Background : Posterior fossa anomalies (PFAs) are considered one of the commonest brain anomalies identified by the fetal imaging techniques. The current study aims to estimate the significance of cerebellar vermis assessment by fetal MRI in fetal brain malformations. Patients and Methods: The study was conducted at a tertiary University hospital in Upper Egypt. Data were gathered prospectively from sixty pregnant women with sonographically diagnosed fetal brain malformations referred for Magnetic Resonance Imaging (MRI) between April 2015 and May 2019 followed by postpartum neonatal MRI brain examination for non-terminated and live birth cases. Results: Of the sixty fetuses with brain malformations, additional cerebellar vermis findings were seen on MRI in 10 cases (16.6%). Fetal MRI sensitivity, specificity, positive and negative predictive values were 100% that were in correlation with those of prenatal ultrasound turned out to be significantly higher. Conclusion: This study recommends fetal MRI for cerebellar vermis assessment in fetal brain malformations to guide the clinical management.
Posterior fossa anomalies (PFAs) are considered one of the commonest brain anomalies identified by the fetal imaging techniques [
Fetal MRI has been shown to be a useful adjunct to ultrasound in suspected fetal anatomic abnormalities and especially used for fetal brain imaging [
The superiority of MRI to prenatal ultrasound in posterior fossa anomalies is owing to evaluation of different structures in the posterior fossa, where it determines vermian dysplasia or aplasia, the shape of the fourth ventricle, the insertion of the tentorium cerebella and if cerebellar compression presents [
The cerebellar vermis per se starts development as a thickening of the alar plate of the rhombencephalon during the fifth week of gestation [
The aim of the work to put the spotlight upon the impact of cerebellar vermis assessment by fetal MRI upon management in fetal brain malformations.
This prospective study was approved by the ethics committee of our institution during the period between April 2015 and May 2019. The study was conducted at a tertiary University hospital in Upper Egypt and included 60 pregnant women with their age ranging from 18 to 45 years & of gestational age ranging from 20 to 32 weeks. We performed fetal MRI to sonographically diagnosed fetal posterior fossa anomalies followed by postnatal MRI brain to 25% of our 60 cases, who weren’t terminated & were live birth.
All the patients were subjected to: -
1) Thorough history taking.
2) Family history.
3) Basic obstetric Sonography examination.
4) Detailed sonographic fetal CNS anomaly scan including 3D & 4D ultrasound.
5) Fetal MRI brain.
6) Postnatal MRI brain to cases who were weren’t terminated and were live birth.
Inclusion criteria
Sonographically diagnosed fetal brain malformations.
Exclusion criteria
· MRI contraindication (as cardiac pace maker)
· Mother’s refusal to do fetal MRI.
U/S technique:
As for the sonographic examination, it was done in supine position with her head slightly raised; using (Voluson E, Toshiba, Japan) with trans-abdominal transducer of a bandwidth 3.5 MHz associated with color Doppler added property. First Basic obstetric sonographic examination will be done, followed by a detailed (2D/3D) fetal CNS anomaly scan with detection of other anomalies associated.
MRI technique:
MRI examination was performed on 1.5-Tesla MR scanner (Ingenia 1.5 Tesla, Philips, Netherland) using a multi-channel phased array coil to allow increased coverage of the fetal head and increased signal-to-noise ratio. The mother was made to lie supine or on her left side (if more comfortable) during the exam. In order to minimize fetal motion, the mother was made as comfortable as possible & she fasted 4 hours prior to the MR exam. Because maternal or fetal sedation was not used, most fetal MRI was primarily performed using ultrafast T2-W sequences known as single-shot rapid acquisition with refocused echoes (i.e. single-shot fast spin-echo or half-Fourier acquired single-shot turbo spin-echo). Using these techniques, a single T2-W image was acquired in less than 1 s, decreasing sensitivity to fetal motion with total scanning time about 4 - 5 minutes.
Typically, an initial localizer was obtained in three orthogonal planes with respect to the mother, using 6- to 8-mm thick slices with a 1- to 2-mm gap and a large field of view. TR 1500 ms; TE 151 ms; slice thickness 4 mm; FOV 260 Å - 350 mm; matrix 192 Å - 256;
Image interpretation parameters:
· The vermis should cover the 4th ventricle by 18 - 19 weeks gestation, but initially may be slightly smaller inferiorly.
· Vermian anomalies were defined when measurements were abnormal based on standardized measurements described by Garel et al. (2004) and Robinson et al., 2007.
o The craniocaudal diameter was calculated on basis of the equation diameter (mm) = 0.74 × gestational age (weeks) – 6.11 as described by Robinson et al., 2007.
o While the tegmento-vermian angle was considered abnormal if >6˚ - 9˚ as was stated by Robinson et al., 2007.
· Foliation of the vermis was evaluated and was noted to be normal for gestational age with the exception of those identified with DWMs and rhomben-cyphalo-synapsis cases.
· Our cases were diagnosed on that basis as follows:
o DWM was diagnosed if complete agenesis of vermis.
o DW variant was diagnosed if partial agenesis of vermis.
o Chiari II &III malformations were diagnosed if cerebellar vermis is noted as a portion of downwards cerebellar herniation through the spinal canal.
ü Rhombencyphalosynapsis was diagnosed if absent vermis with the cerebellar hemispheres closely opposed to each other, with transversely oriented inferior cerebellar folia and rounded shaped fourth ventricle.
Statistical analysis
Statistic Package for Social Sciences (SPSS v 17.0 for Windows, Chicago, IL) software was used for data analysis. Statistical significance was assessed using the chi square χ2 test as all data are expressed as nominal. Significance was interpreted as p < 0.05.
Sixty pregnant females were enrolled in our study with their age ranging from 18 to 45 years of mean value about 27.5 ± 8.3 years. In addition our results revealed that about 80% of our pregnant females were above 35 years old which was statistically significant (p = 0.041) (
Regarding the gestational age (GA) of the involved fetuses, it ranged from 20 to 32 weeks with mean value of 26 ± 4.5 weeks. Fetal MRI additional abnormalities (about 16.6%) & changing diagnosis (8.3%) were more pronounced after 24 weeks GA (
Maternal Age | Minimum to maximum | Range | Percent | P-value |
---|---|---|---|---|
>35 years <35 years | 18 - 45 years | 27.5 ± 8.3 | 80% 20% | 0.041 |
Gestational age | MRI over US | P-value | ||||
---|---|---|---|---|---|---|
Minimum to maximum | Range | Add | Change diagnosis | Confirm | ||
20 to 32 weeks | 26 ± 4.5 weeks | >24 weeks <24 weeks | 10 (16.6%) 0 | 5 (8.3%) 0 | 18 (30%) 27 (45%) | 0.016 |
Vermian malformation | Total number by U/S | Total number by fetal MRI | Isolated PFAs | Associations | ||
---|---|---|---|---|---|---|
Isolated vermian malformation | Associated brain stem malformations (hypoplasia, or aquiductal stenosis) | Associated cerebral anomalies. (C.C dysgenesis, lissencephaly, VM, IH cyst, encephalocele) | Associated extra-cranial anomalies (spinaldysraphism with meningocele, renal dysplasia, HSM. Post urethral valve, imperforate anus with limb anomalies) | |||
Number | 12 | 24 | 4 | 3 | 10 | 7 |
Percent from total cases | 20% | 40% | 6.7% | 5% | 16.6% | 11.6% |
Sonographic diagnosis | Number | Fetal MRI Cerebellar additional findings or changed diagnosis | Management based on US diagnosis. | Management based on fetal MRI diagnosis. | Postnatal MRI for live-birth non-terminated cases |
---|---|---|---|---|---|
Post F malformations | |||||
Small retrocerebellar cyst | 1 | Partial vermian agenesis…DW variant | Follow up | Termination if not precious | As fetal MRI |
Mega cisterna magna | 1 | Global cerebellar and vermian hypoplasia | Follow up | Termination if not precious | As fetal MRI |
Chiari malformation | 7 | · Degree of cerebellar herniation including the vermis · Demonstrate of exact site of encephalocele in ChiariIII. · Cerebral associations as corpus callosaldysgenesis · Demonstration of exact site, size and content of meningocele for proper prenatal or postnatal surgery. | Termination on confirmation | · Termination if not precious baby, · If precious baby; fetal MRI additional findings will aid in managmenet especially in prenatal surgery. | As fetal MRI |
DW malformation | 6 | Ø Confirmed vermian agenesis Ø Corpus callosaldysgenesis | Termination | Termination if was diagnosed earlier and if not precious. | As fetal MRI |
Cortical malformation | |||||
Lissencephaly with VM and cleft lip | 1 | Rhomboncephalosynapsis with C.C dysgenesis and z-shaped brain stem…… Walker-Warburg syndrome (WWS) or HARDE syndrome (AR) | Termination if not precious | Lethal form of congenital muscular dystrophy so Termination | ……….. |
Exencephaly | |||||
Hydranencephaly | 1 | Pontocerebellar dysplasia…. Fowler syndrome (AR) | Termination only | Termination with Genetic counseling which confirmed the diagnosis. | ----------- |
Midline anomalies | |||||
Interhemispheric cyst versus schizencephaly | 3 | Cerebellar and vermian compression by the cyst …. confirmed inter-hemispheric cyst. | Needs confirmation as … Follow up if cyst versus termination if schizencephaly | Follow up | As fetal MRI |
Sensitivity | Specificity | PPV | NPV | |
---|---|---|---|---|
Ultrasound | 60% | 86% | 84.5% | 54% |
Fetal MRI | 100% | 100% | 100% | 100% |
Lastly,
Despite the rapid progress in fetal imaging, the prenatal diagnosis of posterior fossa dysgenesis remains challenging due to both false-positive and false-negative diagnoses [
When an intracranial abnormality is detected on US specifically within the posterior fossa, a fetal MRI is the next investigation of choice. MRI assessment of the cerebellum and the vermis is based on morphological and biometrical data [
The maternal age in our study was of significance; where 80% of our patients were older than 34 years old which denoted that advanced maternal age is directly proportional to increased risk of congenital anomalies including CNS anomalies. That was equivalent to the study conducted by Hollier et al., 2000 [
Regarding our cases, Cerebellar vermian malformations accounted for one of the most common brain malformations, where they accounted for about 40% of the fetal brain anomalies based on fetal MRI diagnosis in our study. This result was in rapprochement to the study addressed by Llorens Salvador et al., 2017 [
Fetal MRI additional findings were more pronounced after 24 weeks GA which was in coherence with and based on what was postulated by ACR, 2010 [
The Vermian malformations in our study were nearly categorized on basis of fetal MRI according to their associations, either as a part of isolated posterior fossa malformations which was further classified into isolated vermian dysgenesis or associated with brain stem abnormalities as pontine hypoplasia or aquiductal stenosis ((which accounted for 6.7% and 5% of cases respectively). The second category was those associated with cerebral malformations as VM, corpus callosal dysgenesis, lissencephaly, periventricular heterotopia or interhemipheric cyst (accounting for about 16.6% of total cases). Then the third category was those with associated extra-cranial malformations as spinal dysraphism, renal dysplasia, posterior urethral valve, imperforate anus or limb anomalies (about 11.6% of total cases). This categorization is crucial;for it has a great influence upon the neurodevelopmental outcome of the fetuses as formerly proved by other studies as that of Patek et al., 2012 [
Similar to previous studies, our results revealed that accurate depiction of vermis proved to be better by fetal MRI rather than prenatal ultrasound, where fetal MRI added cerebellar findings in 10 cases out of 60 (16.6%), while it changed diagnosis of prenatal ultrasound in 4 cases out of 60 (8.3.%) and confirmed the diagnosis of 75% of the cases. The study of Amaresh Indravadan et al., 2012 [
The results in our study has proven that reliable and proper assessment of vermis in fetal brain malformations tremendously impact the management of the cases; where some cases were misinterpreted by US as being retro-cerebellar cyst or mega cisterna magna, and proved by fetal and postnatal MRI to be partial vermian agenesis or vermian hypoplasia (Dandy Walker variant), that changed the management from just follow up to termination if not precious baby as this will impact the baby’s neurodevelopmental outcome. So we can safely say that fetal MRI can be used for differentiating variable conditions in the retro-cerebellar space with subsequent different management of each. That was in agreement with what was reported by Limperopoulos et al., 2006 [
Like-wise, we figured out that Fetal MRI vermian and cerebellar assessment; turned out to be also helpful in differentiating two supratentorial entities as well; the postero-inferiorly located open lip schizencephaly and interhemispheric cyst, where the latter performs compression upon the surrounding brain structures including the cerebellum and vermis if located postero-inferior; unlike the open lip schizencephaly which is evident in terms of fetal MRI.
Regarding Chiari malformations, in addition to confirming the diagnosis, Fetal MRI determine the degree of cerebellar herniation, the size, site and content of the meningocele and the exact site and size of the encephalocele if Chiari III. Moreover, it determines if there are cerebral structural associations as corpus callosal dysgenesis. All these information aid in the management of the fetuses especially nowdays with the ongoing advances in the prenatal surgery of spina bifida which definitely improve the hind brain herniation. That was in accordance to what was stated in the study of NielsGeerdink., et al. [
In addition to aiding in management and prediction of the neurodevelopmental outcome, we also noted that fetal MRI additional abnormalities regarding the cerebellar vermis give a clue about the possibility of recurrence & the need for genetic testing in the diagnosed fetal brain malformations. An example for these two cases in our study which were formerly diagnosed by US as hydranencephaly and lissencephaly; On the other hand fetal MRI cerebellar and vermian additional findings rendered the diagnoses as Fowler and Walker Warburg (HARDE) syndrome respectively; which were proved to be autosomal recessive syndromes with the imminent need for genetic testing. That was in agreement with what was postulated by TejaswiKandula et al., 2015 [
We have performed confirmatory postnatal MRI for cases which were not terminated & were live birth (about 25%) which revealed almost the same fetal MRI findings with almost nil additional findings. That rendered the fetal MRI sensitivity & specificity in assessment of vermian abnormalities far beyond that of ultrasound with high MRI positive & negative predictive value nearly about 100%, coping with the study conducted by Trompoukis et al., 2012 [
Regarding the similarity in the results between the fetal MRI and the postnatal MRI; we came to a conclusion in our study that no demanding need for performing postnatal MRI for confirmation in cases of vermian abnormalities. That was in contrary to what was concluded by Limperopoulos et al., 2008 [
Limitations in our study included the relatively narrowed number of the performed postnatal MRI owing to the high ratio of termination decision, IUFD and still birth of our cases, in addition, the study needed to be applied on a larger cohort of pregnant women with fetal brain malformations which will be considered in the next study.
Our recommendations in the future is adding fetal MRI to prenatal ultrasound in fetal brain malformations to well assess the cerebellar vermis; where it is of great sensitivity & specificity compared to the prenatal ultrasound & it greatly manipulates the fetal management with better demonstration of the fetal and child’s neurodevelopmental outcome.
Accurate antenatal diagnosis of the posterior fossa malformations is still a diagnostic challenge. Proper cerebellar vermis assessment by Fetal MRI, greatly manipulates management of fetal brain malformations and determines the fetal outcome where it proved better than prenatal ultrasound in reaching the correct diagnosis. In addition, similarity between fetal MRI and postnatal MRI in findings rendered usage of post natal MRI as a confirmatory tool of limited need.
The authors declare no conflicts of interest regarding the publication of this paper.
Ragaee, S.M., Mourad, M.A.-F., Hamed, S.T. and Abbas, A.M. (2019) Fetal Cerebellar Vermis Assessment by MRI. What Does It Add? Open Journal of Obstetrics and Gynecology, 9, 1290-1303. https://doi.org/10.4236/ojog.2019.99125