Pathological shifts in tryptophan metabolism in human term placenta exposed to LPS or poly I:C†.

Maternal immune activation during pregnancy is a risk factor for offspring neuropsychiatric disorders. Among the mechanistic pathways by which maternal inflammation can affect fetal brain development and programming, those involving tryptophan (TRP) metabolism have drawn attention because various TRP metabolites have neuroactive properties. This study evaluates the effect of bacterial (lipopolysaccharides/LPS) and viral (polyinosinic:polycytidylic acid/poly I:C) placental infection on TRP metabolism using an ex vivo model. Human placenta explants were exposed to LPS or poly I:C, and the release of TRP metabolites was analyzed together with the expression of related genes and proteins and the functional activity of key enzymes in TRP metabolism. The rate-limiting enzyme in the serotonin pathway, tryptophan hydroxylase, showed reduced expression and functional activity in explants exposed to LPS or poly I:C. Conversely, the rate-limiting enzyme in the kynurenine pathway, indoleamine dioxygenase, exhibited increased activity, gene, and protein expression, suggesting that placental infection mainly promotes TRP metabolism via the kynurenine (KYN) pathway. Furthermore, we observed that treatment with LPS or poly I:C increased activity in the kynurenine monooxygenase branch of the KYN pathway. We conclude that placental infection impairs TRP homeostasis, resulting in decreased production of serotonin and an imbalance in the ratio between quinolinic acid and kynurenic acid. This disrupted homeostasis may eventually expose the fetus to suboptimal/toxic levels of neuroactive molecules and impair fetal brain development.

Fully automated planning for anatomical fetal brain MRI on 0.55T.

PURPOSE: Widening the availability of fetal MRI with fully automatic real-time planning of radiological brain planes on 0.55T MRI. METHODS: Deep learning-based detection of key brain landmarks on a whole-uterus echo planar imaging scan enables the subsequent fully automatic planning of the radiological single-shot Turbo Spin Echo acquisitions. The landmark detection pipeline was trained on over 120 datasets from varying field strength, echo times, and resolutions and quantitatively evaluated. The entire automatic planning solution was tested prospectively in nine fetal subjects between 20 and 37 weeks. A comprehensive evaluation of all steps, the distance between manual and automatic landmarks, the planning quality, and the resulting image quality was conducted. RESULTS: Prospective automatic planning was performed in real-time without latency in all subjects. The landmark detection accuracy was 4.2 ± $$ \pm $$ 2.6 mm for the fetal eyes and 6.5 ± $$ \pm $$ 3.2 for the cerebellum, planning quality was 2.4/3 (compared to 2.6/3 for manual planning) and diagnostic image quality was 2.2 compared to 2.1 for manual planning. CONCLUSIONS: Real-time automatic planning of all three key fetal brain planes was successfully achieved and will pave the way toward simplifying the acquisition of fetal MRI thereby widening the availability of this modality in nonspecialist centers.

Fetal development of functional thalamocortical and cortico-cortical connectivity.

Measuring and understanding functional fetal brain development in utero is critical for the study of the developmental foundations of our cognitive abilities, possible early detection of disorders, and their prevention. Thalamocortical connections are an intricate component of shaping the cortical layout, but so far, only ex-vivo studies provide evidence of how axons enter the sub-plate and cortex during this highly dynamic phase. Evidence for normal in-utero development of the functional thalamocortical connectome in humans is missing. Here, we modeled fetal functional thalamocortical connectome development using in-utero functional magnetic resonance imaging in fetuses observed from 19th to 40th weeks of gestation (GW). We observed a peak increase of thalamocortical functional connectivity strength between 29th and 31st GW, right before axons establish synapses in the cortex. The cortico-cortical connectivity increases in a similar time window, and exhibits significant functional laterality in temporal-superior, -medial, and -inferior areas. Homologous regions exhibit overall similar mirrored connectivity profiles, but this similarity decreases during gestation giving way to a more diverse cortical interconnectedness. Our results complement the understanding of structural development of the human connectome and may serve as the basis for the investigation of disease and deviations from a normal developmental trajectory of connectivity development.

Real-time fetal brain tracking for functional fetal MRI.

PURPOSE: To improve motion robustness of functional fetal MRI scans by developing an intrinsic real-time motion correction method. MRI provides an ideal tool to characterize fetal brain development and growth. It is, however, a relatively slow imaging technique and therefore extremely susceptible to subject motion, particularly in functional MRI experiments acquiring multiple Echo-Planar-Imaging-based repetitions, for example, diffusion MRI or blood-oxygen-level-dependency MRI. METHODS: A 3D UNet was trained on 125 fetal datasets to track the fetal brain position in each repetition of the scan in real time. This tracking, inserted into a Gadgetron pipeline on a clinical scanner, allows updating the position of the field of view in a modified echo-planar imaging sequence. The method was evaluated in real-time in controlled-motion phantom experiments and ten fetal MR studies (17 + 4-34 + 3 gestational weeks) at 3T. The localization network was additionally tested retrospectively on 29 low-field (0.55T) datasets. RESULTS: Our method achieved real-time fetal head tracking and prospective correction of the acquisition geometry. Localization performance achieved Dice scores of 84.4% and 82.3%, respectively for both the unseen 1.5T/3T and 0.55T fetal data, with values higher for cephalic fetuses and increasing with gestational age. CONCLUSIONS: Our technique was able to follow the fetal brain even for fetuses under 18 weeks GA in real-time at 3T and was successfully applied "offline" to new cohorts on 0.55T. Next, it will be deployed to other modalities such as fetal diffusion MRI and to cohorts of pregnant participants diagnosed with pregnancy complications, for example, pre-eclampsia and congenital heart disease.

Total and Regional Brain Volumes in Fetuses With Congenital Heart Disease.

BACKGROUND: Congenital heart disease (CHD) is common and is associated with impaired early brain development and neurodevelopmental outcomes, yet the exact mechanisms underlying these associations are unclear. PURPOSE: To utilize MRI data from a cohort of fetuses with CHD as well as typically developing fetuses to test the hypothesis that expected cerebral substrate delivery is associated with total and regional fetal brain volumes. STUDY TYPE: Retrospective case-control study. POPULATION: Three hundred eighty fetuses (188 male), comprising 45 healthy controls and 335 with isolated CHD, scanned between 29 and 37 weeks gestation. Fetuses with CHD were assigned into one of four groups based on expected cerebral substrate delivery. FIELD STRENGTH/SEQUENCE: T2-weighted single-shot fast-spin-echo sequences and a balanced steady-state free precession gradient echo sequence were obtained on a 1.5 T scanner. ASSESSMENT: Images were motion-corrected and reconstructed using an automated slice-to-volume registration reconstruction technique, before undergoing segmentation using an automated pipeline and convolutional neural network that had undergone semi-supervised training. Differences in total, regional brain (cortical gray matter, white matter, deep gray matter, cerebellum, and brainstem) and brain:body volumes were compared between groups. STATISTICAL TESTS: ANOVA was used to test for differences in brain volumes between groups, after accounting for sex and gestational age at scan. PFDR -values <0.05 were considered statistically significant. RESULTS: Total and regional brain volumes were smaller in fetuses where cerebral substrate delivery is reduced. No significant differences were observed in total or regional brain volumes between control fetuses and fetuses with CHD but normal cerebral substrate delivery (all PFDR > 0.12). Severely reduced cerebral substrate delivery is associated with lower brain:body volume ratios. DATA CONCLUSION: Total and regional brain volumes are smaller in fetuses with CHD where there is a reduction in cerebral substrate delivery, but not in those where cerebral substrate delivery is expected to be normal. EVIDENCE LEVEL: 3 TECHNICAL EFFICACY: Stage 3.

Morphological development of the human fetal striatum during the second trimester.

The morphological development of the fetal striatum during the second trimester has remained poorly described. We manually segmented the striatum using 7.0-T MR images of the fetal specimens ranging from 14 to 22 gestational weeks. The global development of the striatum was evaluated by volume measurement. The absolute volume (Vabs) of the caudate nucleus (CN) increased linearly with gestational age, while the relative volume (Vrel) showed a quadratic growth. Both Vabs and Vrel of putamen increased linearly. Through shape analysis, the changes of local structure in developing striatum were specifically demonstrated. Except for the CN tail, the lateral and medial parts of the CN grew faster than the middle regions, with a clear rostral-caudal growth gradient as well as a distinct "outside-in" growth gradient. For putamen, the dorsal and ventral regions grew obviously faster than the other regions, with a dorsal-ventral bidirectional developmental pattern. The right CN was larger than the left, whereas there was no significant hemispheric asymmetry in the putamen. By establishing the developmental trajectories, spatial heterochrony, and hemispheric dimorphism of human fetal striatum, these data bring new insight into the fetal striatum development and provide detailed anatomical references for future striatal studies.

Deciphering the developmental order and microstructural patterns of early white matter pathways in a diffusion MRI based fetal brain atlas.

White matter (WM) of the fetal brain undergoes rapid development to form early structural connections. Diffusion magnetic resonance imaging (dMRI) has shown to be a useful tool to depict fetal brain WM in utero, and many studies have observed increasing fractional anisotropy and decreasing diffusivity in the fetal brain during the second-to-third trimester, whereas others reported non-monotonic changes. Unbiased dMRI atlases of the fetal brain are important for characterizing the developmental trajectories of WM and providing normative references for in utero diagnosis of prenatal abnormalities. To date, the sole fetal brain dMRI atlas was collected from a Caucasian/mixed population and was constructed based on the diffusion tensor model with limited spatial resolution. In this work, we proposed a fiber orientation distribution (FOD) based pipeline for generating fetal brain dMRI atlases, which showed better registration accuracy than a diffusion tensor based pipeline. Based on the FOD-based pipeline, we constructed the first Chinese fetal brain dMRI atlas using 89 dMRI scans of normal fetuses at gestational age between 24 and 38 weeks. Complex non-monotonic trends of tensor- and FOD-derived microstructural parameters in eight WM tracts were observed, which jointly pointed to different phases of microstructural development. Specifically, we speculated that the turning point of the diffusivity trajectory may correspond to the starting point of pre-myelination, based on which, the developmental order of WM tracts can be mapped and the order was in agreement with the order of myelination from histological studies. The normative atlas also provided a reference for the detection of abnormal WM development, such as that in congenital heart disease. Therefore, the established high-order fetal brain dMRI atlas depicted the spatiotemporal pattern of early WM development, and findings may help decipher the distinct microstructural events in utero.

BEAN: Brain Extraction and Alignment Network for 3D Fetal Neurosonography.

Brain extraction (masking of extra-cerebral tissues) and alignment are fundamental first steps of most neuroimage analysis pipelines. The lack of automated solutions for 3D ultrasound (US) has therefore limited its potential as a neuroimaging modality for studying fetal brain development using routinely acquired scans. In this work, we propose a convolutional neural network (CNN) that accurately and consistently aligns and extracts the fetal brain from minimally pre-processed 3D US scans. Our multi-task CNN, Brain Extraction and Alignment Network (BEAN), consists of two independent branches: 1) a fully-convolutional encoder-decoder branch for brain extraction of unaligned scans, and 2) a two-step regression-based branch for similarity alignment of the brain to a common coordinate space. BEAN was tested on 356 fetal head 3D scans spanning the gestational range of 14 to 30 weeks, significantly outperforming all current alternatives for fetal brain extraction and alignment. BEAN achieved state-of-the-art performance for both tasks, with a mean Dice Similarity Coefficient (DSC) of 0.94 for the brain extraction masks, and a mean DSC of 0.93 for the alignment of the target brain masks. The presented experimental results show that brain structures such as the thalamus, choroid plexus, cavum septum pellucidum, and Sylvian fissure, are consistently aligned throughout the dataset and remain clearly visible when the scans are averaged together. The BEAN implementation and related code can be found under www.github.com/felipemoser/kelluwen.

Morphological Development Trajectory and Structural Covariance Network of the Human Fetal Cortical Plate during the Early Second Trimester.

During the early second trimester, the cortical plate, or "the developing cortex", undergoes immensely complex and rapid development to complete its major complement of neurons. However, morphological development of the cortical plate and the precise patterning of brain structural covariance networks during this period remain unexplored. In this study, we used 7.0 T high-resolution magnetic resonance images of brain specimens ranging from 14 to 22 gestational weeks to manually segment the cortical plate. Thickness, area expansion, and curvature (i.e., folding) across the cortical plate regions were computed, and correlations of thickness values among different cortical plate regions were measured to analyze fetal cortico-cortical structural covariance throughout development of the early second trimester. The cortical plate displayed significant increases in thickness and expansions in area throughout all regions but changes of curvature in only certain major sulci. The topological architecture and network properties of fetal brain covariance presented immature and inefficient organizations with low degree of integration and high degree of segregation. Altogether, our results provide novel insight on the developmental patterning of cortical plate thickness and the developmental origin of brain network architecture throughout the early second trimester.

The Prenatal Origins of Human Brain Asymmetry: Lessons Learned from a Cohort of Fetuses with Body Lateralization Defects.

Knowledge about structural brain asymmetries of human fetuses with body lateralization defects-congenital diseases in which visceral organs are partially or completely incorrectly positioned-can improve our understanding of the developmental origins of hemispheric brain asymmetry. This study investigated structural brain asymmetry in 21 fetuses, which were diagnosed with different types of lateralization defects; 5 fetuses with ciliopathies and 26 age-matched healthy control cases, between 22 and 34 gestational weeks of age. For this purpose, a database of 4007 fetal magnetic resonance imagings (MRIs) was accessed and searched for the corresponding diagnoses. Specific temporal lobe brain asymmetry indices were quantified using in vivo, super-resolution-processed MR brain imaging data. Results revealed that the perisylvian fetal structural brain lateralization patterns and asymmetry indices did not differ between cases with lateralization defects, ciliopathies, and normal controls. Molecular mechanisms involved in the definition of the right/left body axis-including cilium-dependent lateralization processes-appear to occur independently from those involved in the early establishment of structural human brain asymmetries. Atypically inverted early structural brain asymmetries are similarly rare in individuals with lateralization defects and may have a complex, multifactorial, and neurodevelopmental background with currently unknown postnatal functional consequences.

Global Network Organization of the Fetal Functional Connectome.

Recent advances in brain imaging have enabled non-invasive in vivo assessment of the fetal brain. Characterizing brain development in healthy fetuses provides baseline measures for identifying deviations in brain function in high-risk clinical groups. We examined 110 resting state MRI data sets from fetuses at 19 to 40 weeks' gestation. Using graph-theoretic techniques, we characterized global organizational features of the fetal functional connectome and their prenatal trajectories. Topological features related to network integration (i.e., global efficiency) and segregation (i.e., clustering) were assessed. Fetal networks exhibited small-world topology, showing high clustering and short average path length relative to reference networks. Likewise, fetal networks' quantitative small world indices met criteria for small-worldness (σ > 1, ω = [-0.5 0.5]). Along with this, fetal networks demonstrated global and local efficiency, economy, and modularity. A right-tailed degree distribution, suggesting the presence of central areas that are more highly connected to other regions, was also observed. Metrics, however, were not static during gestation; measures associated with segregation-local efficiency and modularity-decreased with advancing gestational age. Altogether, these suggest that the neural circuitry underpinning the brain's ability to segregate and integrate information exists as early as the late 2nd trimester of pregnancy and reorganizes during the prenatal period. Significance statement. Mounting evidence for the fetal origins of some neurodevelopmental disorders underscores the importance of identifying features of healthy fetal brain functional development. Alterations in prenatal brain connectomics may serve as early markers for identifying fetal-onset neurodevelopmental disorders, which in turn provide improved surveillance of at-risk fetuses and support the initiation of early interventions.

Brain fetal magnetic resonance imaging to evaluate maturation of normal white matter during the third trimester of pregnancy.

BACKGROUND: Quantitative magnetic resonance imaging (MRI) could improve the estimation of fetal brain maturation and the interpretation of white matter signal intensity in pathological conditions. OBJECTIVE: To investigate T2-based and diffusion-weighted imaging (DWI) measurements for the evaluation of fetal brain maturation during the last trimester of pregnancy. MATERIALS AND METHODS: One hundred sixty-eight fetal brain MRIs were retrospectively analyzed (age range: 28-37 weeks of gestation) after ensuring that none of the children developed psychomotor or cognitive impairment (median follow-up: 4.7 years). Bilateral regions of interest were drawn on the frontal, occipital, parietal and temporal lobes from T2-W imaging and DWI, when available, to evaluate signal intensity and apparent diffusion coefficient (ADC) values. Ratios were calculated with two references (pons or thalamus and cerebrospinal fluid) to standardize signal intensities. Reproducibility was evaluated with intraclass correlation coefficients (ICCs) and Bland-Altman plots. Correlations with gestational age were evaluated with univariate and multivariate linear regressions. RESULTS: T2 measurements were achieved in all cases, and DWI was available in 37 cases. Measurements and ratios were reproducible in eight localizations (i.e. intra- and interobserver ICCs >0.5): frontal T2/thalamus, parietal T2/thalamus, occipital T2/pons, parietal ADC/thalamus, occipital ADC/pons, temporal ADC/pons, occipital ADC and temporal ADC. The frontal T2/thalamus and parietal T2/thalamus correlated with gestational age (P<0.0001 and P=0.014, respectively). In the multivariate modeling, frontal T2/thalamus remained an independent predictor of the gestational age (P<0.0001). CONCLUSION: The frontal T2/thalamus ratio emerged as a potential additional biomarker of fetal brain maturation during the last trimester of pregnancy.

Morphometric development of the human fetal cerebellum during the early second trimester.

The protracted nature of development makes the cerebellum vulnerable to a broad spectrum of pathologic conditions, especially during the early fetal period. This study aims to characterize normal cerebellar growth in human fetuses during the early second trimester. We manually segmented the fetal cerebellum using 7.0-T high-resolution MR images obtained in 35 specimens with gestational ages ranging from 15 to 22 weeks. Volume measurements and shape analysis were performed to quantitatively evaluate global and regional cerebellar growth. The absolute volume of the fetal cerebellum showed a quadratic growth with increasing gestational age, while the pattern of relative volume changes revealed that the cerebellum grew at a greater pace than the cerebrum after 17 gestational weeks. Shape analysis was used to examine the distinctive development of subregions of the cerebellum. The extreme lateral portions of both cerebellar hemispheres showed the lowest rate of growth. The anterior lobe grew faster than most of the posterior lobe. These findings expand our understanding of the early growth pattern of the human cerebellum and could be further used to assess the developmental conditions of the fetal brain.

Sublaminar organization of the human subplate: developmental changes in the distribution of neurons, glia, growing axons and extracellular matrix.

The objective of this paper was to collect normative data essential for analyzing the subplate (SP) role in pathogenesis of developmental disorders, characterized by abnormal circuitry, such as hypoxic-ischemic lesions, autism and schizophrenia. The main cytological features of the SP, such as low cell density, early differentiation of neurons and glia, plexiform arrangement of axons and dendrites, presence of synapses and a large amount of extracellular matrix (ECM) distinguish this compartment from the cell-dense cortical plate (CP; towards pia) and large fiber bundles of external axonal strata of fetal white matter (towards ventricle). For SP delineation from these adjacent layers based on combined cytological criteria, we analyzed the sublaminar distribution of different microstructural elements and the associated maturational gradients throughout development, using immunocytochemical and histological techniques on postmortem brain material (Zagreb Neuroembryological Collection). The analysis revealed that the SP compartment of the lateral neocortex shows changes in laminar organization throughout fetal development: the monolayer in the early fetal period (presubplate) undergoes dramatic bilaminar transformation between 13 and 15 postconceptional weeks (PCW), followed by subtle sublamination in three 'floors' (deep, intermediate, superficial) of midgestation (15-21 PCW). During the stationary phase (22-28 PCW), SP persists as a trilaminar compartment, gradually losing its sublaminar organization towards the end of gestation and remains as a single layer of SP remnant in the newborn brain. Based on these sublaminar transformations, we have documented developmental changes in the distribution, maturational gradients and expression of molecular markers in SP synapses, transitional forms of astroglia, neurons and ECM, which occur concomitantly with the ingrowth of thalamo-cortical, basal forebrain and cortico-cortical axons in a deep to superficial fashion. The deep SP is the zone of ingrowing axons - 'entrance (ingrowth) zone'. The process of axonal ingrowth begins with thalamo-cortical fibers and basal forebrain afferents, indicating an oblique geometry. During the later fetal period, deep SP receives long cortico-cortical axons exhibiting a tangential geometry. Intermediate SP ('proper') is the navigation and 'nexus' sublamina consisting of a plexiform arrangement of cellular elements providing guidance and substrate for axonal growth, and also containing transient connectivity of dendrites and axons in a tangential plane without radial boundaries immersed in an ECM-rich continuum. Superficial SP is the axonal accumulation ('waiting compartment') and target selection zone, indicating a dense distribution of synaptic markers, accumulation of thalamo-cortical axons (around 20 PCW), overlapping with dendrites from layer VI neurons. In the late preterm brain period, superficial SP contains a chondroitin sulfate non-immunoreactive band. The developmental dynamics for the distribution of neuronal, glial and ECM markers comply with sequential ingrowth of afferents in three levels of SP: ECM and synaptic markers shift from deep to superficial SP, with transient forms of glia following this arrangement, and calretinin neurons are concentrated in the SP during the formation phase. These results indicate developmental and morphogenetic roles in the SP cellular (transient glia, neurons and synapses) and ECM framework, enabling the spatial accommodation, navigation and establishment of numerous connections of cortical pathways in the expanded human brain. The original findings of early developmental dynamics of transitional subtypes of astroglia, calretinin neurons, ECM and synaptic markers presented in the SP are interesting in the light of recent concepts concerning its functional and morphogenetic role and an increasing interest in SP as a prospective substrate of abnormalities in cortical circuitry, leading to a cognitive deficit in different neurodevelopmental disorders.

Automatic Measurement of Fetal Brain Development from Magnetic Resonance Imaging: New Reference Data.

BACKGROUND: Accurate fetal brain volume estimation is of paramount importance in evaluating fetal development. The aim of this study was to develop an automatic method for fetal brain segmentation from magnetic resonance imaging (MRI) data, and to create for the first time a normal volumetric growth chart based on a large cohort. SUBJECTS AND METHODS: A semi-automatic segmentation method based on Seeded Region Growing algorithm was developed and applied to MRI data of 199 typically developed fetuses between 18 and 37 weeks' gestation. The accuracy of the algorithm was tested against a sub-cohort of ground truth manual segmentations. A quadratic regression analysis was used to create normal growth charts. The sensitivity of the method to identify developmental disorders was demonstrated on 9 fetuses with intrauterine growth restriction (IUGR). RESULTS: The developed method showed high correlation with manual segmentation (r2 = 0.9183, p < 0.001) as well as mean volume and volume overlap differences of 4.77 and 18.13%, respectively. New reference data on 199 normal fetuses were created, and all 9 IUGR fetuses were at or below the third percentile of the normal growth chart. DISCUSSION: The proposed method is fast, accurate, reproducible, user independent, applicable with retrospective data, and is suggested for use in routine clinical practice.

Development of the human fetal hippocampal formation during early second trimester.

Development of the fetal hippocampal formation has been difficult to fully describe because of rapid changes in its shape during the fetal period. The aims of this study were to: (1) segment the fetal hippocampal formation using 7.0 T MR images from 41 specimens with gestational ages ranging from 14 to 22 weeks and (2) reveal the developmental course of the fetal hippocampal formation using volume and shape analyses. Differences in hemispheric volume were observed, with the right hippocampi being larger than the left. Absolute volume changes showed a linear increase, while relative volume changes demonstrated an inverted-U shape trend during this period. Together these exhibited a variable developmental rate among different regions of the fetal brain. Different sub-regional growth of the fetal hippocampal formation was specifically observed using shape analysis. The fetal hippocampal formation possessed a prominent medial-lateral bidirectional shape growth pattern during its rotation process. Our results provide additional insight into 3D hippocampal morphology in the assessment of fetal brain development and can be used as a reference for future hippocampal studies.

Functional brain development in growth-restricted and constitutionally small fetuses: a fetal magnetoencephalography case-control study.

OBJECTIVE: Fetal magnetoencephalography records fetal brain activity non-invasively. Delayed brain responses were reported for fetuses weighing below the tenth percentile. To investigate whether this delay indicates delayed brain maturation resulting from placental insufficiency, this study distinguished two groups of fetuses below the tenth percentile: growth-restricted fetuses with abnormal umbilical artery Doppler velocity (IUGR) and constitutionally small-for-gestational-age fetuses with normal umbilical artery Doppler findings (SGA) were compared with fetuses of adequate weight for gestational age (AGA), matched for age and behavioural state. DESIGN: A case-control study of matched pairs. SETTING: Fetal magnetoencephalography-Center at the University Hospital of Tuebingen. POPULATION: Fourteen IUGR fetuses and 23 SGA fetuses were matched for gestational age and fetal behavioural state with 37 healthy, normal-sized fetuses. METHODS: A 156-channel fetal magentoencephalography system was used to record fetal brain activity. Light flashes as visual stimulation were applied to the fetus. The Student's t-test for paired groups was performed. MAIN OUTCOME MEASURE: Latency of fetal visual evoked magnetic responses (VER). RESULTS: The IUGR fetuses showed delayed VERs compared with controls (IUGR, 233.1 ms; controls, 184.6 ms; P = 0.032). SGA fetuses had similar evoked response latencies compared with controls (SGA, 216.1 ms; controls, 219.9 ms; P = 0.828). Behavioural states were similarly distributed. CONCLUSION: Visual evoked responses are delayed in IUGR fetuses, but not in SGA. Fetal behavioural state as an influencing factor of brain response latency was accounted for in the comparison. This reinforces that delayed brain maturation is the result of placental insufficiency.

Examining the relationship between fetal cortical thickness, gestational age, and maternal psychological distress.

In utero exposure to maternal stress, anxiety, and depression has been associated with reduced cortical thickness (CT), and CT changes, in turn, to adverse neuropsychiatric outcomes. Here, we investigated global and regional (G/RCT) changes associated with fetal exposure to maternal psychological distress in 265 brain MRI studies from 177 healthy fetuses of low-risk pregnant women. GCT was measured from cortical gray matter (CGM) voxels; RCT was estimated from 82 cortical regions. GCT and RCT in 87% of regions strongly correlated with GA. Fetal exposure was most strongly associated with RCT in the parahippocampal region, ventromedial prefrontal cortex, and supramarginal gyrus suggesting that cortical alterations commonly associated with prenatal exposure could emerge in-utero. However, we note that while regional fetal brain involvement conformed to patterns observed in newborns and children exposed to prenatal maternal psychological distress, the reported associations did not survive multiple comparisons correction. This could be because the effects are more subtle in this early developmental window or because majority of the pregnant women in our study did not experience high levels of maternal distress. It is our hope that the current findings will spur future hypothesis-driven studies that include a full spectrum of maternal mental health scores.

Placental dysfunction: The core mechanism for poor neurodevelopmental outcomes in the offspring of preeclampsia pregnancies.

Preeclampsia (PE) is a leading condition threatening pregnant women and their offspring. The offspring of PE pregnancies have a high risk of poor neurodevelopmental outcomes and neuropsychological diseases later in life. However, the pathophysiology and pathogenesis of poor neurodevelopment remain undetermined. Abnormal placental functions are at the core of most PE cases, and recent research evidence supports that the placenta plays an important role in fetal brain development. Here, we summarize the relationship between abnormal fetal brain development and placental dysfunction in PE conditions, which include the dysfunction of nutrient and gas-waste exchange, impaired angiogenesis stimulation, abnormal neurotransmitter regulation, disrupted special protectors, and immune disorders. All these factors could lead to poor neurodevelopmental outcomes.

Fetal Brain Anatomy.

"Fetal brain development has been well studied, allowing for an ample knowledge of the normal changes that occur during gestation. Imaging modalities used to evaluate the fetal central nervous system (CNS) include ultrasound and MRI. MRI is the most accurate imaging modality for parenchymal evaluation and depiction of developmental CNS anomalies. The depiction of CNS abnormalities in a fetus can only be accurately made when there is an understanding of its normal development. This article reviews the expected normal fetal brain anatomy and development during gestation. Additional anatomic structures seen on brain imaging sequences are also reviewed."