Ultrasound Obstet Gynecol 2014; 44: 581–587 Published online in Wiley Online Library (wileyonlinelibrary.com). DOI: 10.1002/uog.13312 Assessment of fetal midbrain and hindbrain in mid-sagittal cranial plane by three-dimensional multiplanar sonography. Part 2: application of nomograms to fetuses with posterior fossa malformations Z. LEIBOVITZ*†, C. SHKOLNIK‡, K. KRAJDEN HARATZ*, G. MALINGER§, I. SHAPIRO† and T. LERMAN-SAGIE*¶ *Unit of Fetal Neurology and Prenatal Diagnosis, Department of Obstetrics and Gynecology, Wolfson Medical Center, Holon, Israel, affiliated with the Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel; †Department of Obstetrics and Gynecology, Bnai Zion Medical Center, Haifa, Israel; ‡Carmel Medical Center, Haifa, Israel; §Ob-Gyn Ultrasound Unit, Lis Maternity Hospital, Tel Aviv Sourasky Medical Center and Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel; ¶Pediatric Neurology Unit, Wolfson Medical Center, Holon, affiliated with the Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel KEYWORDS: 3D ultrasound; CNS malformations; hindbrain; midbrain; nomogram; pons; posterior fossa malformations; vermis ABSTRACT those with isolated enlarged posterior fossa cerebrospinal fluid spaces. Use of the nomograms enabled detection Objectives To apply fetal midbrain (MB) and hindbrain of an elongated tectum in fetuses with CMC, C-II and (HB) nomograms, developed using three-dimensional RES, and a flattened pontine belly in cases of CMC, PCH multiplanar sonographic reconstruction (3D-MPR) in the and VD. In the fetuses with VD, the nomograms enabled mid-sagittal cranial plane, to fetuses with known posterior division into three distinctive groups: (1) those with small fossa malformations. SIVD and APVD, (2) those with normal SIVD but small Methods In this retrospective study we examined sono- APVD, and (3) those with small SIVD but normal APVD. graphic volumes obtained by sagittal acquisition in 43 Conclusions Application of our new reference data, that fetuses diagnosed with posterior fossa abnormalities for the first time include the MB, enables accurate and evaluated in the mid-sagittal cranial plane, using diagnosis of brain malformations affecting the MB 3D-MPR, the following: MB parameters tectal length (TL) and HB and makes possible novel characterization of and anteroposterior midbrain diameter (APMD), and previously described features of posterior fossa anomalies. HB parameters anteroposterior pons diameter (APPD), Copyright © 2014 ISUOG. Published by John Wiley & superoinferior vermian diameter (SIVD) and anteropos- Sons Ltd. terior vermian diameter (APVD). Fetuses were grouped, according to malformation, into eight categories: cob- blestone malformation complex (CMC, n = 3), Chiari-II INTRODUCTION malformation (C-II, n = 7), pontocerebellar hypopla- sia (PCH, n = 2), rhombencephalosynapsis (RES, n = 4), Recent studies in neuroembryology, molecular genetics Dandy–Walker malformation (n = 8), vermian dysgen- and central nervous system (CNS) imaging have improved = = our understanding of disorders affecting development esis (VD, n 7), persistent Blake’s pouch cyst (n 6) 1 and megacisterna magna (n = 6).Ineachcaseandfor of the midbrain (MB) and hindbrain (HB) .The each subgroup, the MB-HB biometric parameters and mechanisms most investigated relate to anomalies of MB-HB formation and include abnormal anteroposterior their z-scores were evaluated with reference to our new 2 nomograms. mesencephalic-rhombencephalic patterning , disorders of the Reelin signaling pathway3, defective pial limiting Results The new MB-HB nomograms were able to membrane4 and disorders of the primary cilia5.MB identify the brainstem and vermian anomalies and and HB malformations are seldom isolated, frequently differentiate fetuses with MB-HB malformations from being associated with cerebral malformations6.Anew Correspondence to: Dr Z. Leibovitz, Department of Obstetrics and Gynecology, Wolfson Medical Center, 62 Halohamim Street, POB 5, Holon 58100, Israel (e-mail: [email protected]; [email protected]) Accepted: 9 January 2014 Copyright © 2014 ISUOG. Published by John Wiley & Sons Ltd. ORIGINAL PAPER 582 Leibovitz et al. classification system has been proposed, based upon continuous configuration of the folia. DWM was defined embryology, genetics and neuroimaging7.Itisof by cystic dilatation of the fourth ventricle confluent with the utmost importance to diagnose accurately these an enlarged cisterna magna, elevation of the tentorium abnormalities, in order to give adequate counseling to the and a small dysplastic vermis. Regarding VD (previously parents. Using established nomograms of posterior fossa called Dandy–Walker variant), this term was used rather structures can facilitate the diagnosis. Many authors have than ‘vermian hypoplasia’ or ‘partial agenesis’ because, proposed nomograms for assessment of the fetal pons and even though the vermis was small, rotated slightly vermis8–11. However, despite the increased recognition upward and associated with a mid-sagittal connection of MB involvement in posterior fossa anomalies, until between the fourth ventricle and the cisterna magna, now there have been no reference data on the normal there was always both abnormal vermian lobulation and development of the mesencephalic structures in utero. fastigial shape; the tentorium was normally positioned. Inthefirstpartofthisstudy12, we established nomo- PBPC was defined as a cystic, thin-walled structure grams for assessment of the fetal MB and HB by protruding from the fourth ventricle and causing rotation three-dimensional multiplanar sonographic reconstruc- of a normal vermis without tentorial elevation or tion (3D-MPR) in the mid-sagittal cranial plane. In this distension of the cisterna magna. MCM was defined as second part of the study, we applied the nomograms to a symmetrically enlarged cisterna magna (anteroposterior fetuses with posterior fossa malformations in order to diameter >10 mm, normal cerebellum and brainstem and evaluate their accuracy, their ability to diagnose malfor- absence of vermian rotation and tentorial elevation). mations and their ability to differentiate between overt Using the 3D acquisitions retrieved from our archives, pathology and anomalies with more favorable outcome. we evaluated MB and HB measurements in the mid-sagittal cranial plane by 3D-MPR using 4D View software (GE Healthcare), as described in detail in Part 1 METHODS of the study12. MB measurements included: tectal length This research was conducted as a retrospective study and (TL) and anteroposterior midbrain diameter (APMD). HB was approved by the Institutional Review Board. Fetuses measurements included: anteroposterior pons diameter with known posterior fossa abnormalities were studied (APPD), superoinferior vermian diameter (SIVD) and with reference to our new MB-HB nomograms developed anteroposterior vermian diameter (APVD). These MB-HB by 3D-MPR12. biometric parameters and their z-scores were evaluated in Imaging data of the fetuses with CNS malformations each of the cases and in each subgroup, relative to our affecting posterior fossa anatomy were retrieved from our newly developed prenatal nomograms12. digital sonographic archives from the period 2007–2013. The imaging work-up of the studied subgroups was All examinations were performed using a Voluson E8, based on the fetal sonographic assessment of supratentor- Voluson 730 Expert or Voluson 730 Pro (GE Healthcare ial anatomy, cerebellar hemispheres, vermis, brainstem Ultrasound, Milwaukee, WI, USA) ultrasound machine, and posterior fossa fluid spaces, two-dimensional ultra- using a transvaginal probe for vertex presentation and sound measurements of the HB structures, relative to pre- 8–11 a transabdominal one for non-vertex presentation. Cases viously published nomograms , and prenatal magnetic with 3D cranial volumes acquired sagittally were selected resonance imaging (MRI). As a rule, prenatal diagnosis and grouped, according to malformation, into eight cat- was confirmed either by autopsy results or by postnatal egories: cobblestone malformation complex (CMC), for- examination. In two fetuses with RES and in one with merly known as lissencephaly type II, Chiari-II malforma- VD, no postmortem or postnatal studies were performed, tion (C-II), pontocerebellar hypoplasia (PCH), rhomben- but all three had typical prenatal sonographic and MRI cephalosynapsis (RES), Dandy–Walker malformation findings suggestive of their diagnoses. (DWM), vermian dysgenesis (VD), persistent Blake’s pouch cyst (PBPC) and megacisterna magna (MCM). RESULTS CMC was defined by the absence or under-development of cortical sulcation relative to gestational age, associated We identified 43 fetuses diagnosed with CNS malforma- with ventriculomegaly and one or more of the following tions affecting MB and HB anatomy: three with CMC, associated anomalies: ocular dysplasia, encephalocele, sevenwithC-II,twowithPCH,fourwithRES,eightwith corpus callosal dysgenesis and MB-HB anomalies, DWM, seven with VD, six with PBPC and six with MCM. including a small brainstem with a kink in the Mean z-scores of MB and HB measurements are presented mid-pons, small cerebellar hemispheres and vermis, in Table 1. The distribution of the studied parameters in and a dysmorphic tectum. C-II was defined by the affected fetuses is shown relative to the reference graphs12 presence of an open spina bifida associated with collapse in Figures S1–S5. of the posterior fossa cerebrospinal fluid spaces and Application