Synthetic MRI and MR Fingerprinting-Derived Relaxometry of Antenatal Human Brainstem Myelination: A Postmortem-Based Quantitative Imaging Study.

BACKGROUND AND PURPOSE: The radiologic evaluation of ongoing myelination is currently limited prenatally. Novel quantitative MR imaging modalities provide relaxometric properties that are linked to myelinogenesis. In this retrospective postmortem imaging study, the capability of Synthetic MR imaging and MR fingerprinting-derived relaxometry for tracking fetal myelin development was investigated. Moreover, the consistency of results for both MR approaches was analyzed. MATERIALS AND METHODS: In 26 cases, quantitative postmortem fetal brain MR data were available (gestational age range, 15 + 1 to 32 + 1; female/male ratio, 14/12). Relaxometric measurements (T1-/T2-relexation times) were determined in the medulla oblongata and the midbrain using Synthetic MR imaging/MR fingerprinting-specific postprocessing procedures (Synthetic MR imaging and MR Robust Quantitative Tool for MR fingerprinting). The Pearson correlations were applied to detect relationships between T1-relaxation times/T2-relaxation times metrics and gestational age at MR imaging. Intraclass correlation coefficients were calculated to assess the consistency of the results provided by both modalities. RESULTS: Both modalities provided quantitative data that revealed negative correlations with gestational age at MR imaging: Synthetic MR imaging-derived relaxation times (medulla oblongata [r = -0.459; P = .021]; midbrain [r = -0.413; P = .040]), T2-relaxation times (medulla oblongata [r = -0.625; P < .001]; midbrain [r = -0.571; P = .003]), and MR fingerprinting-derived T1-relaxation times (medulla oblongata [r = -0.433; P = .035]; midbrain [r = -0.386; P = .062]), and T2-relaxation times (medulla oblongata [r =-0.883; P < .001]; midbrain [r = -0.890; P < .001]).The intraclass correlation coefficient analysis for result consistency between both MR approaches ranged between 0.661 (95% CI, 0.351-0.841) (T2-relaxation times: medulla oblongata) and 0.920 (95% CI, 0.82-0.965) (T1-relaxation times: midbrain). CONCLUSIONS: There is a good-to-excellent consistency between postmortem Synthetic MR imaging and MR fingerprinting myelin quantifications in fetal brains older than 15 + 1 gestational age. The strong correlations between quantitative myelin metrics and gestational age indicate the potential of quantitative MR imaging to identify delayed or abnormal states of myelination at prenatal stages of cerebral development.

Neurodevelopmental outcome in preterm infants with intraventricular hemorrhages: the potential of quantitative brainstem MRI.

OBJECTIVES: This retrospective study aimed to identify quantitative magnetic resonance imaging markers in the brainstem of preterm neonates with intraventricular hemorrhages. It delves into the intricate associations between quantitative brainstem magnetic resonance imaging metrics and neurodevelopmental outcomes in preterm infants with intraventricular hemorrhage, aiming to elucidate potential relationships and their clinical implications. MATERIALS AND METHODS: Neuroimaging was performed on preterm neonates with intraventricular hemorrhage using a multi-dynamic multi-echo sequence to determine T1 relaxation time, T2 relaxation time, and proton density in specific brainstem regions. Neonatal outcome scores were collected using the Bayley Scales of Infant and Toddler Development. Statistical analysis aimed to explore potential correlations between magnetic resonance imaging metrics and neurodevelopmental outcomes. RESULTS: Sixty preterm neonates (mean gestational age at birth 26.26 ± 2.69 wk; n = 24 [40%] females) were included. The T2 relaxation time of the midbrain exhibited significant positive correlations with cognitive (r = 0.538, P < 0.0001, Pearson's correlation), motor (r = 0.530, P < 0.0001), and language (r = 0.449, P = 0.0008) composite scores at 1 yr of age. CONCLUSION: Quantitative magnetic resonance imaging can provide valuable insights into neurodevelopmental outcomes after intraventricular hemorrhage, potentially aiding in identifying at-risk neonates. Multi-dynamic multi-echo sequence sequences hold promise as an adjunct to conventional sequences, enhancing the sensitivity of neonatal magnetic resonance neuroimaging and supporting clinical decision-making for these vulnerable patients.

Revisiting the Pathophysiology of Intracranial Hemorrhage in Fetuses with Chiari II Malformation: Novel Imaging Biomarkers of Disease Severity?

BACKGROUND AND PURPOSE: Intracranial hemorrhage (ICH) has emerged as a notable concern in Chiari II malformation (CM II), yet its origins and clinical implications remain elusive. This study aims to validate the in utero prevalence of ICH in CM II and investigate contributing factors, and visualize the findings in a network format. MATERIALS AND METHODS: A single-center retrospective review of fetal MRI scans obtained in fetuses with CM II (presenting January 2007 to December 2022) was performed for ICH utilizing EPI-T2* blood-sensitive sequence. Fetuses with aqueduct stenosis (AS) were included as a control group. The incidence of ICH and corresponding gestational ages were compared between CM II and AS cases, and morphometric measurements (inner/outer CSF spaces, posterior fossa, venous structure) were compared among the 4 1:1 age-matched groups: CM II+ICH, CM II-ICH, AS+ICH, and AS-ICH. Additionally, a co-occurrence network was constructed to visualize associations between phenotypic features in ICH cases. RESULTS: A total of 101 fetuses with CM II and 90 controls with AS at a median gestational age of 24.4 weeks and 22.8 weeks (P = .138) were included. Prevalence of ICH in fetuses with CM II was higher compared with the AS cases (28.7% versus 18.9%, P = .023), accompanied by congested veins (deep vein congestion mainly in young fetuses, and cortical veins may also be affected in older fetuses). ICH was notably correlated with specific anatomic features, essentially characterized by reduced outer CSF spaces and clivus-supraocciput angle. The co-occurrence network analysis reveals complex connections including bony defects, small posterior fossa dimensions, vermis ectopia, reduced CSF spaces, as well as venous congestion and venous sinus stenosis as pivotal components within the network. CONCLUSIONS: The high prevalence of ICH-detected by fetal MRI-among fetuses with CM emphasizes the pathophysiologic importance of venous congestion, ICH, and vasogenic edema. As indicators of disease severity, these features may serve as helpful additional imaging biomarkers for the identification of potential candidates for fetal surgery.

ARID1B controls transcriptional programs of axon projection in an organoid model of the human corpus callosum.

Mutations in ARID1B, a member of the mSWI/SNF complex, cause severe neurodevelopmental phenotypes with elusive mechanisms in humans. The most common structural abnormality in the brain of ARID1B patients is agenesis of the corpus callosum (ACC), characterized by the absence of an interhemispheric white matter tract that connects distant cortical regions. Here, we find that neurons expressing SATB2, a determinant of callosal projection neuron (CPN) identity, show impaired maturation in ARID1B+/- neural organoids. Molecularly, a reduction in chromatin accessibility of genomic regions targeted by TCF-like, NFI-like, and ARID-like transcription factors drives the differential expression of genes required for corpus callosum (CC) development. Through an in vitro model of the CC tract, we demonstrate that this transcriptional dysregulation impairs the formation of long-range axonal projections, causing structural underconnectivity. Our study uncovers new functions of the mSWI/SNF during human corticogenesis, identifying cell-autonomous axonogenesis defects in SATB2+ neurons as a cause of ACC in ARID1B patients.

Multiparametric prenatal imaging characterization of fetal brain edema in Chiari II malformation might help to select candidates for fetal surgery.

OBJECTIVE: To identify brain edema in fetuses with Chiari II malformation using a multiparametric approach including structural T2-weighted, diffusion tensor imaging (DTI) metrics, and MRI-based radiomics. METHODS: A single-center retrospective review of MRI scans obtained in fetuses with Chiari II was performed. Brain edema cases were radiologically identified using the following MR criteria: brain parenchymal T2 prolongation, blurring of lamination, and effacement of external CSF spaces. Fractional anisotropy (FA) values were calculated from regions of interest (ROI), including hemispheric parenchyma, internal capsule, and corticospinal tract, and compared group-wise. After 1:1 age matching and manual single-slice 2D segmentation of the fetal brain parenchyma using ITK-Snap, radiomics features were extracted using pyradiomics. Areas under the curve (AUCs) of the features regarding discriminating subgroups were calculated. RESULTS: Ninety-one fetuses with Chiari II underwent a total of 101 MRI scans at a median gestational age of 24.4 weeks and were included. Fifty scans were visually classified as Chiari II with brain edema group and showed significantly reduced external CSF spaces compared to the nonedema group (9.8 vs. 18.3 mm, p < 0.001). FA values of all used ROIs were elevated in the edema group (p < 0.001 for all ROIs). The 10 most important radiomics features showed an AUC of 0.81 (95%CI: 0.71, 0.91) for discriminating between Chiari II fetuses with and without edema. CONCLUSIONS: Brain edema in fetuses with Chiari II is common and radiologically detectable on T2-weighted fetal MRI sequences, and DTI-based FA values and radiomics features provide further evidence of microstructure differences between subgroups with and without edema. CLINICAL RELEVANCE STATEMENT: A more severe phenotype of fetuses with Chiari II malformation is characterized by prenatal brain edema and more postnatal clinical morbidity and disability. Fetal brain edema is a promising prenatal MR imaging biomarker candidate for optimizing the risk-benefit evaluation of selection for fetal surgery. KEY POINTS: Brain edema of fetuses prenatally diagnosed with Chiari II malformation is a common, so far unknown, association. DTI metrics and radiomics confirm microstructural differences between the brains of Chiari II fetuses with and without edema. Fetal brain edema may explain worse motor outcomes in this Chiari II subgroup, who may substantially benefit from fetal surgery.

Multi-Dynamic-Multi-Echo-based MRI for the Pre-Surgical Determination of Sellar Tumor Consistency: a Quantitative Approach for Predicting Lesion Resectability.

PURPOSE: Pre-surgical information about tumor consistency could facilitate neurosurgical planning. This study used multi-dynamic-multi-echo (MDME)-based relaxometry for the quantitative determination of pituitary tumor consistency, with the aim of predicting lesion resectability. METHODS: Seventy-two patients with suspected pituitary adenomas, who underwent preoperative 3 T MRI between January 2020 and January 2022, were included in this prospective study. Lesion-specific T1-/T2-relaxation times (T1R/T2R) and proton density (PD) metrics were determined. During surgery, data about tumor resectability were collected. A Receiver Operating Characteristic (ROC) curve analysis was performed to investigate the diagnostic performance (sensitivity/specificity) for discriminating between easy- and hard-to-remove by aspiration (eRAsp and hRAsp) lesions. A Mann-Whitney-U-test was done for group comparison. RESULTS: A total of 65 participants (mean age, 54 years ± 15, 33 women) were enrolled in the quantitative analysis. Twenty-four lesions were classified as hRAsp, while 41 lesions were assessed as eRAsp. There were significant differences in T1R (hRAsp: 1221.0 ms ± 211.9; eRAsp: 1500.2 ms ±â€¯496.4; p = 0.003) and T2R (hRAsp: 88.8 ms ± 14.5; eRAsp: 137.2 ms ± 166.6; p = 0.03) between both groups. The ROC analysis revealed an area under the curve of 0.72 (95% CI: 0.60-0.85) at p = 0.003 for T1R (cutoff value: 1248 ms; sensitivity/specificity: 78%/58%) and 0.66 (95% CI: 0.53-0.79) at p = 0.03 for T2R (cutoff value: 110 ms; sensitivity/specificity: 39%/96%). CONCLUSION: MDME-based relaxometry enables a non-invasive, pre-surgical characterization of lesion consistency and, therefore, provides a modality with which to predict tumor resectability.

Fetal indusium griseum is a possible biomarker of the regularity of brain midline development in 3T MR imaging: A retrospective observational study.

INTRODUCTION: This study aimed to assess the visibility of the indusium griseum (IG) in magnetic resonance (MR) scans of the human fetal brain and to evaluate its reliability as an imaging biomarker of the normality of brain midline development. MATERIAL AND METHODS: The retrospective observational study encompassed T2-w 3T MR images from 90 post-mortem fetal brains and immunohistochemical sections from 41 fetal brains (16-40 gestational weeks) without cerebral pathology. Three raters independently inspected and evaluated the visibility of IG in post-mortem and in vivo MR scans. Weighted kappa statistics and regression analysis were used to determine inter- and intra-rater agreement and the type and strength of the association of IG visibility with gestational age. RESULTS: The visibility of the IG was the highest between the 25 and 30 gestational week period, with a very good inter-rater variability (kappa 0.623-0.709) and excellent intra-rater variability (kappa 0.81-0.93). The immunochemical analysis of the histoarchitecture of IG discloses the expression of highly hydrated extracellular molecules in IG as the substrate of higher signal intensity and best visibility of IG during the mid-fetal period. CONCLUSIONS: The knowledge of developmental brain histology and fetal age allows us to predict the IG-visibility in magnetic resonance imaging (MRI) and use it as a biomarker to evaluate the morphogenesis of the brain midline. As a biomarker, IG is significant for post-mortem pathological examination by MRI. Therefore, in the clinical in vivo imaging examination, IG should be anticipated when an assessment of the brain midline structures is needed in mid-gestation, including corpus callosum thickness measurements.

A Dempster-Shafer Approach to Trustworthy AI With Application to Fetal Brain MRI Segmentation.

Deep learning models for medical image segmentation can fail unexpectedly and spectacularly for pathological cases and images acquired at different centers than training images, with labeling errors that violate expert knowledge. Such errors undermine the trustworthiness of deep learning models for medical image segmentation. Mechanisms for detecting and correcting such failures are essential for safely translating this technology into clinics and are likely to be a requirement of future regulations on artificial intelligence (AI). In this work, we propose a trustworthy AI theoretical framework and a practical system that can augment any backbone AI system using a fallback method and a fail-safe mechanism based on Dempster-Shafer theory. Our approach relies on an actionable definition of trustworthy AI. Our method automatically discards the voxel-level labeling predicted by the backbone AI that violate expert knowledge and relies on a fallback for those voxels. We demonstrate the effectiveness of the proposed trustworthy AI approach on the largest reported annotated dataset of fetal MRI consisting of 540 manually annotated fetal brain 3D T2w MRIs from 13 centers. Our trustworthy AI method improves the robustness of four backbone AI models for fetal brain MRIs acquired across various centers and for fetuses with various brain abnormalities.

Quantitative Magnetic Resonance Imaging for Neurodevelopmental Outcome Prediction in Neonates Born Extremely Premature-An Exploratory Study.

PURPOSE: Neonates born at < 28 weeks of gestation are at risk for neurodevelopmental delay. The aim of this study was to identify quantitative MR-based metrics for the prediction of neurodevelopmental outcomes in extremely preterm neonates. METHODS: T1-/T2-relaxation times (T1R/T2R), ADC, and fractional anisotropy (FA) of the left/right posterior limb of the internal capsule (PLIC) and the brainstem were determined at term-equivalent ages in a sample of extremely preterm infants (n = 33). Scores for cognitive, language, and motor outcomes were collected at one year corrected-age. Pearson's correlation analyses detected relationships between quantitative measures and outcome data. Stepwise regression procedures identified imaging metrics to estimate neurodevelopmental outcomes. RESULTS: Cognitive outcomes correlated significantly with T2R (r = 0.412; p = 0.017) and ADC (r = -0.401; p = 0.021) (medulla oblongata). Furthermore, there were significant correlations between motor outcomes and T1R (pontine tegmentum (r = 0.346; p = 0.049), midbrain (r = 0.415; p = 0.016), right PLIC (r = 0.513; p = 0.002), and left PLIC (r = 0.504; p = 0.003)); T2R (right PLIC (r = 0.405; p = 0.019)); ADC (medulla oblongata (r = -0.408; p = 0.018) and pontine tegmentum (r = -0.414; p = 0.017)); and FA (pontine tegmentum (r = -0.352; p = 0.045)). T2R/ADC (medulla oblongata) (cognitive outcomes (R2 = 0.296; p = 0.037)) and T1R (right PLIC)/ADC (medulla oblongata) (motor outcomes (R2 = 0.405; p = 0.009)) revealed predictive potential for neurodevelopmental outcomes. CONCLUSION: There are relationships between relaxometry­/DTI-based metrics determined by neuroimaging near term and neurodevelopmental outcomes collected at one year of age. Both modalities bear prognostic potential for the prediction of cognitive and motor outcomes. Thus, quantitative MRI at term-equivalent ages represents a promising approach with which to estimate neurologic development in extremely preterm infants.

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

OBJECTIVES: To 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 METHODS: This 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. RESULTS: MTS 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. CONCLUSION: T1-FFLAIR outperforms the standard T1-FFE sequence in the visualization of fetal brain myelination, as demonstrated by qualitative and quantitative methods. CLINICAL RELEVANCE STATEMENT: T1-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.

Cortical thickness in the right medial frontal gyrus predicts planning performance in healthy children and adolescents.

The ability to plan is an important part of the set of the cognitive skills called "executive functions." To be able to plan actions in advance is of great importance in everyday life and constitutes one of the major key features for academic as well as economic success. The present study aimed to investigate the neuroanatomical correlates of planning in normally developing children, as measured by the cortical thickness of the prefrontal cortex. Eighteen healthy children and adolescents underwent structural MRI examinations and the Tower of London (ToL) task. A multiple regression analysis revealed that the cortical thickness of the right caudal middle frontal gyrus (cMFG) was a significant predictor of planning performance. Neither the cortical thickness of any other prefrontal area nor gender were significantly associated with performance in the ToL task. The results of the present exploratory study suggest that the cortical thickness of the right, but not the left cMFG, is positively correlated with performance in the ToL task. We, therefore, conclude that increased cortical thickness may be more beneficial for higher-order processes, such as information integration, than for lower-order processes, such as the analysis of external information.

Evolution of cortical geometry and its link to function, behaviour and ecology.

Studies in comparative neuroanatomy and of the fossil record demonstrate the influence of socio-ecological niches on the morphology of the cerebral cortex, but have led to oftentimes conflicting theories about its evolution. Here, we study the relationship between the shape of the cerebral cortex and the topography of its function. We establish a joint geometric representation of the cerebral cortices of ninety species of extant Euarchontoglires, including commonly used experimental model organisms. We show that variability in surface geometry relates to species' ecology and behaviour, independent of overall brain size. Notably, ancestral shape reconstruction of the cortical surface and its change during evolution enables us to trace the evolutionary history of localised cortical expansions, modal segregation of brain function, and their association to behaviour and cognition. We find that individual cortical regions follow different sequences of area increase during evolutionary adaptations to dynamic socio-ecological niches. Anatomical correlates of this sequence of events are still observable in extant species, and relate to their current behaviour and ecology. We decompose the deep evolutionary history of the shape of the human cortical surface into spatially and temporally conscribed components with highly interpretable functional associations, highlighting the importance of considering the evolutionary history of cortical regions when studying their anatomy and function.

Initial Evidence for Positive Effects of a Psychological Preparation Program for MRI "iMReady" in Children with Neurofibromatosis Type I and Brain Tumors-How to Meet the Patients' Needs Best.

To provide an effective alternative to sedation during MRI examinations in pediatric cancer and NF1 patients, the aims of the present study were to (1) exploratively evaluate a behavioral MRI training program, to (2) investigate potential moderators, as well as to (3) assess the patients' well-being over the course of the intervention. A total of n = 87 patients of the neuro-oncology unit (mean age: 6.83 years) underwent a two-step MRI preparation program, including training inside the scanner, and were recorded using a process-oriented screening. In addition to the retrospective analysis of all data, a subset of 17 patients were also analyzed prospectively. Overall, 80% of the children receiving MRI preparation underwent the MRI scan without sedation, making the success rate almost five times higher than that of a group of 18 children that opted out of the training program. Memory, attentional difficulties, and hyperactivity were significant neuropsychological moderators for successful scanning. The training was associated with favorable psychological well-being. These findings suggest that our MRI preparation could present an alternative to sedation of young patients undergoing MRI examinations as well as a promising tool for improving patients' treatment-related well-being.

Reproducibility of 2D versus 3D radiomics for quantitative assessment of fetal lung development: a retrospective fetal MRI study.

PURPOSE: To investigate the reproducibility of radiomics features extracted from two-dimensional regions of interest (2D ROIs) versus whole lung (3D) ROIs in repeated in-vivo fetal magnetic resonance imaging (MRI) acquisitions. METHODS: Thirty fetal MRI scans including two axial T2-weighted acquisitions of the lungs were analysed. 2D (lung at the level of the carina) and 3D (whole lung) ROIs were manually segmented using ITK-Snap. Ninety-five radiomics features were extracted from 2 and 3D ROIs in initial and repeat acquisitions using Pyradiomics. Radiomics feature intra-class correlation coefficients (ICC) were calculated between 2 and 3D ROIs in the initial acquisition, and between 2 and 3D ROIs in repeated acquisitions, respectively. RESULTS: MRI data of 11 (36.7%) female and 19 (63.3%) male fetuses acquired at a median 25 + 0 gestational weeks plus days (GW) (interquartile range [IQR] 23 + 4 - 27 + 0 GW) were assessed. Median radiomics feature ICC between 2 and 3D ROIs in the initial MRI acquisition was 0.733 (IQR 0.313-0.814, range 0.018-0.970). ICCs between radiomics features extracted using 3D ROIs in initial and repeat acquisitions (median 0.908 [IQR 0.824-0.929, range 0.335-0.996]) were significantly higher compared to 2D ROIs (0.771 [0.699-0.835, 0.048-0.965]) (p < 0.001). CONCLUSION: Fetal MRI radiomics features extracted from 3D whole lung segmentation masks showed significantly higher reproducibility across repeat acquisitions compared to 2D ROIs. Therefore, fetal MRI whole lung radiomics features are robust diagnostic and potentially prognostic tools in the image-based in-vivo quantitative assessment of lung development.

Fetal MRI based brain atlas analysis detects initial in utero effects of prenatal alcohol exposure.

Prenatal alcohol exposure (PAE) can change the normal trajectory of human fetal brain development and may lead to long-lasting neurodevelopmental changes in the form of fetal alcohol spectrum disorders. Currently, early prenatal patterns of alcohol-related central nervous system changes are unclear and it is unknown if small amounts of PAE may result in early detectable brain anomalies. This super-resolution fetal magnetic resonance imaging (MRI) study aimed to identify regional effects of PAE on human brain structure. Fetuses were prospectively assessed using atlas-based semi-automated 3-dimensional tissue segmentation based on 1.5 T and 3 T fetal brain MRI examinations. After expectant mothers completed anonymized PRAMS and TACE questionnaires for PAE, fetuses without gross macroscopic brain abnormalities were identified and analyzed. Linear mixed-effects modeling of regional brain volumes was conducted and multiple comparisons were corrected using the Benjamini-Hochberg procedure. In total, 500 pregnant women were recruited with 51 reporting gestational alcohol consumption. After excluding confounding comorbidities, 24 fetuses (26 observations) were identified with PAE and 52 age-matched controls without PAE were analyzed. Patients with PAE showed significantly larger volumes of the corpus callosum (P ≤ 0.001) and smaller volumes of the periventricular zone (P = 0.001). Even minor (1-3 standard drinks per week) PAE changed the neurodevelopmental trajectory.

Fetal MRI radiomics: non-invasive and reproducible quantification of human lung maturity.

OBJECTIVES: To assess the reproducibility of radiomics features extracted from the developing lung in repeated in-vivo fetal MRI acquisitions. METHODS: In-vivo MRI (1.5 Tesla) scans of 30 fetuses, each including two axial and one coronal T2-weighted sequences of the whole lung with all other acquisition parameters kept constant, were retrospectively identified. Manual segmentation of the lungs was performed using ITK-Snap. One hundred radiomics features were extracted from fetal lung MRI data using Pyradiomics, resulting in 90 datasets. Intra-class correlation coefficients (ICC) of radiomics features were calculated between baseline and repeat axial acquisitions and between baseline axial and coronal acquisitions. RESULTS: MRI data of 30 fetuses (12 [40%] females, 18 [60%] males) at a median gestational age of 24 + 5 gestational weeks plus days (GW) (interquartile range [IQR] 3 + 3 GW, range 21 + 1 to 32 + 6 GW) were included. Median ICC of radiomics features between baseline and repeat axial MR acquisitions was 0.92 (IQR 0.13, range 0.33 to 1), with 60 features exhibiting excellent (ICC > 0.9), 27 good (> 0.75-0.9), twelve moderate (0.5-0.75), and one poor (ICC < 0.5) reproducibility. Median ICC of radiomics features between baseline axial and coronal MR acquisitions was 0.79 (IQR 0.15, range 0.2 to 1), with 20 features exhibiting excellent, 47 good, 29 moderate, and four poor reproducibility. CONCLUSION: Standardized in-vivo fetal MRI allows reproducible extraction of lung radiomics features. In the future, radiomics analysis may improve diagnostic and prognostic yield of fetal MRI in normal and pathologic lung development. KEY POINTS: • Non-invasive fetal MRI acquired using a standardized protocol allows reproducible extraction of radiomics features from the developing lung for objective tissue characterization. • Alteration of imaging plane between fetal MRI acquisitions has a negative impact on lung radiomics feature reproducibility. • Fetal MRI radiomics features reflecting the microstructure and shape of the fetal lung could complement observed-to-expected lung volume in the prediction of postnatal outcome and optimal treatment of fetuses with abnormal lung development in the future.

SARS-CoV-2 variant-related abnormalities detected by prenatal MRI: a prospective case-control study.

Background: There are known complications for fetuses after infection with SARS-CoV-2 during pregnancy. However, previous studies of SARS-CoV-2 in pregnancy have largely been limited to histopathologic studies of placentas and prenatal studies on the effects of different SARS-CoV-2 variants are scarce to date. To examine the effects of SARS-CoV-2 variants on the placenta and fetus, we investigated fetal and extra-fetal structures using prenatal MRI. Methods: For this prospective case-control study, two obstetric centers consecutively referred pregnant women for prenatal MRI after confirmed SARS-CoV-2 infection. Thirty-eight prenatal MRI examinations were included after confirmed infection with SARS-CoV-2 and matched 1:1 with 38 control cases with respect to sex, MRI field strength, and gestational age (average deviation 1.76 ± 1.65, median 1.5 days). Where available, the pathohistological examination and vaccination status of the placenta was included in the analysis. In prenatal MRI, the shape and thickness of the placenta, possible lobulation, and vascular lesions were quantified. Fetuses were scanned for organ or brain abnormalities. Findings: Of the 38 included cases after SARS-CoV-2 infection, 20/38 (52.6%) were infected with pre-Omicron variants and 18/38 (47.4%) with Omicron. Prenatal MRIs were performed on an average of 83 days (±42.9, median 80) days after the first positive PCR test. Both pre-Omicron (P = .008) and Omicron (P = .016) groups showed abnormalities in form of a globular placenta compared to control cases. In addition, placentas in the pre-Omicron group were significantly thickened (6.35, 95% CI .02-12.65, P = .048), and showed significantly more frequent lobules (P = .046), and hemorrhages (P = .002). Fetal growth restriction (FGR) was observed in 25% (n = 5/20, P = .017) in the pre-Omicron group. Interpretation: SARS-CoV-2 infections in pregnancy can lead to placental lesions based on vascular events, which can be well visualized on prenatal MRI. Pre-Omicron variants cause greater damage than Omicron sub-lineages in this regard. Funding: Vienna Science and Technology Fund.

Fetal temporal sulcus depth asymmetry has prognostic value for language development.

In most humans, the superior temporal sulcus (STS) shows a rightward depth asymmetry. This asymmetry can not only be observed in adults, but is already recognizable in the fetal brain. As the STS lies adjacent to brain areas important for language, STS depth asymmetry may represent an anatomical marker for language abilities. This study investigated the prognostic value of STS depth asymmetry in healthy fetuses for later language abilities, language localization, and language-related white matter tracts. Less right lateralization of the fetal STS depth was significantly associated with better verbal abilities, with fetal STS depth asymmetry explaining more than 40% of variance in verbal skills 6-13 years later. Furthermore, less right fetal STS depth asymmetry correlated with increased left language localization during childhood. We hypothesize that earlier and/or more localized fetal development of the left temporal cortex is accompanied by an earlier development of the left STS and is favorable for early language learning. If the findings of this pilot study hold true in larger samples of healthy children and in different clinical populations, fetal STS asymmetry has the potential to become a diagnostic biomarker of the maturity and integrity of neural correlates of language.

Visual outcomes after anterior temporal lobectomy and transsylvian selective amygdalohippocampectomy: A quantitative comparison of clinical and diffusion data.

OBJECTIVE: Anterior temporal lobectomy (ATL) and transsylvian selective amygdalohippocampectomy (tsSAHE) are effective treatment strategies for intractable temporal lobe epilepsy but may cause visual field deficits (VFDs) by damaging the optic radiation (OpR). Due to the OpR's considerable variability and because it is indistinguishable from surrounding tissue without further technical guidance, it is highly vulnerable to iatrogenic injury. This imaging study uses a multimodal approach to assess visual outcomes after epilepsy surgery. METHODS: We studied 62 patients who underwent ATL (n = 32) or tsSAHE (n = 30). Analysis of visual outcomes was conducted in four steps, including the assessment of (1) perimetry outcome (VFD incidence/extent, n = 44/40), (2) volumetric OpR tractography damage (n = 55), and the (3) relation of volumetric OpR tractography damage and perimetry outcome (n = 35). Furthermore, (4) fixel-based analysis (FBA) was performed to assess micro- and macrostructural changes within the OpR following surgery (n = 36). RESULTS: Altogether, 56% of all patients had postoperative VFDs (78.9% after ATL, 36.36% after tsSAHE, p = .011). VFDs and OpR tractography damage tended to be more severe within the ATL group (ATL vs. tsSAHE, integrity of contralateral upper quadrant: 65% vs. 97%, p = .002; OpR tractography damage: 69.2 mm3 vs. 3.8 mm3 , p = .002). Volumetric OpR tractography damage could reliably predict VFD incidence (86% sensitivity, 78% specificity) and could significantly explain VFD extent (R2  = .47, p = .0001). FBA revealed a more widespread decline of fibre cross-section within the ATL group. SIGNIFICANCE: In the context of controversial visual outcomes following epilepsy surgery, this study provides clinical as well as neuroimaging evidence for a higher risk and greater severity of postoperative VFDs after ATL compared to tsSAHE. Volumetric OpR tractography damage is a feasible parameter to reliably predict this morbidity in both treatment groups and may ultimately support personalized planning of surgical candidates. Advanced diffusion analysis tools such as FBA offer a structural explanation of surgically induced visual pathway damage, allowing noninvasive quantification and visualization of micro- and macrostructural tract affection.