Imaging of Fetal Brain and Spine: An Atlas and Guide [1st ed.] 978-981-13-5843-2;978-981-13-5844-9

Table of contents :
Front Matter ....Pages i-xix
Neurosonoanatomy (B. S. Rama Murthy)....Pages 1-32
Anomalies of Corpus Callosum and Septum Pellucidum (B. S. Rama Murthy)....Pages 33-59
Anomalies of Ventral Induction: Holoprosencephaly (B. S. Rama Murthy)....Pages 61-76
Malformations of Cortical Development (B. S. Rama Murthy)....Pages 77-121
Anomalies of the Cerebellum (B. S. Rama Murthy)....Pages 123-146
Anomalies of Dorsal Induction: Neural Tube Defects (B. S. Rama Murthy)....Pages 147-188
Ventriculomegaly (B. S. Rama Murthy)....Pages 189-202
CNS Anomalies Between 11 and 14 Weeks (B. S. Rama Murthy)....Pages 203-220
Hemorrhage, Infection and Destructive Lesions (B. S. Rama Murthy)....Pages 221-258
Cysts and Tumors (B. S. Rama Murthy)....Pages 259-294
Orbits (B. S. Rama Murthy)....Pages 295-325
Back Matter ....Pages 327-330

Citation preview

B. S. Rama Murthy

Imaging of Fetal Brain and Spine An Atlas and Guide

123

Imaging of Fetal Brain and Spine

B. S. Rama Murthy

Imaging of Fetal Brain and Spine An Atlas and Guide

B. S. Rama Murthy Srinivasa Ultrasound Scanning Centre Bangalore, Karnataka India

ISBN 978-981-13-5843-2    ISBN 978-981-13-5844-9 (eBook) https://doi.org/10.1007/978-981-13-5844-9 © Springer Nature Singapore Pte Ltd. 2019 This work is subject to copyright. All rights are reserved by the Publisher, whether the whole or part of the material is concerned, specifically the rights of translation, reprinting, reuse of illustrations, recitation, broadcasting, reproduction on microfilms or in any other physical way, and transmission or information storage and retrieval, electronic adaptation, computer software, or by similar or dissimilar methodology now known or hereafter developed. The use of general descriptive names, registered names, trademarks, service marks, etc. in this publication does not imply, even in the absence of a specific statement, that such names are exempt from the relevant protective laws and regulations and therefore free for general use. The publisher, the authors, and the editors are safe to assume that the advice and information in this book are believed to be true and accurate at the date of publication. Neither the publisher nor the authors or the editors give a warranty, express or implied, with respect to the material contained herein or for any errors or omissions that may have been made. The publisher remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. This Springer imprint is published by the registered company Springer Nature Singapore Pte Ltd. The registered company address is: 152 Beach Road, #21-01/04 Gateway East, Singapore 189721, Singapore

This book is dedicated to The Omniscient Lord Venkateswara and Benevolent Baba Sai You are the written. You are the act of writing. You are the writer. My mother, Smt. Soundaryavalli For having made me what I am. For having shown me how to live. For teaching me to believe in myself. My father, Padmashri BLS Murthy You are the epitome of ‘Work is Worship’. You taught us to do good to all who come our way. Your exemplary life has been an inspiration.

Foreword

Imaging of the Fetal Brain and Spine is a book that is a must for everyone working in the field of diagnostic fetal ultrasound, from the beginner to the expert. Clearly written and easy to read, it is a reflection of Dr. Rama Murthy’s personality and innate communication skills. I met Dr. Rama Murthy a few years ago in Bangalore, his home town, and it took me seconds to realize that he is not only a gifted speaker but a star communicator as well. During his lecture, more than 500 attendees were actively participating and answering his questions. It is a spectacle one sees in religious congregations but rarely in scientific conferences. In this book, Dr. Rama Murthy has been able to put in writing what he has done for years as one of the education leaders in the field of fetal ultrasound, and I truly hope and believe that through this book he will be able to continue his educational role around the world. I call upon the international scientific societies to use his talents to the benefit of their members. The evolution and development of fetal brain image techniques has occurred in a relatively short period, propelled by the introduction of high resolution transvaginal ultrasound probes and MRI. Ultrasound of the fetal brain has grown from a simple evaluation of the BPD, HC, and ventricular width to a very detailed evaluation of structures such as the cortex, white matter, and vermian lobules. The book chapters have been wisely planned and written in a didactic manner. It provides a clear answer to every diagnostic query that is raised in clinical practice. Impressive, also, is the large number of cases, many of them extremely rare, collected in a single center. The images are of top quality and this translates into easy and effortless interpretation. From the composition of the figures through the book, one understands that the author was not only keeping in mind his patients while performing the examinations but also his students and future readers. Every image is provided with an exhaustive legend which includes the gestational age, diagnosis, plane of section, and a detailed annotation of findings. Imaging of the Fetal Brain and Spine and Dr. Rama Murthy’s work are a fantastic demonstration of the fact that knowledge and its excellence is not the realm of a few working in the “First world” and this fact gives the book an extraordinary significance. Prof. Gustavo Malinger Director OB-GYN Ultrasound Division Lis Maternity Hospital Tel Aviv Sourasky Medical Center Sackler Faculty of Medicine Tel Aviv University Tel Aviv, Israel

vii

Preface

The fetal brain is an enigma for two reasons, structural complexity and continuous development. It is important to understand the ultrasound anatomy of the fetal brain in health and in disease, through the time-line of development. The incidence of congenital anomalies of the brain is second only to that of the heart. Constant improvement and innovation in ultrasound technology, during the past decade, have made it possible to obtain high-definition images of the fetal brain. Burgeoning research in the field has been instrumental in the recognition of a plethora of fetal brain abnormalities. This atlas and guide has given me an opportunity to collate ultrasound case studies chosen from the archives of Srinivasa Ultrasound Scanning Centre, Bangalore, India. As this work is an atlas, the emphasis is on the ultrasound images and their description. The legend for every figure provides information regarding the gestational age, route of the ultrasound examination (in parenthesis), diagnosis (italics), sectional planes and annotated ultrasound findings. Application of 3D ultrasound and MRI has been included in a number of cases. Laboratory reports and clinical/autopsy pictures have been added, wherever necessary. The definition, embryology, pathogenesis, spectrum of disease and genetics have been described, in paragraph form, for each abnormality. This is followed by ultrasound findings and differential diagnosis in an easy-to-read, numbered, point-by-point format. This eliminates the need to pore through long winding text to glean the necessary information. Schematic diagrams in the book enable easy understanding. Counselling, prognostication and treatment are beyond the scope of this book. Relevant genetic etiology has been discussed as prenatal diagnosis in the future will heavily rely on genetic testing and specific labelling. This book is organised into eleven chapters. The first chapter lays the foundation with sonoanatomy. The ensuing chapters deal with malformations of the brain grouped on the basis of abnormal embryogenesis followed by chapters that deal with first trimester diagnosis, space-­ occupying lesions and destructive abnormalities. The last chapter is dedicated to the orbit. Fetal spine has been dealt with in the chapter on anomalies of dorsal induction. I hope this book will help all specialists involved in fetal care to understand the fetal brain, in health and in disease. Bangalore, India

B. S. Rama Murthy

ix

Acknowledgements

To my dear wife Rama and my lovely children Rachita and Roshan, Thank you for your unconditional and unstinting love, support and encouragement. To the staff members of Srinivasa Ultrasound Scanning Centre, all of you have made it possible for me to practise for over 30 years. Many thanks to you all. To Dr. Jayalakshmi Vijayan and Dr. Rachita Rama Murthy, my colleagues at Srinivasa, thank you both for the extraordinary professional support. To the expectant mothers and their unborn children, it is from you that I have learnt, and it is for you that I teach. I thank each and every one of you. To my obstetrician colleagues, thank you for your faith in me. To Dr. Ganesh Rao, thank you for the excellent MRI support. To Dr. Supriya Sheshadri, you appraised the manuscript from a reader’s viewpoint. Your recommendations have immensely enhanced the text. Thank you for all the effort. To Dr. Rachita Rama Murthy, you read the lines and in between. Your hawk-eyed scrutiny has ridden the text of its improprieties. Thanks a million. To Ms. Ankita, you understood the schematic diagrams and then promptly drew them so very well. Thank you very much indeed. To Dr. Mala Sibal, you believed I could do this! Thank you. To Team Springer Nature, you are truly professional. Thank you.

xi

Contents

1 Neurosonoanatomy�����������������������������������������������������������������������������������������������������   1 1.1 Echopattern of Intracranial Structures�����������������������������������������������������������������   1 1.2 Sections of Basic Examination ���������������������������������������������������������������������������   1 1.2.1 11–14 Weeks �������������������������������������������������������������������������������������������   1 1.2.2 18–22 Weeks �������������������������������������������������������������������������������������������   4 1.3 Sulcation and Gyration ���������������������������������������������������������������������������������������  18 1.3.1 Classification of Sulci �����������������������������������������������������������������������������  18 1.3.2 Ultrasound Appearance and Evolution of Sulci and Lateral Fissure�������  19 Suggested Reading�������������������������������������������������������������������������������������������������������  32 2 Anomalies of Corpus Callosum and Septum Pellucidum���������������������������������������  33 2.1 Complete Agenesis of Corpus Callosum�������������������������������������������������������������  33 2.1.1 Indirect Signs in the Transventricular Axial Section�������������������������������  34 2.1.2 Indirect Signs on Transcaudate Coronal Section�������������������������������������  34 2.1.3 Indirect Signs on the Midsagittal Section �����������������������������������������������  35 2.1.4 Direct Sign on Midsagittal, Transcaudate and Transthalamic Coronal Sections ���������������������������������������������������������������������������������������������������  35 2.1.5 Associated Intracranial Findings�������������������������������������������������������������  35 2.1.6 Associated Extracranial Findings �����������������������������������������������������������  35 2.1.7 Differential Diagnosis �����������������������������������������������������������������������������  35 2.2 Partial Agenesis of Corpus Callosum �����������������������������������������������������������������  42 2.2.1 Indirect Signs on Axial Sections �������������������������������������������������������������  42 2.2.2 Direct Signs on Midsagittal Section �������������������������������������������������������  42 2.3 Other Callosal Abnormalities�������������������������������������������������������������������������������  49 2.4 Septal Agenesis ���������������������������������������������������������������������������������������������������  54 Suggested Reading�������������������������������������������������������������������������������������������������������  59 3 Anomalies of Ventral Induction: Holoprosencephaly���������������������������������������������  61 3.1 Ultrasound Findings of HPE�������������������������������������������������������������������������������  62 3.1.1 Alobar Holoprosencephaly ���������������������������������������������������������������������  62 3.1.2 Semilobar Holoprosencephaly�����������������������������������������������������������������  66 3.1.3 Lobar Holoprosencephaly�����������������������������������������������������������������������  66 3.1.4 Middle Hemispheric Variant �������������������������������������������������������������������  70 3.1.5 Common Findings in All Types of HPE �������������������������������������������������  72 3.1.6 Midline Facial Defects in HPE ���������������������������������������������������������������  72 3.1.7 Associated Anomalies�����������������������������������������������������������������������������  76 Suggested Reading�������������������������������������������������������������������������������������������������������  76

xiii

xiv

4 Malformations of Cortical Development �����������������������������������������������������������������  77 4.1 Disorders of Neuronal Proliferation���������������������������������������������������������������������  77 4.1.1 Microcephaly�������������������������������������������������������������������������������������������  77 4.1.2 Macrocephaly�������������������������������������������������������������������������������������������  82 4.2 Disorders of Neuronal Migration�������������������������������������������������������������������������  82 4.2.1 Classical Lissencephaly���������������������������������������������������������������������������  83 4.2.2 Cobblestone Complex�����������������������������������������������������������������������������  98 4.2.3 Neuronal Heterotopia������������������������������������������������������������������������������� 105 4.2.4 Hemimegalencephaly������������������������������������������������������������������������������� 109 4.3 Disorders of Neuronal Organisation ������������������������������������������������������������������� 109 4.3.1 Tuberous Sclerosis����������������������������������������������������������������������������������� 109 4.3.2 Schizencephaly ��������������������������������������������������������������������������������������� 112 4.3.3 Polymicrogyria����������������������������������������������������������������������������������������� 119 Suggested Reading������������������������������������������������������������������������������������������������������� 121 5 Anomalies of the Cerebellum������������������������������������������������������������������������������������� 123 5.1 Mega Cisterna Magna ����������������������������������������������������������������������������������������� 123 5.2 Blake’s Pouch Cyst ��������������������������������������������������������������������������������������������� 125 5.3 Vermian Hypoplasia��������������������������������������������������������������������������������������������� 128 5.4 Dandy-Walker Malformation������������������������������������������������������������������������������� 132 5.5 Cerebellar Hypoplasia����������������������������������������������������������������������������������������� 134 5.6 Rhombencephalosynapsis ����������������������������������������������������������������������������������� 138 5.7 Joubert Syndrome and Related Cerebellar Disorders ����������������������������������������� 141 Suggested Reading������������������������������������������������������������������������������������������������������� 146 6 Anomalies of Dorsal Induction: Neural Tube Defects��������������������������������������������� 147 6.1 Anencephaly ������������������������������������������������������������������������������������������������������� 147 6.2 Iniencephaly��������������������������������������������������������������������������������������������������������� 148 6.3 Cephalocele��������������������������������������������������������������������������������������������������������� 148 6.3.1 Occipital Cephalocele ����������������������������������������������������������������������������� 150 6.3.2 Frontal Cephalocele��������������������������������������������������������������������������������� 155 6.3.3 Parietal Cephalocele��������������������������������������������������������������������������������� 155 6.3.4 Atretic Cephalocele��������������������������������������������������������������������������������� 158 6.4 Sonoanatomy of the Normal Spine ��������������������������������������������������������������������� 158 6.4.1 Sagittal Section ��������������������������������������������������������������������������������������� 159 6.4.2 Axial Section������������������������������������������������������������������������������������������� 160 6.4.3 Coronal Section��������������������������������������������������������������������������������������� 160 6.5 Spina Bifida��������������������������������������������������������������������������������������������������������� 160 6.5.1 Open Spina Bifida ����������������������������������������������������������������������������������� 163 6.5.2 Closed Spina Bifida��������������������������������������������������������������������������������� 174 6.6 Craniorachischisis ����������������������������������������������������������������������������������������������� 177 6.7 Diastematomyelia, Hemivertebra, Neurenteric Cyst and Sacral Agenesis ��������� 178 6.7.1 Diastematomyelia ����������������������������������������������������������������������������������� 178 6.7.2 Hemivertebra������������������������������������������������������������������������������������������� 179 6.7.3 Neurenteric Cyst ������������������������������������������������������������������������������������� 184 6.7.4 Sacral Agenesis ��������������������������������������������������������������������������������������� 185 Suggested Reading������������������������������������������������������������������������������������������������������� 188 7 Ventriculomegaly�������������������������������������������������������������������������������������������������������� 189 7.1 Mild & Moderate Lateral Ventriculomegaly������������������������������������������������������� 189 7.2 Severe Lateral Ventriculomegaly������������������������������������������������������������������������� 196 7.2.1 Obstructive Hydrocephalus��������������������������������������������������������������������� 196 Suggested Reading������������������������������������������������������������������������������������������������������� 202

Contents

Contents

xv

8 CNS Anomalies Between 11 and 14 Weeks��������������������������������������������������������������� 203 8.1 Screening for Open Neural Tube Defects ����������������������������������������������������������� 203 8.2 Exencephaly-Anencephaly Sequence ����������������������������������������������������������������� 208 8.3 Iniencephaly��������������������������������������������������������������������������������������������������������� 209 8.4 Cephalocele��������������������������������������������������������������������������������������������������������� 210 8.5 Holoprosencephaly ��������������������������������������������������������������������������������������������� 215 8.6 Ventriculomegaly������������������������������������������������������������������������������������������������� 219 Suggested Reading������������������������������������������������������������������������������������������������������� 220 9 Hemorrhage, Infection and Destructive Lesions����������������������������������������������������� 221 9.1 Intracranial Hemorrhage ������������������������������������������������������������������������������������� 221 9.1.1 Ultrasound Findings in GMH-IVH��������������������������������������������������������� 221 9.1.2 Ultrasound Findings in Subdural Hemorrhage ��������������������������������������� 237 9.1.3 Ultrasound Findings in Infratentorial Hemorrhage��������������������������������� 237 9.2 Infections of Fetal Brain ������������������������������������������������������������������������������������� 242 9.2.1 Ultrasound Findings in CMV Infection��������������������������������������������������� 242 9.2.2 Ultrasound Findings in Toxoplasma Infection����������������������������������������� 243 9.2.3 Ultrasound Findings of Multisystem Involvement ��������������������������������� 243 9.3 Lesions due to Destructive Processes ����������������������������������������������������������������� 256 9.3.1 Porencephaly������������������������������������������������������������������������������������������� 256 9.3.2 Hydranencephaly������������������������������������������������������������������������������������� 257 Suggested Reading������������������������������������������������������������������������������������������������������� 258 10 Cysts and Tumors������������������������������������������������������������������������������������������������������� 259 10.1 Intracranial Cysts����������������������������������������������������������������������������������������������� 259 10.2 Arachnoid Cyst ������������������������������������������������������������������������������������������������� 260 10.3 Vein of Galen Malformation ����������������������������������������������������������������������������� 272 10.4 Dural Sinus Thrombosis������������������������������������������������������������������������������������ 277 10.5 Dural Sinus Malformation��������������������������������������������������������������������������������� 279 10.6 Cerebral Parenchymal and Intraventricular Cysts��������������������������������������������� 282 10.6.1 Periventricular Pseudocyst������������������������������������������������������������������� 282 10.6.2 Connatal Cysts������������������������������������������������������������������������������������� 285 10.6.3 Periventricular Leukomalacia��������������������������������������������������������������� 285 10.6.4 Choroid Plexus Cysts��������������������������������������������������������������������������� 287 10.7 Intracranial Tumors������������������������������������������������������������������������������������������� 290 Suggested Reading������������������������������������������������������������������������������������������������������� 294 11 Orbits��������������������������������������������������������������������������������������������������������������������������� 295 11.1 Ultrasound Technique ��������������������������������������������������������������������������������������� 295 11.2 Sonoanatomy����������������������������������������������������������������������������������������������������� 295 11.3 Eyelids��������������������������������������������������������������������������������������������������������������� 301 11.3.1 Ectropion ��������������������������������������������������������������������������������������������� 301 11.3.2 Cryptophthalmos ��������������������������������������������������������������������������������� 302 11.3.3 Hypertrichosis ������������������������������������������������������������������������������������� 303 11.4 Nasolacrimal Duct��������������������������������������������������������������������������������������������� 304 11.4.1 Dacryocystocele����������������������������������������������������������������������������������� 304 11.5 Lens������������������������������������������������������������������������������������������������������������������� 305 11.5.1 Congenital Aphakia ����������������������������������������������������������������������������� 305 11.5.2 Cataract������������������������������������������������������������������������������������������������� 305

xvi

Contents

11.6 Globe (Eyeball)������������������������������������������������������������������������������������������������� 308 11.6.1 Microphthalmia and Anophthalmia����������������������������������������������������� 308 11.6.2 Chorioretinal Coloboma����������������������������������������������������������������������� 310 11.6.3 Exophthalmos��������������������������������������������������������������������������������������� 312 11.6.4 Abnormality of Vitreous Vasculature��������������������������������������������������� 314 11.6.5 Retinal Disorders��������������������������������������������������������������������������������� 315 11.7 Orbital Tumors��������������������������������������������������������������������������������������������������� 319 11.8 Abnormalities of Interorbital Distance ������������������������������������������������������������� 321 11.8.1 Hypotelorism��������������������������������������������������������������������������������������� 321 11.8.2 Hypertelorism��������������������������������������������������������������������������������������� 321 Suggested Reading������������������������������������������������������������������������������������������������������� 324 Index������������������������������������������������������������������������������������������������������������������������������������� 327

Abbreviations

3D Three-dimensional AP Anteroposterior AV Arteriovenous BPC Blake’s pouch cyst BPD Biparietal diameter BPNH Bilateral periventricular nodular heterotopia BS Brainstem BSOB Brainstem occipital bone CACC Complete agenesis of corpus callosum CC Corpus callosum CHARGE Coloboma, heart defects, atresia of choanae, retardation of growth, genitourinary and ear defects CMV Cytomegalovirus CNS Central nervous system CPC Choroid plexus cyst CRL Crown-rump length CSB Closed spina bifida CSF Cerebrospinal fluid CSP Cavum septum pellucidum CV Cavum vergae CVI Cavum veli interpositi DSM Dural sinus malformation DWM Dandy-Walker malformation FISH Fluorescent in situ hybridization GA Gestational age GMH Germinal matrix hemorrhage HC Head circumference HPE Holoprosencephaly ICH Intracranial hemorrhage IHF Interhemispheric fissure IT Intracranial translucency IUGR Intrauterine growth restriction IVH Intraventricular hemorrhage MCA Middle cerebral artery MCM Mega cisterna magna MHz Megahertz MoM Multiples of median MRI Magnetic resonance imaging NT Nuchal translucency OSB Open spina bifida PACC Partial agenesis of corpus callosum PCF Posterior cranial fossa xvii

xviii

PCR Polymerase chain reaction PFV Persistent fetal vasculature PHPV Persistent hyperplastic primary vitreous PMG Polymicrogyria PVL Periventricular leukomalacia SD Standard deviation SP Septum pellucidum T1W T1 weighted T2W T2 weighted TAS Transabdominal sonography TCD Transcerebellar diameter TORCH Toxoplasmosis, rubella, cytomegalovirus, Herpes simplex I TVS Transvaginal sonography US Ultrasound VACTERL Vertebral defect, anal atresia, tracheoesophageal fistula, renal anomaly, limb defect VH Vermian hypoplasia

Abbreviations

About the Author

B. S. Rama Murthy is a radiologist at Srinivasa Ultrasound Scanning Centre, Bangalore. He is a graduate of Bangalore Medical College. He also holds a diploma and a master’s degree in radiodiagnosis from Bangalore Medical College and Christian Medical College, respectively. He has been awarded the Diplomate of National Board in radiodiagnosis by the National Board of Medical Examiners. With more than 30 years of experience in fetal imaging, he has contributed chapters to several textbooks on fetal medicine and given numerous lectures on fetal ultrasound imaging around the globe.

xix

1

Neurosonoanatomy

The brain is the most complex organ in the human being. From a humble beginning of three simple vesicles, it develops into an organ with millions of orderly neurons and synaptic connections. Ultrasound enables us to image and study the brain throughout its journey of development and growth in the fetus. The US anatomy of the normal brain at various stages of fetal life must be understood before one attempts to diagnose abnormality. The fetal brain can be imaged by the transabdominal or transvaginal routes. The transabdominal approach is used routinely in the first trimester NT scan, in the midtrimester anomaly scan and in the third trimester scan. Low-frequency (1–5 MHz) convex array transducers are used for routine imaging. Whenever maternal habitus is conducive, high-frequency (6–9  MHz) convex or linear array transducers must be used to obtain high-resolution images. In the NT scan, the transvaginal approach yields high-­ resolution images. Transvaginal ultrasound can also be used in the second and third trimesters if the fetal head is the presenting part. Coronal and sagittal sections are easily obtained with this approach. Axial sections are used in the routine study of the fetal brain. When there are signs of abnormality in the basic examination, one must obtain the requisite sagittal and coronal sections to complete the fetal neurosonogram. Gentle and skilled manoeuvring of the cranium by abdominal transducer pressure helps to obtain the desired sections. While scanning the fetal brain by transvaginal approach, the operator may suprapubically manoeuvre the cranium using the other hand to facilitate scanning through the fontanelles or sutures. Adequate magnification is essential. All standard sections of a neurosonogram can be obtained from a 3D volume data set acquired in any plane (axial, coronal or sagittal) either by transabdominal or transvaginal approach. 3D volume data sets also enable image optimisation and application of rendering algorithms.

1.1

Echopattern of Intracranial Structures

1. The cerebral mantle is hypoechoic with a faintly stippled appearance, seen on high-resolution (high-frequency US) images. 2. Clear fluid in the cavum septum pellucidum (CSP) and CSF in the ventricular system render these structures anechoic. 3. The basal cisterns are hyperechoic due to pial reflectivity. The exception is the cisterna magna which is large enough to appear anechoic.

1.2

Sections of Basic Examination

All sections in the basic examination are axial except the midsagittal section. 11–14 weeks Transventricular Midsagittal

18–22 weeks Transventricular Transthalamic Transcerebellar

1.2.1 11–14 Weeks Axial Transventricular Section 1. The shape of the cranium is oval. 2. The calvarial bones (frontal, parietal and occipital) are ossified and are seen as an echogenic ring. 3. The midline echogenic line represents the falx and divides the intracranium into two symmetric lateral halves. 4. The choroid plexuses are prominent, hyperechoic and fill the width of the lateral ventricles. They may be asymmetric in size and shape. 5. The ventricular CSF can be recognised in the anterior (frontal) horn, anterior to the choroid plexus. 6. The midline (falx) and the choroid plexuses together form the ‘butterfly sign’ (Fig. 1.1a).

© Springer Nature Singapore Pte Ltd. 2019 B. S. Rama Murthy, Imaging of Fetal Brain and Spine, https://doi.org/10.1007/978-981-13-5844-9_1

1

2

1 Neurosonoanatomy

a

b

Fig. 1.1 (a) 12 weeks (transabdominal – TAS) axial transventricular section – choroid plexuses (*) and midline (solid arrow) forming the ‘butterfly sign’, cerebral mantle (layer between the two arrowheads), calvarial suture (dotted arrow). Note that the choroid plexus is filling the width of the lateral ventricle. (b) 12 weeks (TAS and TVS – transvaginal) axial

thalamopeduncular section – thalamus (solid arrow), third ventricle (*), cerebral peduncles (dotted arrow) and aqueduct (arrowhead). The peduncles and aqueduct do not extend to the occipital bone. Note the convergence of the lines along the borders of the thalami and peduncles

7. The cerebral mantle is relatively thin and can be recognised on transabdominal sections obtained with a high gain setting or with high-frequency US. 8. The CSP is not seen as it has not yet appeared.

3. In a strict midsagittal section, the faintly hyperechoic falx cerebri is seen in the supratentorial region. A part of the lateral ventricle may be seen in a slightly off-median section. The diencephalon (thalamus) is seen as a hypoechoic, rounded structure just beneath the falx. 4. In the posterior cranial fossa, three hypoechoic bands separated by two echogenic lines are seen (Fig. 1.2a). The anterior and posterior echogenic lines are the posterior border of the brainstem and the choroid plexus, respectively. The anterior, middle and posterior hypoechoic bands are the brainstem, fourth ventricle (the intracranial translucency) and cisterna magna, respectively. The intracranial translucency (IT) is measured at the widest region.

This section corresponds to the axial transventricular section in the midtrimester examination.

Midsagittal Section 1. A magnified midsagittal section, obtained in a spine posterior fetal position, enables the study of intracranial anatomy. 2. The calvarial outline, nasal tip, nasal bone, maxilla and mandible are seen.

1.2  Sections of Basic Examination

3

a

b

c

Fig. 1.2 (a) 12 weeks (TAS) midsagittal section – brainstem (small arrowhead), posterior margin of the brainstem (solid arrow), intracranial translucency (IT) or fourth ventricle (midsized arrowhead), choroid plexus (dotted arrow) and cisterna magna (large arrowhead), thalamus (*), falx (**). (b) 12 weeks (TAS) midsagittal section – technique or cursor placement for IT measurement. (c) 12 weeks (TAS) midsagittal

section – line through the posterior aspect of the sphenoid bone (small arrowhead), line through the posterior border of the brainstem (large arrowhead); distance between these two lines is the brainstem diameter (solid double-headed arrow); distance between the posterior border of the brainstem and the inner aspect of the occipital bone is the brainstem occipital bone distance (dotted double-headed arrow)

‘+’ callipers are placed on the inner aspects of the anterior and posterior echogenic lines (Fig. 1.2b). The IT increases linearly with crown-rump length (CRL). A nomogram with reference ranges (mean, 5th and 95th percentiles) of IT according to CRL enables objective assessment. 5. The anteroposterior diameter of the brainstem (BS) and the distance between the posterior border of the brainstem and the inner aspect of the occipital bone (BSOB distance) can be measured (Fig.  1.2c). These measurements

increase with CRL. The BS to BSOB ratio decreases with CRL. Nomograms with 5th and 95th reference ranges of all three parameters enable objective assessment. The IT, BS and BSOB are abnormal in open spina bifida (OSB) and hence serve as screening parameters for OSB. When there is an abnormality in the axial transventricular or midsagittal sections, the transthalamopeduncular and transcerebellar sections should be studied.

4

Axial Transthalamopeduncular Section 1. This section is obtained by a slight caudal parallel shift from the transventricular plane. 2. The thalami (diencephalon) and cerebral peduncles (mesencephalon/midbrain) are seen as hypoechoic and symmetric structures. The thalami are anterior to and wider than the peduncles. Hence, tangents drawn on either side of these structures converge towards the occiput. The vesicles of diencephalon and the mesencephalon, namely, the third ventricle and aqueduct, are also seen (Fig. 1.1b). 3. The midbrain (cerebral peduncles) does not extend to juxtapose with the occipital bone. The aqueduct is away from the occipital bone. Axial Transcerebellar Section 1. This oblique axial section includes the posterior cranial fossa and is best obtained in the spine posterior fetal position.

Fig. 1.3  12 weeks (TAS) axial transcerebellar sections at subtly ­cephalad and caudad levels – brainstem (small arrowhead), posterior margin of the brainstem (solid arrow), intracranial translucency (IT) or

1 Neurosonoanatomy

2. The brainstem, fourth ventricle and cisterna magna are seen as three hypoechoic bands separated by two echogenic lines, as described in the midsagittal section (Fig. 1.3). 3. In a slightly cephalad section, the cerebellar hemispheres are seen with a midline communication between the fourth ventricle and cisterna magna (open fourth ventricle) as the development of the vermis is not yet complete.

1.2.2 18–22 Weeks Axial Transventricular Section 1. The anterior horn, atrium and posterior horn of the far lateral ventricle are seen in this section (Fig. 1.4a, b). The cranial midline is oriented horizontally in all the axial sections. The near half of the intracranium is obscured by reverberation from the near parietal bone. To visualise the near hemisphere and its ventricle, the transducer is manoeuvred so that the midline is around 30° to the horizontal (Fig. 1.5).

fourth ventricle (midsized arrowhead), choroid plexus (dotted arrow), cisterna magna (large arrowhead) and open fourth ventricle (*)

Fig. 1.4 (a) 18 weeks (TAS and MRI) axial transventricular section – medial wall of the posterior horn of the lateral ventricle (solid arrows), lateral wall of the posterior horn (dotted arrow), choroid plexus (**), cavum septum pellucidum (CSP) (*), interhemispheric fissure (double arrowhead), lateral fissure (single arrowhead). The near hemisphere is masked by reverberation echoes. (b) 21 weeks (TAS) axial transventricular section – CSP (*), anterior horns of the lateral ventricles (double arrowheads), posterior horn (solid arrow), choroid plexus (dotted arrow), parieto-occipital sulcus (small arrowhead), interhemispheric fissure (midsized arrowheads), lateral fissure (large arrowhead) and atrium of the lateral ventricle (**). Most of the near hemisphere is masked by reverberation echoes. (c) 21 weeks (TAS) axial transventricular section – thalamus (T), head of the caudate nucleus (C), lentiform nucleus (L) and anterior horns of lateral ventricles (solid arrows). The caudate nucleus and the lentiform nucleus (putamen and globus pallidus) are termed the dorsal striatum of the basal ganglia. (d) 21 weeks (TAS) magnified axial transventricular section – technique of measurement of the transverse diameter of the lateral ventricle at atrium; ‘+’ callipers are placed from the inner margin of the medial wall to the inner margin of the lateral wall, perpendicular to the ventricular walls at the level of the parieto-occipital sulcus. This sulcus has just appeared and is seen as a shallow indentation on the medial surface of the cerebrum (arrowhead)

1.2  Sections of Basic Examination

5

a

b

c

d

6

1 Neurosonoanatomy

2. The atrium of the lateral ventricle is marked by the presence of the echogenic choroid plexus filling or almost filling the lumen (Fig. 1.4a, b). 3. In a true axial section characterised by symmetric hemispheres on either side of the midline, the atrium of the far lateral ventricle is measured at the level of the parieto-­ occipital sulcus. The image settings must be optimised to

Fig. 1.5  23 weeks (TAS) axial transventricular section – posterior horn of the lateral ventricle in the near hemisphere (solid arrow) is seen when the midline is brought to about 30° to the horizontal, parieto-­occipital sulci (double arrowheads), echogenic cerebral surface (arrowhead), lateral fissure (dotted arrow), subarachnoid space (*) seen on the far side

a

Fig. 1.6 (a) 21 weeks (TAS) magnified axial transventricular section of anterior complex – anterior horns (solid arrows), interhemispheric fissure (dotted arrow), CSP (*), genu of the corpus callosum (double arrowhead), callosal sulci (small arrowheads), head of the caudate nucleus (C) and thalamus (T). (b) 30 weeks (TAS) magnified oblique

display sharp ventricular margins. ‘+’ callipers are placed on the inner aspect of the medial and lateral walls. The measurement should be perpendicular to the walls of the atrium (Fig. 1.4d). The normal lateral ventricle measures less than 10 mm in the second and third trimesters. The near lateral ventricle should also be visualised in all cases. Measurement in an oblique section and improper placement of cursors result in erroneous values. 4. The CSP is a rectangular, clear fluid-filled structure seen anteriorly in the midline. The midline echoes are ­interrupted by the CSP. On either side, the anterior horns of the lateral ventricles are immediately adjacent to the CSP (Figs. 1.4a, b and 1.6a). The anterior and inferior limits of the CSP are the genu and rostrum of the corpus callosum (CC), respectively. The CSP is posteriorly limited by the columns of the fornix. Beyond the forniceal columns, the posterior extension of the CSP is termed the cavum vergae (CV). A prominent CV is an anatomical variant (Fig. 1.7). 5. The anterior part of interhemispheric fissure (IHF) extends from the frontal bone to abut on the genu of the CC (Figs. 1.4a, b and 1.6a). The posterior part of the IHF extends from the occipital bone to abut on the splenium of the CC (Fig. 1.6b). 6. The CSP, anterior horns, genu of CC, IHF and the callosal sulci are collectively termed the ‘anterior complex’ (Fig. 1.6a). The CSP, atria of the lateral ventricles, splenium of CC and the callosal sulci are collectively termed the ‘posterior complex’ (Fig. 1.6b). The callosal sulcus is the reflective pia covering the outer aspect of the CC.

b

axial section of posterior complex – choroid plexus in the atria of the lateral ventricles (CP), interhemispheric fissure (solid arrow), CSP (*), splenium of CC (double arrowhead), callosal sulci (arrowheads), parieto-­occipital sulci (dotted arrows)

1.2  Sections of Basic Examination

7

Fig. 1.7  26 weeks (TAS) axial transventricular sections B mode and color Doppler, midsagittal section – large midline subcallosal cyst flanked by the anterior horns (solid arrows) on either side. Cyst is wider posteriorly.

No flow in the cyst lumen on color Doppler. The part of the cyst posterior to the vertical line through the foramen of Monro is a large CV (**) (anatomical variant). It is anteriorly continuous with the CSP (*)

7. Just caudal and parallel to the transventricular plane, the columns of the fornix (including the midline) are seen as three parallel echogenic lines. This should not be mistaken for the CSP which does not have the midline echoes (Fig. 1.8). 8. The head of the caudate nucleus is posterolateral to the anterior horn. The lentiform nuclei (putamen and globus pallidus) are seen as faintly hyperechoic structures, lateral to the head of caudate nucleus and medial to the developing lateral fissure (Fig. 1.4c). 9. The parieto-occipital sulcus is progressively better seen from 22 weeks. It is seen on the medial surface of the

cerebral hemisphere. The sulcus demarcates the parietal lobe from the occipital lobe (Fig.  1.4b). The cortex underlying the parieto-occipital sulcus indents the occipital horn medially and is termed the calcar avis. 10. The cingulate sulcus may be seen anterior to the CSP, perpendicular to the IHF. 11. The lateral (Sylvian) fissure is seen on the cerebral convexity in the frontoparietal region (Figs. 1.4b and 1.5). 12. The sulci and lateral fissure evolve with advancing gestational age. 13. The subarachnoid space may be seen around the cerebral convexity, especially on the far side (Fig. 1.5).

8

1 Neurosonoanatomy

Fig. 1.8  25 and 19 weeks (TAS) sections slightly inferior and parallel to axial transthalamic plane – the midbrain with its cerebral peduncles (solid arrow) surrounded by a ring of communicating cisterns comprising of the interpeduncular (medium arrowhead), ambient (small arrowheads)

lateral to the cerebral peduncles (P) and medial to the hippocampal gyri (H) and the quadrigeminal cistern (large arrowhead). Forniceal columns are seen on either side of the midline (dotted circle) and should not be mistaken for the CSP

14. The body of the lateral ventricle and the posterior cranial fossa are not seen in this section.

Axial Transcerebellar Section The posterior cranial fossa is visualised in this section. The major structures seen are cerebellar hemispheres, vermis, fourth ventricle, Blake’s pouch and the cisterna magna.

Several structures (described above) are visualised in the axial transventricular section. However, in practice we study the anterior complex, lateral ventricular atrium and posterior 1 . The hypoechoic cerebellar hemispheres and the relatively horn in the basic examination. The lateral fissure, parieto-­ hyperechoic bridging vermis together resemble a dumbbell occipital and cingulate sulci are studied when sulcation (Fig. 1.10). The fourth ventricle is not seen in this section. needs to be assessed. 2. A slight caudal angulation brings the fourth ventricle into view (Fig. 1.11). The vermis separates the fourth ventricle Axial Transthalamic Section from the cisterna magna. 1. This section passes through the CSP and the thalami 3. The cerebellar size is assessed by the transverse cerebellar diameter (TCD). This is the maximum linear dimension of (Fig. 1.9a, b). the cerebellar hemispheres. Gestational age-dependent 2. The biparietal diameter and head circumference are meanomograms help to objectively assess the TCD. sured in this section. 4. Blake’s pouch is a midline cystic space seen in the 3. The ‘anterior complex’ is seen. cisterna magna (Fig.  1.11). It is bound laterally by two 4. The third ventricle may be seen as a thin slit between the thin septa, running anteroposteriorly across the cisterna thalami. magna. The Blake’s pouch communicates with the fourth 5. The parieto-occipital sulcus, cingulate sulcus, hippocamventricle, inferior to the lower pole of the vermis. The pal gyrus and lateral fissure are seen in this section. fluid on either side of the Blake’s pouch is the CSF in the 6. The posterior cranial fossa is not seen in this section. cisterna magna. 7. In a slightly caudal and parallel section, the interpeduncular, ambient and quadrigeminal cisterns are seen anterior, 5. The anteroposterior dimension of the cisterna magna is normally 10 mm or lesser. lateral and posterior to the cerebral peduncles respectively (Fig. 1.8). The cisterns appear echogenic due to the 6. Moving anteriorly from the cerebellum, the cerebral peduncles (midbrain) continue imperceptibly into the thalami. pial reflectivity.

1.2  Sections of Basic Examination

9

a

b

Fig. 1.9 (a) 19 weeks (TAS and MRI) axial transthalamic section – thalami (T) on either side with the third ventricle in between (solid arrow), the anterior complex, hippocampal gyrus (arrowhead), echogenic cerebral surface (dotted arrow) and the subarachnoid space (*). (b) 23 weeks (TAS) axial transthalamic section – hypoechoic thalami

(T) on either side with the third ventricle in between (solid arrow), the anterior complex, hippocampal gyrus (arrowhead), echogenic cerebral surface (dotted arrows), subarachnoid space (*), lateral fissure (double arrowhead), head of the caudate nucleus (C) and lentiform nucleus (L)

The fetal neurosonogram includes four coronal and three 7 . The anterior complex is anterior to the thalami. 8. The inferior (temporal) horn of the lateral ventricle is lat- sagittal sections. eral to the hippocampal gyrus which is in turn lateral to Coronal Sagittal the cerebral peduncle and ambient cistern (Fig. 1.10). Transfrontal Midsagittal 9. In a slightly caudal and parallel section, the pentagon-­ Transcaudate Right parasagittal shaped suprasellar cistern is seen with the pulsatile arter- Transthalamic Left parasagittal ies of the circle of Willis. The circle of Willis can be Transcerebellar demonstrated by color Doppler in this section (Fig. 1.12). These sections are obtained by transvaginal neurosonography, if the fetal head is the presenting part. High-resolution Any abnormal finding seen in the three axial sections images are obtained by this approach. If the fetus is not in (described above) is an indication for a detailed fetal cephalic presentation, these sections may be obtained transneurosonogram. abdominally. Depending on the position of the fetal cranium,

10

Fig. 1.10  22 weeks (TAS) axial transcerebellar section – faintly echogenic cerebellar vermis (*), cerebellar hemispheres (small arrowheads), cisterna magna (large arrowhead), occipital bone (dotted arrow), ­thalami (T), cerebral peduncle (P), inferior (temporal) horns of lateral

1 Neurosonoanatomy

ventricles (solid arrows) and hippocampal gyrus (H). The third ventricle, anterior complex, echogenic cerebral convexity surface, lateral fissure and subarachnoid space are also seen

Fig. 1.11  19 weeks (TAS) axial transcerebellar sections at slightly cephalad and caudad angulations – the fourth ventricle is seen in the caudad section (arrowhead). Two echogenic linear bridging septa in the cisterna magna are the walls of Blake’s pouch (asterisk marks the lumen of the pouch)

1.2  Sections of Basic Examination

11

Fig. 1.12  22 weeks (TAS) section caudal and parallel to the axial transcerebellar plane B mode and color Doppler – pentagon-shaped suprasellar cistern (highlighted in the color image) anterior to the cerebral peduncles (*) with color flow in the circle of Willis

coronal sections may be obtained either by vertex approach (acoustic window of the midline fontanelles and sagittal suture) or lateral approach (acoustic window of sphenoidal fontanelle and parietotemporal bones). Vertex approach through the anterior fontanelle yields the best coronal and sagittal images. In the coronal sections obtained by the lateral approach, the near hemisphere cannot be well visualised due to the reverberation artefact (Fig.  1.13a). Coronal and sagittal sections can also be obtained from a transabdominal axial 3D volume.

Coronal Transfrontal Section 1. The transfrontal section passes through the frontal lobes, anterior to the genu of the CC (Fig.  1.13b). Hence, the IHF is uninterrupted as the section is anterior to the CSP. 2. The anterior horns on either side are symmetric and comma shaped with medial convexity. 3. The olfactory sulci, when formed, are seen on the inferior cerebral surface on either side of the midline. 4. The bony orbits are seen.

Coronal Transcaudate Section 1. This section passes through the frontal lobes, anterior horns, CSP, heads of the caudate nuclei, lentiform nuclei and the lateral fissures (Figs. 1.14 and 1.15). The anterior horns are immediately lateral to the CSP. 2. The IHF is interrupted by the body of the CC, the callosal sulcus and the CSP (Fig. 1.15). 3. The cystic space immediately inferior to the CC is the CSP. Inferiorly, the CSP is limited by the rostrum of the CC.

4. The chiasmatic (suprasellar) cistern with the circle of Willis arteries and the optic chiasma may be seen in the midline, superior to the base of the skull.

Coronal Transthalamic Section 1. This section passes through the bodies of the lateral ventricles, posterior body of the CC, CSP, IHF, thalami, third ventricle, foramina of Monro, cingulate sulci and the lateral fissures (Fig.  1.16). The IHF is interrupted by the body of the CC, callosal cistern and CSP. 2. The inferior horns of the lateral ventricles and the hippocampal gyri are seen inferiorly (Fig. 1.17). Coronal Transcerebellar Section This section passes through the occipital lobes, calcarine sulci, posterior horns, uninterrupted IHF, tentorium and cerebellum (vermis and hemispheres) (Fig. 1.18). This section is also known as the ‘owl’s eye’ view. Midsagittal Section 1. The midsagittal section is characterised by the presence of the CC and vermis (Fig. 1.19). 2. The entire length of CC is seen as a curvilinear hypoechoic band with superior and inferior hyperechoic margins representing the callosal sulcus and the roof of the CSP, respectively. The rostrum, genu, body and the splenium of the CC are visualised (Figs. 1.19 and 1.20). 3. The callosal length is a linear rostrocaudal measurement from the anterior margin of the genu to the posterior margin of the splenium. The callosal thickness can be measured at the genu, body and splenium (Fig. 1.21).

12

1 Neurosonoanatomy

a

b

Fig. 1.13 (a) 23 weeks (TAS) coronal transcaudate (lateral approach) and transthalamic (vertex approach) sections – near field is masked by reverberation artefact in the image obtained with the lateral approach. Reverberation artefact is not seen in the image obtained with vertex

approach. (b) 22 weeks (TVS and MRI) coronal transfrontal section. Uninterrupted interhemispheric fissure (large arrowhead), anterior horns of lateral ventricles (small arrowheads), orbits (O) and orbital roof (solid arrow)

1.2  Sections of Basic Examination

Fig. 1.14  22 weeks (TVS and MRI) coronal transcaudate section – interrupted interhemispheric fissure (large arrowhead), anterior horns of lateral ventricles (small arrowhead), the head of the caudate nucleus

13

(C), the body of the corpus callosum (CC) (dotted arrow) and CSP (*). The lateral fissure (solid arrow) and suprasellar cistern (double arrowheads) are also seen

Fig. 1.15  22 and 24 weeks (TVS) coronal transcaudate section – interrupted interhemispheric fissure (large arrowhead), anterior horns of lateral ventricles (small arrowheads), the head of the caudate nucleus (C), callosal sulcus (dotted arrow) and CSP (*)

14

1 Neurosonoanatomy

Fig. 1.16  19 weeks (TAS) coronal transthalamic section – interhemispheric fissure (large arrowhead) interrupted by the CC and callosal sulcus (dotted arrow), bodies of lateral ventricles (small arrowheads) and thalami (T)

Fig. 1.17  24 weeks (TVS and MRI) coronal transthalamic section – interrupted interhemispheric fissure (large arrowhead), bodies of lateral ventricles (small arrowheads), thalami (T), CC and callosal sulcus (dotted arrow), CSP (solid arrow), lateral fissure (**) and hippocampal gyrus (H)

4. After 20 weeks, the splenium of the CC is fully developed and extends posteriorly to overlie the tectum of the midbrain (Figs. 1.22 and 1.23). 5. In a perfect midsagittal section, the falx is seen as a faintly hyperechoic structure superior to the CC and may obscure it. Hence, the CC, the CSP and the medial hemispheric sulci (cingulate, parieto-occipital and calcarine) are best visualised in subtly off-midline sections (Figs. 1.23 and 1.24).

6. The third ventricle is a thin slit-like space between the thalami. Hence, the midsagittal section often cuts through the right or left thalamus rather than the third ventricle. The thalamus is seen as a hypoechoic rounded structure inferior to the subcallosal cystic space. The hyperechoic, comma-shaped tela choroidea is the roof of the third ventricle and is seen along the superior aspect of the thalamus (Fig.  1.25). Anteriorly, the tela choroidea tapers to a point which marks the junction of

1.2  Sections of Basic Examination

15

Fig. 1.18  25 weeks (TVS and MRI) coronal transcerebellar section – uninterrupted interhemispheric fissure (large arrowhead), posterior horns of lateral ventricles (small arrowheads), calcarine sulcus (solid arrow) and cerebellar hemispheres (C)

the foramen of Monro and third ventricle. Posteriorly, it is broad and stops anteroinferior to the splenium of CC. A vertical line passing through the anterior limit of the tela choroidea (foramen of Monro) divides the subcallosal cystic space into an anterior CSP and a posterior CV. The CV may occasionally be prominent (Fig. 1.7). 7. The cingulate sulcus is seen as a curvilinear hyperechoic line, parallel and superior to the CC (Figs. 1.26 and 1.27). 8. The parieto-occipital and calcarine sulci are mutually perpendicular and are seen posterior to the splenium (Fig. 1.28). 9. The potential space inferior to the splenium, which may sometimes be fluid filled, is the cavum veli interpositi (Fig. 1.24). 10. Caudally, the thalamus imperceptibly continues into the hypoechoic midbrain which is characterised by a dorsal hump (the tectum, colliculi or quadrigeminal plate).

11. Further caudally, the midbrain in turn imperceptibly continues into the hypoechoic pons, characterised by a ventral bulge (pontine belly) (Figs. 1.19, 1.20, 1.23 and 1.24). 12. The pons caudally continues as the hypoechoic medulla oblongata. 13. The vermis is seen posterior to the pons and medulla oblongata as a markedly hyperechoic kidney bean-­ shaped structure (Figs. 1.19, 1.20, 1.23, 1.24 and 1.30). The hyperechogenicity is due to dense folia and pial infolding in the vermis. 14. The hilum of the vermis is the fastigium, the highest point in the roof of the fourth ventricle (Figs. 1.19, 1.24 and 1.30). 15. The primary fissure of the vermis is seen as an indentation on the dorsal contour, dividing the vermis into an upper third (anterior lobe) and a lower two third (posterior lobe) (Figs. 1.24 and 1.30). The primary fissure is

16

Fig. 1.19  25 weeks (TAS and MRI) midsagittal section – CC (arrowhead), CSP and cavum vergae (*), parieto-occipital sulcus (double arrowhead), calcarine sulcus (dotted arrow), thalamus (T), cerebellar

1 Neurosonoanatomy

vermis (V), cisterna magna (M), brainstem (BS) and fastigium of the fourth ventricle (solid arrow)

a

d c Fig. 1.20  26 weeks (TVS) midsagittal section – rostrum (R), genu (G), body (B), splenium (S) of CC, CSP (*), cavum vergae (CV), cavum veli interpositi (solid arrow), vermis (V), thalamus (T), brainstem (BS); callosal sulcus (dotted arrow) is the echogenic superior margin of the CC

b Fig. 1.21  Schematic diagram of corpus callosal measurements – CC length (a), thickness of the rostrum (b), body (c) and splenium (d)

1.2  Sections of Basic Examination

seen at 18 weeks in about 40% of fetuses. It is seen in all fetuses by 24 weeks. The presence of the primary fissure and anterior and posterior lobes indicate normal vermian shape. 16. The vermian length (cephalocaudal) and anteroposterior (AP) dimension are the parameters used to confirm normality of size using nomograms. The vermian length is the maximum cephalocaudal measurement from the upper pole to the lower pole. The AP dimension is

Fig. 1.22  Schematic diagram of the midsagittal section of the brain. The splenium of the CC (green) overlies the tectum (quadrigeminal plate) of the midbrain (blue). The splenium crosses the vertical line drawn through mid-tectum

17

measured from the fastigium to the point of greatest convexity (Fig. 1.30). 17. The fourth ventricle is usually not seen as a distinct cystic structure due to its small size. 18. The brainstem-vermis angle is the angle between the two straight lines drawn tangential to the dorsal aspect of the brainstem and the ventral contour of the vermis (Fig.  1.31). The normal brainstem-vermis angle is 5.5–12.5°. 19. The pericallosal artery and the vein of Galen (great cerebral vein) are demonstrated by color Doppler in the midsagittal section (Fig. 1.29). The pericallosal artery arises from the anterior cerebral artery and sweeps along the CC. The vein of Galen is seen just inferior to the splenium of the CC.

 he Parasagittal Sections T 1. A parasagittal section passes through the entire right or left lateral ventricle (anterior horn, body, atrium, posterior horn, inferior horn and the choroid plexus) (Figs.  1.32 and 1.33). As all three horns are seen, this section is called the ‘three horn’ view. 2. The ventricular margins, cerebral parenchyma and cortical surface are best seen in the parasagittal sections (Fig. 1.34). 3. A parasagittal section further lateral displays the lateral fissure, which is seen as a triangle with its apex pointing posterosuperiorly and base oriented anteroinferiorly (Fig. 1.35). The axial, coronal and sagittal planes of the neurosonogram can be obtained from 3D volume data sets (Fig. 1.28).

Fig. 1.23  19 and 20 weeks (TAS) midsagittal section – CC (large arrowhead), CSP and CV (*), thalamus (T), cerebellar vermis (V), cisterna magna (M) and brainstem (BS)

18

Fig. 1.24  24 weeks (TVS – 3D) 2D and 3D VCI (volume contrast imaging) midsagittal sections – the splenium of CC (double arrowhead), thalamus (T), midbrain and its dorsal tectum (Tc), pons and its

1 Neurosonoanatomy

ventral belly (P), vermis (V), primary fissure of vermis (arrowhead), fastigium (solid arrow), cavum veli interpositi (dotted arrow). Note the splenium crosses the dotted vertical line through the mid-tectum.

1.3

Sulcation and Gyration

The surface of the fetal brain is smooth prior to 16 weeks. Thereafter, the sulci and gyri begin to appear. Visualisation of a sulcus by ultrasound is possible about 2–4 weeks after its anatomical appearance. For example, the parieto-occipital sulcus develops at 16 weeks. However, it is seen on US at 20 weeks in most fetuses. The US sections in which a sulcus is seen depends on the orientation of the sulcus on the cerebral surface (Figs. 1.36 and 1.26). These sections are perpendicular to the anatomical plane of the sulcus. For example, the calcarine sulcus, oriented in the axial plane, is seen in the coronal and sagittal sections. The callosal and cingulate sulci are seen in all the three orthogonal planes. The entire surface course of the medial hemispheric sulci can be traced in the midsagittal section. The labelled figures graphically describe the anatomical location of the sulci (Figs. 1.36 and 1.26).

1.3.1 Classification of Sulci

Fig. 1.25  24 weeks (TVS – 3D) 3D VCI (volume contrast imaging) midsagittal section – the third ventricle is a thin slit-like space between the thalami. The midsagittal section, therefore, often cuts through the right or left thalamus (T) rather than the third ventricle. Hyperechoic, comma-shaped tela choroidea is the roof of the third ventricle and is seen to border the thalamus superiorly. Anteriorly, the tela choroidea tapers to a point (solid arrow) which marks the junction of the foramen of Monro and third ventricle. Posteriorly, it is broad and terminates anteroinferior to the splenium of CC (solid arrow). A vertical line passing through the anterior limit of the tela choroidea (foramen of Monro) divides the subcallosal cystic space into an anterior CSP (*) and a posterior CV (**). The CSP and CV are superior to tela choroidea

The major sulci are classified based on the cerebral surface that they are present on.

 edial Hemispherical Group M (a) The parieto-occipital sulcus (axial transventricular and midsagittal sections) (Figs. 1.4b, d, 1.5, 1.6b, 1.26, 1.37 and 1.38). (b) The calcarine sulcus (coronal transcerebellar and midsagittal sections) (Figs. 1.26 and 1.39). (c) The cingulate sulcus (axial transventricular, coronal transcaudate and transthalamic and midsagittal sections) (Figs. 1.26, 1.27, 1.38 and 1.40).

1.3 Sulcation and Gyration

19

Coronal - CaS Axial – POS, CiS

Sagittal - POS, CaS & CiS

Fig. 1.26  Plane of section is determined by the orientation of sulcus. POS parieto-occipital, CaS calcarine sulcus, CiS cingulate sulcus

(d) The callosal sulcus is seen along the superior surface of the CC (axial transventricular, coronal transcaudate and transthalamic and midsagittal sections) (Figs.  1.6a, b, 1.15, 1.16, 1.17 and 1.20).

Convexity Group (a) The central, precentral and postcentral sulci (axial transventricular and transthalamic and parasagittal sections) (Figs. 1.41 and 1.42) (b) The superior temporal sulcus (coronal transcaudate and axial transcerebellar) (Figs. 1.40 and 1.42)

Inferior Group (a) The hippocampal fissure (axial transcerebellar, coronal transcaudate and transthalamic sections) (Fig. 1.39) (b) The olfactory sulcus (coronal transfrontal and transcaudate sections) (Fig. 1.38)

Lateral Fissure The lateral fissure (axial transthalamic, transcerebellar and coronal transcaudate sections)

1.3.2 U  ltrasound Appearance and Evolution of Sulci and Lateral Fissure Sulci 1. A sulcus is a furrow-like indentation on the cerebral surface dipping into the cortex, lined by pia. The pia is essentially hyperechoic and hence the sulcus is seen as a hyperechoic linear structure. 2. The evolution of a sulcus can be studied in a section orthogonal to the anatomical plane of the sulcus. A sulcus begins as a subtle indentation of the cerebral surface along its course. As it evolves with advancing gestational age, the indentation deepens to form a broad-based ‘V’ followed by a narrow-based ‘V’. The arms of the ‘V’ then appose to form an ‘I’, and finally the sulcus may branch to appear as a ‘Y’. Each major sulcus appears at a different gestational age but follows the same pattern of evolution as described above (Table 1.1 and Figs. 1.37 and 1.41). 3. The medial hemispheric group of sulci appear earlier than the convexity and the inferior groups. 4. In axial sections, the sulci in the far hemisphere are better seen. Sulci in both hemispheres are seen well in coronal sections.

1 Neurosonoanatomy

20

Fig. 1.27  30 weeks (TAS 3D US) multiplanar sectional display – cingulate sulcus seen in axial, coronal and sagittal planes (solid arrow)

5. Asymmetry in location, time of appearance and evolution of the corresponding sulci on either side is often seen. In other words, paired sulci may not be mirror images of each other. 6. The major sulci appear in a set chronological order. The following is the list of sulci and the gestational ages at which they are seen in at least 75% of normal fetuses. Sulcus Callosal Hippocampal Parieto-­occipital Calcarine Cingulate Central Precentral Postcentral Olfactory sulcus

GA at which the sulcus is seen in 75% of fetuses (weeks) 18 18 20 22 24 28 30 30 30

The ‘I’ configuration is seen by 30–32 weeks for the medial hemispheric sulci and 33–35 weeks for the convexity sulci.

 he Lateral Fissure T 1. The lateral fissure appears as a shallow pit or depression in the frontoparietotemporal region of the cerebral convexity by 21–22 weeks. 2. The shallow depression deepens to develop distinct obtuse angular margins at the circular sulcus by 23–24 weeks (Fig. 1.43). 3. With the growth of the parietal and temporal lobes, the obtuse angular borders become perpendicular by 24–25 weeks and then acute angled by 25–26 weeks. 4. The frontal, parietal and temporal lobes grow to overhang the underlying cortex (insula). This process is called operculisation. By 30–32 weeks, the posterior half of the insula is covered by the temporal operculum.

1.3 Sulcation and Gyration

21

Fig. 1.28  31 weeks (TAS 3D US) multiplanar sectional display – images in the top row are a sagittal section with navigation dot on the parieto-occipital (PO) sulcus (solid arrow) and the corresponding derived axial section with the PO sulcus marked by the navigation dot.

Images in the bottom row are a sagittal section with navigation dot on the calcarine sulcus (dotted arrow) and the corresponding derived axial section with the calcarine sulcus marked by the navigation dot. Note the PO and calcarine sulci are mutually perpendicular to each other

The frontoparietal operculisation follows temporal ­operculisation. The frontoparietal operculum forms the superior bank of the lateral fissure. The temporal operculum is the inferior bank. Apposition of the frontoparietal and temporal opercula occurs by 36 weeks, covering most of the insula. Complete closure of the anterior

most portion of the insula occurs postnatally by 2 years of age (Table 1.2, Fig. 1.44). Delayed sulcal or lateral fissure development is indicative of malformation of cortical development. Sulcation can also be assessed by fetal MRI (Fig. 1.40).

22

1 Neurosonoanatomy

Fig. 1.29  24 weeks (TAS) midsagittal section – pericallosal artery (dotted arrow) arising from the anterior cerebral artery (solid arrow) seen sweeping over the CC, the vein of Galen (arrowhead), the straight sinus (double arrowhead)

Fig. 1.30  25 weeks (TAS and MRI) midsagittal section – cerebellar vermis is depicted as a kidney bean-shaped structure in blue. The fastigium (small arrowhead), primary fissure (solid arrow), fourth ventricle in red (*),

brainstem (BS), cisterna magna (CM), cephalocaudal and anteroposterior dimensions of the vermis (yellow dotted double arrows)

1.3 Sulcation and Gyration

23

Fig. 1.30 (continued)

Fig. 1.31  23 weeks (TVS) midsagittal section – angle between a straight line along the dorsal aspect of the brainstem (solid line) and another straight line (dotted line) along the ventral aspect of the vermis is the brainstem-vermis angle

24

1 Neurosonoanatomy

Fig. 1.32  19 weeks (TAS) parasagittal section – anterior horn (A), body (B), atrium (At), posterior horn (P), inferior horn (I) of the lateral ventricle (three horn view), thalamus (T), cerebral mantle (C), convexity surface (small arrowheads), choroid plexus (CP) and subarachnoid space (*)

Fig. 1.33  25 weeks (TAS and MRI) parasagittal section – anterior horn (A), body (B), atrium (At), posterior horn (P) and inferior horn (I) of the lateral ventricle: three horn view. Thalamus (T), cerebral mantle

(C), convexity surface (small arrowheads), choroid plexus (CP) and subarachnoid space (*)

1.3 Sulcation and Gyration

25

Fig. 1.34  22 weeks (TVS 3D US) coronal plane acquisition, omniview sectional imaging – Line 1 (yellow) yields midsagittal plane; Lines 2 and 3 (magenta and blue) yield the two parasagittal planes

26

1 Neurosonoanatomy

Fig. 1.36  Plane of section depends on the orientation of sulcus. The vertically oriented central, pre- and postcentral sulci (solid arrows) are seen in the axial section. The horizontally oriented calcarine sulcus (dotted arrow) is seen in the coronal section

coronal

Fig. 1.35  26 weeks (TAS) parasagittal section through the lateral fissure – the lateral fissure is not fully closed and hence is seen as a triangle. Cerebral convexity is marked by small arrowheads

axial

1.3 Sulcation and Gyration

27

Fig. 1.37 (TAS) axial transventricular sections of parieto-occipital sulcus – (arrowheads mark the near sulcus of the pair) 18 weeks, flat; 20 weeks, shallow indentation; 23 and 25 weeks, broad ‘V’; 28 weeks, narrow ‘V’; 31 weeks, ‘I’

Fig. 1.38  36 weeks (TAS) coronal transfrontal and midsagittal sections – olfactory sulci (arrowheads), cingulate sulcus (double arrowheads)

28

1 Neurosonoanatomy

Fig. 1.39 (TAS) coronal transcaudate and transcerebellar sections – hippocampal gyrus and sulcus (solid arrows) and calcarine sulcus (dotted arrows)

Fig. 1.40  (MRI T2W) axial transventricular sections at 20 weeks and 30 weeks – shallow lateral fissures (solid arrows) and parieto-occipital sulcus (*), operculation covering more than half of the insula (double

arrowheads), ‘I’ form of parieto-occipital sulcus (small arrowhead), cingulate sulcus (dotted arrow), superior temporal sulcus (large arrowhead)

1.3 Sulcation and Gyration

29

Fig. 1.41 (TAS) axial transventricular sections of convexity sulci. 24 weeks, flat; 26 weeks, shallow indentation to broad ‘V’; 28 and 30 weeks, broad ‘V’ to narrow ‘V’; 35 and 37 weeks, ‘I’

Fig. 1.42 (TAS) Axial transventricular sections at 28 and 30 weeks – central sulcus (solid arrow), precentral sulcus (dotted arrow), postcentral sulcus (arrowhead) and superior temporal sulcus (double arrow

heads). The subarachnoid space is seen between the cortical convexity surface and the calvarium (*)

1 Neurosonoanatomy

30 Table 1.1  Evolution of parieto-occipital sulcus in axial transventricular section Mean gestational age in weeks 18

Appearance in axial sections Flat. Not visible

21

Shallow indentation

24

Broad ‘V’ Width > Height

27

Narrow ‘V’ Width ≤ Height

30

‘I’ shaped

Fig. 1.43  23 weeks (TAS) axial transthalamic section – the lateral fissure is obtuse angled (boxed). The insula, the circular sulcus and the obtuse angle are marked by arrows

Insula Circular sulcus

Obtuse angle

31

1.3 Sulcation and Gyration Table 1.2  Evolution of lateral fissure on axial transcerebellar section Gestational age in weeks 18–20

Appearance in axial sections Not visible

21–22

Shallow indentation

23–24

Obtuse angled

24–25

Right angled

25–26

Acute angled

36

Complete operculisation

Fig. 1.44 Axial transventricular, transthalamic and transcerebellar sections for grading of the lateral fissure (arrowheads) 20 weeks, shallow pit; 23 weeks, obtuse angle; 24 weeks, right angle; 27 weeks, acute

angle; 29 weeks, operculation covering more than half of insula; 32 weeks, full operculation

32

Suggested Reading 1. Malinger G, Monteagudo A, Pilu G, Timor-Tritsch I, Toi A, International Society of Ultrasound in Obstetrics & Gynecology Education Committee. Sonographic examination of the fetal central nervous system: guidelines for performing the ‘basic examination’ and the ‘fetal neurosonogram’. Ultrasound Obstet Gynecol. 2007;29:109–16.

1 Neurosonoanatomy 2. Cohen-Sacher B, Lerman-Sagie T, Lev D, Malinger G. Sonographic developmental milestones of the fetal cerebral cortex: a longitudinal study. Ultrasound Obstet Gynecol. 2006;27:494–502. 3. Toi A, Lister WS, Fong KW.  How early are fetal cerebral sulci visible at prenatal ultrasound and what is the normal pattern of early fetal sulcal development? Ultrasound Obstet Gynecol. 2004;24:706–15. 4. Quarello E, Stirnemann J, Ville Y, Guibaud L. Assessment of fetal Sylvian fissure operculization between 22 and 32 weeks: a subjective approach. Ultrasound Obstet Gynecol. 2008;32:44–9.

2

Anomalies of Corpus Callosum and Septum Pellucidum

Soon after closure, the cephalic end of the neural tube expands to form three primary vesicles, prosencephalon, mesencephalon and rhombencephalon. They are the progeni­ tors of the forebrain, midbrain and hindbrain, respectively. The prosencephalon, during 4–10 weeks of gestation, develops by the process of ventral induction which includes formation, cleavage and midline development. Failure of formation results in aprosencephaly or atelencephaly. Total or partial failure of cleavage results in the spectrum of holoprosencephaly. Abnormal midline development results in agenesis of CC or septal agenesis. Holoprosencephaly is dealt with in Chap. 3. Anomalies of the CC and septum pellucidum will be described in this chapter. The corpus callosum (CC) is the largest commissure connecting the two cerebral hemispheres. It is a broad plate made up of tightly packed axonal fibres crossing from side to side. In the midsagittal section, the corpus callosum extends from the frontal region anteriorly to overlie the tectum or quadrigeminal plate posteriorly. The segments of the CC rostrocaudally are the rostrum, genu, body and splenium. The CC begins to develop at 12 weeks in the region of the genu and progresses posteriorly, forming the body and splenium. The rostrum is the last segment to develop. The corpus callosal development is complete by 18–20 weeks gestational age. Total absence of corpus callosum (complete agenesis of corpus callosum — CACC) is due to primary embryologic failure. The axons which should have constituted the CC are oriented anteroposteriorly to form a tract medial to the lateral ventricle on either side. These white matter tracts, Probst bundles, medially indent the lateral ventricle. Incomplete development of the CC results in varying degrees of corpus callosal shortening. The splenium, body or rostrum may be absent. This is termed partial agenesis of the CC (PACC). The term hypoplasia of CC refers to a CC which is normal in length but thin. Corpus callosal dysgenesis refers to a CC which is thinner or thicker than normal or partially developed. CACC or PACC can also be secondary to destructive processes such as ischaemia or infection.

Table 2.1  The relationship between the CSP and CC CSP Normal Absent Absent Abnormal Normal

CC Present Absent Present Abnormal Absent

Condition Normal CACC Septal agenesis PACC, dysgenesis Not possible

The septum pellucidum is a two-layered membrane between the anterior horns of the lateral ventricles. The two layers in the fetus are separated by fluid. Hence, it is termed cavum septum pellucidum (CSP). The development of the CSP is closely related to and dependent on the development of the CC. A normal CC is associated with a normal-sized CSP. The length of the CSP (anteroposterior dimension) is directly proportional to the length of the CC. A short CC as in PACC is associated with a CSP of short length. CSP is absent in CACC. Presence of CC with absence of CSP occurs in septal agenesis. Hence, a CSP seen (on axial sections) indirectly indicates the presence of CC (on midsagittal section). As the CC development is complete by 18–20 weeks, CSP can be identified only after this gestational age. The CSP is not visualised after 37  weeks, as the fluid in the cavum is absorbed. The CSP then becomes the septum pellucidum as seen postnatally (Table 2.1).

2.1

 omplete Agenesis of Corpus C Callosum

US findings in the axial, coronal or sagittal sections which help suspect CACC are the indirect signs. The indirect signs on the axial sections are important and serve as initial clues that lead to a detailed “neurosonogram”. The direct sign is the inability to visualize CC on midsagittal or coronal sections. These signs are best seen at or after 22 weeks. Although present, the signs are subtle and may be missed at 18–22 weeks.

© Springer Nature Singapore Pte Ltd. 2019 B. S. Rama Murthy, Imaging of Fetal Brain and Spine, https://doi.org/10.1007/978-981-13-5844-9_2

33

34

2.1.1 I ndirect Signs in the Transventricular Axial Section 1. The CSP is absent. It must be emphasized that CACC cannot be diagnosed only on the basis of absent CSP (Figs. 2.1, 2.2 and 2.3a). One must directly demonstrate the absence of CC on midsagittal sections. 2. Teardrop-shaped lateral ventricle is a combination of colpocephaly (selective mild dilatation of the atria and posterior horns of the lateral ventricles) with pinched anterior horns (Figs. 2.1, 2.2 and 2.3a). 3. The anterior horns are laterally placed (Figs.  2.1, 2.3a and 2.4). 4. Cephalad extension of the third ventricle to extend up to the level of the lateral ventricles (Fig. 2.1).

Fig. 2.1  24 weeks (TAS and MRI) indirect signs of complete agenesis of corpus callosum. Axial transventricular and transthalamic, coronal transfrontal section and T2W MR coronal transthalamic section – absent CSP on the axial sections, CC not seen in the coronal MR

2  Anomalies of Corpus Callosum and Septum Pellucidum

5. The interhemispheric fissure (IHF) is wide with CSF separating the medial surfaces of the cerebral hemispheres from the falx as there is no CC to hold them together. This is called the “three line” sign (Figs. 2.1 and 2.4).

2.1.2 I ndirect Signs on Transcaudate Coronal Section 1. The CSP is absent and hence the IHF is uninterrupted (Fig. 2.3a). 2. The anterior horns are laterally placed (Fig. 2.3a). 3. The anterior horns are crescent or comma shaped with an outward convexity (“steerhorn” or “Viking helmet” sign). The medial indentation of the lateral ventricles is due to the Probst bundles (Figs. 2.3a and 2.5).

section, three-line sign seen of IHF (circled), colpocephaly/teardrop shape of lateral ventricle (**), laterally placed anterior horns which are steerhorn in shape (dotted arrows), cephalad extension of the third ventricle (solid arrow), uninterrupted IHF (arrowheads)

2.1  Complete Agenesis of Corpus Callosum

4 . Wide IHF (“three line” sign) is seen (Figs. 2.1 and 2.3a). 5. Cephalad extension of the third ventricle is seen in the coronal transthalamic section. 6. Prominent anterior commissure may be seen (Fig. 2.6).

2.1.3 Indirect Signs on the Midsagittal Section 1. The cingulate sulcus and gyrus are absent (Figs. 2.3a, b and 2.4). 2. The presence of radiating medial hemispheric sulci and gyri is typically seen in the third trimester (“sunburst” sign) (Fig. 2.7). 3. Abnormal course of the pericallosal artery is seen on color Doppler (Fig. 2.8).

2.1.4 D  irect Sign on Midsagittal, Transcaudate and Transthalamic Coronal Sections The corpus callosum is not seen (Figs. 2.2, 2.3a, b, 2.4, 2.7 and 2.8).

2.1.5 Associated Intracranial Findings 1. The roof of third ventricle (tela choroidea) balloons out dorsally with CSF to form an interhemispheric cyst. It may extend on any one side of the falx cerebri (Fig. 2.9). 2. A nodular lipoma, when present, is seen as a focal hyperechoic lesion in the anterior midline just under the IHF (anatomical location of the genu). It may extend through

35

the choroidal fissures on either side to reach the choroid plexuses in the lateral ventricles. Very rarely a ribbon or curvilinear lipoma may extend along the course of the missing CC (Figs. 2.10 and 2.11). 3. CACC may be associated with lissencephaly, schizencephaly, heterotopia and polymicrogyria (Fig. 2.12).

2.1.6 Associated Extracranial Findings 1. Sporadic extracranial anomalies such as genitourinary, skeletal or congenital heart defects may be present. 2. CACC may be a part of a syndrome. CACC associated with dysmorphic face (hypotelorism, small nose, micrognathia, cleft lip) and polydactyly is suggestive of Acrocallosal syndrome (autosomal recessive) (Fig. 2.13) or Orofaciodigital syndrome (X-linked dominant). Aicardi syndrome (X-linked dominant) is suspected in a female fetus with CACC, polymicrogyria, heterotopia, microphthalmia, coloboma, hemivertebra, scoliosis and brain tumor. CACC can occur in inborn errors of metabolism. Diagnosis is by testing for the specific gene mutations. 3. Karyotyping is indicated to rule out chromosomal abnormalities.

2.1.7 Differential Diagnosis Occasionally, a SP without fluid between its layers may be seen. Most often, the CC is normal in such cases (Fig. 2.14).

Fig. 2.2  33 weeks (TAS and TVS) complete agenesis of corpus callosum. Axial transthalamic and midsagittal sections – absent CSP, colpocephaly (**), vermis (arrowheads) confirms section to be midsagittal. The CC is absent

36

2  Anomalies of Corpus Callosum and Septum Pellucidum

a

b

Fig. 2.3 (a) 27 weeks (TAS and TVS) complete agenesis of corpus callosum (direct and indirect signs). Axial transventricular, midsagittal and coronal transthalamic sections – CSP is absent on axial section; colpocephaly (*), corpus callosum and cingulate sulcus are absent on midsagittal and coronal sections; vermis (solid arrow);

laterally placed, steerhorn-shaped lateral ventricles (dotted arrows). (b). 27  weeks (TVS 3D US and MRI) complete agenesis of corpus callosum (direct sign). 3D Multiplanar midsagittal section with volume contrast imaging (VCI) and T2W MR midsagittal section – the entire CC is not seen

2.1  Complete Agenesis of Corpus Callosum

37

Fig. 2.4  19  weeks (TAS) complete agenesis of corpus callosum (direct and indirect signs). Axial transventricular and midsagittal sections – colpocephaly (**), pinched and laterally placed anterior horns (solid arrows), absent CSP and three line sign (circled), entire CC is absent on midsagittal section

Fig. 2.5  35 weeks (TVS 3D US) complete agenesis of corpus callosum – 3D multiplanar coronal, axial and parasagittal sections – navigation dot (*) is placed on the Probst bundle

Absence of CSP is not unique to CACC. It is absent in holoprosencephaly (HPE), septal agenesis, schizencephaly and hydrocephaly. Absence of IHF and presence of monoventricle and dorsal sac confirm alobar HPE. Failure of cleavage of anterior horns results in an abnormal shape and is seen in semilobar and lobar HPE. The CC is not normal in these disorders. In septal agenesis, the shape of the anterior horns is normal in the coronal transcaudate section. They are, however, continuous with each other across the midline. The CC is normal in septal agenesis. The presence of full thickness cerebral parenchymal cleft distinguishes schizencephaly.

Mild lateral ventriculomegaly is a common finding seen in chromosomal abnormalities, malformation of cortical development, infections and other conditions. Colpocephaly in CACC has to be differentiated from mild lateral ventriculomegaly. Pinched appearance of the anterior horns (teardrop shape of the lateral ventricle) and the increased distance from the midline are the features of colpocephaly. In the absence of associated intracranial, extracranial and karyotype abnormalities, CACC is considered to be isolated. MRI in addition to confirming the absence of CC will also confirm or rule out associated CNS anomalies. Prognostication depends on whether CACC is isolated or not.

38

2  Anomalies of Corpus Callosum and Septum Pellucidum

Fig. 2.6  24 weeks (TVS) complete agenesis of corpus callosum with hypertrophy of the anterior commissure – coronal transcaudate section and transcaudate section magnified – interhemispheric cyst (*), prominent anterior commissure inferior to the cyst anteriorly (solid arrows)

Fig. 2.7  31 weeks (TAS) complete agenesis of corpus callosum – midsagittal section – absent corpus callosum and cingulate sulcus with radially arranged medial hemispheric sulci (arrows)

2.1  Complete Agenesis of Corpus Callosum

39

Fig. 2.8  25 weeks (TAS) complete agenesis of corpus callosum – midsagittal sections B mode and color Doppler – abnormal course of pericallosal artery

Fig. 2.9  26 weeks (TAS and MRI) complete agenesis of corpus callosum with left interhemispheric cyst – axial transventricular, axial section at a slightly cephalic plane, coronal transthalamic and midsagittal sections and T2W MR coronal transthalamic section – interhemispheric

cyst extending to left of the falx cerebri (*), the cyst inferiorly is communicating with the third ventricle (solid arrow). The other indirect and direct signs of CACC are seen

40

2  Anomalies of Corpus Callosum and Septum Pellucidum

Fig. 2.10  36 weeks (TAS) complete agenesis of corpus callosum with lipomas – axial transventricular and midsagittal sections – midline and bilateral intraventricular lipomas (solid arrows), ribbon lipoma (dotted arrow) replaces CC

Fig. 2.11  25 weeks (TAS 3D US) complete agenesis of corpus callosum with lipomas – axial transventricular section obtained with 3D omniview and volume contrast imaging (VCI) and 3D rendered axial

transventricular section – midline and bilateral intraventricular lipomas (arrowheads). The bilateral lipomas are seen tipping the choroid plexuses anteriorly

2.1  Complete Agenesis of Corpus Callosum

41

Fig. 2.12  24  weeks (TAS) complete agenesis of corpus callosum with lissencephaly – axial transventricular and coronal transcaudate sections – shallow parieto-occipital sulcus (arrowhead) and shallow lateral fissure (dotted arrows). Other direct and indirect signs of CACC are seen

Fig. 2.13  23  weeks pregnancy in a second-degree consanguineous couple (TAS). Acrocallosal syndrome – midsagittal section of the cranium, coronal sections of both hands and 3D surface rendered images

of the face – complete absence of CC in the midsagittal section, bilateral postaxial polydactyly (arrowheads) and facial dysmorphism

Fig. 2.14  32 weeks (TAS) no fluid in the CSP with a normal CC – axial transventricular and midsagittal sections – mild left lateral ventriculomegaly (*), no fluid in the CSP (solid arrow), normal CC (dotted arrows)

42

2.2

2  Anomalies of Corpus Callosum and Septum Pellucidum

Partial Agenesis of Corpus Callosum

US findings in the axial, coronal or sagittal sections which help suspect PACC are the indirect signs. The indirect signs on the axial sections are important and serve as initial clues that lead to a detailed “neurosonogram”. A CC of short length and inability to visualize all segments are direct signs seen on the midsagittal section.

2.2.1 Indirect Signs on Axial Sections 1. The length of the CSP is directly related to the length of the CC.  Hence, the CSP is short in PACC. This serves as an indirect sign on axial sections. In severe PACC (only a small length of the CC is present), the CSP is very small and could even verge on absence. In less severe PACC (variable lengths of CC present), the CSP is short and wide. The normally rectangular CSP tends to be a square (Fig. 2.15). 2. The length of the CSP is measured from the callosal sulcus anteriorly to the fornices posteriorly. The width of the CSP is measured in its midportion (“on to on”). The length-to-width ratio is termed the CSP ratio. In a short and wide CSP (as in PACC), the ratio is less than 1.5 (Figs. 2.16, 2.17, 2.18a and 2.19). 3. Other indirect signs on axial view include colpocephaly (Fig.  2.18a) and teardrop shape of the lateral ventricle. These signs may be subtle.

4. Associated intracranial findings such as lissencephaly, polymicrogyria, heterotopias, interhemispheric cyst (Fig.  2.20a, b), midline lipoma (nodular or curvilinear types) and Dandy-Walker malformation may be present.

2.2.2 Direct Signs on Midsagittal Section 1. The length of the CC is lesser than the fifth percentile or −2SD (Fig. 2.18a, b). 2. In the absence of the splenium and posterior body, the CC does not extend posteriorly to overlie the quadrigeminal (tectal) plate of the midbrain (Figs. 2.16, 2.17, 2.18b, 2.19 and 2.20b). 3. In some cases the splenium and rostrum may be absent (Fig.  2.16). Absence of bulbosity of the splenium is a subtle sign of PACC. 4. The cingulate sulcus is seen parallel to the extant CC (Fig. 2.17). It is not seen in the regions where the CC is absent. 5. The medial hemispheric sulci are radially arranged in the regions where the CC (and hence the cingulate sulcus) is absent (Fig. 2.17). 6. The pericallosal artery sweep is present only over the segment of the CC that is present. The artery subsequently has an abnormal course (Fig. 2.19).

2.2 Partial Agenesis of Corpus Callosum

43

Normal

PACC

Fig. 2.15  Schematic diagram showing the relation of the length of the CSP (axial section) to the length of the CC (midsagittal section). The normally rectangular CSP reflects a CC of normal length. A short CSP

reflects a CC of short length, as in partial agenesis of CC. This relationship is understandable given that the CSP is immediately subcallosal in location

44

Fig. 2.16  24 weeks (TAS and TVS) partial agenesis of corpus callosum – axial transventricular, coronal transthalamic, midsagittal (without and with color Doppler) sections – short and wide CSP (arrowhead), short thick CC, splenium and rostrum are absent, body of CC is present,

2  Anomalies of Corpus Callosum and Septum Pellucidum

posterior limit of CC (solid arrow) does not overlie the quadrigeminal plate (*), dysmorphic lateral ventricles (dotted arrows), abnormal course of pericallosal artery

2.2 Partial Agenesis of Corpus Callosum

Fig. 2.17  32 weeks (TAS and TVS) partial agenesis of corpus callosum – axial transventricular, midsagittal and midsagittal magnified sections – short and wide CSP (double arrowhead), short CC, body of CC is thin posteriorly, splenium, rostrum and genu absent, posterior limit of the

45

CC (solid arrow) does not extend to overlie the quadrigeminal plate (*), cingulate sulcus stops exactly where the CC ends (dotted arrow) beyond which a few radial sulci are seen (arrowheads), thalamus (T), vermis (V)

46

2  Anomalies of Corpus Callosum and Septum Pellucidum

a

b

2.2 Partial Agenesis of Corpus Callosum

Fig. 2.19  25 weeks (TVS) partial agenesis of corpus callosum – midsagittal, midsagittal magnified, midsagittal with color Doppler and coronal transcaudate sections – only the rostrum and genu are present, most of the body and splenium are absent (solid arrows), CC does not extend posteriorly to overlie the quadrigeminal plate (**), CSP is small (*),

47

pericallosal artery sweep stops at posterior limit of CC and takes a radial course (dotted arrow), anterior horns are laterally placed with a hint of steerhorn configuration (arrowheads), thalamus (T), vermis (V). The CSP on axial section was almost absent (US image not included)

Fig. 2.18 (a) 23 weeks (TAS) partial agenesis of corpus callosum – axial transventricular, axial transventricular magnified section and corresponding line diagram – unilateral mild lateral ventriculomegaly (**) short and narrow CSP (*), asymmetric size and shape of anterior horns (arrowheads), anterior IHF (solid arrow) not collinear with CSP, the genu of CC (dotted arrow). (b) 23 weeks (TAS) partial agenesis of c­ orpus callosum – midsagittal and midsagittal section magnified – CC is short (CC length of 2.0 cm is less than fifth percentile or −2SD) (double-headed solid arrow), the genu (dotted arrow), body of CC (solid arrow) are present, rostrum and splenium are absent, posterior limit of CC (arrowhead) does not overlie the quadrigeminal plate (**), CSP (*), thalamus (T)

48

2  Anomalies of Corpus Callosum and Septum Pellucidum

a

Fig. 2.20 (a) 26 weeks (TAS, TVS and MRI) partial agenesis of corpus callosum with interhemispheric cyst (right parafalcine) – axial transventricular, cephalad to transventricular plane, coronal transcaudate and midsagittal sections – CSP is normal (*), lateral ventricles are normal, interhemispheric cyst to the right of the falx (**), side-to-side asymmetry of CC, right side of the CC is thicker compared to the left side (solid arrows), CC is short, and the splenium is absent (dotted arrows). Differential diagnosis is interhemispheric arachnoid cyst with

compression of the splenium. (b) 26 weeks (TAS, TVS and MRI) partial agenesis of corpus callosum with interhemispheric cyst (right parafalcine) – Coronal transthalamic and midsagittal US and T2W MRI sections – interhemispheric cyst (**) is inferiorly communicating (solid arrow) with third ventricle (fluid space between the thalami), CC is short with absent splenium (dotted arrows), thalamus (T). As the cyst is in communication with the third ventricle, it is likely to be an interhemispheric cyst associated with PACC rather than an arachnoid cyst

2.3 Other Callosal Abnormalities

49

b

Fig. 2.20 (continued)

2.3

Other Callosal Abnormalities

1. In CC hypoplasia, the entire length of CC is present; however, the thickness is reduced (lesser than −2SD) (Fig. 2.21a, b). This is due to fewer axons crossing from side to side and is associated with other brain anomalies such as lissencephaly. It can also occur due to teratogenic effects of radiation or alcohol or due to compression in hydrocephalus.

2. Subtle changes in the harmonious contour of the CC may be seen in callosal hypoplasia (Fig. 2.21b). 3. The CC is termed abnormally thick CC when the thickness is more than the +2SD (Figs.  2.22 and 2.23a–c). This is always associated with other intracranial findings such as PACC, abnormalities of sulcation, ventriculomegaly, encephalocele, macrocephaly and vermian abnormalities.

50

2  Anomalies of Corpus Callosum and Septum Pellucidum

a

b

Fig. 2.21 (a) 29 weeks (TAS) corpus callosal hypoplasia and lissencephaly. Axial transthalamic and transventricular sections – bilateral mild lateral ventriculomegaly (**), normal CSP (*), lateral fissure is “open” without operculation (dotted arrows), shallow parieto-occipital sulcus (solid arrows). (b) 29 weeks (TAS) corpus callosal hypoplasia

with lissencephaly – coronal transcaudate, midsagittal and parasagittal sections – mild lateral ventriculomegaly (**), normal CSP (*), lateral fissure is “open” without operculation (dotted arrows), CC is thin (entire length seen) with midcallosal subtle angulation (solid arrow), convexity sulci are not seen (arrowhead)

2.3 Other Callosal Abnormalities

Fig. 2.22  23 weeks (TAS and TVS) thick corpus callosum with partial agenesis – axial transventricular, axial magnified (anterior complex), midsagittal and midsagittal magnified sections – CSP is broad and short (*),

51

short CC (solid arrows) does not extend posteriorly (arrowhead) to overlie the quadrigeminal plate (**), rostrum and splenium are absent, thalamus (T), vermis (V)

52

2  Anomalies of Corpus Callosum and Septum Pellucidum

a

Fig. 2.23 (a) 26 weeks (TAS) thick corpus callosum with lissencephaly – axial transventricular, coronal transcaudate and midsagittal sections – CSP appears narrow (*), shallow lateral fissure (**), parieto-occipital sulcus not seen (solid arrow), right subependymal cyst (dotted arrow), entire length of CC is present but thick (arrowheads), retrocerebellar cyst (C). (b) 26 weeks (TVS) thick corpus callosum with lissencephaly – midsagittal, parasagittal, coronal transcaudate and

t­ ranscerebellar sections – CSP (*), thick CC (solid arrow), retrocerebellar cyst (C), cingulate and calcarine sulci are not seen (dotted arrows). (c) 26 weeks (MRI) thick corpus callosum with lissencephaly – T2W midsagittal, coronal transcaudate, axial transventricular and transcerebellar and parasagittal sections – thick CC (solid arrows), shallow lateral fissure (arrowheads), subependymal cyst (dotted arrow), retrocerebellar cyst (C)

2.3 Other Callosal Abnormalities

b

c

Fig. 2.23 (continued)

53

54

2.4

2  Anomalies of Corpus Callosum and Septum Pellucidum

Septal Agenesis

Absence or agenesis of cavum septum pellucidum or septum pellucidum (SP) in the background of normal prosencephalic cleavage is termed septal agenesis. Septal agenesis can either occur as an isolated finding or as a part of septo-optic dysplasia. Septo-optic dysplasia is a grave disorder characterised by septal agenesis with optic chiasma and nerve hypoplasia and hypothalamic-pituitary dysfunction. 1. The frontal horns are continuous across the midline as a result of the absence of CSP or septum pellucidum (Fig. 2.24a, b). 2. The IHF and CC are normal (Fig. 2.24a, b). 3. Mild lateral ventriculomegaly may be a finding. 4. The normal optic nerves and chiasma may be demonstrated directly in the axial or coronal sections of the

chiasmatic cistern obtained by high-frequency transabdominal or transvaginal ultrasonography especially in the late second or third trimester. Rendered images of coronal or axial 3D volumes help in the imaging of the optic chiasma (Figs. 2.24c and 2.26b). The presence of a normal-sized optic chiasma may help to rule out or decrease the possibility of septo-optic dysplasia. An optic chiasma that is difficult to be seen may indicate hypoplasia and hence the possibility of septo-optic dysplasia. MRI helps to assess the status of the optic chiasma (Fig.  2.25a, b). Fetal blood sampling for investigation of pituitary function confirms hypopituitarism. 5. Septal agenesis may be associated with malformations of cortical development, schizencephaly, holoprosencephaly, callosal abnormalities or facial clefting (Fig. 2.26a, b).

a

Fig. 2.24 (a) 32 weeks (TAS) isolated septal agenesis – axial transventricular and coronal transcaudate sections – anterior horns continuous across the midline with absence of CSP (solid arrows), IHF (dotted arrow) is normal. (b) 32 weeks (TVS) isolated septal agenesis – coronal transcaudate, midsagittal and midsagittal magnified sections – anterior horns continuous with each other across the midline due to absence

of CSP (solid arrows), optic chiasma (dotted arrows), CC (arrowheads), vermis (V). (c) 32  weeks (TVS) isolated septal agenesis – coronal transcaudate (sepia, magnified) – anterior horns continuous with each other across the midline due to absence of CSP (solid arrow), optic chiasma (dotted arrows), CC (arrowheads), temporal lobes (t), head of caudate nucleus (c)

2.4 Septal Agenesis

55

b

c

Fig. 2.24 (continued)

56

2  Anomalies of Corpus Callosum and Septum Pellucidum

a

Fig. 2.25 (a) 22 weeks (TAS and MRI) septo-optic dysplasia – axial transventricular and coronal transthalamic US sections, T2W coronal transcaudate, coronal transthalamic and midsagittal sections – CC (solid arrows), anterior horns continuous across the midline with absence of CSP (dotted arrows), chiasma not seen in the chiasmatic cistern (arrowheads). (b) 22 weeks (Autopsy) septo-optic dysplasia –

basal view of brain, coronal section, the globes and optic nerves – optic tracts (arrowheads) are smaller than the oculomotor nerves (white dotted arrows), anterior horns are continuous with each other across the midline due to absence of CSP (black dotted arrow), optic nerves are thin (black solid arrow)

2.4 Septal Agenesis

b

Fig. 2.25 (continued)

57

58

2  Anomalies of Corpus Callosum and Septum Pellucidum

a

Fig. 2.26 (a) 22 weeks (TAS and TVS) septal agenesis with bilateral congenital talipes equinovarus – axial transventricular and coronal transcaudate of the cranium and coronal sections of right and left legs – anterior horns continuous with each other across the midline due to absence of CSP (solid arrows), CC (arrowhead), bilateral talipes

e­ quinovarus (dotted arrows). (b) 22 weeks (TVS) septal agenesis with bilateral congenital talipes equinovarus – axial and coronal sections through chiasmatic cistern, 3D axial rendered images of the chiasmatic cistern with edit light option – optic chiasma (H shaped in the 3D rendered mode) (solid arrows) anterior (a), posterior (p)

Suggested Reading

59

b

Fig. 2.26 (continued)

Suggested Reading 1. Karl K, Esser T, Heling KS, Chaoui R. Cavum septi pellucidi (CSP) ratio: a marker for partial agenesis of the fetal corpus callosum. Ultrasound Obstet Gynecol. 2007;50:336–41. 2. Pilu G, Tani G, Carletti A, Malaigia S, Ghi T, Rizzo N.  Difficult early sonographic diagnosis of absence of the fetal septum pellucidum. Ultrasound Obstet Gynecol. 2005;25:70–2. 3. Malinger G, Lev D, Kidron D, Heredia F, Hershkovitz R, Lerman-­ Sagie T. Differential diagnosis in fetuses with absent septum pellucidum. Ultrasound Obstet Gynecol. 2005;25:42–9. 4. Malinger G, Lev D, Oren M, Lerman-Sagie T. Non-visualization of the cavum septi pellucidi is not synonymous with agenesis of the corpus callosum. Ultrasound Obstet Gynecol. 2012;40:165–70. 5. Paladini D, Pastore G, Cavallaro A, Massaro M, Nappi C. Agenesis of the fetal corpus callosum: sonographic signs change with advancing gestational age. Ultrasound Obstet Gynecol. 2013;42:687–90. 6. Lepinard C, Coutant R, Boussion F, Loisel D, Delorme B, Biquard F, Bonneau D, Guichet A, Descamps P.  Prenatal diagnosis of absence of the septum pellucidum associated with septo-optic dysplasia. Ultrasound Obstet Gynecol. 2005;25:73–5.

7. Lerman-Sagie T, Ben-Sira L, Achiron R, Schreiber L, Hermann G, Lev D, Kidron D, Malinger G. Thick fetal corpus callosum: an ominous sign? Ultrasound Obstet Gynecol. 2009;34:55–61. 8. Pilu G, Sandri F, Perolo A, Pittalis MC, Grisolia G, Cocchi G, Foschini MP, Salvioli GP, Bovicelli L. Sonography of fetal agenesis of the corpus callosum: a survey of 35 cases. Ultrasound Obstet Gynecol. 1993;1:318–29. 9. Shen O, Gelot AB, Moutard ML, Jouannic JM, Sela HY, Garel C. Abnormal shape of the cavum septi pellucidi: an indirect sign of partial agenesis of the corpus callosum. Ultrasound Obstet Gynecol. 2015;46:595–9. 10. Ghi T, Carletti A, Contro E, Cera E, Falco P, Tagliavini G, Michelacci L, Tani G, Youssef A, Bonasoni P, Rizzo N, Pelusi G, Pilu G.  Prenatal diagnosis and outcome of partial agenesis and hypoplasia of the corpus callosum. Ultrasound Obstet Gynecol. 2010;35:35–41. 11. Malinger G, Zakut H. The corpus callosum: normal fetal development as shown by transvaginal sonography. AJR. 1993;161:1041–3. 12. Cignini P, Padula F, Giorlandino M, Brutti P, Alfo M, Giannarelli D, Mastrandrea ML, D’Emidio L, Vacca L, Aloisis A, Giorlandino C. Reference charts for fetal corpus callosum length. J Ultrasound Med. 2014;33:1065–78.

3

Anomalies of Ventral Induction: Holoprosencephaly

The prosencephalon (progenitor of the forebrain) is the most rostral of the three embryonic brain vesicles. It develops into the telencephalon (cerebral hemispheres and lateral ventricles) and the diencephalon (thalami and third ventricle). The prosencephalon cleaves (5–6  weeks gestational age) into right and left halves resulting in the two cerebral hemispheres and sets of basal ganglia on either side of the midline. Failure of formation of prosencephalic vesicle and hence the prosencephalon is termed aprosencephaly. Failure of formation of telencephalon (cerebral hemispheres) with the presence of diencephalon (thalami) is termed atelencephaly. These are very rare disorders. Defective ventral induction results in total or subtotal failure of cleavage resulting in totally or partially uncleaved forebrain. This spectrum of disorders is termed holoprosencephaly (HPE).

Following is the DeMyer classification of HPE based on the severity (Fig. 3.1): 1. Alobar: This is the most severe form of HPE. Complete failure of cleavage of the prosencephalon results in absence of midline structures. The cerebrum is uncleaved and has a single ventricle called the primitive monoventricle. As there are no right and left hemispheres, the interhemispheric fissure and corpus callosum are absent. Failure of diencephalic cleavage leaves the thalamus without an interthalamic fissure (third ventricle). The tela choroidea of the roof of the primitive monoventricle may balloon out with CSF to form a dorsal sac or cyst. Depending on the shape of the cerebral mantle, three morphological types, namely, pancake, cup and ball forms,

Fig. 3.1  Schematic diagram of the types of holoprosencephaly

Alobar

Semilobar

© Springer Nature Singapore Pte Ltd. 2019 B. S. Rama Murthy, Imaging of Fetal Brain and Spine, https://doi.org/10.1007/978-981-13-5844-9_3

Middle hemispheric variant

Lobar

61

62

have been described. The dorsal sac is present only in the pancake and cup forms. In the ball type the uncleaved cerebrum completely encloses the primitive monoventricle, and there is no dorsal sac. The cortical sulcation and operculation are often defective in alobar HPE. 2. Semilobar: Cleavage of the prosencephalon occurs only in the occipital region. The parietal and frontal regions of the cerebrum are uncleaved. Correspondingly, only the posterior horns of the lateral ventricles are cleaved. The bodies and the anterior horns are uncleaved and hence are continuous with each other across the midline. The IHF is present between the occipital lobes. 3. Lobar: The occipital and parietal lobes with the posterior horns and bodies of the lateral ventricles have cleaved. The frontal region (with the anterior horns) is not cleaved. The IHF is present between the occipital and parietal lobes but is absent anteriorly. The rostrum, genu and anterior body of the CC are deficient. 4. Middle hemispheric variant (syntelencephaly): In this type, cleavage occurs in the frontal and occipital regions. The parietal region alone is uncleaved. Correspondingly, the body of the lateral ventricle is uncleaved, and the anterior and posterior horns are cleaved (Fig. 3.1).

3  Anomalies of Ventral Induction: Holoprosencephaly

It should be noted that the word ‘fused’ has not been used to denote the lateral ventricular or thalamic status. The word ‘fused’ implies a previously cleaved state with ‘fusion’ occurring later on. In HPE, cleavage has not occurred to begin with and hence ‘fusion’ is not possible. Midline facial defects are embryologically related to holoprosencephaly (polytopic field defect). They include cyclopia, hypotelorism, proboscis (ethmocephaly or cebocephaly), absent nose (arrhinia) and median cleft lip and palate.

3.1

Ultrasound Findings of HPE

Absent cavum septum pellucidum and abnormal anterior complex are the first clue to the presence of abnormality.

3.1.1 Alobar Holoprosencephaly 1. The CSP and CC are not seen (Figs. 3.2a, b, 3.3, 3.4 and 3.5). 2. The anterior complex is not seen. The IHF is completely absent.

a

b

Fig. 3.2 (a) 25  weeks (TAS) alobar holoprosencephaly – axial, coronal transthalamic and transfrontal sections – absent interhemispheric fissure (IHF) and cavum septum pellucidum (CSP), primitive uncleaved ventricle (*), dorsal cyst (**), hippocampal ridges (arrowheads), cup-shaped cortical configuration with no sulcation (solid arrow), uncleaved thalamus (dotted arrow). (b) 25 weeks (TAS, 3D US)

alobar holoprosencephaly – facial findings. Coronal section of face, axial section of orbits, midsagittal section of face, 3D surface rendering of fetal face – median cleft lip (solid arrow), protuberant eyes and hypotelorism (arrowheads), absent nose with flat facial profile (dotted arrow), 3D surface rendering of the face displaying all the findings in B mode images

3.1  Ultrasound Findings of HPE

3. A single primitive ventricle is seen and is often dilated. 4. Generalised paucity of the cerebral mantle is noted. 5. Dorsal cyst or sac is seen in the cup and pancake types and strongly correlates with an uncleaved thalamus. 6. Uncleaved thalamus is seen projecting into primitive monoventricle.

63

7. Third ventricle is absent. 8. The cranial size can be normal, small or large for gestational age. 9. The sulcation and operculation are abnormal. 10. Single or azygous anterior cerebral artery is seen. 11. The circle of Willis is abnormal. 12. Associated Dandy-Walker malformation may be seen.

Fig. 3.3  23 weeks (TAS 3D US) alobar holoprosencephaly – multiplanar midsagittal section and 3D inversion – cup-shaped cortical configuration (*), dorsal cyst (**), membrane forming the ballooned dorsal cyst (solid arrow)

Fig. 3.4  26 weeks (TAS) alobar holoprosencephaly – axial transventricular and transcerebellar sections – absent interhemispheric fissure (IHF) and cavum septum pellucidum (CSP), primitive uncleaved

ventricle with two choroid plexuses(*), no dorsal cyst, ball type of cortical configuration with no sulcation (solid arrow), uncleaved thalamus projecting into the uncleaved monoventricle (dotted arrow)

64

3  Anomalies of Ventral Induction: Holoprosencephaly

Fig. 3.5  20 weeks (TAS) alobar holoprosencephaly with cebocephaly – axial transthalamic section of cranium, coronal section of face, picture of abortus – primitive monoventricle (solid arrow), single nostril (dotted arrow)

Differential Diagnosis 1. Hydranencephaly: The absence of recognisable cerebral mantle, presence of falx (IHF) and normal face differentiate this from alobar HPE. The absence of intracranial arteries on color Doppler supports the diagnosis of hydranencephaly. 2. Hydrocephalus: The presence of falx (IHF), thin cerebral mantle and normal face differentiate hydrocephalus from alobar HPE.

Alobar HPE should be diagnosed in the first trimester (11–14 weeks) scan. Absence of the midline falx and choroid plexuses (butterfly sign) and presence of monoventricle with uncleaved thalamus confirm the diagnosis. Accelerated frontal bone ossification and premature closure of metopic suture may be seen (Fig. 3.6a–c).

3.1  Ultrasound Findings of HPE

65

a

b

Fig. 3.6 (a) 13  weeks (TAS) alobar holoprosencephaly – axial and coronal sections – uncleaved thalamus (solid arrows), primitive monoventricle extending from side to side (*), choroid plexuses (dotted arrows). (b) 13 weeks (TVS 3D US) alobar holoprosencephaly – rendered image of the fetal face in maximum mode – accelerated frontal bone ossification (arrowheads) and premature metopic suture closure

(solid arrow), normal metopic suture at 13 weeks in a normal fetus (dotted arrow). (c) 13  weeks (TVS, 3D US) alobar holoprosencephaly – midsagittal section of face, axial sections through orbits and upper lip, 3D surface rendering of the fetal face – flat facial profile (solid arrow), proptosis (arrowheads), median cleft lip (dotted arrow)

66

3  Anomalies of Ventral Induction: Holoprosencephaly

c

Fig. 3.6 (continued)

3.1.2 Semilobar Holoprosencephaly

3.1.3 Lobar Holoprosencephaly

1. The CSP is not seen. 2. The posterior horns are discrete and seen separately. 3. The body and anterior horns are continuous across the midline (Figs. 3.7a, b and 3.8a–c). 4. IHF is only seen between the occipital lobes. 5. The cerebral mantle is relatively better formed. 6. Frontoparietal side to side cortical continuity is seen. 7. The splenium and posterior part of body of CC are present. The rostrum, genu and anterior part of body are not seen. 8. Dorsal sac or cyst may be present. 9. Single or azygous anterior cerebral artery is seen on color Doppler. 10. The circle of Willis is abnormal.

1 . The CSP is not seen. 2. The body and posterior horns of the lateral ventricles are seen separately on either side. 3. The anterior horns of the lateral ventricles are continuous across the midline (Fig. 3.9). 4. The IHF is not seen anteriorly. The mid and posterior parts of the IHF are seen. 5. The frontal cortex is continuous across the midline. 6. Well-formed cerebral mantle is seen. 7. Posterior part of the body and the splenium of CC are seen. 8. Single or azygous anterior cerebral artery may be seen.

Semilobar HPE can be diagnosed by TVS in the first trimester (11–14 weeks).

Detection of lobar HPE is difficult before 18 weeks.

3.1  Ultrasound Findings of HPE

67

a

b

Fig. 3.7 (a) 24  weeks (TAS) semilobar holoprosencephaly – axial transventricular and transcerebellar sections – CSP and anterior IHF not seen with frontal cortical mantle continuous from side to side (*), uncleaved poorly formed anterior horns (solid arrow), posterior horns are cleaved (arrowheads), uncleaved thalami (dotted arrow), absent

IHF, uncleaved parietal cortex (**). (b) 24 weeks (TAS, 3D US) semilobar holoprosencephaly – midsagittal section and 3D surface rendering of face – flat facial profile due to arrhinia, median cleft lip, flat nose and proptosis

68

3  Anomalies of Ventral Induction: Holoprosencephaly

a

b

Fig. 3.8 (a) 38 weeks (TAS) semilobar holoprosencephaly – CSP is not seen, anterior horns are uncleaved (solid arrow), posterior horns are cleaved (dotted arrows). (b) 38  weeks (TVS) semilobar holoprosencephaly – coronal, transfrontal, anterior and posterior, transthalamic and transcerebellar sections – uncleaved anterior horns (**), uncleaved superior and inferior frontal cortex (arrowheads), no interhemispheric fissure (IHF) seen in transfrontal section, flat superior margin of uncleaved horns, olfactory sulci are absent, IHF is present in the transthalamic and transcerebellar sections (dotted arrows), the bodies of

l­ ateral ventricles are uncleaved and CC not seen in the anterior transthalamic section, bodies of lateral ventricles are cleaved and the CC is seen in the posterior transthalamic section, posterior horns are cleaved (*). (c) 38 weeks (TVS 3D US) semilobar holoprosencephaly – multiplanar midsagittal and coronal sections – uncleaved anterior horns and body of lateral ventricles (*), anterior segment of the body of CC seen (dotted arrows), rostrum, genu, posterior body and splenium of CC are absent, cingulate sulcus is absent, radiating medial sulci seen (solid arrow), vermis (v). Navigation dot is on CC

3.1  Ultrasound Findings of HPE

69

c

Fig. 3.8 (continued)

Fig. 3.9  23 weeks (TAS) lobar holoprosencephaly – axial transventricular and transcerebellar sections of the cranium, coronal section and 3D surface rendering of face – CSP and anterior IHF not seen, body and posterior

horns are cleaved (solid arrows), posterior IHF (dotted arrow), frontal lobes are uncleaved continuous from side to side(*), anterior IHF not seen, bilateral paramedian cleft lip and cleft of primary palate (arrowheads)

70

Differential Diagnosis 1. Hydrocephalus: Barotraumatic destruction of the septum pellucidum may cause the lateral ventricles to be continuous with each other across the midline. However, the presence of the anterior falx (IHF) and well-formed anterior horns helps rule out lobar HPE. 2. Septal agenesis: The presence of well-formed anterior horns, IHF and normal CC helps to rule out lobar holoprosencephaly and confirm septal agenesis.

3  Anomalies of Ventral Induction: Holoprosencephaly

3.1.4 Middle Hemispheric Variant 1 . The CSP is not seen. 2. The anterior and posterior horns are discrete. The body of lateral ventricles is continuous across the midline (Fig. 3.10a–e). 3. The IHF is absent in the posterior frontal and parietal regions. 4. The parietal cortex is continuous across the midline.

a

Fig. 3.10 (a) 19  weeks (TAS, TVS and 3D US) middle interhemispheric variant – axial transventricular sections TAS and TVS, 3D multiplanar midsagittal section with polyline omniview-derived axial section – uncleaved body (*), dorsal interhemispheric cyst (**), genu of CC (arrowhead), cleaved anterior horns (dotted arrow), cleaved posterior horns (solid arrow). (b) 19 weeks (TVS) middle interhemispheric variant – coronal transfrontal, transcaudate, transthalamic and transcerebellar sections – uncleaved body and posterior region of anterior horns (*), uncleaved thalamus (**), cleaved anterior horns (dotted arrows), cleaved posterior horns (solid arrows), anterior IHF (double arrowheads), posterior frontal and parietal cortex uncleaved with no IHF (single arrowhead), posterior IHF (double small arrowheads). (c) 19  weeks (TVS) middle interhemispheric variant – midsagittal

s­ections without and with color Doppler – uncleaved body (dotted arrow), dorsal interhemispheric cyst (solid arrow), genu of CC (arrowhead), abnormal course of anterior cerebral artery under the calvarium on color Doppler. (d) 19 weeks (TAS and TVS 3D) middle interhemispheric variant – axial section through a plane just caudal and parallel to the transcerebellar section and 3D rendered image with inversion – incomplete circle of Willis (solid arrow), uncleaved body with cleaved anterior and posterior horns on inversion mode. Dorsal interhemispheric cyst is seen in posterior IHF (dotted arrows). (e) 19  weeks (TAS) middle interhemispheric variant – midsagittal, posterior and anterior coronal sections of the fetal face – facial profile (solid arrow), orbits (arrowheads) and upper lip (dotted arrow) are normal

3.1  Ultrasound Findings of HPE

b

c

Fig. 3.10 (continued)

71

72

3  Anomalies of Ventral Induction: Holoprosencephaly

d

e

Fig. 3.10 (continued)

5. The splenium, genu and rostrum of the CC are seen. The body of the CC is absent. 6. The circle of Willis is abnormal.

3.1.5 Common Findings in All Types of HPE 1 . CSP is absent. 2. CC is segmentally absent in the uncleaved regions. 3. IHF is absent in the uncleaved regions. 4. The circle of Willis and course of anterior cerebral artery are abnormal.

3.1.6 Midline Facial Defects in HPE Ninety percent of cases of alobar and semilobar HPE have midline facial defects. The face is therefore normal in the other 10% (Figs. 3.10e and 3.11). The facial defects in lobar HPE are less common and subtle.

The following are the facial defects: 1. Cyclopia: Single midline orbit with single or partially cleaved globes is seen. Presence of a tubular proboscis is seen arising superior to the midline orbit (Fig. 3.13a). 2. Arrhinia: The nose, nasal bones and septum are absent (Figs. 3.2, 3.6c, 3.7b, 3.12a and 3.13a). 3. Hypotelorism: Interorbital distance is less than fifth percentile (Figs. 3.2b and 3.12a). 4. Ethmocephaly: Hypotelorism with a proboscis (tubular appendage) attached to the forehead above the level of the orbits. The nose is absent (Figs. 3.12a and 3.13a). 5. Cebocephaly: Hypotelorism with nose having a single nostril (Fig. 3.5). 6. Median cleft lip may be seen (Figs. 3.2b, 3.6c and 3.7b). 7. Low-set ears may be present.

3.1  Ultrasound Findings of HPE

73

Fig. 3.11  24 weeks (TAS) alobar holoprosencephaly with normal face – axial transventricular section of cranium, midsagittal section of face and axial section of the orbits – primitive monoventricle (*), dorsal sac (**), no abnormality seen in the fetal face

a

Fig. 3.12 (a) 17 weeks (TAS) alobar holoprosencephaly with extracraniofacial anomalies, trisomy 13 – axial transcerebellar, axial section through the orbits, axial section through the proboscis, midsagittal ­section of face, axial section of the abdomen and section through fetal hand – uncleaved thalamus (*), monoventricle (**), bilateral m ­ icrophthalmia

and hypotelorism (arrowheads), proboscis (dotted arrows), hyperechoic kidneys (solid arrows) and polydactyly – trisomy 13 (next figure). (b) 17  weeks alobar holoprosencephaly with extracraniofacial anomalies, trisomy 13 – amniocentesis – three green signals seen in the interphase FISH, three copies of chromosome 13 in the karyotype

74

3  Anomalies of Ventral Induction: Holoprosencephaly

b 1

6

2

19

8

7

13

14 20

3

9

15 21

4

5

10

11

12

16

17

18

22

X

Y

Fig. 3.12 (continued)

a

Fig. 3.13 (a) 23 weeks (TAS and MRI) semilobar holoprosencephaly with extracraniofacial anomalies, trisomy 13 – coronal transfrontal, axial transventricular and transcerebellar sections of the cranium, midsagittal section of face, T2W coronal images of the face – CSP is not seen, anterior horns are uncleaved (*), occipital lobes are cleaved (arrowheads), Dandy-Walker malformation (PCF cyst) (**), cyclopia (dotted arrows), proboscis (solid arrows). Associated anomalies in the following figure. (b) 23  weeks (TAS) semilobar holoprosencephaly

with extracraniofacial anomalies, trisomy 13 – bilateral hyperechoic kidneys (dotted arrows), congenital heart disease (solid arrow) and single umbilical artery (arrowhead). Fetal karyotyping and picture of abortus in the following figure. (c) 23 weeks semilobar holoprosencephaly with extracraniofacial anomalies – fetal blood sampling for karyotyping reveals trisomy 13 (13:14 translocation). Parental karyotyping is indicated. Picture of face of abortus

3.1  Ultrasound Findings of HPE

b

Fig. 3.13 (continued)

75

76

c

3  Anomalies of Ventral Induction: Holoprosencephaly

Trisomy 13 (translocation type)

13 14

t(13;14)

13 46,-14,t(13;14)

pe:46,-14,t(13;14)(qter-cen-qter)

Fig. 3.13 (continued)

3.1.7 Associated Anomalies

Suggested Reading

Associated anomalies are common and include cardiac, skeletal, renal and other defects. When associated anomalies are present, there is a high risk of chromosomal abnormalities (trisomy 13, triploidy, trisomy 18, deletions, duplications and translocations) (Figs. 3.12a, b and 3.13a–c). Nonchromosomal syndromes should also be considered depending on the nature of the associated anomalies. These include SmithLemli-Opitz and Meckel syndromes. Nonsyndromic, autosomal dominant HPE must be considered in cases of recurrence. Incomplete penetrance and variable expression may make clinical detection of the abnormality in the parents difficult. Maternal diabetes increases the risk of HPE.

1. McGahan JP, Nyberg DA, Mack LA.  Sonography of facial features of alobar and semilobar holoprosencephaly. AJR. 1990;154:143–8. 2. Winter TC, Kennedy AM, Woodward PJ. Holoprosencephaly: a survey of the entity, with embryology and fetal imaging. Radiographics. 2015;35:275–90. 3. Simon EM, Hevner RF, Pinter JD, Clegg NJ, Delgado M, Kinsman SL, Hahn JS, Barkovich AJ. The middle interhemispheric variant of holoprosencephaly. AJNR. 2002;23:151–5. 4. Blaas HG, Eriksson AG, Salvesen KA, Isaksen CV, Christensen B, Møllerløkken G, Eik-Nes SH. Brains and faces in holoprosencephaly: pre- and postnatal description of 30 cases. Ultrasound Obstet Gynecol. 2002;19:24–38. 5. Malinger G, Lev D, Kidron D, Heredia F, Hershkovitz R, Lerman-­Sagie T.  Differential diagnosis in fetuses with absent septum pellucidum. Ultrasound Obstet Gynecol. 2005;25:42–9.

4

Malformations of Cortical Development

Human cerebral cortical development is a complex process and occurs in three overlapping stages, namely, neuronal proliferation, migration and organisation. Neuronal proliferation (6–16  weeks gestational age) is the differentiation of stem cells in the periventricular subependymal layer (germinal matrix) into neuroblasts. The neuroblasts migrate outwards along the radial glial scaffolding to reach and populate the future cortex from the innermost layer outwards. This process, termed neuronal migration, results in the formation of the normal six-layered (hexalaminar) cortex. Neuronal migration begins at 6 weeks of gestation and continues postnatally till 5 months of age. Sulcation and gyration are directly related to neuronal migration and serves to maximise the cortical surface area without increasing the brain volume. The phase of neuronal organisation (20 weeks gestational age to postnatal life) involves separation of neurons from the radial glial fibres, dendrite and axonal formation and establishment of synaptic connections. The above processes are regulated by specific genes and complex signalling pathways. Malformation of cortical development may be caused by a genetic abnormality, infection, teratogen or trauma. Knowledge of the genetic basis is essential for prenatal molecular confirmation by invasive testing. Malformations of cortical development (MCD) may be broadly classified as:

The genes that control cortical development may also be involved in the development of other organ systems of the body. Hence associated anomalies in the eyes, hindbrain, face and skeletal system, if detected, may help to make a specific diagnosis. For example, classical lissencephaly with dysmorphic facies, congenital heart disease and polydactyly is indicative of Miller-Dieker syndrome. Mild lateral ventriculomegaly is very often the first finding seen in the US examination done at 18–20 weeks. Sulcation is just about beginning at this stage. Repeat scan at 26 weeks is necessary to recognise sulcatory landmarks as well as to reassess the lateral ventricular size.

4.1

Disorders of Neuronal Proliferation

4.1.1 Microcephaly Impairment of neuronal proliferation (decrease in the number of progenitor cells in the germinal matrix) results in a small-sized brain which is reflected as a small-sized head. The causes are varied and include single gene/syndromic disorders (autosomal dominant/recessive, X-linked recessive forms), chromosomal abnormalities and infections (CMV and toxoplasma). Hydantoin and aminopterin teratogenicity, maternal phenylketonuria and maternal alcohol abuse can cause microcephaly in the fetus. The ultrasound findings are as follows:

Phase of development Neuronal proliferation Neuronal migration

Neuronal organisation

Disorders Microcephaly Megalencephaly Heterotopia Lissencephaly Cobblestone malformation Hemimegalencephaly Polymicrogyria Schizencephaly

A particular MCD may be a combination of any of the disorders mentioned above. An excellent example is the association of periventricular heterotopia with polymicrogyria.

1. Head circumference (HC) of −3SD or lesser at any gestational age is indicative of microcephaly. Progressive growth lag of HC seen on serial monitoring at three to four weekly intervals is confirmatory in cases with borderline HC (Figs. 4.1a, b, 4.2 and 4.3). 2. Primary microcephaly is diagnosed when there are no associated intracranial or extracranial abnormalities. 3. Microcephaly may manifest early or late in pregnancy. In a significant number of cases, the HC may become lesser than the cut-off of −3SD in the third trimester or during the first few years of life (Fig. 4.2).

© Springer Nature Singapore Pte Ltd. 2019 B. S. Rama Murthy, Imaging of Fetal Brain and Spine, https://doi.org/10.1007/978-981-13-5844-9_4

77

78

4  Malformations of Cortical Development

a

Fig. 4.1 (a) 23 weeks (TAS) microcephaly – axial transventricular and oblique sections of cranium, axial section of orbits and head circumference growth curve – thin cerebral parenchyma with no sulcation (**), increased subarachnoid space (dotted arrows), bilateral periventricular calcification (solid arrows), bilateral cataract (arrowheads), HC less than −3SD.  Maternal serology is positive for CMV. (b) 23  weeks (TAS)

microcephaly – midsagittal section of face (profile), 3D surface rendering of the head and face, lateral and oblique rotational views, right upper limb and both lower limbs – receding forehead is seen in facial 2D and 3D views, right clenched fist (arrowhead), flexion contracture of right elbow (solid arrow) (right fist not seen due to flexion contracture of the wrist) and adduction contractures of both hips (dotted arrows)

4.1 Disorders of Neuronal Proliferation

b

Fig. 4.1 (continued)

79

80

4  Malformations of Cortical Development

Fig. 4.2  31 weeks (TAS) microcephaly – axial transventricular sections – inability to visualise the intracranial structures, growth curves demonstrate HC less than –3SD

4.1 Disorders of Neuronal Proliferation

81

Fig. 4.3  25 weeks (TAS) severe microcephaly – transverse section of cranium, axial orbital section, midsagittal facial profile section – inability to visualise intracranial structures, relatively large orbits (arrowheads),

severely receding forehead (solid arrow), extreme lag of biparietal diameter and head circumference

4. Receding forehead (due to frontal lobe hypoplasia) is seen in the midsagittal section of the face (Fig. 4.1a, b). 5. The intracranium may be difficult to visualise due to poor acoustic window as the calvarial sutures are narrow (Fig. 4.3). 6. Increased subarachnoid space, lissencephaly, holoprosencephaly, periventricular heterotopia, polymicrogyria,

hydrocephaly, callosal abnormalities and infection sequelae (Fig. 4.1a, b) may be seen. Counselling by a geneticist with fetal karyotyping/chromosomal microarray, infection screening and possible molecular testing should be considered.

82

4  Malformations of Cortical Development

Fig. 4.4  33 weeks (TAS) macrocephaly – axial transthalamic section – more than 98th percentile head circumference with normal intracranial findings

4.1.2 Macrocephaly Rapid cell proliferation or decreased cell apoptosis results in an increase in the number of the neurons produced. This results in a large brain and large cranium.

7. Serial monitoring of HC at four weekly intervals should be planned in cases where there is a suspicion (borderline HC). 8. Majority of fetuses with macrocephaly with normal intracranial findings do well postnatally.

The ultrasound findings are as follows:

4.2

Disorders of Neuronal Migration

1 . HC is more than 98th percentile (Fig. 4.4). 2. Hydrocephalus, intracranial tumors, subdural bleed and malformations of cortical development should be excluded. 3. Most cases present in the third trimester with HC being normal in the second trimester. 4. Increased subarachnoid space is a feature of benign familial macrocephaly. Family history of a large head should be sought for as benign familial macrocephaly is inherited as an autosomal dominant or recessive trait. 5. Rarely macrocephaly could be part of a syndrome such as Sotos syndrome or skeletal dysplasia like achondroplasia and thanatophoric dysplasia. 6. As diagnosis is usually made in the third trimester, a thorough examination of the intracranium is often not possible by ultrasonography. In these instances, fetal MRI may help to assess the intracranium better.

Disorders of neuronal migration are mostly due to genetic etiology. The causative gene mutation results in defective initiation or migration or arrest which manifests as periventricular heterotopia or classical lissencephaly or cobblestone malformation, respectively (Fig. 4.5). Lissencephaly is a lack of or poor sulcation and gyration resulting in a smooth brain. The genetic abnormality that causes lissencephaly may also result in abnormalities in the corpus callosum and cerebellum. Detailed neurosonography is indicated when a neuronal migration disorder is suspected. Suspicion may be aroused by any of the following: 1. Family history 2. Finding or findings on basic US examination: (a) Mild lateral ventriculomegaly (b) CSP abnormalities

4.2 Disorders of Neuronal Migration

Disorder of Initiation Periventricular nodular heterotopia

83

Disorder of migration Classical lissencephaly

Disorder of arrest Cobblestone malformation

Fig. 4.5  Schematic diagram of the pathogenesis of malformation of neuronal migration. Periventricular zone (yellow line), nodular heterotopia (red dots), band heterotopia (red band), pia mater (green line)

(c) Irregular ventricular wall (d) Thin cerebral mantle (e) Microcephaly or macrocephaly

normally by 26 weeks. Hence, delay or failure of these sulcatory events can only be recognised at 26 weeks or later. The ultrasound findings are as follows:

Fetal MRI may supplement the findings seen on detailed neurosonogram.

4.2.1 Classical Lissencephaly In classical lissencephaly (type I lissencephaly), the radial migration is defective, and neurons fail to reach the cortical surface. This results in poor or absent sulcation and gyration. LIS1 gene mutation (autosomal dominant) is the commonest mutation causing classical lissencephaly. Deletion of genes in the region (17p13.3) contiguous with the LIS1 gene mutation results in Miller-Dieker syndrome which is classical lissencephaly with facial dysmorphism. LIS1 gene mutations are of de novo origin in most cases. DCX gene mutation (X-linked dominant) results in full-blown classical lissencephaly in the male and milder disease in the female (subcortical band heterotopia or double cortex). ARX mutation (X-linked dominant) results in classical lissencephaly with genital ambiguity. RELN mutation (autosomal recessive) causes classical lissencephaly with cerebellar hypoplasia. A working knowledge of these genetic abnormalities helps to look for associated anomalies and recognising patterns. Molecular testing can be tailored on a case-to-case basis. The anatomic abnormalities can only be detected at or after a gestational age when a particular sulcatory landmark should be seen. For example, acute angle shape of the lateral fissure and appearance of cerebral convexity sulci are seen

1. Figure of eight or hourglass configuration of the brain on axial sections due to its small size (micrencephaly) and absent operculation of the lateral fissure (Fig. 4.12a, b). 2. Delayed (shallow for gestational age) or absent sulcation is detected by a systematic study of the medial hemispheric sulci (parieto-occipital, calcarine and cingulate), lateral fissure and convexity sulci (central, pre- and postcentral and temporal) (Figs. 4.6a–d, 4.7a, b and 4.8a, b). Widely spaced shallow sulci and broad gyri are termed pachygyria. 3. Mild lateral ventriculomegaly and abnormal shape of the lateral ventricle may be seen particularly on coronal sections (Figs. 4.6a–d and 4.7a, b). 4. Complete or partial callosal agenesis and callosal hypoplasia may be present and can be detected on the midsagittal section (Figs. 4.9a, b and 4.10a, b). 5. Associated cerebellar hypoplasia (Fig.  4.11a, b) and ambiguous genitalia help in suspecting RELN and ARX gene mutations, respectively. 6. X-linked genetic basis should be considered if the condition is recurrent and the fetal sex is male. 7. In Miller-Dieker syndrome, in addition to the classical lissencephaly, there could be facial dysmorphism (frontal bossing, hypertelorism, small upturned nose, protuberant arched upper lip, small jaw), IUGR, polyhydramnios, congenital heart defects, polydactyly and cryptorchidism (Fig. 4.12a, b). FISH testing for the 17p13.3 microdeletion on the amniotic fluid is diagnostic of the condition.

84

8. Tubulin genes encode tubulin proteins which are fundamental components of microtubules. Microtubules participate in intracellular transport, cell division, and neuronal migration. The tubulin genes include TUBA1A, TUBA8, TUB2B, TUBB3, TUBBS and TUBG1. Mutations in the tubulin genes result in a spectrum of abnormalities termed ‘tubulin-

4  Malformations of Cortical Development

opathies’. These disorders manifest as combinations of cortical defect (lissencephaly, microlissencephaly or polymicrogyria), subcortical defect (CACC, PACC or callosal dysgenesis) and cerebellar or brain stem hypoplasia. Fetal MRI can confirm US findings.

a

Fig. 4.6 (a) 26 weeks (TAS and MRI) classical lissencephaly – axial transventricular and transcerebellar US and T2W sections – mild left lateral ventriculomegaly (*), atrial diameter of 11 mm, obtuse-angled lateral fissure (solid arrows), parieto-occipital sulcus (dotted arrows) and cingulate sulcus (arrowheads) are wider than taller indicating lag in development. (b) 26 weeks (TAS and MRI) classical lissencephaly – coronal transfrontal, transcaudate and transthalamic US and T2W

s­ ections – obtuse-angled shape of lateral fissure (solid arrows), abnormal shape of lateral ventricles (dotted arrows). (c) 26 weeks (TAS and MRI) classical lissencephaly – left and right parasagittal US and T2W sections – mild left lateral ventriculomegaly (*), convexity sulci absent (solid arrows), abnormal shape of left posterior horn (dotted arrows). (d) 26 weeks (TAS and MRI) classical lissencephaly – midsagittal US and T2W sections – corpus callosum is normal (solid arrows)

4.2 Disorders of Neuronal Migration

b

Fig. 4.6 (continued)

85

86

c

d

Fig. 4.6 (continued)

4  Malformations of Cortical Development

4.2 Disorders of Neuronal Migration

87

a

Fig. 4.7 (a) 25 and 27  weeks (TAS) classical lissencephaly – axial transventricular and transcerebellar sections, coronal transcaudate and transcerebellar sections and midsagittal section – lateral ventricles are normal, CSP is wide (solid arrows), parieto-occipital (dotted arrow) and calcarine (arrowhead) sulci are shallow indentations, lateral fissure is shallow and obtuse angled in shape (double arrowheads), corpus callosum is normal (*). (b) 25 and 27 weeks (TAS and MRI) classical lissencephaly – axial transventricular and transcerebellar sections, coronal transcaudate and transcerebellar sections and parasagittal section – lateral ventricles are normal, CSP appears wide (*), no progress in the development of parieto-occipital sulci (dotted arrows)

and calcarine sulci (single arrowhead), lateral fissure continues to be shallow and obtuse angled (double arrowheads), convexity sulci have not appeared (solid arrow). No progress in sulcation when compared to the 25  weeks study. (c) 25 and 27  weeks (TAS and MRI) classical lissencephaly – axial transventricular, coronal transcaudate and parasagittal T2W sections – lateral ventricles are normal, CSP appears wide (*), parieto-occipital sulci (dotted arrow) are barely visualised, lateral fissure is shallow and obtuse angled (double arrowheads), cerebral convexity sulci have not appeared (solid arrow). US findings are confirmed by MRI.  Note that the MRI was planned at 27  weeks rather than 25 weeks

88

4  Malformations of Cortical Development

b

c

Fig. 4.7 (continued)

4.2 Disorders of Neuronal Migration

89

a

Fig. 4.8 (a) 28 weeks (TAS and MRI) classical lissencephaly due to LIS1 (PAFAH1B1) gene mutation – axial transventricular and transcerebellar and coronal transcaudate US and T2W sections – lateral ventricles are normal, CSP appears narrow (arrowheads), parieto-occipital (solid arrow) and calcarine (dotted arrow) sulci are barely visualised, lateral fissure (double arrowheads) is shallow and obtuse angled.

Amniocentesis and clinical exome sequencing were done. (b) 28 weeks (TAS and MRI) classical lissencephaly due to LIS1 (PAFAH1B1) autosomal dominant gene mutation – mid- and parasagittal US and T2W MR sections – CC is normal (solid arrow), cerebral convexity sulci are not seen (dotted arrow), cingulate sulcus is not seen. The genetic report is shown

90

b

Fig. 4.8 (continued)

4  Malformations of Cortical Development

4.2 Disorders of Neuronal Migration

91

a

b

Fig. 4.9 (a) 27 weeks (TAS and TVS) classical lissencephaly with complete agenesis of corpus callosum – axial transventricular and slightly superior sections – mild bilateral lateral ventriculomegaly (**), laterally placed pinched anterior horns (arrowheads), wide IHF (*), shallow right angle-shaped lateral fissure (double arrowhead), parieto-­occipital sulcus not seen (dotted arrow), cingulate sulcus not seen (solid arrow). Note CSP is not seen. (b) 27 weeks (TAS and TVS 3D multiplanar) classical

lissencephaly with complete agenesis of corpus callosum – coronal transthalamic and transcerebellar sections, midsagittal and parasagittal sections – mild bilateral lateral ventriculomegaly (**), laterally placed ‘steerhorn’-shaped anterior horns (arrowheads), wide IHF (*), shallow right angle-shaped lateral fissure (double arrowhead), cingulate sulcus not seen (solid arrow), corpus callosum is absent, vermis (V) well seen, increased subarachnoid space (dotted arrow)

92

4  Malformations of Cortical Development

a

Fig. 4.10 (a) 25  weeks (TAS and MRI) lissencephaly with partial agenesis of corpus callosum, dilated cystic fourth ventricle, sinus pericranii and persistent primitive falcine vein – transventricular and midsagittal US and T2W sections – shallow parieto-occipital sulcus (arrowheads) and obtuse-angled lateral fissure (dotted arrows), splenium of CC is absent, posterior limit of CC (solid arrow) does not overlie the tectal plate, dilated fourth ventricle (*), the vermis is posteriorly displaced (V), its size is normal (cephalocaudal dimension of 1.3 cm

and AP dimension of 0.8 mm). (b) 25 weeks (TAS and MRI) lissencephaly with partial agenesis of corpus callosum, dilated cystic fourth ventricle, sinus pericranii and persistent primitive falcine vein – slightly off-centre midsagittal sections B mode and color Doppler, T2W midsagittal section with magnification – small scalp cystic lesion overlying the posterior fontanelle is the sinus pericranii (solid arrows), persistent primitive falcine vein (dotted arrows) extending to the sinus pericranii

4.2 Disorders of Neuronal Migration

b

Fig. 4.10 (continued)

93

94

4  Malformations of Cortical Development

a

Fig. 4.11 (a) 26  weeks (TAS and MRI) classical lissencephaly with cerebellar hypoplasia – axial transventricular and transcerebellar sections, right and left hands – prominent subarachnoid space (*), shallow obtuse angle-shaped lateral fissure (arrowhead), parieto-occipital sulcus is barely seen (dotted arrow), cerebellar hypoplasia (TCD