 minutes or more should be considered potentially hazardous.45 In addition, in febrile patients, extra precaution may be needed to avoid unnecessary additional embryonic and fetal risk from ultrasound examinations. Precautions are much softer regarding mechanical phenomena, which, in the absence of gas nuclei (as is the case in fetal lungs and bowels and assuming no use of contrast agents) are probably negligible.

2.5

1

FUTURE DIRECTIONS Scientists continue to be interested in biophysics of ultrasound and remain worried about potential harmful effects. Hence, research in this area is continuing. Ideally, epidemiological studies should be performed on large populations, blindly randomizing 50% to ultrasound testing and 50% to ∗

Italics ours.

no testing. Given the extensive indications for DUS in pregnancy and the fact that most (and in certain countries, all) pregnant patients are referred for an ultrasound examination, this would be extremely difficult to realize in a human population. More accurate techniques to measure in-vivo real exposure may appear, allowing more precise assessment of safety, possibly by generating actual safety indices. In the meantime, areas of uncertainty persist and caution is justified, particularly in Doppler mode, early in pregnancy, but also when insonating the fetal skull for relatively long periods. Education of the end users will continue to be vital to maintaining the good safety record of ultrasound and preventing possible harmful bioeffects. KEY POINTS 1. Know the machine you use. 2. Perform a scan only when indicated. 3. Keep the examination as short as possible. The longer the exposure, the higher the risk. 4. Always start a scan at the lowest possible output (default) and increase only if necessary. 5. Use receiver gain, PRF, and amplitude change output. Output and receiver gain can affect the image in the same way, and receiver gain changes are without any effect on the intensity of the outgoing beam (and hence are completely safe). 6. Follow the ALARA principle. 7. Keep track of the TI and MI values on the screen. 8. Keep TI below 1. 9. Keep MI below 1 (although some recommend 0.5). 10. Be extremely cautious when using Doppler in the first trimester.

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162. Jensh RP, Lewin PA, Poczobutt MT, Goldberg BB, Oler J, Brent RL. The effects of prenatal ultrasound exposure on postnatal growth and acquisition of reflexes. Radiat Res 1994;140:284-93. 163. Jensh RP, Lewin PA, Poczobutt MT, et al. Effects of prenatal ultrasound exposure on adult offspring behavior in the Wistar rat. Proc Soc Exp Biol Med 1995;210:171-9. 164. Schneider-Kolsky ME, Ayobi Z, Lombardo P, Brown D. Ultrasound exposure of the fetal chick brain: effects on learning and memory. Internat J Develop Neuroscience.2009; 27: 677-683. 165. Williams AR. Effects of ultrasound on blood and the circulation. In: Nyborg WL, Ziskin MC, eds. Clinics in Diagnostic Ultrasound: Biological Effects of Ultrasound. New York: Churchill Livingstone, 1985 (vol 16). 166. Abramowicz JS, Miller MW, Battaglia LF, Mazza S. Comparative hemolytic effectiveness of 1 MHz ultrasound on human and rabbit blood in vitro. Ultrasound Med Biol 2003;29:867-73. 167. Tarantal AF. Effects of ultrasound exposure on fetal development in animal models. In: Barnett SB, Kossoff G, eds. Safety of Diagnostic Ultrasound. New York: The Parthenon Publishing Group, 1998. 168. AIUM: Conclusions Regarding Epidemiology for Obstetric Ultrasound, 2005. http://www.aium.org/publications/statements.aspx. Accessed 8/10/08 169. Naumburg E, Bellocco R, Cnattingius S, Hall P, Ekbom A. Prenatal ultrasound examinations and risk of childhood leukaemia: casecontrol study. BMJ 2000;320:282-3. 170. Newnham JP, Evans SF, Michael CA, Stanley FJ, Landau LI. Effects of frequent ultrasound during pregnancy: a randomized controlled trial. Lancet 1993;342:887-91. 171. Abramowicz JA, Fowlkes JB, Skelly AC, Stratmeyer ME, Ziskin MC. Conclusions regarding epidemiology for obstetric ultrasound. J. Ultrasound Med. 2008; 27: 637-644. 172. Campbell JD, Elford RW, Brant RF. Case-control study of prenatal ultrasonography exposure in children with delayed speech. CMAJ 1993;149:1435-40. 173. Stark CR, Orleans M, Haverkamp AD, Murphy J. Short- and longterm risks after exposure to diagnostic ultrasound in utero. Obstet Gynecol 1984;63:194-200. 174. Kieler H, Axelsson O, Haglund B, Nilsson S, Salvesen KA. Routine ultrasound screening in pregnancy and the children’s subsequent handedness. Early Hum Dev 1998;50:233-45. 175. Salvesen KA, Eik-Nes SH. Ultrasound during pregnancy and subsequent childhood non-right handedness: a meta-analysis. Ultrasound Obstet Gynecol 1999;13:241-6. 176. Moore RM Jr, Barrick MK, Hamilton TM. Effect of sonic radiation on growth and development. Am J Epidemiol 1982;116:571. 177. Moore RM Jr, Diamond EL, Cavalieri RL. The relationship of birth weight and intrauterine diagnostic ultrasound exposure. Obstet Gynecol 1988;71:513-7. 178. Lyons EA, Dyke C, Toms M, Cheang M. In utero exposure to diagnostic ultrasound: a 6-year follow-up. Radiology 1988;166: 687-90. 179. Newnham JP, Doherty DA, Kendall GE, Zubrick SR, Landau LL, Stanley FJ. Effects of repeated prenatal ultrasound examinations on childhood outcome up to 8 years of age: follow-up of a randomised controlled trial. Lancet 2004;364:2038-44. 180. Bakketeig LS, Eik-Nes SH, Jacobsen G, et al. Randomised controlled trial of ultrasonographic screening in pregnancy. Lancet 1984;2:207-11. 181. Saari-Kemppainen A, Karjalainen O, Ylostalo P, Heinonen OP. Ultrasound screening and perinatal mortality: controlled trial of systematic one-stage screening in pregnancy. The Helsinki Ultrasound Trial. Lancet 1990;336:387-91. 182. Waldenstrom U, Axelsson O, Nilsson S, et al. Effects of routine onestage ultrasound screening in pregnancy: a randomised controlled trial. Lancet 1988;2:585-8. 183. Salvesen KA, Vatten LJ, Bakketeig LS, Eik-Nes SH. Routine ultrasonography in utero and speech development. Ultrasound Obstet Gynecol 1994;4:101-3. 184. Eik-Nes SH, Okland O, Aure JC, Ulstein M. Ultrasound screening in pregnancy: a randomised controlled trial. Lancet 1984;1:1347. 185. Salvesen KA, Bakketeig LS, Eik-nes SH, Undheim JO, Okland O. Routine ultrasonography in utero and school performance at age 8-9 years. Lancet 1992;339:85-9.

186. Salvesen KA, Vatten LJ, Jacobsen G, et al. Routine ultrasonography in utero and subsequent vision and hearing at primary school age. Ultrasound Obstet Gynecol 1992;2:243-4, 245-7. 187. Salvesen KA, Vatten LJ, Eik-Nes SH, Hugdahl K, Bakketeig LS. Routine ultrasonography in utero and subsequent handedness and neurological development. BMJ 1993;307:159-64. 188. Salvesen KA, Eik-Ness SH, Vatten LJ, Hugdahl K, Bakketeig LS. Routine ultrasound scanning in pregnancy. Authors’ reply. BMJ 1993;307:1562. 189. Newnham JP. Studies of ultrasound safety in human: clinical benefit vs. risk. In: Barnett SB, Kossoff G, eds. Safety of Diagnostic Ultrasound. New York, London: The Parthenon Publishing Group, 1998. 190. Kossoff G, Griffiths KA, Garrett WJ, Warren PS, Roberts AB, Mitchell JM. Thickness of tissue intervening between the transducer and fetus and models for fetal exposure calculations in transvaginal sonography. Ultrasound Med Biol 1993;19:59-65. 191. Sheiner E, Shoham-Vardi I, Hussey MJ, et al. First-trimester sonography: is the fetus exposed to high levels of acoustic energy? J Clin Ultrasound 2007;35:245-9. 192. Sheiner E, Shoham-Vardi I, Pombar X, Hussey MJ, Strassner HT, Abramowicz JS. An increased thermal index can be achieved when performing Doppler studies in obstetric sonography. J Ultrasound Med 2007;26:71-6. 193. Sheiner E, Hackmon R, Shoham-Vardi I, et al. A comparison between acoustic output indices in 2D and 3D/4D ultrasound in obstetrics. Ultrasound Obstet Gynecol 2007;29:326-8. 194. Cardinale A, Lagalla R, Giambanco V, Aragona F. Bioeffects of ultrasound: an experimental study on human embryos. Ultrasonics 1991;29:261-3. 195. Bello SO. How we may be missing some harmful effects of ultrasound—a hypothesis. Med Hypotheses 2006;67:765-7. 196. Chudleigh T. Scanning for pleasure. Ultrasound Obstet Gynecol 1999;14:369-71. 197. Rados C. FDA cautions against ultrasound “keepsake” images. FDA Consumer Magazine: U.S Food and Drug Administration, JanuaryFebruary 2004. 198. http://www.fda.gov/cdrh/consumer/fetalvideos.html, 2005. 199. AIUM. Prudent Use in Obstetrics: American Institute of Ultrasound in Medicine, 2007. http://www.aium.org/publications/statements.aspx. Accessed 8/10/08 200. Thermal teratology. European Committee for Medical Ultrasound Safety (ECMUS). Eur J Ultrasound 1999;9:281-3. 201. AIUM. Keepsake Fetal Imaging, 2007. http://www.aium.org/ publications/statements.aspx. accessed 8/10/08.

Highlighted References 1. Tarantal AF, O’Brien WD, Hendrickx AG. Evaluation of the bioeffects of prenatal ultrasound exposure in the cynomolgus macaque (Macaca fascicularis): III. Developmental and hematologic studies. Teratology 1993;47:159-70. A classical animal study of the bioeffects of ultrasound. The authors published several such reports detailing the possible effects of ultrasound in monkeys. 2. Miller MW, Ziskin MC. Biological consequences of hyperthermia. Ultrasound Med Biol 1989;15:707-22. One of the studies that formed the basis of modern analysis of ultrasound bioeffects. It solidified the notions of a correlation between duration of exposure and temperature increase. 3. Sheiner E, Shoham-Vardi I, Abramowicz JS. What do clinical users know regarding safety of ultrasound during pregnancy? J UltrasoundMed 2007;26:319-25; quiz 326-7. A recent, very disturbing study demonstrating a general lack of knowledge about bioeffects and safety of ultrasound, among users of this technology in obstetrics in the United States of America (#95 is a study with similar results from Europe).

Chapter 2

Normal Pelvic Anatomy As Depicted with Transvaginal Sonography

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Chapter 2

NORMAL PELVIC ANATOMY AS DEPICTED WITH TRANSVAGINAL SONOGRAPHY Arthur C. Fleischer

Definitions 1. Coronal: images obtained in the “elevational” plane. 2. Curved (convex) array transducer: transducer elements arranged in curved fashion. 3. Linear array: transducer elements linearly arranged. 4. Phased array transducer: aims beam by selective activation of transducer elements. 5. Sagittal: images obtained in the long axis of the body. 6. Sector transducer: provides a pie-shaped field of view. 7. Transverse: images obtained in the short axis of the body.

INTRODUCTION Transvaginal sonography (TVS) affords improved resolution of the uterus and ovaries over that which can be obtained with the conventional transabdominal sonography (TAS) approach. Although TVS allows a closer proximity of the transducer/probe to the pelvic organs and more detailed depiction, it may be more, rather than less, difficult for the sonographer to become oriented to the images when compared with conventional TAS because of the limited field of view and unusual scanning planes depicted with TVS. As one develops a systematic approach to the examination of the uterus and adnexal structures with TVS, however, the examination becomes much easier to perform. Appendix 2-1 lists the American Institute of Ultrasound in Medicine (AIUM) guidelines for a complete pelvic sonogram. In this chapter, the sonographic appearances of the uterus, ovary, and other adnexal and pelvic structures will be described, with particular emphasis on how they are best depicted in a real-time TVS examination.

SCANNING TECHNIQUE AND INSTRUMENTATION (Figures 2-1 to 2-3) The 3 scanning maneuvers that are used in TVS include: 1. Vaginal insertion of the probe with side-to-side movement within the upper vagina for sagittal imaging. 2. Transverse orientation of the probe for imaging in various degrees of semiaxial to semicoronal planes.

3. Variation in depth of probe insertion for optimal imaging of the fundus to the cervix by gradual withdrawal of the probe into the lower vagina for imaging of the cervix. In contrast to conventional TAS, bladder distention is not necessary for TVS. In fact, overdistention can hinder TVS by placing the desired field of view outside the optimal focal range of the transducer. Minimal distention is useful in a patient with a severely anteflexed uterus to straighten the uterus relative to the imaging plane. As is true for conventional sonographic equipment, the highest-frequency transducer possible should be used that allows adequate penetration and depiction of a particular region of interest. Thus, transducers with a high-central frequency are preferred (broad band 5.5 to 7.8 MHz). Higher-frequency (>8 MHz) transducers may limit the field of view to within only 6 cm of the probe. The major types of transducer/probes that are used for TVS include those that contain a single-element oscillating transducer, multiple small transducer elements that are arranged in a curved linear array, and those that consist of multiple small elements steered by an electronic phased array. All of these depict the anatomy in a sector format that usually encompasses 100 to 120 degrees. In our experience, the greatest resolution is achieved with a curved linear array that contains multiple (up to 200) separate transmit-receive elements. Mechanical sector transducers may be subject to minor image distortions at the edges of the field due to the hysteresis (lag in effect when stopping and starting) that occurs with an oscillating transducer. Reverberation artifacts can be created by suboptimal coupling of the condom/probe/vagina surfaces. Although degradation of image quality by side-lobe artifacts can occur in the far field in a phased array transducer, they do not significantly degrade the image in the near field. Therefore, phased array transducers have similar resolution capabilities to sector as curved linear array transducers for use in transvaginal examinations. Practioners should follow the AIUM guidelines for the disinfection of transvaginal probes. These guidelines are included as Appendix 2-2. For infection control purposes, a disposable protective sheath is used to cover the transducer. After completely

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C Figure 2-2 A-C. Major scanning planes for transabdominal sonography

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Figure 2-1 A-C. Scan planes (A) and representative transabdominal pelvic sonograms (B and C). Transabdominal Sonograms (TAS) in long (B) and short (C) axis with accompanying typical sonograms showing uterus and right ovary in sagittal plane and right ovary and uterus in transverse plane (between cursors). By convention, the left of the image depicts the cephalic or superior of the patient whereas the right of the patient is depicted on the left of the image of the transverse scans.

(TAS) and transvaginal sonography (TVS). A: Normal adult, parous uterus in long and short axis as depicted with transabdominal sonography (TAS) through a fully distended urinary bladder. B: Transvaginal sonography (TVS) of an anteflexed uterus in long axis. The hand not holding the probe can be used to gently manipulate the uterus and ovaries to an optimal position for scanning. C: TVS of a patient with a retroflexed uterus. The probe is within the posterior fornix of the vagina and is in direct line of the uterine corpus and fundus.

Chapter 2

Normal Pelvic Anatomy As Depicted with Transvaginal Sonography

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Figure 2-3 A-D. Typical scan planes used for TVS of the uterus. A: First, the long axis of the uterus is imaged. B: The probe is angled toward the right, then the left, cornu in the semi-sagittal plane. A sonohysterography catheter is shown in its long axis. C: Next, the probe is rotated to image the uterus in short axis, sweeping from fundus to cervix. D: Additional views can be obtained by directing the probe in a semi-coronal plane. In this plane, the transverse endometrial width is obtained.

covering the transducer/probe with a sheath such as a condom and securing the sheath to the shaft of the probe with a rubber band, the transducer is lubricated on its tip and periphery and then inserted into the vagina and manipulated around the cervical lips and into the fornix to depict the structures of interest in best detail. When the transducer is oriented in the longitudinal or sagittal plane, the long axis of the uterus can usually be depicted by slight angulation off midline. The uterus is used as a landmark for depiction of other adnexal structures. Once the uterus is identified, the transducer can be angled to the right or left of midline in the sagittal plane to depict the ovaries. The internal iliac artery and vein appear as tubular structures along the pelvic side wall. Low-level blood echoes can occasionally be seen streaming within these vessels. The ovaries typically lie medial to those vessels.

After appropriate images are obtained in the sagittal plane, the transducer can be turned 90 degrees counterclockwise to depict these structures in their axial or semicoronal planes. Particularly in larger patients, it is helpful for the sonographer to use one hand to scan while the other is used for gentle abdominal palpation to move structures, such as the ovaries, as close as possible to the transducer/probe.

UTERUS (Figures 2-4 to 2-7) Examination of the uterus begins with its depiction in long axis. The endometrial interface, which is typically echogenic, is a useful landmark to depict in long axis. The actual sonographic texture of the endometrium varies according to its consistency, which is elaborated upon in

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Figure 2-4. TVS of normal uterus. A:Transducer/probe motion to enhance depiction of the uterus and endometrium in an anteflexed uterus. The probe is placed in the anterior vaginal fornix and directed anteriorly. B: Midline sagittal view (left) depicting uterus is long axis with accompanying transvaginal sonogram. The sagittal image (right) is oriented with anterior or superior aspect of the patient to left of image. C: Transducer probe showing direction of probe used to enhance depiction of a retroflexed uterus. Corresponding TVS of drawing shown in C showing retroflexed uterus with secretory phase endometrium (between cursors).

Chapter 2

Normal Pelvic Anatomy As Depicted with Transvaginal Sonography

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Figure 2-4. (Continued) D: Diagram showing short-axis image of endometrium. Corresponding TVS of image plane in D showing short-axis view of the endometrium with surrounding hypoechoic inner myometrium. E: Diagram (left) and TVS (right) showing angled imaging of cervix. The TVS probe is inserted into the anterior vornix of the vagina.

other sections of this chapter. Once the endometrium is identified in long axis, images of the uterus can be obtained in the sagittal and semiaxial/coronal planes.1 It may be difficult to determine the flexion of the uterus on the hard-copy images obtained solely from transvaginal scanning except in extreme cases of anteflexion or retroflexion; however, one can obtain an impression of uterine flexion during the examination by the relative orientation of the transducer/probe needed to obtain the most optimal images of the uterus. For example, retroflexed uteri are best depicted when the probe is in the anterior fornix and angulated in a posterior direction. The fundus of the anteflexed uterus is directed to the upper left corner of the image. Conversely, the retroflexed uterus will demonstrate the fundus directed to the inferior right corner of the image.

The endometrium has a variety of appearances depending on its stage of development. In the proliferative phase, the endometrium measures 5 to 7 mm in anteriorposterior (AP) dimension. This measurement includes 2 layers of endometrium. A hypoechoic interface can be seen within the luminal aspects of echogenic layers of endometrium in the periovulatory phase and probably represents edema and increased glycogen and mucus in the inner layers of endometrium. In the few days after ovulation, a small amount of secretion into the endometrial lumen can be seen. During the secretory phase the endometrium typically measures between 6 and 12 mm in bilayer thickness; is homogeneously echogenic, most likely as a result of multiple interfaces resulting from stromal edema; and is surrounded by a hypoechoic band,

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Figure 2-5. A: Diagram (left) and TV-CDS (right) of the uterine arterial network. The arcuate arterioles branch into radial arteries that course across the myometrium ending in the spiral arteries within the endometrium B: Diagram (left) and TV-CDS (right) of arterial vascularity of the uterus. The main uterine artery branches from the hypogastric artery (internal iliac artery) and courses along the lateral edges of the uterus, branching off into the arcuates. The radial arteries then course toward the endometrium, branching into the basal and spiral arteries within the endometrium.

representing the inner layer of the myometrium. This inner layer of myometrium appears hypoechoic on TVS and corresponds roughly to the “junctional zone” seen on magnetic resonance imaging (MRI). The junctional zone, however, may be thicker than the hypoechoic band seen in TVS, perhaps because of different physical interaction with the myometrium in this area.2 This layer is hypoechoic probably due to the longitudinal arrangement of the myometrial fibers. Endometrial volume may be calculated by measuring its long axis and multiplying by the AP and transverse dimension.3 One can use the axial plane landmark where the endometrium invaginates into the area of ostia in the region of the uterine cornu.

Because of the proximity of the transducer/probe to the cervix, the cervix is not as readily visualized as the remainder of the uterus. If one withdraws the probe into the vagina, however, images of the cervix can be obtained. The mucus within the endocervical canal usually appears as an echogenic interface. This interface may become hypoechoic during the periovulatory period because the cervical mucus has a higher fluid content.

OVARIES (Figure 2-8) Ovaries are typically depicted as oblong structures measuring approximately 3 cm in long axis and 2 cm in AP and transverse dimensions. On angled long-axis scans, they are immediately

Chapter 2

Normal Pelvic Anatomy As Depicted with Transvaginal Sonography

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Figure 2-6. Transvaginal sonography (TVS) planes for depiction of the endometrium A: Long axis of an anteflexed uterine showing orientation of the endometrium to the transducer. The transducer can be advanced into the anterior fornix for better delineation of the endometrium. The opposite is true for retroflexed uteri. B: Short-axis image of the endometrium. With pressure on the probe and placement of the probe head in the anterior fornix for an anteflexed uterus, the endometrium is imaged in its short axis. C: Coronal view depicting “endometrial width.” This plane is most readily obtained in a “neutral” positioned (neither ante- nor retroflexed) uterus. D: Long axis of endometrium in the retroflexed uterus. With pressure on the posterior fornix, the endometrium becomes more horizontal to the transducer, allowing better detection. (Diagrams by Paul Gross, MS).

medial to the pelvic vessels. They are particularly well depicted when they contain a mature follicle that is typically in the 1.5- to 2.0-cm range. It is not unusual to depict multiple immature or atretic follicles in the 3- to 7-mm range. The size of an ovary is related to the patient’s age and phase of follicular development. When the ovary contains a mature follicle, it can become twice as large in volume as one that does not contain mature follicles. The greatest dimension of a normal ovary, however, is typically less than 3 cm.4 The ovaries of postmenopausal women may be difficult to recognize because they are relatively small and usually do not contain follicles that enhance their sonographic recognition. Ovarian volumes can be estimated by measurement of the greater transverse, longitudinal, and AP dimensions. The average ovarian volumes measured in menstruating

women were 9.8 cm3, in postmenopausal women were 5.8 cm3, and in premenarchal females were 3.0 cm3.5 There is a gradual decrease in ovarian volume after menopause except in women receiving hormone replacement.6 Echogenic foci can be seen on TVS within the center and/or periphery of the ovary. Most of the central foci are due to tiny cysts or calcifications within atretic follicles. Those that are peripherally located are probably of no clinical significance and represent calcified foci within superficial epithelial inclusion cysts.7 Recent studies have further elucidated the origin of echogenic foci within the ovary. Those without an associated shadow may represent specular reflections from unresolved microscopic (5 mm). Whether or not this finding is associated with a distinct clinical entity, such as “pelvic congestion syndrome,” is controversial because many women with distended veins do not experience pain. The nondistended fallopian tube is difficult to depict on TVS, which is probably related to its small intraluminal size and serpiginous course. Occasionally, one can identify the origin of the tubes by finding the invagination of endometrium depicting the area of the tubal ostia and following these structures laterally in the axial or coronal plane. The ovarian and infundibulopelvic ligaments usually cannot be depicted. Sonographic delineation of the tubes is facilitated by intraperitoneal fluid that may be present in the cul-desac.10 Placing the patient in a reverse Trendelenburg position (head higher than hips), may augment intraperitoneal fluid around the fallopian tubes. When surrounded by fluid, the normal tube appears as a 0.5- to 1-cm wide tubular echogenic structure that usually comes from the lateral aspect of the uterine cornu posterolaterally into the adnexal regions and cul-de-sac. The flaring of the fimbriated end of the tube can be appreciated in some patients because it approximates its nearby ovary. Transvaginal sonographic depiction of the tubes is also facilitated when they contain intraluminal fluid. Rarely, small (6 mm) is associated with embryonic demise as well as those that are compromised and small.15 The embryo/yolk sac complex lies adjacent to the edge of the gestational sac and has been described as forming a “double bleb,” representing the amniotic sac-embryo/yolk sac complex.13 By the end of the first half of the embryonic period, the choriodecidua forms the boundaries of the gestational sac, which appears as an echogenic ring of tissue. At 4 weeks of menstrual age, the gestational sac measures only 3 to 5 mm in diameter and grows to approximately 1 cm at 5 weeks. During the early embryonic period the embryo may be barely visible on TVS. Although many of the structures are present, they cannot be resolved sonographically. The neural tube is closed in its midportion but open at its rostral and caudal ends. Brachial arches form, and the somites develop as rounded surface elevations. Fortytwo or forty-four somites form; these paired structures eventually give rise to the axial skeleton and associated musculature.

7 to 8 Weeks During the latter half of the embryonic period, sonographic scanning can depict a gestational sac, the developing embryo and its heartbeat, the surrounding membranes, and the choriodecidua. During this period, organogenesis of the major body viscera occurs (Figures 3-3 to 3-6).

A B Figure 3-3. Normal 6- to 7-week IUP. A: Magnified TV sonogram of 3-mm embryo/yolk sac (arrow). Compare to Figure 3-1H. B: TV sonogram of 6-week IUP with 6-mm embryo (between x’s) adjacent to the yolk sac.

Chapter 3

Transvaginal Sonography of Early Intrauterine Pregnancy

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G Figure 3-3. (Continued) C: Magnified TV scan of 6-week IUP demonstrating embryo within embryonic cavity (1), extraembryonic coelom (2), and yolk sac (3). D: Magnified TV sonogram of 6-week IUP demonstrating embryo/yolk sac complex and decidua capsularis and vera. Compare to Figure 3-1L. E: Yolk sac/embryo surrounded by choriodecidual layers. F: TVS showing embryo/yolk sac complex. The embryo is 3 mm in size, and heart motion was seen. G: TVS of “deflated” gestational sac with enlarged yolk sac but no definite embryo. This is consistent with embryonic demise.

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E Figure 3-4. Normal embryo at 7 to 8 weeks. A: TVS of 8-mm embryo with a yolk sac adjacent to embryo. B: Ten-millimeter embryo demonstrating limb and yolk sac. C: TV scan of 8-week embryo in coronal plane, demonstrating early ossification of clavicle (arrow). D: Seven-week embryo with adjacent yolk sac. The arm buds are seen. E: Eight- to nine-week pregnancy showing the developing head (rhombencephalon). The choriodecidua now is intact.

Chapter 3

Transvaginal Sonography of Early Intrauterine Pregnancy

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Figure 3-5. Normal fetal anatomy. A: TVS of 17-mm embryo demonstrating prominent cystic area of brain corresponding to rhombencephalon. B: TVS of 28-mm fetus. C: TV scan of 10-week fetus demonstrating arms and legs. D: Transverse of same fetus showing umbilical cord insertion within some physiologic herniation of bowel into base of umbilical cord. E: TVS showing hands on or near face of 11-week fetus. F: TAS of 11-week fetus (between +’s).

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C D Figure 3-6. Other normal features. A: Hypoechoic lacunae (curved arrow) around decidual basalis of 10-week IUP. B: Magnified TVS of 11-week fetus with bowel herniated into base of cord. C: TAS of corpus luteum cyst of pregnancy. D: TAS showing unoccupied lumen (curved arrow) at 6 weeks.

Chapter 3

Transvaginal Sonography of Early Intrauterine Pregnancy

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Figure 3-6. (Continued) E: Same patient as shown in (D), 1 week later, showing embryo within sac and persistence of unobliterated lumen. F: TVS showing amnion (arrow) surrounding 6-week embryo. G: Unfused chorioamnion at 10 weeks shown on this magnified TAS. H: TAS of 6-week IUP within the right cornu of a bicornuate uterus. I: TAS showing prominent retrochorionic blood pool (curved arrow).

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On both TVS and TAS, heart pulsations can be depicted during this period of gestation. Transvaginal sonography is most precise in depicting early heart pulsation after 6 postmenstrual weeks, when the developing embryo forms from 2 enfolding fusiform tubes and begins contractile activity. During the seventh postmenstrual week (fifth week of gestational age), the developing embryo grows from 6 to 11 mm in CRL. During this phase of development, the head growth is extensive and results primarily from rapid development of the brain. A cystic area can be identified in the brain, representing the rhombencephalon.16 The yolk sac is relatively large, measuring less than 6 mm inner-to-inner dimensions, and floats within the gestational sac between the chorion and amnion, attached to the developing umbilical cord. During the eighth postmenstrual week of embryonic development (6 weeks of gestational age), the embryo grows from 14 to 21 mm in length. The head remains a large and prominent structure and is bent over the heart prominence. The yolk sac becomes progressively smaller, and the intestines enter the base of the umbilical cord, beginning the normal process of umbilical herniation. By the end of the ninth postmenstrual week (seventh week of gestational age), the embryo has attained human features.17 The head, body, and extremities can be identified sonographically. The intestine is still within the proximal portion of the umbilical cord. Occasionally, this physiologic umbilical herniation of bowel is particularly well depicted with TVS. Because this process of physiologic herniation of bowel into the umbilical cord is normal, abnormalities of the ventral wall should be suspected only if the bowel remains outside of the abdomen at 12 weeks or beyond. Another structure that can be depicted in the late embryonic period is the amniotic membrane.18 The amni-

After 9 weeks, the fetus is clearly depicted both with TAS and TVS. Nomograms for measurement of the embryo and fetus have been established.20 The fetus begins to move its trunk and extremities, and it can be seen to do an occasional somersault within the uterus. Movement is rapid in nature and often appears convulsive. Upper extremity movement is followed by lower extremity. The fetal brain has relatively large lateral ventricles that are mostly filled with choroid plexus (Figures 3-5 to 3-10). Small cysts within the umbilical cord can be seen but usually are resolved by 12 weeks.21 Herniated bowel also returns into the abdomen by 12 weeks. Before 12 weeks, however, the physiologically herniated bowel can measure up to 1.5 times the umbilical cord at its abdominal insertion. Color Doppler sonography may be used to assess the size of the herniated bowel in relation to the cord.

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otic cavity forms from an area deep in the trilaminar embryo, and the amniotic membrane can be seen on a fully floating linear interface in the outer portion of the amniotic cavity. The amnion approximates with the chorion only late in the first trimester of pregnancy (14 to 18 weeks).19 At 6 to 8 weeks, the membrane can be seen as a thin, rounded structure that encircles the embryo/fetus on TVS. Prior to this, the amniotic membrane may appear as a linear echogenic interface projected within the gestational sac in proximity to the embryo. Besides depiction of the embryo/fetus, the choriodecidua is seen as it begins to thicken at the implantation site during the late embryonic and early fetal period. The anatomic and functional fusing of decidua basalis and chorion frondosum forms the future placenta. Certain parameters provide useful prognostic signs, including the heart rate and the relative size of the embryo to the amniotic sac.

9 to 11 Weeks

Figure 3-7. Multifetal pregnancy. A: TAS of normal 7-week diamniotic, dichorionic twin IUP. B: TVS of demised embryo (+’s) adjacent to living twin at 7 weeks.

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Figure 3-7. (Continued) C: TAS of “vanished” twin within an empty sac adjacent to a living embryo with an intact sac (between +’s). D: Diamniotic/dichorionic twin gestation showing thick interface between gestational sacs. E: Triplet intrauterine pregnancy showing thick membrane between sacs most likely representing trichorionic. F: Twin IUP with hypoechoic area to the left of the sacs most likely representing either unobliterated lumen or small retrochorionic hemorrhage. G: Intrauterine gestation with small sac, probably remnant of a second sac that contained an embryo. This most likely represents twin pregnancy with embryonic demise of one twin. H: Twin gestation with thin membrane most likely representing monoamniotic. The upper twin was adjacent to the choriodecidua and had a very short umbilical cord, suggesting the possibility of a body stalk anomaly.

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Figure 3-8. Complicated early pregnancy. A: TVS of an embryonic demise. B: Semi-axial TVS of incomplete abortion with irregular choriodecidua and deflated sac. C: TVS of retrochorionic hemorrhage (arrow) surrounding normal gestational sac with a living fetus. D: TV sonogram of retained choriodecidua within lower uterine lumen (curved arrow). E: TAS showing sloughed decidua (between arrows) in lower uterine lumen. F: TAS of extremely irregular sac. On repeat scan 2 weeks later, a living fetus was found.

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Figure 3-8. (Continued) G: TVS of septated uterus with clot within right uterine lumen. The fetus (between +’s) within left side of uterus was living. H: TAS of completed abortion. Note thinness and regularity of endometrial interfaces (arrow). I: TVS of embryonic demise at 6 weeks. No heart activity was detected. J: TV scan of fetal demise at 9 weeks. No heart motion was detected. K: TAS showing retrochorionic hemorrhage surrounding an IUD (curved arrow). The deflated sac is seen inferior to the IUD. L: TVS showing large fibroid on maternal right and normal gestational sac to the left of midline.

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A

B

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Figure 3-9. Gestational sac anomalies. A: Yolk sac within an overall small gestation sac. B: Large gestational sac. The amnion could be seen within the sac but no definite embryo. These are 2 ends of the spectrum seen in intrauterine fetal demise. C: Vitelline duct leading to a deflated yolk sac. D: Large sac size with deflated yolk sac indicating embryonic demise. E: Large area of retrochorionic hemorrhage that extends behind the choriodecidua. F: TVS of a cervical inclusion cyst adjacent to gestational sac and embryo in a spontaneous abortion.

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Figure 3-10. Normal anatomy of embryo/fetus in first trimester of pregnancy. A: The stomach and umbilical cord seen in this 9-week pregnancy. There is herniation of some bowel into the cord. B: Transverse TVS showing herniated bowel into the base of the cord, which is a physiologic process up to 12 weeks. C: TVS showing normal configuration of the abdominal wall of this 10- to 12-week fetus after bowel has returned into the abdomen. D: The rhombencephalon is seen in this 8-week fetus. E: Fetal heart motion detected in this normal fetus. F: Rhombencephalon seen in this 9-week embryo showing measurement of crown-rump length.

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G

H

Figure 3-10. (Continued) G: Amnion surrounding embryo should not to be mistaken for nuchal thickening. H: TVS of nuchal membrane. Although this multiloculated nuchal fluid collection looked like a cystic hygroma, it regressed and the karyotype was normal.

Heart rate progressively increases to 120 to 160 beats per minute after 6 to 7 weeks.21 Heart rates of less than 85 beats per minute have been associated with pregnancy failure and necessitate follow-up sonograms.22 In another study, heart rates of less than 90 beats per minute in the first trimester were associated with a dismal diagnosis.23 Clearly, however, one could give the fetus the benefit of the doubt if slow heart rates are seen and confirm this finding on a follow-up study rather than terminate based on one abnormal examination. 24 Another parameter that seems to have prognostic value is the size of the amniotic sac relative to the embryonic length. The yolk sac is typically 6 mm or less in normal pregnancies.25 An enlarged amniotic sac may be seen with embryonic demise as calculated by CRL − Da > 0.8 cm (diameter of the amniotic cavity).26 In normal pregnancies, the amniotic sac minus embryonic length should be greater than 5 mm.23 This measurement is less helpful because it may be difficult to completely visualize the amnion at this early stage of development. Several studies have shown a gradual increase in velocity and diastolic flow in choriodecidual (spiral) arteries in early pregnancies.27,28 However, the actual Doppler indices do not discriminate between viable and nonviable pregnancies. Increased venous flow within the choriodecidua can be seen in nonviable pregnancies associated with embryonic or early fetal demise. Failed or failing early pregnancies seem to be more vascular than normal gestation.29 Thus, color Doppler sonography (CDS) may help define the etiologic mechanism for early pregnancy failure. However, uncomplicated involution of the uterus may contain echogenic material with low-impedance flow.30 Thus, the role of CDS is yet to be detemined. Another study has reported that pregnancy failure is more common when the retrochorionic hemorrhagic is

over two-thirds the size of the gestational sac, when the patient is over 35 years old, and when the pregnancy is less than 8 weeks.

COMPLICATED EARLY INTRAUTERINE PREGNANCY As stated previously, it is not unusual for the pregnant patient to experience painless spotting in the first few weeks of pregnancy. This probably is related to trophoblastic implantation within the decidualized endometrium. As the gestational sac develops, small (2- to 5-mm) hypoechoic areas may be seen immediately beneath the echogenic choriodecidua that probably represent areas of blood pools or lacunae (see Figure 3-8). On transvaginal color Doppler sonography (TV-CDS), arterial and venous flow can be seen within the choriodecidua prior to sonographic visualization of the embryo (Figure 3-11). Arterial velocities within the choriodecidua gradually increase. Failing or failed IUPs tend to demonstrate an increase in venous flow beneath the choriodecidua (see Figure 3-11). There does not seem to be a statistically significant difference in their arterial velocities in normal versus abnormal early pregnancies, however. Patients who present with extensive bleeding may have retrochorionic hemorrhage. In this disorder, there is more extensive bleeding behind the chorion, which appears as a hypoechoic area surrounding the gestational sac. Using the formula for a prolate ellipse volume (cc)—length (cm) × width (cm) × height (cm) × 0.5—the relative size of the retrochorionic hemorrhage can be quantified in relation to the size of the gestational sac itself. It has been shown that the relative size of the retrochorionic hemorrhage has some implications as to whether or not the pregnancy will

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A Figure 3-11. TV-CDS of early intrauterine pregnancy. A: Diagram showing arterial and venous flow to the choriodecidua. The arcuate vessels branch into the radials, which traverse the myometrium ending in the spiral vessels within the choriodecidua.

progress.31 When the area of the retrochorionic hemorrhage is less than one-fourth of the gestational sac or less than 60 mL, it is likely that the pregnancy will progress.3 In spontaneous incomplete abortions, there is usually passage of the fetus or embryo with retained choriodecidua. This tissue typically appears as echogenic material within the uterine lumen. The choriodecidua is irregular, and the gestational sac itself appears “deflated” or irregular in shape. In cases of failed embryonic development, there is a failed or abnormal development of the embryo and its associated umbilical cord and body stalk. Thus, even though a gestational sac may appear normally formed, no embryo or, on occasion, no yolk sac will be identified within the uterus. An early pregnancy failure is usually a reflection of a chromosomally aberrant conceptus. Embryonic demise can be documented by TVS when there is lack of heart motion in an embryo that measures over 6 mm in length. In general, heart motion can usually be detected if an embryo can be delineated.32 In some cases of failed embryonic development, amorphous internal debris can be present within the sac. They probably represent strands of blood or sloughed decidual tissues. In completed miscarriages, there is close apposition of relatively thin and regular endometrial interfaces.

Although one might argue that ectopic pregnancies may demonstrate this appearance, correlation with β-hCG values may be helpful in confirming a completed miscarriage. In completed miscarriage, serial β-hCG values will typically fall precipitously, whereas in ectopic pregnancy this value slowly decreases or reaches a plateau.33 In induced abortions, β-hCG was detectable from 16 to 60 days with a mean of 30 days after uterine evaluation, as opposed to spontaneous abortions where it was detectable from 9 to 35 days with a mean of 19 days, and in ectopic pregnancies, it was detectable for 1 to 31 days with a mean of 8 days, 5 days after laparoscopic tubal removal.32

CAVEATS Nature has a healthy range of normal variations. So it is true for sonographic features of early pregnancy. One variant that can be confused for a pathologic condition involves overgrowth of chorion to simulate the sonographic appearance of a polyp or abnormal embryo. This condition has been termed a chorionic “bump.”34 Figure 3-12 illustrates a patient whose transvaginal sonogram was initially interpreted as representing a demised embryo. However, on repeat TVS, the structure thought to represent the demised embryo was found separate from a normal yolk sac/embryo.

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B Figure 3-11. (Continued) B: (Top) Diagram of changes in spiral arterioles and accompanying veins at 8 weeks, 16 weeks, 20 weeks, 32 weeks, and full term. The side bar indicates relative size/depth of endometrial/decidualized choriodecidua/placenta relative to myometrium. (Bottom) Diagram of placental vessels in third trimester.

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Figure 3-11. (Continued) C: TV-CDS of a normal 5-week IUP showing flow in the arcuate vessels and a form within the choriodecidua adjacent to the chorionic sac. D: TV-CDS showing low impedance arterial flow within the choriodecidua in same patient as in (C). E: TV-CDS of abnormal or failed IUP. F: TV-CDS showing increased venous flow between choriodecidua and myometrium. G: TV-CDS of failed IUP with circumferential subchorionic hemorrhage. H: TV-CDS of embryonic demise showing high-velocity venous flow.

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J I

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M N Figure 3-11. (Continued) I: TV-CDS of embryonic demise with increased subchorionic venous flow. J: Retained products of conception showing hypervascular area. K: Six-week fetus with heart blood flow. L: Seven-week IUP with flow within developing fetus and adjacent choriodecidua. M: Eight-week fetus showing flow in both right and left ventricles. N: Eight-week IUP showing absent diastolic flow in umbilical arteries.

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Figure 3-11. (Continued) O: Same as (N) at 10 weeks. P: Flow within developing decidua basalis. Q: Flow within myometrium adjacent to placenta in 11-week IUP. (Courtesy of C. Peery, MD.) R: Cerebral blood flow in a 12-week fetus. S: Cerebral blood flow in major intracranial arteries in a 13-week fetus. T: Same as (S) showing internal carotid.

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U Figure 3-11. (Continued) U: TV-CDS showing physiologic herniation of bowel adjacent to cord.

OTHER APPLICATIONS It is important in some patients with IUCDs and complicated pregnancies to confirm the presence of an IUCD and establish its location relative to the gestainal sac in the developing choriodecidua. Clearly, IUCDs that are implanted superior to the gestational sac are more difficult to extract than those that are inferior. The amount of retrochorionic hemorrhage associated with an IUCD can also be quantified using TVS. Transvaginal sonography may also be helpful in the evaluation of first-trimester pregnancies complicated by trophoblastic disease. Although large hydropic villi may not be present in trophoblastic disease at this stage, the abnormal tissue can be diagnosed as well as its relative amount. Trophoblastic tissue, however, frequently has the

A

sonographic appearance of retained choriodecidua. This disorder is discussed in detail in Chapter 29.

SUMMARY The recent development of TVS has been discussed in this chapter. Transvaginal sonography primarily has a role in the diagnosis of early intrauterine pregnancy in patients suspected of ectopic pregnancy and in detecting embryonic or fetal life in those patients with extensive bleeding, cramping, or both in the first trimester. Transvaginal color Doppler sonography can be useful as a problem solver in selected cases (Figs. 3-13 through 13-17). 3D transvaginal sonography may also be helpful in certain cases (Figure 3-19).

B

Figure 3-12. Chorionic “bump.” Initial TVS (A) and M-mode (B) suggested that there was a demised 6-week embryo. On follow-up exam 2 days later, the supposedly demised embryo was found separate from a living yolk sac/embryo.

Chapter 3

Transvaginal Sonography of Early Intrauterine Pregnancy

Figure 3-13. Drawing showing changes in arterial and venous structures at 8 weeks, 16 weeks, 20 weeks, 22 weeks, and full term. The relative thickness of the endometrium/choriodecidua is shown on the left of the drawing. On the maternal side, the coiled spiral arterioles develop wide-mouthed orifices due to erosion by trophoblasts. A similar widening of the venous structures occurs concomitantly.

Figure 3-14. Drawing showing arterial blood spurting into the intervillous space to be bathed by the chorionic villus vessels to supply oxygenated blood to the fetus. Venous blood returns from the fetus via the paired umbilical veins. Deoxygenated blood then trickles into a venous lake or chorionic villus. From there, it drains into the placental septum.

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A

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Figure 3-15. Intrauterine fetal demise at 6 to 7 weeks. A: TVS showing morphologically normal 6- to 7-week fetus. B: TV-CDS showing increased vascularity in the retrochorionic space. C: M-mode showing no heart motion.

A

B

Figure 3-16. Normal 7-week intrauterine pregnancy with normal lacunar space. A, B: TVS showing small lacunar space.

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C A

D Figure 3-16. (Continued) C, D: TVS-CDS showing normal retrochoronic

B

vascularity.

C Figure 3-17. Incomplete abortion. TV-CDS showing no flow within the sloughing choriodecidua.

Figure 3-18. Fetal cerebral anomalies. A: TVS normal rhombencephalon in 8-week fetus. B: TVS of cystic hygroma. C: TVS of encephalocele.

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B

A

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D

Figure 3-19. A: Multiplanar images of 8-week gestation. B: Multiplanar images of 10-week fetus. Bottom right is volume rendered image. C: Volume rendered image of 10-week fetus. D: Volume rendered image of 12-week fetus.

KEY POINTS 1. TVS can accurately depict embryonic and fetal development. 2. TVS is helpful in distinguishing normal from abnormal early intrauterine pregnancy. 3. A yolk sac should be seen in a gestational sac of approximately 10 mm, an embryo at 16 to 20 mm.

REFERENCES 1. Pennell RG, Needleman L, Pajak T, et al. Prospective comparison of vaginal and abdominal sonography in normal early pregnancy. J Ultrasound Med 1991;10:63-7. 2. Pritchard L, MacDonald PC, Gant NF, eds. Williams Obstetrics, 16th ed. Norwalk, CT: Appleton-Century-Crofts, 1985.

3. Sauerbrei EE, Pham DH. Placental abruption and subchorionic hemorrhage in the first half of pregnancy: US appearance and clinical outcome. Radiology 1986;160:109-12. 4. Pennell RG, Baltarowich OH, Kurtz AB, et al. Complicated firsttrimester pregnancies: evaluation with endovaginal US versus transabdominal technique. Radiology 1987;165:79-83. 5. Timor-Tritsch IE, Rottem S, Thaler I. Review of transvaginal ultrasonography: a description with clinical application. Ultrasound Q 1988;6(1):1-34. 6. Batzer FR, Weiner S, Corson SL. Landmarks during the first fortytwo days of gestation demonstrated by the _ subunit of human chorionic gonadotrophin and ultrasound. Am J Obstet Gynecol 1983;146:973. 7. Nyberg DA, Filly RA, Mahony BS, et al. Early gestation: correlation of hCG levels and sonographic identification. AJR 1985; 144:951. 8. Bree RL, Edwards M, Boöhm Vélez M, et al. Transvaginal sonography in the evaluation of normal early pregnancy: correlation with hCG level. AJR 1989;153:75-9. 9. Daya S, Woods S, Ward S, et al. Early pregnancy assessment with transvaginal ultrasound scanning. Can Med Assoc J 1991;144(4):441-6.

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10. Nyberg DA, Mac LA, Harvey D, et al. Value of the yolk sac in evaluating early pregnancies. J Ultrasound Med 1988;7:129-35. 11. Lasser DM, Peisner DB, Vollebergh J, Timor-Tritsch I. First-trimester fetal biometry using transvaginal sonography. Ultrasound Obstet Gynecol 1993;3:104-8. 12. de Crespigny L, Cooper D, McKenna M. Early detection of intrauterine pregnancy with ultrasound. J Ultrasound Med 1988;7:7-10. 13. Yeh HC, Rabinowitz JG. Amniotic sac development: ultrasound features of early pregnancy-the double bleb sign. Radiology 1988; 166:97103. 14. Timor-Tritsch IE, Rottem S. Transvaginal Sonography. New York: Elsevier, 1988:98. 15. Kurtz A, Needleman L, Pennell P, et al. Can detection of yolk sac in first trimester be used to predict the outcome of pregnancy? A prospective sonographic study. AJR 1992;158:843. 16. Cyr D, Mack L, Nyberg D, et al. Fetal rhombencephalon: normal US findings. Radiology 1988;166:691-2. 17. Moore K. The Developing Human. Philadelphia: Saunders, 1987. 18. Jeanty P. Sonographic appearance of normal amnion. J Ultrasound Med 1982;1:243. 19. Torpin R. Fetal malformations caused by amnion rupture during gestation. In: Torpin R, ed. The Human Placenta. Springfield, IL: Thomas, 1968:1-76. 20. Lasser DM, Peisner DB, Vollebergh J, et al. First-trimester fetal biometry using transvaginal sonography. Ultrasound Obstet Gynecol 1993;3:104-8. 21. Skibo LK, Lyons EA, Levi CS. First-trimester umbilical cord cysts. Radiology 1992;182:719-22. 22. Laboda LA, Estroff JA, Benacerraf BR. First trimester bradycardia: a sign of impending fetal loss. J Ultrasound Med 1989;8:561-3. 23. Bromley B, Harlow BL, Laboda LA, et al. Small sac size in the first trimester: a predictor of poor fetal outcome. Radiology 1991; 178:375-7.

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24. Benson CB, Doubilet PM: Slow embryonic heart rate in early first trimester: indicator of poor pregnancy outcome. Radiology 1994;192:343-4. 25. Kurtz A, Needleman L, Pennell R, et al. Can detection of the yolk sac in the first trimester be used to predict the outcome of pregnancy? A prospective sonographic study. AJR 1992;158:843. 26. Horrow MM. Enlargedamniotic cavity: a new sonographic sign of early embryonic death. AJR 1992;158:359-62. 27. Arduini D, Rizzo G, Romanini C. Doppler ultrasonography in early pregnancy does not predict adverse pregnancy outcome. Ultrasound Obstet Gynecol 1991;1:180-5. 28. Kurjak A, Zudenigo D, Funduk-Kurjak B, et al. Transvaginal color Doppler in the assessment of the uteroplacental circulation in normal early pregnancy. J Perinat Med 1992;21:25-34. 29. Jaffe R, Warsof SL. Color Doppler imaging in the assessment of uteroplacental blood flow in abnormal first trimester intrauterine pregnancies: an attempt to define etiologic mechanisms. J Ultrasound Med 1992;11:41-4. 30. Dillon EH, Case CQ, Ramos IM, et al. Endovaginal US and Doppler findings after first-trimester abortion. Radiology 1993; 186:87-91. 31. Pedersen JF, Mantoni M. Prevalence and significance of subchorionic hemorrhage in threatened abortion: a sonographic study. AJR 1990;154:535-7. 32. Levi CS, Lyons EA, Zheng XH, et al. Endovaginal US: demonstration of cardiac activity in embryos of less than 5.0 mm in crown-rump length. Radiology 1990;176:71-4. 33. Steier JA, Bergsjo P, Myking OL. Human chorionic gonadotrophin in maternal plasma after induced abortion, spontaneous abortion, and removed ectopic pregnancy. Obstet Gynecol 1984;64:391. 34. Harris RD, Couto C, Karpovsky C, et al. The chorionic bump: a firsttrimester pregnancy sonographic finding associated with a guarded prognosis. J Ultrasound Med 2006;25:757-63.

Appendix 3-1 Ultrasound Examination of the Female Pelvis in the First 10 Weeks (Embryonic Period) of Pregnancy INTRODUCTION This portion of the guideline has been developed for use by practitioners performing sonographic studies only during the first 10 menstrual weeks of pregnancy. Such sonography should be performed only when there is a valid medical reason, and the lowest possible ultrasonic exposure settings should be used to gain the necessary diagnostic information. A limited examination may be performed in clinical emergencies or in specific clinical scenarios, such as evaluation of fetal or embryonic cardiac activity. A limited follow-up examination may be appropriate if a complete prior examination is on record. While this guideline describes the key elements of standard sonographic examinations in the first 10 weeks of pregnancy, in some cases, other specialized examinations may be necessary as well.

SPECIFICATIONS OF THE EXAMINATION 1. Indications A sonographic examination can be of benefit in many circumstances in the embryonic period of pregnancy, including but not limited to the following indications:

a. To confirm the presence of an intrauterine pregnancy b. To evaluate a suspected ectopic pregnancy c. To define the cause of vaginal bleeding d. To evaluate pelvic pain e. To date the pregnancy f. To diagnose or evaluate multiple gestations g. To confirm cardiac activity h. To evaluate maternal pelvic masses and/or uterine abnormalities i. To evaluate a suspected hydatidiform mole Comment A limited examination may be performed to assess the presence of cardiac activity.

2. Imaging Parameters Overall Comment Scanning in the first 10 weeks of pregnancy may be performed either transabdominally or transvaginally, although transvaginal scanning is preferred. Patients should be questioned about latex allergy prior to use of a latex sheath.

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Part 1 GENERAL OBSTETRIC SONOGRAPHY a. The uterus, including the cervix, and adnexa should be evaluated for the presence of a gestational sac. If a gestational sac is seen, its location should be documented. The gestational sac should be evaluated for the presence or absence of a yolk sac or embryo, and the embryonic size should be measured and recorded, when possible.

Comment The presence, location, and size of adnexal masses should be recorded. The presence of leiomyomata should be recorded, and measurements of the largest or any potentially clinically significant leiomyomata should be recorded. The cul-de-sac should be scanned for the presence of absence of fluid.

Comment Embryonic size is a more accurate indicator of gestational (menstrual) age than mean gestational sac diameter. However, the mean gestational sac diameter may be measured and recorded when an embryo is not identified. Caution should be used in making the presumptive diagnosis of a gestational sac in the absence of a definite embryo or yolk sac. Without these findings, an intrauterine fluid collection could represent a pseudo-gestational sac associated with an ectopic pregnancy. b. Presence or absence of cardiac activity should be reported. Comment With transvaginal scans, cardiac motion is usually observed when the embryo is 5 mm or greater in length. If an embryo less than 5 mm in length is seen without cardiac activity, a subsequent scan at a later time may be needed to document cardiac activity. If possible, the M-mode function of the scanner should be used to document cardiac activity. c. Embroyonic number should be reported. Comment Amnionicity and chorionicity should be documented for all multiple pregnancies when possible. d. Evaluation of the uterus, adnexal structures, and cul-desac should be performed.

3. Equipment Specifications These studies should be conducted with real-time scanners, using a transabdominal and/or a transvaginal approach. A transducer of appropriate frequency should be used. Comment Real-time sonography is necessary to confirm the presence of cardiac activity. A transvaginal scanning approach is preferred for this indication.

4. Fetal Safety Diagnostic ultrasound studies of the fetus are generally considered to be safe during pregnancy. This diagnostic procedure should be performed only when there is a valid medical indication, and the lowest possible ultrasonic exposure setting should be used to gain the necessary diagnostic information under the as low as reasonably achievable (ALARA) principle. The promotion, selling, or leasing of ultrasound equipment for making “keepsake fetal videos” is considered by the US Food and Drug Administration (FDA) to be an unapproved use of a medical device. Use of a diagnostic ultrasound system for these purposes, without a physician’s order, may be in violation of state laws or regulations.

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Transvaginal Sonography of Ectopic Pregnancy

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Chapter 4

TRANSVAGINAL SONOGRAPHY OF ECTOPIC PREGNANCY Arthur C. Fleischer

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Michael P. Diamond

Definitions 1. Discriminatory zone: β-hCG value above which evidence of an intrauterine pregnancy should be seen on transvaginal sonography. 2. Doubling time: Expected time interval when the βhCG level doubles in a normal early intrauterine pregnancy. The expected normal increase of hCG is greater than or equal to 50% in 48 hours. 3. Pregnancy of “unknown location”: pregnancy whose location (intra- or extrauterine) cannot be determined sonographically.

INTRODUCTION Recent improvements in the sonographic depiction of uterine and adnexal structures with transvaginal sonography and refinements in the assay for human chorionic gonadotropin (hCG) have markedly enhanced the sonologist’s ability to define the location of early pregnancy. Although the sonographic findings in ectopic pregnancy can be subtle, a definitive diagnosis of this entity is possible in most cases when sonographic findings are combined with results of a single hCG assay or with serial hCG assays. Most importantly, sonography is useful in the evaluation of patients with suspected ectopic pregnancy both to verify the presence or absence of an intrauterine pregnancy, as well as to identify an adnexal ectopic pregnancy. Earlier diagnosis often results in less invasive treatment options and avoidance of rupture, which is a surgical emergency. Early and confident diagnosis is vital in optimizing the outcome of women with an ectopic pregnancy. Furthermore, sonography plays a vital role in distinguishing women with an ectopic pregnancy that can be treated medically versus those requiring surgical intervention. Also, the possibility that a fallopian tube containing an ectopic pregnancy can be “salvaged” by linear salpingostomy as opposed to partial or complete salpingectomy is closely related to the stage at which the ectopic pregnancy is detected. Once the tube has ruptured, it usually cannot be salvaged. Therefore, it is most desirable to diagnose an ectopic pregnancy as early as possible.

●

Peter S. Cartwright

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Melinda New

If left unrecognized, an ectopic pregnancy can result in significant maternal morbidity and mortality. Ectopic pregnancy is responsible for 4% to 10% of all maternal deaths.1,2 Even though the diagnosis of ectopic pregnancy is often considered in women who present with lower abdominal pain and amenorrhea, it is missed by the initial examining physician in up to 70% of cases.3 Expeditious and accurate diagnosis of patients who are suspected of having ectopic pregnancy is important so that timely intervention and proper management can be instituted. If it is recognized early, before tubal rupture, it may be possible to surgically remove the gestational sac by linear salpingostomy, thereby preserving the tube and future chances of achieving pregnancy. Advanced ectopic pregnancies can result in significant damage to tubal architecture, which often leads to salpingectomy. If the remaining tube is compromised, fertility can be significantly decreased as a result. Once a patient has had an ectopic pregnancy, there is a significant chance (about 1 in 4) of recurrence in a future pregnancy.3 Early diagnosis is also important for patients undergoing medical treatment of ectopic pregnancy. The success of medical treatment appears to be greatest with lower βhCG levels (≤10,000) and absence of fetal heart motion, which presumably may indicate the amount of trophoblastic infiltration of the tubal musculature, as reflected by the serum hCG level, and the intrinsic viability of the conceptus. It should be noted that a significant number of ectopic pregnancies are karotypically abnormal and may spontaneously regress.1 Transvaginal color Doppler sonography (CDS) will have an important role in determining which type of treatment (medical, local methotrexate, or KCl injections) is most appropriate based on the relative vascularity of the choriodecidua within the tube and the presence or absence of embryonic heart motion. The use of transvaginal sonography (TVS) has greatly enhanced the sonographic evaluation of patients with suspected ectopic pregnancy. Specifically, the presence or absence of an intrauterine gestation can be documented approximately 1 week earlier with TVS than with transabdominal sonography (TAS). In addition, adnexal masses created by ectopic pregnancies can be more frequently detected by TVS. The additional use of transvaginal color Doppler sonography (TV-CDS) seems to further enhance detection

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of ectopic pregnancies that might not be apparent on TVS.4,5 Viable trophoblastic tissue typically produces a vascular ring within the tube that can be recognized by TV-CDS. This ring can be seen as being separate from the ovary but may be similar to that of a functioning corpus luteum. The obstetrical applications of CDS are discussed further in Chapter 12. Transvaginal CDS may have an important role in determining which type of treatment (medical, local methotrexate, or KCI injections) that is most appropriate based on the relative vascularity of the choriodecidua within the tube and the presence or absence of embryonic heart motion. In fact, in the future, TV-CDS may have a role in monitoring the effectiveness of medical treatment because with effective treatment blood flow is altered.6 With these modalities and laboratory tests, a very high degree of accuracy (>90%) is possible in establishing the presence or excluding the possibility of ectopic pregnancy.7

INCIDENCE Several epidemiologic studies have shown that the incidence of ectopic pregnancy is increasing, probably as a reflection of increased prevalence of partially treated salpingitis as well as earlier diagnosis of pregnancy and monitoring of hCG levels.8,9 For example, the age-adjusted incidence of ectopic pregnancy rose from 55.5 to 84.2 per 100,000 women in northern California from 1972 to 1978.8 Nationwide, the number of ectopic pregnancies has ranged from 17,800 in 1970 to 42,000 in 1978.9 The death rate, however, decreased by 75% during this period, which is a reflection of an increase in suspicion of ectopic pregnancies by patients and care providers and an improvement in the ability to diagnose this entity in its earliest stages. The incidence of ectopic pregnancies is greatest in patients with a history of salpingitis, previous tubal surgery, previous ectopic pregnancy, or current use of progesteronedominant contraception.10-12

PATHOGENESIS The term ectopic pregnancy refers to an implantation of the conceptus outside the endometrial cavity. Ninety-five percent of ectopic pregnancies are tubal, and the majority of these occur in the ampullary or isthmic portions of the tube. The remaining 5% of nontubal ectopic gestations occur in the abdomen, ovary, cervix, and the retroperitoneal space. In ampullary ectopic tubal pregnancies, the conceptus implants beneath the epithelium of the fallopian tube to form a fluid-filled gestational sac, which is lined with trophoblastic tissue, in the wall of the tube. Because the fallopian tube has only 2 thin layers of muscle, the trophoblastic cells that burrow deep into the tubal wall distend it and can eventually cause it to rupture. The gestational sac within the tube of a ruptured ectopic pregnancy is usually surrounded by fluid or blood due to erosion of adjacent vessels. In the vast majority of cases, the separation of the decidua from the wall of the tube causes death of the embryo. It has been theorized that in rare cases, the embryo may survive by reimplantation within

the abdomen and reestablishment of the blood supply from the omentum or the mesentery. Mild uterine enlargement and decidualization of the endometrium are usually present with an ectopic pregnancy and can occasionally be detected clinically. In the absence of a heterotopic pregnancy, if dilatation and curettage (D&C) is performed on a patient with an ectopic pregnancy, only decidua without chorionic villi will be obtained. Studies have indicated that up to one-third of all ectopic embryos have an abnormal karyotype, a factor that contributes to their demise and resultant deficient decidual support.1,12 Because the ectopic implanted embryo frequently dies before the sixth week of gestation, decidualization may be interrupted and faulty.13 Another possible etiology of recurrent ectopic pregnancies is the transperitoneal migration of sperm or of the fertilized egg into the contralateral tube. Possibly, this would result in delayed and faulty implantation of the trophoblasts into the tubal wall. As the relative contributions of those factors to the development of ectopic pregnancy are better understood, measures that can prevent ectopic pregnancy may be determined.14

CLINICAL ASPECTS Proposed explanations for development of ectopic pregnancy include delayed fertilization or delayed transit of the fertilized zygote secondary to fallopian tube malfunction; ovulation from the contralateral ovary with delayed passage of the zygote through the tube; obstruction of zygote passage secondary to intratubal adhesions from pelvic inflammatory disease; endometriosis, surgery, and other pelvoabdominal infection; and abnormal angulation of the tube relative to the uterine cornu.1 Before the use of antibiotics for pelvic inflammatory disease, tubal inflammation resulted in a much higher incidence of complete tubal closure and subsequent sterility. The recent 2- to 3-fold increased incidence of ectopic gestations among previously pregnant patients has been attributed paradoxically to the use of antibiotics for treatment of tubal infection.15 Antibiotics have reduced the incidence of tubal occlusion and sterility but have resulted in more women with open, but malfunctioning, tubes. The result is an increased incidence of ectopic pregnancy among patients with previous tubal infection. In addition to patients who have a history of pelvic inflammatory disease, patients who have undergone tubal surgery, have a history of infertility, or who have used intrauterine devices (IUDs) have an increased chance of developing an ectopic pregnancy.10 Ectopic pregnancy is a proverbial doubleedged sword because it both results in a nonviable pregnancy and has the ability to render the patient infertile.11 Once a patient has had an ectopic pregnancy, there is a 1 in 4 or 15% or greater chance of recurrence in a future pregnancy.3 In the United States, the incidence of ectopic pregnancy is between 1 in 100 and 1 in 400 pregnancies, but in some populations it is as high as 1 in 32 live births.1,3 Clinically, however, ectopic pregnancy should be considered in the differential diagnosis of any patient presenting

Chapter 4 with lower abdominal pain because the sometimes massive intraperitoneal bleeding associated with rupture of an ectopic pregnancy is such a serious complication.16 An analogy can be made between ectopic pregnancy in the 1990s and the great masquerade of pulmonary tuberculosis in the 1930s; its clinical symptoms at presentation differ so much in type and severity.1 In fact, clinicians are now taught to “think ectopic” for any woman of child-bearing age who presents with lower abdominal pain or until an intrauterine gestation is confirmed. The most common presenting symptoms of ectopic pregnancy are pelvic pain, which may be mild and intermittent or persistent and severe, and abnormal vaginal bleeding.17 The clinical symptomatology and routine laboratory findings in ectopic pregnancy are usually not diagnostic by themselves. Abnormal vaginal bleeding is seen in approximately three-fourths of patients with such pregnancies and can be confused with other causes of firsttrimester bleeding, such as a threatened or spontaneous abortion. There is, however, no bleeding or menstrual history that is inconsistent with an ectopic gestation. Statistically, vaginal bleeding is more commonly associated with other first-trimester conditions (such as spontaneous threatened abortion, cervical polyp, or infection) than with ectopic pregnancy.18 Diffuse abdominal pain may be present, as may rebound tenderness from peritoneal irritation resulting from free intraperitoneal bleeding. The presence of an adnexal mass is not specific for the diagnosis of ectopic pregnancy as adnexal masses are frequently seen in early pregnancy, such as corpus luteum cyst, which must be present if the patient is pregnant. A palpable adnexal mass was noted in less than one-third of cases and did not predict whether or not the gestation had ruptured.19 Although uncommon, the presence of a palpable adnexal mass (that is, separate from both ovaries and uterine fundus) is highly suggestive of an ectopic pregnancy. In an emergency setting, culdocentesis (the transvaginal aspiration of fluid from the posterior cul-de-sac) remains an alternative diagnostic aid for evaluating patients suspected of having a ruptured ectopic gestation. The aspiration of nonclotting blood indicates the presence of a hemoperitoneum. This finding is not diagnostic of an ectopic pregnancy, however, as it may also result from a hemorrhagic corpus luteum, complete or incomplete abortion, ovulation, or previous attempts at culdocentesis. In our experience, 70% of patients with an ectopic pregnancy who underwent this procedure had positive taps; this was one of the key factors resulting in the patient’s admission to the hospital.20 In 56% of these patients, however, the tube had ruptured; intact tubal pregnancy may produce several liters of hemoperitoneum by bleeding out through the fimbriated end of the tube. A negative culdocentesis generally excludes tubal rupture. A recently published study has reported that the sonographic finding of hemoperitoneum is more predictive of ectopic pregnancy than of culdocentesis. The authors concluded that culdocentesis should not play a role in the evaluation of ectopic pregnancy except in the unusual circumstances in which TVS cannot be performed.21 The clinical course of an ectopic pregnancy is related to its site of implantation.22 The ampullary portion of the

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73

tube is the most common location for ectopic implantation. As in other sites, the ectopic pregnancy can expand until it ruptures the wall of the tube. Complete or partial tubal abortion may also occur, with the contents of the sac extruded through the fimbriated end of the tube into the peritoneal cavity. If the fimbriated end of the tube is occluded, hematosalpinx will result. Ectopic pregnancies that occur in the narrow isthmic portion of the tube usually distend it eccentrically and, because of the tube’s small diameter, rupture early in the pregnancy. Ectopic pregnancy in the interstitial portion of the tube is uncommon (3% to 4% of all ectopic pregnancies), but it has the most serious potential complications. Because of its location within the muscular portion of the uterus near the major uterine vessels, the pregnancy can survive until 3 to 4 months’ gestation. Massive bleeding from the uterine arteries and veins can then result. Chronic ectopic pregnancies may occur, resulting in hematoma formation in the cul-de-sac.23 Such patients usually present with recurrent, intermittent low-grade fever associated with a palpable solid mass. On physical examination, there is usually a firm pelvic mass located in the midline and difficult to separate from the uterus. Culdocentesis may be negative because the blood in the cul-de-sac is clotted. In very rare cases, the embryo and products of conception will undergo dehydration in situ with the formation of a lithopedion pregnancy. Other rare sites of implantation include intra-abdominal, ovarian, cervical, and extraperitoneal. True advanced abdominal ectopic pregnancies may be difficult to differentiate from normal intrauterine pregnancies; the uterus must be defined separately from the amniotic sac and its contents.24 Abdominal pregnancies are postulated by some to be the result of reimplantation of an aborted fetus after it passes out the fimbriated end of the tube and reimplants on the mesentery or omentum.24 These pregnancies can progress to term without symptoms, and may first present because of difficulty during the initial stages of labor, growth problems, pain, or absence of labor. Extraperitoneal ectopic pregnancies are quite rare and are probably the result of tubal rupture, with expulsion of the fetus between the leaves of the broad ligament. The rupture occurs between the fimbriated end of the tube (where it is not covered by peritoneum) and the site where the 2 folds of the broad ligament are loosely opposed.24 The tubal contents may empty into the soft tissue and mesosalpinx and thereafter remain in that region.

hCG ASSAY To properly evaluate the vast majority of patients in whom an early ectopic pregnancy is suspected, it is absolutely imperative to correlate the sonographic findings with the results of a quantitative serum pregnancy test. In addition, it is important for the sonographer and sonologist to know the type of assay used and its relative sensitivity. The enzyme-linked immunoassays that detect urine human chorionic gonadotropin (hCG) are nonquantitative but very sensitive and may easily be performed in an office or clinic. These tests are useful for determining the presence or absence of a pregnancy and are routinely positive

Part 1 GENERAL OBSTETRIC SONOGRAPHY

when the serum hCG level is at least 50 mIU/mL (8 to 10 days postconception). They are positive in about 99% of patients with a symptomatic ectopic pregnancy. The enzyme-linked immunoabsorbant assays (ELISAs) detecting the β subunit of the serum hCG molecule are quantitative and most helpful in cases where a problem arises during an early pregnancy, such as suspected ectopic pregnancy or threatened abortion. All commercially available kits that measure serum hCG now use nonradioactive technology and the older radioimmunoassays (RIAs) have been replaced. In addition, the earlier confusion over different “international standards” has been resolved, and all kits now use the same standard. Most of the urine pregnancy tests assay for the whole intact hCG molecule. They may, however, also detect metabolized core fragments of hCG, which contain portions of both the α and β chains of the molecule, but where the β subunit is “nicked.” These “nicked” β subunit chains may not be detected by a serum hCG assay, thereby giving the impression of a “false-positive” urine pregnancy test.25 Clinically, this may be encountered when a patient has a nonviable pregnancy (usually intrauterine) that is in the process of resolving.26 The trophoblast has ceased producing hCG, and has often been expelled, and the serum hCG level is very low. Such patients may present with complaints of pain and abnormal bleeding, and an ectopic pregnancy is in the differential diagnosis. Usually, the urine pregnancy test also becomes negative when repeated in 48 hours. Most laboratories test for the whole hCG molecule when performing a quantitative serum assay. At Duke University Medical Center, a whole-molecule electrochemiluminescent immunoassay is used. The assay that detects both the whole molecule and free β subunit is generally only used when following patients with gestational trophoblastic disease. An ectopic pregnancy does not produce free β-hCG subunits and testing for this is not necessary. What is critically important, however, is that when performing serial quantitative hCG assays, the same assay should be used throughout. The ability to quantitate serum levels of hCG allows the clinician to grossly approximate the gestational age of the pregnancy, assuming it is normal. The hCG level can then be correlated with the sonographic findings in looking for certain developmental “milestones” (Table 4-1). Transvaginal sonographic features that are expected at the various hCG levels are summarized in Figure 4-1. Correlating the serum hCG level with the sonographic findings enables the clinician to evaluate the normalcy of the pregnancy in question. However, there appears to be significant overlap in these values, and they are limited in multiple gestations. The sonographic “milestones” that are helpful and more commonly used include the delineation of a “chorionic sac” at the fifth week, detection of a yolk sac within the gestational sac of approximately 1 cm at 5 to 6 weeks, and an embryo within a sac of approximately 1.5 mm at 6 weeks. A discriminatory zone for the level of serum hCG has been defined for discerning an intrauterine pregnancy from an ectopic pregnancy by means of TVS. This varies somewhat depending on the sonographer’s expertise and equipment

TRANSVAGINAL ULTRASOUND AND EMBRYOLOGIC MILESTONES

Table 4-1 Gestational Age (weeks)

Range of Chorionic Sac Mean Dimension (mm)a

4

1.5 × 2.8

5

8–15

1.5–3

300

6

15–40

4–8

3000

7

40–100

9–16

Embryo Length (mm)b

Mean β-hCG mIU/mLb,c

0.5

28

50,000

a

Data from Davies J. Human Developmental Anatomy. New York: Ronald Press; 1962. Data from Cartwright P, DiPietro D. Beta hCG is a diagnostic and for suspected ectopic pregnancy. Obstet Gynecol. 1984;63:76. c Second International Standard.25 b

10,000

1,000

Serum β-hCG in miu/ml

74

100

10

NO IUP + – adnexal mass

5

10

15

Gest sac S pole

20

25

30

Gest sac W pole

35

40

Pole with FHM

45

50

Days

Figure 4-1. β-hCG and TAS milestones. (Cartwright P, DiPietro D. Ectopic pregnancy: change in serum hCG concentrations. Obstet Gynecol 1984;63:76.) (I.R.P., international reference preparation)

used. With an experienced sonographer, this level is between 1500 and 2000 mIU/mL. This means every viable singleton intrauterine pregnancy should be visible sonographically by the time the serum hCG is 1500-2000 mIU/mL or more. An exception to this is multiple gestation. The absence of an intrauterine gestational sac when the serum level is above the discriminatory zone is highly suspicious for an ectopic pregnancy. If no intrauterine gestational sac is seen while the serum hCG is below the discriminatory zone, the pregnancy may be either very early intrauterine or ectopic. Even when an adnexal mass is visualized, this may simply be a self-contained hemorrhagic corpus luteum cyst. Measuring the thickness of the endometrial stripe is a limited value. Some have observed that normal, early intrauterine pregnancies tend to be associated with a thickened (>6 mm) endometrium, whereas the stripe is thinner with an ectopic pregnancy or spontaneous abortion.17 When ambiguity persists, serial hCG determinations should be drawn to look for a normal or abnormal progression, and the sonogram should be repeated once the level has risen above the discriminatory zone. It must be emphasized, however, that these criteria represent guidelines, not absolute end points.18 It is possible for a viable intrauterine pregnancy to demonstrate a low hCG level and/or slow progression. Conversely, a normal rise in the hCG level may sometimes be associated with an ectopic pregnancy.18 Also, a multiple gestation or a heterotopic pregnancy may show an uncharacteristically elevated hCG level for any given gestational age. The amount of hCG produced by an ectopic pregnancy is generally less than that by a viable intrauterine pregnancy of the same gestational age,26 which may be due to an unfavorable location for trophoblast proliferation. This fact is useful, however, only if the date of conception is known. The serum hCG level for 192 women with a proven ectopic pregnancy at the time of their initial presentation is shown in Figure 4-2. It is clear that the majority of these patients presented with the serum hCG level below the discriminatory zone.

n = 192

1

10

100 1000 Serum b hCG miu/ml

10000

100000

Figure 4-2. β-hCG at time of presentation in 192 surgically proven ectopic pregnancies. (Cartwright P, DiPietro D. Ectopic pregnancy: change in serum hCG concentrations. Obstet Gynecol 1984;63:76.) (I.R.P.)

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75

100000 10000 Serum βhCG miu/ml

Chapter 4

1000 100 10 = Ruptured = Not ruptured

0 1 cm 2 cm 3 cm 4 cm 5 cm 6 cm 7 cm 8 cm Size of mass

Figure 4-3. β-hCG versus size of mass. (I.R.P.)

The level of serum hCG tends to be proportional to the size of a tubal pregnancy (Figure 4-3). A ruptured tubal pregnancy tends to be associated with a higher level than one that has not ruptured. The range of serum hCG levels for any given situation, however, is so broad that this observation has little clinical relevance. Visualizing an intrauterine sac when the serum hCG is below the discriminatory zone may signify an abnormal gestation (Figure 4-4). An intrauterine “blighted ovum” may appear this way. Also, there is the “pseudogestational sac,” which is sometimes associated with an ectopic pregnancy. A pseudogestational sac lacks the “double-sac” sign and is smaller and more irregular than a true gestational sac at a comparable gestational age. Serial determinations of the serum hCG level have proven useful in the clinically stable patient when ambiguity persists even after the sonographic findings have been correlated with a single quantitative hCG. Figure 4-5 shows the hCG progression in 19 clinically stable patients with an ectopic pregnancy.26 The first known value is arbitrarily placed on the standard line, and subsequent values are plotted accordingly. It is apparent that most patients showed a plateau or fall in the level during the period of preoperative evaluation. This plateau or fall is diagnostic of a nonviable pregnancy when it occurs at levels below 3000 mIU/mL during at least a 48-hour period. It does not, however, distinguish between a nonviable intrauterine and an ectopic pregnancy. It is also apparent from Figure 4-5 that some ectopic pregnancies may show an initial “normal” rise in the level of hCG. This normal rise, however, is usually short-lived, and an abnormal progression soon develops. Serial hCG determinations are also essential after treatment of an ectopic pregnancy by either medical or surgical means. A plateau or rise in the level may be the first indication of a persistent ectopic pregnancy indicating the need for further treatment.27 Furthermore, a negative hCG may signify a resolution of the ectopic pregnancy, which may proceed normalization of any sonographic findings. Some groups consider a nondiagnostic TVS to represent a “pregnancy of unknown location” and advocate a repeat hCG after 48 hours. In normal intrauterine

Part 1 GENERAL OBSTETRIC SONOGRAPHY

76 6,000

10,000 x

BD SA

1,000

x

GL

LB

x

Serum β-hCG in ng/ml

xx xx

100

x

1,000 x

x x

x x

x x x xx x xx

xx

DK

Serum β-hCG in miu/ml

x x x

x

JG

MD

PK LM MD

BY GI

100

x TW

x x

10

SM

x

xx

MS

ST

KH

10

x

IUP

No IUP adnexal mass

KM

No IUP NI adnexa

Figure 4-4. β-hCG, ultrasound (TA) findings in 46 proven ectopic pregnancies. (Cartwright P, DiPietro D. Ectopic pregnancy: change in serum hCG concentrations. Obstet Gynecol 1984;63:76.) x, unruptured; •, ruptured. (I.R.P.)

5

10

15

20

25 30 Days

35

40

45

50

Figure 4-5. Serial β-hCG in 19 clinically stable patients. (Cartwright P, DiPietro D. Ectopic pregnancy: change in serum hCG concentrations. Obstet Gynecol 1984;63:76.) (I.R.P.)

pregnancies, hCG increases by an average of 66% in 48 hours. Not all intrauterine pregnancies (IUPs) have this expected increase, and up to 15% of normal IUPs will have less than the expected rise.28

SONOGRAPHIC EVALUATION The use of TVS has greatly enhanced the accuracy of sonographic evaluation of patients with suspected ectopic pregnancy.29,30 In particular, the presence or absence of an intrauterine gestation can be documented or excluded at an earlier stage (approximately 1 week) than with TAS. Most importantly, transvaginal transducer/probes allow accurate and definitive inclusion or exclusion of an intrauterine pregnancy by demonstration of an intrauterine gestational sac. Transvaginal sonography can also be used to demonstrate an extrauterine gestational sac,

corpus luteum, or both. Transabdominal sonography can be used to evaluate these parameters but is, in general, less accurate or definitive. In addition, adnexal masses and reliable collections of intraperitoneal fluid created by ectopic pregnancies can more frequently be detected and identified by TVS. The use of TVS with highly sensitive pregnancy tests has markedly enhanced the ability to detect ectopic pregnancies over techniques and tests available in the recent past. A very high degree of accuracy now exists in the ability to establish the presence or exclude the possibility of an ectopic pregnancy.29,31 Transvaginal sonography plays a major role in the evaluation of patients with suspected ectopic pregnancy. Most importantly, transvaginal transducer/probes allow accurate and definitive inclusion or exclusion of an

Chapter 4 intrauterine pregnancy by demonstration of an intrauterine gestational sac. Transvaginal sonography can also be used to demonstrate an extrauterine gestational sac, corpus luteum, or both. Transabdominal sonography can be used to evaluate these parameters but is, in general, less accurate or definitive. Because the field of view of TVS is limited, TAS can be helpful in the identification of intraperitoneal fluid associated with ectopic pregnancy hemorrhage, rupture, or both. As mentioned previously, TV-CDS may be a useful adjunct to TVS in that the “vascular ring” of the ectopic pregnancy can be visualized (see Figure 4-5). Functioning corpora lutea may also have this appearance on TV-CDS. In most cases, the vascular ring of an ectopic pregnancy is sparser (discontinuous) than that of a functioning corpus luteum. Additionally, most nonviable ectopic pregnancies may not demonstrate flow. Under treatment, most ectopic pregnancies demonstrate increased vascularity as defined by the number of colorized pixel elements in the tubal ring. This may reflect vasodilatation that occurs with effective treatment. CDS can be used to delineate the boundary of the extraovarian mass of the ectopic pregnancy from the ovary itself. Three-dimensional (3D) sonography may provide an additional means to depict the anatomic proximity of an ectopic pregnancy to the ovary.

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thickening. Once the uterus is adequately evaluated, the adnexal region should be carefully examined. If possible, both ovaries should be identified because some ectopic pregnancies are associated with coexisting corpus luteum. On a transverse transvaginal scan, the relative position of the proximal segment of tube can be approximated by recognition of several anatomic landmarks. These include delineation of the round ligament as it courses directly anterior to the tube near the uterine fundus, and the location of the interstitial portion of the tube by its proximity to the endometrium, which invaginates into the uterine cornu on a transverse scan in the region of the tubal ostia. If color Doppler is used, the pulse repetition frequency should be low to maximize detection of slow flow. Acquisition of multiplanar images is needed for 3D reconstruction.

SONOGRAPHIC FINDINGS The sonographic findings that are encountered in a patient with ectopic pregnancy differ according to the stage of pregnancy in which the patient is examined, and whether or not rupture has occurred. In addition, findings depend on what type of transducer/probe is used. The following discussion is organized into uterine, adnexal, and peritoneal sonographic findings.

Uterine

On both TAS and TVS, sonographic examinations should begin by delineation of the uterus in its long axis. One should carefully evaluate the endometrial interfaces for the presence or absence of a gestational sac or decidual

In most ectopic pregnancies, the uterus demonstrates a thickened endometrial interface due to the decidualization of the endometrium (Figure 4-6). Particularly with TVS, the increased fluid content of the decidualized endometrium can be appreciated due to enhanced through transmission distal to this layer. In more advanced ectopic pregnancies,

A

B

SCANNING TECHNIQUE

Figure 4-6. Ectopic pregnancy: uterine sonographic findings. A: Longitudinal TA sonogram of unruptured ectopic pregnancy appearing as a complex retrouterine mass posterior to uterus (curved arrow). Uterus contains thickened, decidualized endometrium (arrow). B: Transverse TAS of (A) showing thickened endometrium (arrow) and left adnexal ectopic gestation (curved arrow).

78

C

Part 1 GENERAL OBSTETRIC SONOGRAPHY

D

E

F

G

H

Figure 4-6. (Continued) C: TVS of unruptured ectopic pregnancy. Long axis of uterus shows thickened decidualized endometrium (arrow). D: Semiaxial TVS of (C) showing right adnexal mass (arrow), which represents an unruptured ectopic pregnancy. A yolk sac is present within gestational sac. E: TVS of pseudogestational sac in a patient with proven ectopic pregnancy. The irregular sac (between +’s) was mistaken for deformed intrauterine sac. F: Transverse TAS of a 6-week intrauterine pregnancy showing typically eccentric location of gestational sac (arrow) within uterine lumen. G: TAS showing irregularly thickened decidualized endometrium (curved arrow). H: TVS of patient in (G), more clearly showing irregular decidualized endometrium (arrow) of proven ectopic pregnancy.

Chapter 4

Transvaginal Sonography of Ectopic Pregnancy

I

J

K

L

M

N

79

Figure 4-6. (Continued) I: TVS of decidual cast (curved arrow) with blood-distended uterine lumen. Intraperitoneal fluid was also present in cul-de-sac. J, K, L: Unruptured left ectopic pregnancy demonstrating all of the typical sonographic findings. J: TVS of left adnexa showing adnexal “ring” (between +’s). K: TVS of right adnexa showing right corpus luteum (between +’s). L: TVS of uterus showing decidual thickening and small amount of intraluminal fluid or “pseudosac.” M: TVS of necrotic decidual cast showing irregular decidua and intraluminal fluid. N: TVS of decidual cysts associated with an ectopic pregnancy, which are thought to represent areas of decidual necrosis.

80

Part 1 GENERAL OBSTETRIC SONOGRAPHY

fluid or blood may be present within the decidualized endometrium, simulating the appearance of an early gestational sac. In some cases, before sloughing of the decidua, a hypoechoic interface beneath the decidua can be seen that represents hemorrhage between the necrotic decidua and inner myometrium. In contradistinction to normal intrauterine pregnancies, where the gestational sac is spherical and well defined, the pseudogestational sac created by sloughing decidua found in some advanced ectopic pregnancies is more irregular and angulated. For a more detailed discussion of the sonographic changes that occur within the uterus in early intrauterine pregnancy, refer to Chapter 3. As opposed to the decidualized endometrium in normal intrauterine pregnancy, the decidualized endometrium of ectopics usually demonstrates little or no diastolic flow on TV-CDS. The myometrium typically shows a poorly vascularized or “cold” pattern. The waveform from the decidualized endometrium of the ectopic pregnancy demonstrates little or no diastolic flow as compared with the decidua of an early intrauterine pregnancy. Tiny (a few millimeters) cysts can be seen within the decidua, and they have been reported to correspond to areas of decidual necrosis.32

Typically, ectopic pregnancies occur as rounded masses, from 1 to 3 cm in size, which are located in the parauterine region. Masses that result from an ectopic pregnancy typically consist of a central hypoechoic area surrounded by an echogenic rim of trophoblastic tissue and a muscle layer (“adnexal ring”). An embryo can rarely be identified within the gestational sac of an ectopic pregnancy; a yolk

sac may be present more frequently. In general, a corpus luteum appears as a hypoechoic structure surrounded by a rim of ovarian tissue. Usually, the corpus luteum is more eccentrically located within the ovarian structure than the more concentric halo representing the rim of trophoblastic tissue and muscle of an ectopic pregnancy. On TV-CDS both viable ectopics and corpora lutea demonstrate a vascular ring surrounding a relatively hypoechoic center. Transvaginal sonography is particularly helpful in identification of adnexal masses resulting from ectopic gestations (Figure 4-7). In our study, TVS was able to identify adnexal masses in the 1- to 3-cm range that had β-hCGs between 800 and 1000 mIU/mL.29 On TV-CDS unruptured ectopic pregnancies with viable trophoblasts demonstrate an interrupted vascular ring. This structure can usually be identified as separate from the ipsilateral ovary. A functioning corpus luteum typically has a concentric ring of vascularity, typically more circumferential than that of an ectopic pregnancy. The blood flow typically demonstrates low-impedance, highdiastolic flow, but there is a significant range in flow observed in ectopic pregnancies, ranging from low impedance to high impedance with reversed diastolic flow, probably a reflection of the intactness of the trophoblasts within the muscular layers of the tube. The vascularity of ectopic pregnancies changes, probably depending on the viability of the trophoblast as they invade the circular muscle of the tube. With treatment, an increase of vascularity or flow has been observed, which may reflect vasodilation of the vessels involved in trophoblastic implantation.5

A

B

Adnexal

Figure 4-7. Ectopic pregnancy; adnexal findings. A: TV sonogram showing lack of gestational sac within uterus and right adnexal “ring.” B: TVS of an unruptured ectopic pregnancy that contains a dead embryo and deflated yolk sac.

Chapter 4

C

Transvaginal Sonography of Ectopic Pregnancy

81

D

E F

G

H

Figure 4-7. (Continued) C: TV sonogram of uterus in long axis and (D) left adnexa in advanced (8-week) unruptured ectopic pregnancy. Fetus demonstrated heart activity. E: TV sonogram of advanced (9-week) ruptured ectopic pregnancy. There is clotted blood (arrow) within cul-de-sac adjacent to ectopic gestation secondary to rupture of this ectopic pregnancy. Pregnancy had intraluminal fluid as depicted in E. F: Magnified transverse TAS of an unruptured right-tubal pregnancy (arrow). (Courtesy of Gary Thieme, MD.) G: Transverse TAS of ectopic gestation with embryo within sac (arrow). H: Magnified longitudinal TAS of a 7-week ectopic pregnancy showing embryo (between +’s). (Courtesy of Philippe Jeanty, MD, PhD.)

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Part 1 GENERAL OBSTETRIC SONOGRAPHY

I

J1

J2

J3

J4

K

Figure 4-7. (Continued) I: TVS of an ectopic pregnancy adjacent to a corpus luteum. J1: TVS showing corpus luteum as mostly cystic mass with fine internal lacelike interfaces. J2: Short axis of same patient showing ectopic adjacent to corpus luteum. J3: TVS of tubal ring adjacent to right corpus luteum. J4: TVS of same patient showing interval development of hematosalpinx. TVS of hematosalpinx secondary to ruptured ectopic pregnancy. K: TVS of hemorrhagic corpus luteum (arrow) that simulated an ovarian ectopic pregnancy.

Chapter 4

Transvaginal Sonography of Ectopic Pregnancy

83

L

M

N

O

Figure 4-7. (Continued) L: TVS of an unruptured ectopic (arrow). M: TVS of unruptured ectopic pregnancy adjacent to distended arcuate veins and the unruptured ectopic in the left tube. A yolk sac is present within the gestational sac. N,O: TVS and picture of unruptured right tubal ectopic. The grasper is lifting up the affected tube that has a bulge in the area of the ectopic.

Peritoneal Along with evaluation of the uterus and adnexa, sonography can detect intraperitoneal fluid that may be associated with hemorrhage, rupture, or both of an ectopic pregnancy (Figure 4-8). The presence of intraperitoneal fluid does not always correlate with the presence of tubal rupture because

there may be hemorrhage out of the fimbriated ends of tubes in patients with unruptured ectopic pregnancies, or hemorrhage from a ruptured corpus luteum in a pregnant or nonpregnant woman. Large amounts of intraperitoneal fluid, such as that seen when this fluid extends into the hepatorenal pouch, is usually associated with rupture of an ectopic pregnancy and significant hemoperitoneum.

84

A

Part 1 GENERAL OBSTETRIC SONOGRAPHY

B

C

D

E

F

Figure 4-8. Ectopic pregnancy: peritoneal findings. Longitudinal (A) and (B) transverse sonogram of “leaking” left tubal ectopic pregnancy with unclotted cul-de-sac hemorrhage (curved arrow). C: Transverse TAS of clotted hemorrhage secondary to chronic ruptured ectopic pregnancy. Transverse TAS of intraperitoneal hemorrhage associated with ruptured abdominal pregnancy. D: Magnified longitudinal TAS showing partially clotted cul-de-sac hemorrhage (arrow) secondary to ruptured ectopic pregnancy. E: TVS long axis showing clotted blood (*) superior to fundus. F: TVS showing intraperitoneal free blood (*). Low-level echoes were within this partially clotted blood collection in cul-de-sac.

Chapter 4

G Figure 4-8. (Continued) G: TVS of free blood (*) in cul-de-sac secondary to ruptured ectopic pregnancy.

RARE TYPES OF ECTOPIC PREGNANCY Although the majority of ectopic pregnancies (95%) occur within the tube, there are some rare types that can occur within the interstitial or cornual portion of the tube, cervix, ovary, and peritoneal (abdominal) spaces (Figure 4-9). Rarely, a patient can present after tubal rupture with a chronic ectopic pregnancy.

Transvaginal Sonography of Ectopic Pregnancy

85

Transvaginal sonography is helpful in diagnosing interstitial ectopic pregnancies. One should be aware that the normal intrauterine pregnancy may have a very eccentrically located gestational sac early in development (at approximately 5 to 7 weeks). In interstitial ectopic pregnancies, however, a gestational sac can be identified that is separate from the decidualized endometrium. It may sometimes be difficult to distinguish a cornual ectopic pregnancy that is very eccentrically located within the uterus from one located within the isthmic portion of the tube. The myometrium surrounding a cornual ectopic pregnancy is typically abnormally thin (