Machine learning in prenatal MRI predicts postnatal ventricular abnormalities in fetuses with isolated ventriculomegaly.

OBJECTIVES: To evaluate the intracranial structures and brain parenchyma radiomics surrounding the occipital horn of the lateral ventricle in normal fetuses (NFs) and fetuses with ventriculomegaly (FVs), as well as to predict postnatally enlarged lateral ventricle alterations in FVs. METHODS: Between January 2014 and August 2023, 141 NFs and 101 FVs underwent 1.5 T balanced steady-state free precession (BSSFP), including 68 FVs with resolved lateral ventricles (FVM-resolved) and 33 FVs with stable lateral ventricles (FVM-stable). Demographic data and intracranial structures were analyzed. To predict the enlarged ventricle alterations of FVs postnatally, logistic regression models with 5-fold cross-validation were developed based on lateral ventricle morphology, blended-cortical or/and subcortical radiomics characteristics. Validation of the models' performance was conducted using the receiver operating characteristic curve (ROC), calibration curve, and decision curve analysis (DCA). RESULTS: Significant alterations in cerebral structures were observed between NFs and FVs (p < 0.05), excluding the maximum frontal horn diameter (FD). However, there was no notable distinction between the FVM-resolved and FVM-stable groups (all p > 0.05). Based on subcortical-radiomics on the aberrant sides of FVs, this approach exhibited high efficacy in distinguishing NFs from FVs in the training/validation set, yielding an impressive AUC of 1/0.992. With an AUC value of 0.822/0.743 in the training/validation set, the Subcortical-radiomics model demonstrated its ability to predict lateral ventricle alterations in FVs, which had the greatest predictive advantages indicated by DCA. CONCLUSIONS: Microstructural alterations in subcortical parenchyma associated with ventriculomegaly can serve as predictive indicators for postnatal lateral ventricle variations in FVs. CLINICAL RELEVANCE STATEMENT: It is critical to gain pertinent information from a solitary fetal MRI to anticipate postnatal lateral ventricle alterations in fetuses with ventriculomegaly. This approach holds the potential to diminish the necessity for recurrent prenatal ultrasound or MRI examinations. KEY POINTS: Fetal ventriculomegaly is a dynamic condition that affects postnatal neurodevelopment. Machine learning and subcortical-radiomics can predict postnatal alterations in the lateral ventricle. Machine learning, applied to single-fetal MRI, might reduce required antenatal testing.

Asymmetric cortical development and prognosis in fetuses with isolated mild fetal ventriculomegaly: an observational prospective study.

BACKGROUND: Assessments of cortical development and identifying factors that may result in a poor prognosis for fetuses with isolated mild ventriculomegaly (IMVM) is a hot research topic. We aimed to perform a constant, detailed assessment of cortical development in IMVM fetuses using ultrasound and determine whether asymmetric cortical development occurred. Moreover, we aimed to estimate the prognosis of IMVM fetuses and compare the difference in the prognosis of IMVM fetuses presenting symmetric and asymmetric cortical maturation. METHODS: IMVM was diagnosed by regular ultrasound, neurosonography and fetal MRI. Genetic and TORCH examinations were conducted to exclude common genetic abnormalities and TORCH infection of fetuses. Ultrasound examinations were conducted at an interval of 2-3 weeks to record sulcus development in IMVM fetuses using a scoring system. The neonatal behavioral neurological assessment (NBNA), the Ages and Stages Questionnaire, Third Edition (ASQ-3) and the Bayley Scales of Infant Development, First Edition (BSID-I) were performed after birth. RESULTS: Forty fetuses with IMVM were included: twenty showed asymmetric cortical maturation and twenty showed symmetric cortical maturation. For IMVM fetuses presenting asymmetric cortical maturation, the mean gestational age (GA) at the first diagnosis of relatively delayed development was 24.23 weeks for the parieto-occipital sulcus, 24.71 weeks for the calcarine sulcus, and 26.43 weeks for the cingulate sulcus. All the sulci with delayed development underwent 'catch-up growth' and developed to the same grade as the sulci of the other hemisphere. The mean GA at which the two sides developed to the same grade was 29.40 weeks for the parieto-occipital sulcus, 29.30 weeks for the calcarine sulcus and 31.27 weeks for the cingulate sulcus. The NBNA, ASQ-3 and BSID-I scores of all patients were in the normal range. CONCLUSIONS: IMVM fetuses may show mild asymmetric cortical maturation in the second trimester, but the relatively delayed sulci undergo 'catch-up growth'. The neurodevelopment of IMVM fetuses presenting asymmetric cortical maturation and 'catch-up growth' is not statistically significantly different from IMVM fetuses presenting symmetric cortical maturation.

Prognostic Analysis and Risk Factors Associated with Fetal Ventriculomegaly.

BACKGROUND: This study aimed to investigate the clinical outcome and related risk factors of fetal lateral ventriculomegaly (VM). METHODS: A retrospective analysis was performed on 255 cases diagnosed as fetal VM. Prenatal imaging examination was carried out. The pregnancy outcomes were investigated through follow-up. According to the prognosis of children, they were divided into case group and control group. Multivariate logistic regression was used to analyze the factors influencing the prognosis of hydrocephalus. RESULTS: After excluding the cases with either loss of follow-up or incomplete information, 102 cases were followed up. Twelve cases with poor prognosis were set as the case group. According to the maternal age, gestational age, gender of children, and follow-up time, 3 cases were selected from the other 90 cases for each child in the case group, respectively, and selected as the control group. Paired comparative analysis was performed on 48 cases. Using prognosis as a dependent variable, multivariate logistic regression analysis of the statistically significant factors indicated that the change speed of width ratio (CSWR) and maximum lateral ventricular width (MW) were associated with fetal prognosis. CONCLUSIONS: Our results suggested that CSWR and MW may have the value of predicting fetal prognosis.

Why a focus session on fetal ventriculomegaly and congenital hydrocephalus?

Introduction to the Special Focus Session on Fetal ventriculomegaly and Congenital Hydrocephalus.

Not all ventriculomegaly is created equal: diagnostic overview of fetal, neonatal and pediatric ventriculomegaly.

Fetal ventriculomegaly refers to a condition in which there is enlargement of the ventricular spaces, typically on prenatal ultrasound. It can be associated with other CNS or extra-CNS abnormalities, and this relationship is crucial to understand as it affects overall neonatal outcome. Isolated ventriculomegaly has been described in the literature with variable clinical outcome. Typically, outcome is based on the etiology and degree of ventriculomegaly. When associated with a pathologic condition, ventriculomegaly can be a result of hydrocephalus. While initial diagnosis is usually made on prenatal ultrasound, fetal magnetic resonance imaging is preferred to further elucidate any associated CNS malformations. In this paper, the authors aim to provide a comprehensive review of the diagnosis, associated etiologies, prognosis, and treatment options related to fetal, neonatal, and pediatric ventriculomegaly and hydrocephalus. In addition, preliminary data is provided from our institutional cohort of patients with a prenatal diagnosis of ventriculomegaly followed through the perinatal period.

Prenatal genetic considerations in congenital ventriculomegaly and hydrocephalus.

BACKGROUND: Fetal ventriculomegaly (VM) is a frequent finding in prenatal ultrasound. Rather than a proper diagnosis, VM is a sonographic sign, making prenatal counseling a complex and challenging undertaking. VM can range from severe pathologic processes leading to severe neurodevelopmental delay to normal variants. DISCUSSION: A growing number of genetic conditions with different pathophysiological mechanisms, inheritance patterns, and long-term prognosis have been associated both to isolated and complex fetal VM. These include chromosomal abnormalities, copy number variants, and several single gene diseases. In this review, we describe some of the most common genetic conditions associated with fetal VM and provide a simplified diagnostic workflow for the clinician.

Ventriculo-amniotic shunting for severe fetal ventriculomegaly.

INTRODUCTION: Severe fetal cerebral ventriculomegaly, observed in about 1 in 1000 newborns, is associated with a high risk of perinatal death and neurodevelopmental delay in survivors. The objective of this study was to evaluate the efficiency of ventriculo-amniotic shunting for drainage of severe fetal cerebral ventriculomegaly and the neurodevelopment of survivors at the age of 2 years. MATERIAL AND METHODS: This was a retrospective study of 44 fetuses with severe bilateral ventriculomegaly treated with ventriculo-amniotic shunting in a tertiary fetal therapy center between 2010 and 2015. RESULTS: Shunt insertion was successfully carried out at a median gestational age of 25 weeks (range 20-33 weeks). There were three fetal deaths within 24 hours of the procedure and 41 live births at a median gestational age of 37 weeks (range 28-39 weeks). Neurodevelopment at 2 years of age was evaluated using the Bayley scale in the 38 survivors. In the 27 cases with isolated ventriculomegaly 19 (70.4%; 95% confidence interval [95% CI] 51.5%-84.2%) had normal or mild neurodevelopmental delay and 8 (29.6%; 95% CI 15.6%-48.5%) were moderately or severely delayed. In the 11 with non-isolated ventriculomegaly 2 (18.2%; 95% CI 5.1%-4.8%) had normal or mild neurodevelopmental delay and 9 (81.8%; 95% CI 52.3%-94.9%) babies were moderately or severely delayed. CONCLUSIONS: Ventriculo-amniotic shunting is an option for the management of severe ventriculomegaly and results in normalization of the ventricular diameter. However, a high proportion of survivors have neurodevelopmental delay and the possible beneficial effect of ventriculo-amniotic shunting needs to be assessed by randomized studies.

Benign Postnatal Outcome after Prenatal Diagnosis of Fetal Ventriculomegaly with Choroid Plexus Hyperplasia: A Case Report.

Prenatal counselling following the diagnosis of fetal ventriculomegaly is challenging. Fetal MRI (magnetic resonance imaging) can be helpful in characterizing ventriculomegaly severity and associated anomalies, hence contributing to prognosis establishment. Choroid plexus hyperplasia (CPH) is a rare entity characterized by enlargement of the choroid plexuses, usually progressing to severe hydrocephalus with an associated poor outcome. We present a case of CPH diagnosed by fetal MRI at 23 weeks of gestation following referral for ventriculomegaly. The pregnancy was carried to term and the child was monitored clinically and radiologically. Despite the persistence of enlarged choroid plexuses, the ventricular size has progressively decreased, and at the 4-year follow-up the child presented normal psychomotor development. This case highlights the added value of MRI in prenatal diagnosis of fetal ventriculomegaly and its management. The unusual benign outcome in this case can be considered for parental counselling when faced with a fetus with similar findings.

Fetal ventriculomegaly: Diagnosis, treatment, and future directions.

Fetal ventriculomegaly (VM) refers to the enlargement of the cerebral ventricles in utero. It is associated with the postnatal diagnosis of hydrocephalus. VM is clinically diagnosed on ultrasound and is defined as an atrial diameter greater than 10 mm. Because of the anatomic detailed seen with advanced imaging, VM is often further characterized by fetal magnetic resonance imaging (MRI). Fetal VM is a heterogeneous condition with various etiologies and a wide range of neurodevelopmental outcomes. These outcomes are heavily dependent on the presence or absence of associated anomalies and the direct cause of the ventriculomegaly rather than on the absolute degree of VM. In this review article, we discuss diagnosis, work-up, counseling, and management strategies as they relate to fetal VM. We then describe imaging-based research efforts aimed at using prenatal data to predict postnatal outcome. Finally, we review the early experience with fetal therapy such as in utero shunting, as well as the advances in prenatal diagnosis and fetal surgery that may begin to address the limitations of previous therapeutic efforts.

Chromosome abnormality incidence in fetuses with cerebral ventriculomegaly.

Ventriculomegaly (VM) is a marker of aneuploidy and warrants a detailed examination of fetal anatomy. Chromosomal abnormalities worsen the fetal and neonatal prognosis significantly and karyotyping of fetuses is critically important when accompanying anomalies are detected. Here, we report the genetic results of 140 fetuses with isolated and non-isolated VM detected during a second trimester ultrasound examination followed by invasive in utero diagnostic procedures for karyotyping. VM was diagnosed in seven (5%) fetuses with abnormal karyotype and the chromosomal abnormality incidence was higher in severe VM (6.8%) than mild (4.2%). Higher chromosomal abnormality rates were detected when VM was isolated (8.6%), rather than associated with any anomaly (3.8%). These results suggest that karyotype analysis should be offered to all patients with any degree of VM, regardless of its association with structural anomalies.

Prenatal diagnosis and pregnancy outcomes in fetuses with ventriculomegaly.

Objective: Genetic etiology plays a critical role in fetal ventriculomegaly (VM). However, the studies on chromosomal copy number variants (CNVs) in fetal VM are limited. This study aimed to investigate the chromosomal CNVs in fetuses with mild to moderate VM, and explore its genotype-phenotype correlation. Methods: A total of 242 fetuses with mild to moderate VM detected by prenatal ultrasound were enrolled in our study from October 2018 to October 2022. All cases underwent chromosomal microarray analysis (CMA) and G-banding simultaneously. All VM cases were classified different subgroups according to the maternal age, severity, VM distribution and presence/absence of other ultrasound abnormalities. The pregnancy outcomes and health conditions after birth were followed up. We also performed a pooled analysis regarding likely pathogenic and pathogenic CNVs (LP/P CNVs) for VM. Results: The detection rate of chromosomal abnormalities by karyotyping was 9.1% (22/242), whereas it was 16.5% (40/242) when CMA was conducted (P < 0.05). The total detection rate of chromosomal abnormalities by karyotyping and CMA was 21.1% (51/242). A 12.0% incremental yield of CMA over karyotyping was observed. The detection rate of total genetic variants in fetuses with bilateral VM was significantly higher than in fetuses with unilateral VM (30.0% vs. 16.7%, P = 0.017). No significant differences were discovered between isolated VM and non-isolated VM, or between mild and moderate VM, or between advanced maternal age (AMA) and non-AMA (all P > 0.05). 28 fetuses with VM were terminated and 214 fetuses were delivered: one presented developmental delay and one presented congenital heart disease. The VM cases with both positive CMA and karyotypic results had a higher rate of termination of pregnancy than those with either a positive CMA or karyotypic result, or both negative testing results (P < 0.001). Conclusion: The combination of CMA and karyotyping should be adopted to improve the positive detection rate of chromosomal abnormalities for VM. The total genetic abnormalities detected using both techniques would affect the final pregnancy outcomes. LP/P CNVs at 16p11.2, 17p13, and 22q11.21 were identified as the top three chromosomal hotspots associated with VM, which would enable genetic counselors to provide more precise genetic counseling for VM pregnancies.

Isolated Fetal Ventriculomegaly: Diagnosis and Treatment in the Prenatal Period.

Fetal ventriculomegaly (VM) is a defect of the central nervous system, typically diagnosed during the second-trimester ultrasound in fetuses with an atrial diameter (AD) of >10 mm. Non-isolated ventriculomegaly (NIVM) is heterogeneous in nature, coexisting with additional intracranial and/or extracranial malformations and genetic syndromes, resulting in an unfavorable prognosis for the further development of the child. Both the pregnancy management and counseling are dependent on the findings of combined ultrasound/MRI, genetic testing, and gestational age at diagnosis. The purpose of this review is to propose a hypothesis that diagnostic advancements allow to define the process of identification of the isolated forms of VM (IVM). Based on the evidence presented in the literature, we consider whether prenatal decompression for severe isolated VM (ISVM) is supported by the experimental trials and whether it might be implemented in clinical practice. Also, we describe the evolution of the diagnostic methods and expert opinions about the previously used prenatal decompression techniques for ISVM. In conclusion, we introduce the idea that fetal surgery centers have either reached or nearly reached the necessary level of expertise to perform such procedures. Endoscopic cystoventriculostomy (ETV) appears to be the most promising, as it is associated with minimal perinatal complications and favorable neurological outcomes in the neonatal period. Randomized trials with long-term neurodevelopmental follow-up of children who underwent prenatal decompression due to ISVM are necessary.

Fetal Cerebral Ventriculomegaly: A Narrative Review and Practical Recommendations for Pediatric Neurologists.

Fetal cerebral ventriculomegaly is one of the most common fetal neurological disorders identified prenatally by neuroimaging. The challenges in the evolving landscape of conditions like fetal cerebral ventriculomegaly involve accurate diagnosis and how best to provide prenatal counseling regarding prognosis as well as postnatal management and care of the infant. The purpose of this narrative review is to discuss the literature on fetal ventriculomegaly, including postnatal management and neurodevelopmental outcome, and to provide practice recommendations for pediatric neurologists.

Concordance between US and MRI Two-Dimensional Measurement and Volumetric Segmentation in Fetal Ventriculomegaly.

We provide a study comparison between two-dimensional measurement and volumetric (3D) segmentation of the lateral ventricles and brain structures in fetuses with isolated and non-isolated ventriculomegaly with 3D virtual organ computer-aided analysis (VOCAL) ultrasonography vs. magnetic resonance imaging (MRI) analyzed with 3D-Slicer software. In this cross-sectional study, 40 fetuses between 20 and 38 gestational weeks with various degrees of ventriculomegaly were included. A total of 71 ventricles were measured with ultrasound (US) and with MRI. A total of 64 sonographic ventricular volumes, 80 ventricular and 40 fetal brain MR volumes were segmented and analyzed using both imaging modalities by three observers. Sizes and volumes of the ventricles and brain parenchyma were independently analyzed by two radiologists, and interobserver correlation of the results with 3D fetal ultrasound data was performed. The semiautomated rotational multiplanar 3D VOCAL technique was performed for ultrasound volumetric measurements. Results were compared to manually extracted ventricular and total brain volumes in 3D-Slicer. Segmentation of fetal brain structures (cerebral and cerebellar hemispheres, brainstem, ventricles) performed independently by two radiologists showed high interobserver agreement. An excellent agreement between VOCAL and MRI volumetric and two-dimensional measurements was established, taking into account the intraclass correlation coefficients (ICC), and a Bland-Altman plot was established. US and MRI are valuable tools for performing fetal brain and ventricular volumetry for clinical prognosis and patient counseling. Our datasets could provide the backbone for further construction of quantitative normative trajectories of fetal intracranial structures and support earlier detection of abnormal brain development and ventriculomegaly, its timing and progression during gestation.

Prenatal findings and associated survival rates in fetal ventriculomegaly: A prospective observational study.

OBJECTIVES: Fetal ventriculomegaly is associated with varying degrees of genetic and structural abnormalities. The objective was to present the experience of fetal ventriculomegaly in a large European center in relation to: 1. grade of ventriculomegaly; 2. additional chromosomal/structural abnormalities; and 3. perinatal survival rates. METHODS: This was a prospective observational study of patients referred with fetal ventriculomegaly from January 2011 to July 2020. Data were obtained from the hospital database and analyzed to determine the rate of isolated ventriculomegaly, associated structural abnormalities, chromosomal/genetic abnormalities, and survival rates. Data were stratified into three groups; mild (Vp = 10-12 mm), moderate (Vp = 13-15 mm) and severe (Vp > 15 mm) ventriculomegaly. RESULTS: There were 213 fetuses included for analysis. Of these 42.7% had mild ventriculomegaly, 44.6% severe and 12.7% had moderate ventriculomegaly. Initial ultrasound assessment reported isolated ventriculomegaly in 45.5% fetuses, with additional structural abnormalities in 54.5%. The rate of chromosomal/genetic abnormalities was high,16.4%. After all investigations, the true rate of isolated VM was 36.1%. The overall survival was 85.6%. Survival was higher for those with isolated VM across all groups (P < 0.05). CONCLUSION: Ventriculomegaly is a complex condition and patients should be counselled that even with apparently isolated VM, there remains the possibility of additional genetic and/or structural problems being diagnosed in up to 10% of fetuses.

Maternal blood inflammatory marker levels increased in fetuses with ventriculomegaly.

Background: Fetal ventriculomegaly (VM) is one of the most common abnormalities of the central nervous system (CNS), which can be significantly identified by brain anomalies prenatally by magnetic resonance imaging (MRI). Aberrant white blood cells (WBCs) levels indicate that the maternal is suffering from the infection. Previous studies have confirmed that prenatal infection can affect fetal brain structure, but there is no research revealed the association between maternal blood parameters with fetal VM until now. Methods: We measured the width of the lateral ventricle of 142 fetuses, which were divided into the fetal VM group (n = 70) and the normal lateral ventricle group (n = 72). We compared maternal blood cell levels between the two groups and investigate potential biomarkers of fetal VM. Result: High levels of maternal WBC and neutrophil (NE#) levels were observed in fetuses with VM (p < 0.001), while lymphocyte percentage, monocytes (MO#), neutrophil/lymphocyte ratio (NLR), and platelet were also increased in the fetal VM group (p = 0.033, 0.027, 0.034, and 0.025, respectively). receiver-operator curve (ROC) analysis suggested that WBC and NE# counts might be useful to distinguish fetuses with enlarged lateral ventricles (AUC = 0.688, 0.678, respectively). Conclusion: The current study emphasizes the importance of maternal infection for fetal brain growth, which could provide important information for prenatal diagnosis of CNS anomalies. Future research needs longitudinal analysis and exploration of the influence of maternal blood inflammatory marker levels on fetal brain development.

Fetal Ventriculomegaly: A Review of Literature.

Fetal ventriculomegaly refers to ventricular enlargement that is diagnosed prenatally. It is one of the most common fetal anomalies. The diagnosis is made by ultrasound when the arterial diameter of the ventricle is more than 10 mm. Once it is diagnosed, further evaluation by detailed ultrasound, fetal MRI, and genetic studies is required. Prenatal surgical management of fetal ventriculomegaly is still limited and associated with high risks. Postnatal management is similar to the treatment of other types of hydrocephalus. Fetal ventriculomegaly is a heterogeneous condition with various etiologies and a wide spectrum of neurodevelopmental outcomes. The outcomes depend mainly on the severity of ventriculomegaly and associated structural abnormalities. This article aims to review the literature about various aspects of fetal ventriculomegaly.

Autosomal recessive LRP1-related syndrome featuring cardiopulmonary dysfunction, bone dysmorphology, and corneal clouding.

We provide the first study of two siblings with a novel autosomal recessive LRP1-related syndrome identified by rapid genome sequencing and overlapping multiple genetic models. The patients presented with respiratory distress, congenital heart defects, hypotonia, dysmorphology, and unique findings, including corneal clouding and ascites. Both siblings had compound heterozygous damaging variants, c.11420G > C (p.Cys3807Ser) and c.12407T > G (p.Val4136Gly) in LRP1, in which segregation analysis helped dismiss additional variants of interest. LRP1 analysis using multiple human/mouse data sets reveals a correlation to patient phenotypes of Peters plus syndrome with additional severe cardiomyopathy and blood vessel development complications linked to neural crest cells.

Prenatal Ventriculomegaly - Diagnosis, Prognostication and Management.

Fetal ventriculomegaly (VM) refers to the abnormal enlargement of one or more ventricles of the brain in-utero. The enlargement may or may not be related to ventricular obstruction and increased intracranial pressure; therefore, the term "hydrocephalus" is not used. VM is diagnosed usually in the mid-trimester when the atrial diameter (AD) of the lateral ventricle is more than 10 mm on one or both sides. A thorough workup is then required to identify the cause as the etiology is diverse. Fetal magnetic resonance imaging (MRI) may yield additional information. Serial ultrasound follow-up would be required to assess its progression with advancing gestation. The prognosis and long-term outcomes greatly depend upon the etiology, the severity at diagnosis, progression, and associations. This article reviews the definitions, diagnosis, and workup of fetal VM, discusses follow-up protocols and prognosis, and examines the role of fetal therapy, including fetoscopic surgery in its prenatal management.

Second trimester fetal MRI features in a fetus with TUBB3 gene mutation.

Tubulinopathies are a heterogeneous group of complex cortical malformations that are associated with mutations in tubulin genes. TUBB3 gene mutation is associated with a broader spectrum of central nervous system malformations and constitutes about 10% of all tubulinopathies. The diagnosis may not be immediately apparent on imaging, though the differential diagnosis may be narrowed based on imaging findings and allow for more directed genetic testing. We report a 22-year-old gravida-1 nulliparous female whose routine second trimester fetal ultrasound revealed ventriculomegaly and possible agenesis of the corpus callosum. Fetal magnetic resonance imaging showed severe lateral and third ventriculomegaly and a dysplastic, z-shaped brainstem without any evidence of ocular abnormalities. Genetic testing revealed a pathogenic mutation in TUBB3.