Fetal MRI Research Articles

Development of a 3D-printed neonatal congenital diaphragmatic hernia model and standardisation of intra-operative measurement

IntroductionThree-dimensional (3D) printing is frequently used for surgical simulation and training, however, no widely available model exists for neonatal congenital diaphragmatic hernia (CDH). The aim of this study was to develop a 3D-printed model of CDH and test interobserver variability in the simulated model for obtaining measurements of the diaphragmatic defect and ipsilateral diaphragm.MethodsA term fetal MRI (3.5 kg) of thorax, diaphragm and defect (15 mm × 5 mm) were delineated and segmented after parental consent to produce 3D-printed models. Consultant and trainee paediatric surgeons were invited to measure the posterior-lateral diaphragmatic defect and ipsilateral diaphragm. Mean measurement error was calculated (millimetres). Data are presented as median (range) and number/total (%).ResultsAn abdominal and thoracoscopic model were produced and tested by 52 participants (20 consultants and 32 trainees). Diaphragmatic defect via laparotomy measured 15 (10–20) mm (AP) × 16 (10–25) mm (ML) and thoracoscopically 14 (11–19) mm (AP) × 15 (11–22) mm (ML). Mean error per measurement was 4 (1–17) mm via laparotomy vs. 3 (0.5–9.5) mm thoracoscopically. Mean error was similar between consultants and trainees via laparotomy (4.3 vs. 3.9 mm, p = 0.70) and thoracoscopically (3 vs. 3 mm, p = 0.79). Error did not correlate with experience as operating surgeon via laparotomy (β = 13.0 [95% CI − 55.9 to 82.0], p = 0.71) or thoracoscopically (β = 1.4[95% CI − 6.4 to 9.2], p = 0.73.ConclusionsWe have designed and built simulation models for CDH repair via laparotomy and thoracoscopically. Operators can reliably measure the diaphragmatic defect and ipsilateral diaphragm, regardless of surgical experience and operative approach.

Congenital Tumors-Magnetic Resonance Imaging Findings with Focus on Rare Tumors.

Congenital tumors are rare and, owing to this rarity, there is limited information on many of them. A total of 839 fetal and postnatal MRI studies performed in the first 3 months of life were retrospectively reviewed. They were performed with the use of 1.5 T scanners. Seventy-six tumors were diagnosed based on fetal MRI between 20 and 37 gestational weeks, and 27 were found after birth, from 1 day of age to 3 months of life. Teratomas were the most common tumors in our dataset, mainly in the sacrococcygeal region (SCT), followed by cardiac rhabdomyomas and subependymal giant cell astrocytomas (SEGA) associated with TSC, and neuroblastomas. The group of less common tumors consisted of infantile fibrosarcomas, malignant rhabdoid tumors, mesoblastic nephromas and Wilms tumor, craniopharyngiomas, brain stem gliomas, desmoplastic infantile astrocytoma, choroid plexus carcinoma, glioblastoma, hemangiopericytoma, rhabdomyosarcoma, melanoma, mesenchymal hamartomas of the chest wall and the liver, and juvenile xanthogranuloma, with special consideration of blue rubber bleb nevus syndrome. MRI plays a significant role in further and better characterization of congenital tumors, leading to a correct diagnosis in many cases, which is crucial for pregnancy and neonatal management and psychological preparation of the parents. No diagnosis is impossible and can be absolutely excluded.

Functional MRI assessment of the lungs in fetuses that deliver very Preterm: An MRI pilot study

ObjectivesTo compare mean pulmonary T2* values and pulmonary volumes in fetuses that subsequently spontaneously delivered before 32 weeks with a control cohort with comparable gestational ages and to assess the value of mean pulmonary T2* as a predictor of preterm birth < 32 weeks’ gestation. MethodsMRI datasets scanned at similar gestational ages were selected from fetuses who spontaneously delivered < 32 weeks of gestation and a control group who subsequently delivered at term with no complications. All women underwent a fetal MRI on a 3 T MRI imaging system. Sequences included T2-weighted single shot fast spin echo and T2* sequences, using gradient echo single shot echo planar sequencing of the fetal thorax. Motion correction was performed using slice-to-volume reconstruction and T2* maps generated using in-house pipelines. Lungs were manually segmented and volumes and mean T2* values calculated for both lungs combined and left and right lung separately. Linear regression was used to compare values between the preterm and control cohorts accounting for the effects of gestation. Receiver operating curves were generated for mean T2* values and pulmonary volume as predictors of preterm birth < 32 weeks’ gestation. ResultsDatasets from twenty-eight preterm and 74 control fetuses were suitable for analysis. MRI images were taken at similar fetal gestational ages (preterm cohort (mean ± SD) 24.9 ± 3.3 and control cohort (mean ± SD) 26.5 ± 3.0). Mean gestational age at delivery was 26.4 ± 3.3 for the preterm group and 39.9 ± 1.3 for the control group. Mean pulmonary T2* values remained constant with increasing gestational age while pulmonary volumes increased. Both T2* and pulmonary volumes were lower in the preterm group than in the control group for all parameters (both combined, left, and right lung (p < 0.001 in all cases). Adjusted for gestational age, pulmonary volumes and mean T2* values were good predictors of premature delivery in fetuses < 32 weeks (area under the curve of 0.828 and 0.754 respectively). ConclusionThese findings indicate that mean pulmonary T2* values and volumes were lower in fetuses that subsequently delivered very preterm. This may suggest potentially altered oxygenation and indicate that pulmonary morbidity associated with prematurity has an antenatal antecedent. Future work should explore these results correlating antenatal findings with long term pulmonary outcomes.

Shape-aware Segmentation of the Placenta in BOLD Fetal MRI Time Series.

Blood oxygen level dependent (BOLD) MRI time series with maternal hyperoxia can assess placental oxygenation and function. Measuring precise BOLD changes in the placenta requires accurate temporal placental segmentation and is confounded by fetal and maternal motion, contractions, and hyperoxia-induced intensity changes. Current BOLD placenta segmentation methods warp a manually annotated subject-specific template to the entire time series. However, as the placenta is a thin, elongated, and highly non-rigid organ subject to large deformations and obfuscated edges, existing work cannot accurately segment the placental shape, especially near boundaries. In this work, we propose a machine learning segmentation framework for placental BOLD MRI and apply it to segmenting each volume in a time series. We use a placental-boundary weighted loss formulation and perform a comprehensive evaluation across several popular segmentation objectives. Our model is trained and tested on a cohort of 91 subjects containing healthy fetuses, fetuses with fetal growth restriction, and mothers with high BMI. Biomedically, our model performs reliably in segmenting volumes in both normoxic and hyperoxic points in the BOLD time series. We further find that boundary-weighting increases placental segmentation performance by 8.3% and 6.0% Dice coefficient for the cross-entropy and signed distance transform objectives, respectively.

Characterization of dynamic patterns of human fetal to neonatal brain asymmetry with deformation-based morphometry.

Despite established knowledge on the morphological and functional asymmetries in the human brain, the understanding of how brain asymmetry patterns change during late fetal to neonatal life remains incomplete. The goal of this study was to characterize the dynamic patterns of inter-hemispheric brain asymmetry over this critically important developmental stage using longitudinally acquired MRI scans. Super-resolution reconstructed T2-weighted MRI of 20 neurotypically developing participants were used, and for each participant fetal and neonatal MRI was acquired. To quantify brain morphological changes, deformation-based morphometry (DBM) on the longitudinal MRI scans was utilized. Two registration frameworks were evaluated and used in our study: (A) fetal to neonatal image registration and (B) registration through a mid-time template. Developmental changes of cerebral asymmetry were characterized as (A) the inter-hemispheric differences of the Jacobian determinant (JD) of fetal to neonatal morphometry change and the (B) time-dependent change of the JD capturing left-right differences at fetal or neonatal time points. Left-right and fetal-neonatal differences were statistically tested using multivariate linear models, corrected for participants' age and sex and using threshold-free cluster enhancement. Fetal to neonatal morphometry changes demonstrated asymmetry in the temporal pole, and left-right asymmetry differences between fetal and neonatal timepoints revealed temporal changes in the temporal pole, likely to go from right dominant in fetal to a bilateral morphology in neonatal timepoint. Furthermore, the analysis revealed right-dominant subcortical gray matter in neonates and three clusters of increased JD values in the left hemisphere from fetal to neonatal timepoints. While these findings provide evidence that morphological asymmetry gradually emerges during development, discrepancies between registration frameworks require careful considerations when using DBM for longitudinal data of early brain development.

Using MRI-derived observed-to-expected total fetal lung volume to predict lethality in fetal skeletal dysplasia.

Pulmonary hypoplasia is the primary cause of perinatal death in lethal skeletal dysplasias. The antenatal ultrasound correlates for lethality are indirect, measuring the thorax (thoracic circumference, TC) or femur compared to the abdomen (TC/AC, FL/AC). A single study has correlated lethality with the observed-to-expected total lung volume (O/E-TFLV) on fetal MRI in 23 patients. Our aim was to define a cutoff value to predict lethality more specifically using MRI-derived O/E-TFLV. Two large fetal center databases were searched for fetuses with skeletal dysplasia and MRI; O/E-TFLV was calculated. Ultrasound measures were included when available. Each was evaluated as a continuous variable against lethality (stillbirth or death in the first month of life). Logistic regression and receiver operating characteristic (ROC) curve analyses evaluated the prediction ability. AUC, sensitivity, and specificity were calculated. P < 0.05 was considered statistically significant. A total of 80 fetuses met inclusion criteria. O/E-TFLV < 0.49 was a significant risk factor in predicting lethality, with sensitivity and specificity of 0.63 and 0.93, respectively, and an AUC of 0.81 (P < 0.001). FL/AC < 0.129 was also a strong variable with sensitivity, specificity, and AUC of 0.73, 0.88, and 0.78, respectively (P < 0.001). TC/AC and TC percentile were not significant risk factors for lethality. An O/E-TFLV of < 0.38 defines a specificity for lethality at 1.00. MRI-derived O/E-TFLV and US-derived FL/AC are significant predictors of lethality in fetuses with skeletal dysplasia. When prognosis is uncertain after ultrasound, calculation of MRI-derived O/E-TFLV may provide additional useful information for prognosis and delivery planning.

T1-weighted fast fluid-attenuated inversion-recovery sequence (T1-FFLAIR) enables the visualization and quantification of fetal brain myelination in utero

ObjectivesTo investigate the advantage of T1-weighted fast fluid-attenuated inversion-recovery MRI sequence without (T1-FFLAIR) and with compressed sensing technology (T1-FFLAIR-CS), which shows improved T1-weighted contrast, over standard used T1-weighted fast field echo (T1-FFE) sequence for the assessment of fetal myelination.Materials and methodsThis retrospective single-center study included 115 consecutive fetal brain MRI examinations (63 axial and 76 coronal, mean gestational age (GA) 28.56 ± 5.23 weeks, range 19–39 weeks). Two raters, blinded to GA, qualitatively assessed a fetal myelin total score (MTS) on each T1-weighted sequence at five brain regions (medulla oblongata, pons, mesencephalon, thalamus, central region). One rater performed region-of-interest quantitative analysis (n = 61) at the same five brain regions. Pearson correlation analysis was applied for correlation of MTS and of the signal intensity ratios (relative to muscle) with GA on each T1-weighted sequence. Fetal MRI–based results were compared with myelination patterns of postmortem fetal human brains (n = 46; GA 18 to 42), processed by histological and immunohistochemical analysis.ResultsMTS positively correlated with GA on all three sequences (all r between 0.802 and 0.908). The signal intensity ratios measured at the five brain regions correlated best with GA on T1-FFLAIR (r between 0.583 and 0.785). T1-FFLAIR demonstrated significantly better correlations with GA than T1-FFE for both qualitative and quantitative analysis (all p < 0.05). Furthermore, T1-FFLAIR enabled the best visualization of myelinated brain structures when compared to histology.ConclusionT1-FFLAIR outperforms the standard T1-FFE sequence in the visualization of fetal brain myelination, as demonstrated by qualitative and quantitative methods.Clinical relevance statementT1-weighted fast fluid-attenuated inversion-recovery sequence (T1-FFLAIR) provided best visualization and quantification of myelination in utero that, in addition to the relatively short acquisition time, makes feasible its routine application in fetal MRI for the assessment of brain myelination.Key Points• So far, the assessment of fetal myelination in utero was limited due to the insufficient contrast.• T1-weighted fast fluid-attenuated inversion-recovery sequence allows a qualitative and quantitative assessment of fetal brain myelination.• T1-weighted fast fluid-attenuated inversion-recovery sequence outperforms the standard used T1-weighted sequence for visualization and quantification of myelination in utero.Graphical abstract

Fetal macrocephaly: Pathophysiology, prenatal diagnosis and management.

Macrocephaly means a large head and is defined as a head circumference (HC) above the 98th percentile or greater than +2SD above the mean for gestational age. Macrocephaly can be primary and due to increased brain tissue (megalocephaly), which in most cases is familial and benign or secondary. The latter may be due to various causes, including but not limited to communicating or non-communicating hydrocephalus, cerebral edema, focal and pericerebral increased fluid collections, thickened calvarium and brain tumors. Megalocephaly can be syndromic or non-syndromic. In the former, gyral and structural CNS anomalies are common. It is important to exercise caution when considering a diagnosis of megalocephaly due to limitations in the accuracy of HC measurement, lack of nomograms for specific populations, inconsistencies between prenatal and postnatal HC growth curves and progression over time. The degree of macrocephaly is important, with mild macrocephaly ≤2.5SD carrying a good prognosis, especially when one of the parents has macrocephaly and normal development. Cases in which the patient history and/or physical exam are positive or when parental HC are normal are more worrisome and warrant a neurosonogram, fetal MRI and genetic testing to better delineate the underlying etiology and provide appropriate counseling.

The Effect of Steroids on Prenatally Diagnosed Lung Lesions

BackgroundOpen fetal resection for large lung lesions has virtually been replaced by maternal steroid administration. Despite this paradigm shift, little is known about the effects steroids have on lung lesion growth in utero. MethodsA 10-year retrospective review of all prenatally diagnosed lung lesions cared for at our fetal care center was performed. We evaluated the effects of prenatal steroids on congenital pulmonary airway malformation (CPAM)-volume-ratio (CVR), distinguishing change in CVR among CPAMs, bronchopulmonary sequestrations (BPS), and bronchial atresias. We also correlated fetal ultrasound and MRI findings with pathology to determine the accuracy of prenatal diagnosis. ResultsWe evaluated 199 fetuses with a prenatal lung lesion. Fifty-four (27 %) were treated with prenatal steroids with a subsequent 21 % mean reduction in the CVR (2.1 ± 1.4 to 1.1 ± 0.4, p = 0.003). Fetuses with hydrops and mediastinal shift who were treated with steroids rarely had resolution of these radiographic findings. Postnatal pathology was available for 91/199 patients (45.7 %). The most common diagnosis was CPAM (42/91, 46 %), followed by BPS (30/91, 33 %), and bronchial atresia (14/91, 15 %). Fetuses who received steroids and had pathology consistent with CPAM were more likely to have a reduction in their CVR (p = 0.02). Fetal ultrasound correctly diagnosed the type of lung lesion in 75 % of cases and fetal MRI in 81 % of cases. ConclusionsPrenatally diagnosed CPAMs are more likely to respond to maternal steroids than BPS or bronchial atresias. Knowing the diagnosis in utero could aid to steward steroid usage, however, fetal imagining modalities are not perfect in distinguishing subtype. Level of evidenceIII.

Multi-task learning for joint weakly-supervised segmentation and aortic arch anomaly classification in fetal cardiac MRI

Congenital Heart Disease (CHD) is a group of cardiac malformations present already during fetal life, representing the prevailing category of birth defects globally. Our aim in this study is to aid 3D fetal vessel topology visualisation in aortic arch anomalies, a group which encompasses a range of conditions with significant anatomical heterogeneity. We present a multi-task framework for automated multi-class fetal vessel segmentation from 3D black blood T2w MRI and anomaly classification. Our training data consists of binary manual segmentation masks of the cardiac vessels’ region in individual subjects and fully-labelled anomaly-specific population atlases. Our framework combines deep learning label propagation using VoxelMorph with 3D Attention U-Net segmentation and DenseNet121 anomaly classification. We target 11 cardiac vessels and three distinct aortic arch anomalies, including double aortic arch, right aortic arch, and suspected coarctation of the aorta. We incorporate an anomaly classifier into our segmentation pipeline, delivering a multi-task framework with the primary motivation of correcting topological inaccuracies of the segmentation. The hypothesis is that the multi-task approach will encourage the segmenter network to learn anomaly-specific features. As a secondary motivation, an automated diagnosis tool may have the potential to enhance diagnostic confidence in a decision support setting. Our results showcase that our proposed training strategy significantly outperforms label propagation and a network trained exclusively on propagated labels. Our classifier outperforms a classifier trained exclusively on T2w volume images, with an average balanced accuracy of 0.99 (0.01) after joint training. Adding a classifier improves the anatomical and topological accuracy of all correctly classified double aortic arch subjects.&lt;br&gt;Our code is available at &lt;a href='https://github.com/SVRTK/MASC-multi-task-segmentation-and-classification'&gt;https://github.com/SVRTK/MASC-multi-task-segmentation-and-classification&lt;/a&gt;

Abstract 13374: The Intersection of Prenatal Clinical and Demographic Factors in Predicting Fetal Brain Volume and Neurodevelopmental Outcome in Single Ventricle CHD

Background: Fetuses with single ventricle (SV) CHD have small total brain volumes (TBV) which has been linked to neurodevelopmental impairment (NDI). Evidence suggests a prenatal origin of NDI for CHD. Our primary aim was to use machine learning methods to identify prenatal variables that predict fetal brain growth and in turn early NDI. Methods: This is a multi-center prospective cohort study of maternal-infant dyads with a fetal diagnosis of SV who underwent fetal brain MRI and in-depth prenatal clinical and sociodemographic data collection (self reported race/ethnicity, income, education, area deprivation index, maternal health, genetics, placental health). Infants had ND testing at 12-30 months with Bayley Scales of Infant and Toddler Development. Machine learning models used recursive partitioning to predict 1) gestational-age (GA) and sex-adjusted fetal TBV and 2) ND outcome while including fetal TBV in the models. Results: A total of 67 maternal-infant dyads were enrolled with a mean GA of 33.4 weeks (SD=3.4) at fetal MRI and male predominance (57%); 48 infants had follow-up at median age of 23.5 months (SD=6.3). Key predictors of fetal brain volume were race/ethnicity, maternal age, and cardiac anatomy (Figure 1A). For NDI, fetal brain volume was the strongest predictor of motor outcomes but was not associated with other domains (Figure 1D). Cardiac anatomy was the strongest predictor of cognitive outcome (Figure 1B), while race/ethnicity was the strongest predictor of language (Figure 1C). Cardiac anatomy, maternal age, and cerebral and placental hemodynamics (e.g., middle cerebral or umbilical artery pulsatility) each predicted multiple domains of neurodevelopment. Conclusions: In regression tree modeling, sociodemographic variables are the strongest predictors of fetal TBV, which in turn predicts motor outcome. Prenatal factors predicting NDI across all domains span sociodemographic, cardiac, and placental characteristics.

Abstract 18571: Fetal Sirolimus Therapy for Giant Cardiac Rhabdomyoma

Background: Cardiac rhabdomyomas in tuberous sclerosis regress spontaneously, large masses can cause hemodynamic compromise. Fetal sirolimus therapy cause regression. We report a case of successful fetal therapy in mother with fetally diagnosed tuberous sclerosis (TS). Case: A 22 year old female with uncomplicated pregnancy and negative cardiac history presented for fetal echocardiogram at 21 weeks due to cardiac masses. Fetal echocardiogram: levocardia, normal segmental cardiac anatomy, d-looped ventricles, normally related great arteries. Multiple masses seen in both ventricles, largest in LV free wall from base to apex and another involving mitral papillary muscle, no initial obstruction, patent ductal and aortic arches. Amniocentesis confirmed diagnosis of TS. Fetus was followed with serial monitoring of cardiac outputs and size of masses. At 30 weeks, LV mass had doubled from 1.7 to 4 cm with LV diastolic dysfunction and reduced cavity size, large pericardial effusion, left ventricular outflow tract obstruction (LVOTO). IVC was mildly dilated with liver enlargement. Fetal MRI confirmed diagnosis of rhabdomyoma with small subependymal nodules. Given LVOTO and large effusion, mother was started on sirolimus therapy with loading dose of 5 mg and subsequent dose adjustments for target trough sirolimus of 10 to 15 ng/ml. Serial mother monitored with labs, weekly ultrasounds and echocardiograms. Mass decreased in size with resolution of effusion and LVOTO. At 37 weeks, due to oligohydramnios, baby was delivered without hemodynamic compromise. Postnatally no LVOTO and normal systolic function with mass measuring ~ 2.0 cm. Baby has been followed off sirolimus therapy. Role of Imaging: Serial echocardiograms enabled optimal decision making to treat mother with sirolimus therapy. Conclusions: Maternal sirolimus therapy can help regress cardiac rhabdomyomas with hemodynamic implications with serial close outpatient monitoring.

Local SAR management strategies to use two-channel RF shimming for fetal MRI at 3 T.

This study evaluates the imaging performance of two-channel RF-shimming for fetal MRI at 3 T using four different local specific absorption rate (SAR) management strategies. Due to the ambiguity of safe local SAR levels for fetal MRI, local SAR limits for RF shimming were determined based on either each individual's own SAR levels in standard imaging mode (CP mode) or the maximum SAR level observed across seven pregnant body models in CP mode. Local SAR was constrained either indirectly by further constraining the whole-body SAR (wbSAR) or directly by using subject-specific local SAR models. Each strategy was evaluated by the improvement of the transmit field efficiency (average |B1 + |) and nonuniformity (|B1 + | variation) inside the fetus compared with CP mode for the same wbSAR. Constraining wbSAR when using RF shimming decreases B1 + efficiency inside the fetus compared with CP mode (by 12%-30% on average), making it inefficient for SAR management. Using subject-specific models with SAR limits based on each individual's own CP mode SAR value, B1 + efficiency and nonuniformity are improved on average by 6% and 13% across seven pregnant models. In contrast, using SAR limits based on maximum CP mode SAR values across seven models, B1 + efficiency and nonuniformity are improved by 13% and 25%, compared with the best achievable improvement without SAR constraints: 15% and 26%. Two-channel RF-shimming can safely and significantly improve the transmit field inside the fetus when subject-specific models are used with local SAR limits based on maximum CP mode SAR levels in the pregnant population.

Novel approach to prenatal predictors of outcomes for fetuses with severe Ebstein anomaly

Objective Ebstein anomaly (EA) is a cardiac malformation with highly variable presentation and severity with limited perinatal management options. We present incorporation of fetal lung measurements into a multidisciplinary evaluation for counseling and predicting postnatal outcomes in patients with severe EA. Methods Five fetuses with severe fetal EA were reviewed. Third trimester sonographic observed/expected total lung area (O/E TLA) and lung to head ratio (O/E LHR), fetal MRI total fetal lung volume ratio (O/E-TFLV), echocardiographic cardio-thoracic ratio (CT ratio), sonographic estimated fetal weight (EFW) by Hadlock formula and presence of hydrops, were used to guide perinatal management. Results Three of five had appropriate fetal growth, were delivered at term in a cardiac operative suite, and underwent immediate intervention with good neonatal outcomes. Two had severe fetal growth restriction (FGR), CT ratios > 0.8 and O/E LHR and TLA < 25%. One of which delivered prematurely with neonatal demise and one suffered in utero demise at 34 weeks. Conclusions FGR, hydrops, increased CT ratio and reduced O/E LHR and TFLV are potential prognosticators of poor outcomes in severe EA, and should be validated in larger cohorts that would allow for a statistical analysis of the predictive utility of these measurements.

Magnetic Resonance Imaging-Based Reference Values for Two-Dimensional Quantitative Brain Metrics in a Cohort of Extremely Preterm Infants

Introduction: Cerebral magnetic resonance imaging (cMRI) is an important diagnostic tool in neonatology. In addition to qualitative analysis, quantitative measurements may help identify infants with impaired brain growth. This study aimed to create reference values for brain metrics of various brain areas in neonates without major brain injuries born before 28 weeks of gestation. Methods: This retrospective study analyzes cMRI imaging data of high-risk patients without severe brain pathologies at term-equivalent age, collected over 4 years since November 2017. Nineteen brain areas were measured, reference values created, and compared to published values from fetal and postnatal MRI. Furthermore, correlations between brain metrics and gestational age at birth were evaluated. Results: A total of 174 cMRI examinations were available for analysis. Reference values including cut-offs for impaired brain growth were established for different gestational age groups. There was a significant correlation between gestational age at birth and larger “tissue” parameters, as well as smaller “fluid” parameters, including intracerebral and extracerebral spaces. Discussion: With quantitative brain metrics infants with impaired brain growth might be detected earlier. Compared to preexisting reference values, these are the first of a contemporary collective of extremely preterm neonates without severe brain injuries. Measurements can be easily performed by radiologists as well as neonatologists without specialized equipment or computational expertise. Conclusion: Two-dimensional cMRI brain measurements at term-equivalent age represent an easy and reliable approach for the evaluation of brain size and growth in infants at high risk for neurodevelopmental impairment.

Automatic biometry of fetal brain MRIs using deep and machine learning techniques

Linear biometric measurements on magnetic resonance images are important for the assessment of fetal brain development, which is expert knowledge dependent and laborious. This study aims to construct a segmentation-based method for automatic two-dimensional biometric measurements of fetal brain on magnetic resonance images that provides a fast and accurate measurement of fetal brain. A total of 268 volumes (5360 images) magnetic resonance images of normal fetuses were included. The automatic method involves two steps. First, the fetal brain was segmented into four parts with a deep segmentation network: cerebrum, cerebellum, and left and right lateral ventricles. Second, the measurement plane was determined, and the corresponding biometric parameters were calculated according to clinical guidelines, including cerebral biparietal diameter (CBPD), transverse cerebellar diameter (TCD), left and right atrial diameter (LAD/RAD). Pearson correlation coefficient and Bland–Altman plots were used to assess the correlation and agreement between computer-predicted values and manual measurements. Mean differences were used to evaluate the errors quantitatively. Analysis of fetal cerebral growth based on the automatic measurements was also displayed. The experiment results show that correlation coefficients for CBPD, TCD, LAD and RAD were as follows: 0.977, 0.990, 0.817, 0.719, mean differences were − 2.405 mm, − 0.008 mm, − 0.33 mm, − 0.213 mm, respectively. The correlation between the errors and gestational age was not statistically significant (p values were 0.2595, 0.0510, 0.1995, and 0.0609, respectively). The proposed automatic method for linear measurements on fetal brain MRI achieves excellent performance, which is expected to be applied in clinical practice and be helpful for prenatal diagnosis and clinical work efficiency improvement.

Fetal circulatory physiology and brain development in complex congenital heart disease: A multi-modal imaging study.

Fetuses with complex congenital heart disease have altered physiology, contributing to abnormal neurodevelopment. The effects of altered physiology on brain development have not been well studied. We used multi-modal imaging to study fetal circulatory physiology and brain development in hypoplastic left heart syndrome (HLHS) and d-transposition of the great arteries (TGA). This prospective, cross-sectional study investigated individuals with fetal congenital heart disease and controls undergoing fetal echocardiography and fetal brain MRI. MRI measured total brain volume and cerebral oxygenation by the MRI quantification method T2*. Indexed cardiac outputs (CCOi) and vascular impedances were calculated by fetal echocardiography. Descriptive statistics assessed MRI and echocardiogram measurement relationships by physiology. Sixty-six participants enrolled (control=20; HLHS=25; TGA=21), mean gestational age 33.8weeks (95% CI: 33.3-34.2). Total brain volume and T2* were significantly lower in fetuses with cardiac disease. CCOi was lower in HLHS, correlating with total brain volume - for every 10% CCOi increase, volume increased 8mm3 (95% CI: 1.78-14.1; p=0.012). Echocardiography parameters and cerebral oxygenation showed no correlation. TGA showed no CCOi or aortic output correlation with MRI measures. In HLHS, lower cardiac output is deleterious to brain development. Our findings provide insight into the role of fetal cardiovascular physiology in brain health.

Fetal lung volumes measured by MRI predict pulmonary morbidity among infants with giant omphaloceles.

Giant omphaloceles (GO) have associated pulmonary hypoplasia and respiratory complications. Total lung volumes (TLV) on fetal MRI can prognosticate congenital diaphragmatic hernia outcomes; however, its applicability to GO is unknown. We hypothesize that late gestation TLV and observed-to-expected TLV (O/E TLV) on fetal MRI correlate with postnatal pulmonary morbidity in GO. A single-institution retrospective review of GO evaluated between 2012 and 2022 was performed. Fetal MRI TLV between 32 and 36weeks' gestation and O/E TLV throughout gestation were calculated and correlated with postnatal outcomes. 86 fetuses with omphaloceles were evaluated; however, only 26 met strict inclusion criteria. MRIs occurred between 18 and 36weeks' gestation. Those requiring delivery room intubation had significantly lower late gestation TLV and O/E TLV. O/E TLV predicted tracheostomy placement and survival. Neither TLV nor O/E TLV predicted the length of hospitalization or supplemental oxygen after discharge. Three fetuses had a TLV less than 35mL: one died of respiratory failure, and the other two required tracheostomy. Fetal MRI TLV measured between 32 and 36weeks' gestation and O/E TLV predict the need for delivery room intubation and tracheostomy. O/E TLV correlated with survival. These data support fetal MRI as a prognostic tool to predict GO associated pulmonary morbidity.

Outcome of partial agenesis of corpus callosum

The diagnosis of corpus callosum anomalies by prenatal ultrasound has improved over the last decade because of improved imaging techniques, scanning skills, and the routine implementation of transvaginal neurosonography. Our aim was to investigate all cases of incomplete agenesis of the corpus callosum and to report the sonographic characteristics, the associated anomalies, and the perinatal outcomes. We performed a retrospective analysis of cases from January 2007 to December 2017 with corpus callosum anomalies, either referred for a second opinion or derived from the prenatal ultrasound screening program in a single tertiary referral center. Cases with complete agenesis were excluded from the analysis. Standardized investigation included a detailed fetal ultrasound including neurosonogram, fetal karyotyping (standard karyotype or array comparative genomic hybridization) and fetal magnetic resonance imaging. The pregnancy outcome was collected, and pathologic investigation in case of termination of the pregnancy or fetal or neonatal loss was compared with the prenatal findings. The pregnancy and fetal or neonatal outcomes were reported. The neurologic assessment was conducted by a pediatric neurologist using the Bayley Scales of Infant Development-II and the standardized Child Development Inventory when the Bayley investigation was unavailable. Corpus callosum anomalies were diagnosed in 148 cases during the study period, 62 (41.9%) of which were excluded because of complete agenesis, and 86 fetuses had partial agenesis (58.1%). In 20 cases, partial agenesis (23.2%) was isolated, whereas 66 (76.7%) presented with different malformations among which 29 cases (43.9%) were only central nervous system lesions, 21 cases (31.8%) were non-central nervous system lesions, and 16 cases (24.3%) had a combination of central nervous system and non-central nervous system lesions. The mean gestational age at diagnosis for isolated and non-isolated cases was comparable (24.29 [standard deviation, 5.05] weeks and 24.71 [standard deviation, 5.35] weeks, respectively). Of the 86 pregnancies with partial agenesis, 46 patients opted for termination of the pregnancy. Neurologic follow-up data were available for 35 children. The overall neurologic outcome was normal in 21 of 35 children (60%); 3 of 35 (8.6%) showed mild impairment and 6 of 35 (17.1%) showed moderate impairment. The remaining 5 of 35 (14.3%) had severe impairment. The median duration of follow-up for the isolated form was 45.6 months (range, 36-52 months) and 73.3 months (range, 2-138 months) for the nonisolated form. Partial corpus callosum agenesis should be accurately investigated by neurosonography and fetal magnetic resonance imaging to describe its morphology and the associated anomalies. Genetic anomalies are frequently present in nonisolated cases. Efforts must be taken to improve ultrasound diagnosis of partial agenesis and to confirm its isolated nature to enhance parental counseling. Although 60% of children with prenatal diagnosis of isolated agenesis have a favorable prognosis later in life, they often have mild to severe disabilities including speech disorders at school age and behavior and motor deficit disorders that can emerge at a later age.

Fetal brain volumes and neurodevelopmental outcome of intrauterine growth restricted fetuses

ObjectiveThis study aims to investigate the correlation of MRI measured fetal brain volumetrics with long-term neurodevelopmental outcome, among intrauterine growth restricted (IUGR) and apparently healthy fetuses. Study designA historical cohort study at a single tertiary referral medical center during 6 years period, of fetuses diagnosed with IUGR due to placental insufficiency, and apparently healthy fetuses, who had fetal brain MRI scan. The volumes of the supratentorial brain region, both hemispheres and the cerebellum were measured by 3D MRI semi-automated volume measurements. The cerebellar to supratentorial ratio (CER/ST) was calculated. Volumes were plotted on normal growth curves. 17 IUGR fetuses, and 53 apparently healthy fetuses adhered to participate in the VABS-II questionnaire, evaluating neurodevelopmental outcome. Results70 patients (mean age at conducting VABS-II questionnaire 4.4 ± 2.1 years, 38 males) were evaluated. Among fetuses born in a gestational age of 36 weeks or later, IUGR fetuses demonstrated a significantly larger number of abnormal results in the VABS-II communication domain (p =.049). No significant differences were found in other domains or in overall neurodevelopmental outcome. The CER/ST ratio correlated with the overall neurodevelopmental outcome of the total study population (r = 0.40, p <.001), and of the IUGR group separately (ρ = 0.58, p =.02). ConclusionCER/ST ratio measured using fetal brain MRI was found to be correlated with long term neurodevelopmental outcome. This result may aid in clinical interpretation of biometric data obtained by fetal brain MRI, linking it with long term neurodevelopmental outcome.