The Developing Human Connectome Project Neonatal Data Release.

The Developing Human Connectome Project has created a large open science resource which provides researchers with data for investigating typical and atypical brain development across the perinatal period. It has collected 1228 multimodal magnetic resonance imaging (MRI) brain datasets from 1173 fetal and/or neonatal participants, together with collateral demographic, clinical, family, neurocognitive and genomic data from 1173 participants, together with collateral demographic, clinical, family, neurocognitive and genomic data. All subjects were studied in utero and/or soon after birth on a single MRI scanner using specially developed scanning sequences which included novel motion-tolerant imaging methods. Imaging data are complemented by rich demographic, clinical, neurodevelopmental, and genomic information. The project is now releasing a large set of neonatal data; fetal data will be described and released separately. This release includes scans from 783 infants of whom: 583 were healthy infants born at term; as well as preterm infants; and infants at high risk of atypical neurocognitive development. Many infants were imaged more than once to provide longitudinal data, and the total number of datasets being released is 887. We now describe the dHCP image acquisition and processing protocols, summarize the available imaging and collateral data, and provide information on how the data can be accessed.

Neonatal multi-modal cortical profiles predict 18-month developmental outcomes.

Developmental delays in infanthood often persist, turning into life-long difficulties, and coming at great cost for the individual and community. By examining the developing brain and its relation to developmental outcomes we can start to elucidate how the emergence of brain circuits is manifested in variability of infant motor, cognitive and behavioural capacities. In this study, we examined if cortical structural covariance at birth, indexing coordinated development, is related to later infant behaviour. We included 193 healthy term-born infants from the Developing Human Connectome Project (dHCP). An individual cortical connectivity matrix derived from morphological and microstructural features was computed for each subject (morphometric similarity networks, MSNs) and was used as input for the prediction of behavioural scores at 18 months using Connectome-Based Predictive Modeling (CPM). Neonatal MSNs successfully predicted social-emotional performance. Predictive edges were distributed between and within known functional cortical divisions with a specific important role for primary and posterior cortical regions. These results reveal that multi-modal neonatal cortical profiles showing coordinated maturation are related to developmental outcomes and that network organization at birth provides an early infrastructure for future functional skills.

Incidental findings on brain MR imaging of asymptomatic term neonates in the Developing Human Connectome Project.

BACKGROUND: Interpretation of incidental findings on term neonatal MRI brain imaging can be challenging as there is a paucity of published normative data on asymptomatic term neonates. Reporting radiologists and clinicians need to be familiar with these incidental findings to avoid over-investigation and misinterpretation particularly in relation to neurodevelopmental outcome. This study aimed to determine the prevalence of incidental findings in a large group of asymptomatic term neonates participating in the Developing Human Connectome Project (dHCP) who were invited for neurodevelopmental assessment at 18 months. METHODS: We retrospectively reviewed MRI brain scans performed on 500 term neonates enrolled in the dHCP study between 2015 and 2019 with normal clinical examination. We reviewed the results of the Bayley Scales of Infant and Toddler Development (Bayley III) applied to participants who attended for neurodevelopmental follow-up at 18 months. Scores considered "delayed" if <70 on language, cognitive or motor scales. FINDINGS: Incidental findings were observed in 47% of term infants. Acute cerebral infarcts were incidentally noted in five neonates (1%). More common incidental findings included punctate white matter lesions (PWMLs) (12%) and caudothalamic subependymal cysts (10%). The most frequent incidental finding was intracranial haemorrhage (25%), particularly subdural haemorrhage (SDH). SDH and PWMLs were more common in infants delivered with ventouse-assistance versus other delivery methods.Neurodevelopmental results were available on 386/500 (77%). 14 infants had a language score < 70 (2 SD below the mean). Of the 386 infants with neurodevelopmental follow up at 18 months, group differences in motor and language scores between infants with and without incidental findings were not significant (p = 0·17 and p = 0·97 respectively). Group differences in cognitive scores at 18 months between infants with (median (interquartile range) -100 (95-105)) and without (100 (95-110)) incidental findings were of small effect size to suggest clinical significance (Cliff's d = 0·15; p<0·05). INTERPRETATION: Incidental findings are relatively common on brain MRI in asymptomatic term neonates, majority are clinically insignificant with normal neurodevelopment at 18 months. FUNDING: This work was supported by the European Research Council under the European Union's Seventh Framework Programme (FP7/20072013/ERC grant agreement no. [319456] dHCP project), by core funding from the Wellcome/EPSRC Centre for Medical Engineering [WT203148/Z/16/Z] and by the National Institute for Health Research (NIHR) Biomedical Research Centre based at Guy's and St Thomas' NHS Foundation Trust and King's College London and/or the NIHR Clinical Research Facility. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health and Social Care.

Neurometabolite mapping highlights elevated myo-inositol profiles within the developing brain in down syndrome.

The neurodevelopmental phenotype in Down Syndrome (DS), or Trisomy 21, is variable including a wide spectrum of cognitive impairment and a high risk of early-onset Alzheimer's disease (AD). A key metabolite of interest within the brain in DS is Myo-inositol (mIns). The NA+/mIns co-transporter is located on human chromosome 21 and is overexpressed in DS. In adults with DS, elevated brain mIns was previously associated with cognitive impairment and proposed as a risk marker for progression to AD. However, it is unknown if brain mIns is increased earlier in development. The aim of this study was to estimate mIns concentration levels and key brain metabolites [N-acetylaspartate (NAA), Choline (Cho) and Creatine (Cr)] in the developing brain in DS and aged-matched controls. We used in vivo magnetic resonance spectroscopy (MRS) in neonates with DS (n = 12) and age-matched controls (n = 26) scanned just after birth (36-45 weeks postmenstrual age). Moreover, we used Mass Spectrometry in early (10-20 weeks post conception) ex vivo fetal brain tissue samples from DS (n = 14) and control (n = 30) cases. Relative to [Cho] and [Cr], we report elevated ratios of [mIns] in vivo in the basal ganglia/thalamus, in neonates with DS, when compared to age-matched typically developing controls. Glycine concentration ratios [Gly]/[Cr] and [Cho]/[Cr] also appear elevated. We observed elevated [mIns] in the ex vivo fetal cortical brain tissue in DS compared with controls. In conclusion, a higher level of brain mIns was evident as early as 10 weeks post conception and was measurable in vivo from 36 weeks post-menstrual age. Future work will determine if this early difference in metabolites is linked to cognitive outcomes in childhood or has utility as a potential treatment biomarker for early intervention.

Development of Microstructural and Morphological Cortical Profiles in the Neonatal Brain.

Interruptions to neurodevelopment during the perinatal period may have long-lasting consequences. However, to be able to investigate deviations in the foundation of proper connectivity and functional circuits, we need a measure of how this architecture evolves in the typically developing brain. To this end, in a cohort of 241 term-born infants, we used magnetic resonance imaging to estimate cortical profiles based on morphometry and microstructure over the perinatal period (37-44 weeks postmenstrual age, PMA). Using the covariance of these profiles as a measure of inter-areal network similarity (morphometric similarity networks; MSN), we clustered these networks into distinct modules. The resulting modules were consistent and symmetric, and corresponded to known functional distinctions, including sensory-motor, limbic, and association regions, and were spatially mapped onto known cytoarchitectonic tissue classes. Posterior regions became more morphometrically similar with increasing age, while peri-cingulate and medial temporal regions became more dissimilar. Network strength was associated with age: Within-network similarity increased over age suggesting emerging network distinction. These changes in cortical network architecture over an 8-week period are consistent with, and likely underpin, the highly dynamic processes occurring during this critical period. The resulting cortical profiles might provide normative reference to investigate atypical early brain development.

Foetal lung volumes in pregnant women who deliver very preterm: a pilot study.

BACKGROUND: Infants born preterm are at increased risk of pulmonary morbidity. The contribution of antenatal factors to impairments in lung structure/function has not been fully elucidated. This study aimed to compare standardized lung volumes from foetuses that were delivered <32 weeks' gestation with foetuses that were delivered >37 weeks. METHODS: Fourteen women who delivered <32 weeks gestation and 56 women who delivered >37 underwent a foetal MRI. Slice-volume reconstruction was then used and the foetal lungs were then segmented using multi-atlas approaches. Body volumes were calculated by manual segmentation and lung:body volume ratios generated. RESULTS: Mean gestation at MRI of the preterm group was 27+2 weeks (SD 2.9, range 20+6-31+3) and control group 25+3 weeks (SD 4.7 range 20+5-31+6). Mean gestation at delivery of the preterm group was 29+2 weeks (SD 2.6, range 22+0-32+0). Lung:body volume ratios and foetal lung volumes were smaller in foetuses that were delivered preterm both with and without preterm premature rupture of membranes compared to those born at term (p < 0.001 in all cases). CONCLUSIONS: Foetuses that were delivered very preterm had reduced lung volumes when standardized for foetal size, irrespective of ruptured membranes. These are novel findings and suggest an antenatal aetiology of insult and possible focus for future preventative therapies.

Early alterations in cortical and cerebellar regional brain growth in Down Syndrome: An in vivo fetal and neonatal MRI assessment.

Down Syndrome (DS) is the most frequent genetic cause of intellectual disability with a wide spectrum of neurodevelopmental outcomes. At present, the relationship between structural brain morphology and the spectrum of cognitive phenotypes in DS, is not well understood. This study aimed to quantify the development of the fetal and neonatal brain in DS participants, with and without a congenital cardiac defect compared with a control population using dedicated, optimised and motion-corrected in vivo magnetic resonance imaging (MRI). We detected deviations in development and altered regional brain growth in the fetus with DS from 21 weeks' gestation, when compared to age-matched controls. Reduced cerebellar volume was apparent in the second trimester with significant alteration in cortical growth becoming evident during the third trimester. Developmental abnormalities in the cortex and cerebellum are likely substrates for later neurocognitive impairment, and ongoing studies will allow us to confirm the role of antenatal MRI as an early biomarker for subsequent cognitive ability in DS. In the era of rapidly developing technologies, we believe that the results of this study will assist counselling for prospective parents.

Three-dimensional visualisation of the fetal heart using prenatal MRI with motion-corrected slice-volume registration: a prospective, single-centre cohort study.

BACKGROUND: Two-dimensional (2D) ultrasound echocardiography is the primary technique used to diagnose congenital heart disease before birth. There is, however, a longstanding need for a reliable form of secondary imaging, particularly in cases when more detailed three-dimensional (3D) vascular imaging is required, or when ultrasound windows are of poor diagnostic quality. Fetal MRI, which is well established for other organ systems, is highly susceptible to fetal movement, particularly for 3D imaging. The objective of this study was to investigate the combination of prenatal MRI with novel, motion-corrected 3D image registration software, as an adjunct to fetal echocardiography in the diagnosis of congenital heart disease. METHODS: Pregnant women carrying a fetus with known or suspected congenital heart disease were recruited via a tertiary fetal cardiology unit. After initial validation experiments to assess the general reliability of the approach, MRI data were acquired in 85 consecutive fetuses, as overlapping stacks of 2D images. These images were then processed with a bespoke open-source reconstruction algorithm to produce a super-resolution 3D volume of the fetal thorax. These datasets were assessed with measurement comparison with paired 2D ultrasound, structured anatomical assessment of the 2D and 3D data, and contemporaneous, archived clinical fetal MRI reports, which were compared with postnatal findings after delivery. FINDINGS: Between Oct 8, 2015, and June 30, 2017, 101 patients were referred for MRI, of whom 85 were eligible and had fetal MRI. The mean gestational age at the time of MRI was 32 weeks (range 24-36). High-resolution (0·50-0·75 mm isotropic) 3D datasets of the fetal thorax were generated in all 85 cases. Vascular measurements showed good overall agreement with 2D echocardiography in 51 cases with paired data (intra-class correlation coefficient 0·78, 95% CI 0·68-0·84), with fetal vascular structures more effectively visualised with 3D MRI than with uncorrected 2D MRI (657 [97%] of 680 anatomical areas identified vs 358 [53%] of 680 areas; p<0·0001). When a structure of interest was visualised in both 2D and 3D data (n=358), observers gave a higher diagnostic quality score for 3D data in 321 (90%) of cases, with 37 (10%) scores tied with 2D data, and no lower scores than for 2D data (Wilcoxon signed rank test p<0·0001). Additional anatomical features were described in ten cases, of which all were confirmed postnatally. INTERPRETATION: Standard fetal MRI with open-source image processing software is a reliable method of generating high-resolution 3D imaging of the fetal vasculature. The 3D volumes produced show good spatial agreement with ultrasound, and significantly improved visualisation and diagnostic quality compared with source 2D MRI data. This freely available combination requires minimal infrastructure, and provides safe, powerful, and highly complementary imaging of the fetal cardiovascular system. FUNDING: Wellcome Trust/EPSRC Centre for Medical Engineering, National Institute for Health Research.

Normative biometry of the fetal brain using magnetic resonance imaging.

The fetal brain shows accelerated growth in the latter half of gestation, and these changes can be captured by 2D and 3D biometry measurements. The aim of this study was to quantify brain growth in normal fetuses using Magnetic Resonance Imaging (MRI) and to produce reference biometry data and a freely available centile calculator ( https://www.developingbrain.co.uk/fetalcentiles/ ). A total of 127 MRI examinations (1.5 T) of fetuses with a normal brain appearance (21-38 gestational weeks) were included in this study. 2D and 3D biometric parameters were measured from slice-to-volume reconstructed images, including 3D measurements of supratentorial brain tissue, lateral ventricles, cortex, cerebellum and extra-cerebral CSF and 2D measurements of brain biparietal diameter and fronto-occipital length, skull biparietal diameter and occipitofrontal diameter, head circumference, transverse cerebellar diameter, extra-cerebral CSF, ventricular atrial diameter, and vermis height, width, and area. Centiles were constructed for each measurement. All participants were invited for developmental follow-up. All 2D and 3D measurements, except for atrial diameter, showed a significant positive correlation with gestational age. There was a sex effect on left and total lateral ventricular volumes and the degree of ventricular asymmetry. The 5th, 50th, and 95th centiles and a centile calculator were produced. Developmental follow-up was available for 73.1% of cases [mean chronological age 27.4 (±10.2) months]. We present normative reference charts for fetal brain MRI biometry at 21-38 gestational weeks. Developing growth trajectories will aid in the better understanding of normal fetal brain growth and subsequently of deviations from typical development in high-risk pregnancies or following premature delivery.

A dedicated neonatal brain imaging system.

PURPOSE: The goal of the Developing Human Connectome Project is to acquire MRI in 1000 neonates to create a dynamic map of human brain connectivity during early development. High-quality imaging in this cohort without sedation presents a number of technical and practical challenges. METHODS: We designed a neonatal brain imaging system (NBIS) consisting of a dedicated 32-channel receive array coil and a positioning device that allows placement of the infant's head deep into the coil for maximum signal-to-noise ratio (SNR). Disturbance to the infant was minimized by using an MRI-compatible trolley to prepare and transport the infant and by employing a slow ramp-up and continuation of gradient noise during scanning. Scan repeats were minimized by using a restart capability for diffusion MRI and retrospective motion correction. We measured the 1) SNR gain, 2) number of infants with a completed scan protocol, and 3) number of anatomical images with no motion artifact using NBIS compared with using an adult 32-channel head coil. RESULTS: The NBIS has 2.4 times the SNR of the adult coil and 90% protocol completion rate. CONCLUSION: The NBIS allows advanced neonatal brain imaging techniques to be employed in neonatal brain imaging with high protocol completion rates. Magn Reson Med 78:794-804, 2017. © 2016 The Authors Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

An exploration of the potential utility of fetal cardiovascular MRI as an adjunct to fetal echocardiography.

OBJECTIVES: Fetal cardiovascular magnetic resonance imaging (MRI) offers a potential alternative to echocardiography, although in practice, its use has been limited. We sought to explore the need for additional imaging in a tertiary fetal cardiology unit and the usefulness of standard MRI sequences. METHODS: Cases where the diagnosis was not fully resolved using echocardiography were referred for MRI. Following a three-plane localiser, fetal movement was assessed with a balanced steady-state free precession (bSSFP) cine. Single-shot fast spin echo and bSSFP sequences were used for diagnostic imaging. RESULTS: Twenty-two fetal cardiac MRIs were performed over 12 months, at mean gestation of 32 weeks (26-38 weeks). The majority of referrals were for suspected vascular abnormalities (17/22), particularly involving the aortic arch (n = 10) and pulmonary vessels (n = 4). Single-shot fast spin echo sequences produced 'black-blood' images, useful for examining the extracardiac vasculature in these cases. BSSFP sequences were more useful for intracardiac structures. Real-time SSFP allowed for dynamic assessment of structures such as cardiac masses, with enhancement patterns also allowing for tissue characterisation in these cases. CONCLUSIONS: Fetal vascular abnormalities such as coarctation can be difficult to diagnose by using ultrasound. Fetal MRI may have an adjunctive role in the evaluation of the extracardiac vascular anatomy and tissue characterisation. © 2016 The Authors. Prenatal Diagnosis published by John Wiley & Sons, Ltd.

Cerebral function in perinatally HIV-infected young adults and their HIV-uninfected sibling controls.

BACKGROUND: Perinatally acquired HIV-infected (PaHIV) young adults undergo neurodevelopment in the presence of HIV infection and antiretroviral therapy, which may lead to neurocognitive (NC) impairment. Knowledge of NC function in this group is sparse and control data lacking. We compared cerebral function in young adults with PaHIV infection to aged matched HIV negative family controls. METHODS: 16-25-year-old PaHIV young adults (Group 1, n = 33) and HIV-uninfected family controls (Group 2, n = 14) were recruited. Cerebral function was evaluated by: a computerized battery assessing NC function (CogState(TM)), International HIV Dementia Scale (IHDS) and the prospective and retrospective memory questionnaire (PRMQ). Eight cases and four controls also underwent (1)H cerebral magnetic resonance spectroscopy ((1)H-MRS) scanning measuring basal ganglia (BG) metabolites. Cases and controls were compared. RESULTS: Group 1 mean (SD) CD4 count; 444 (319) cells/µl, plasma HIV viral load < 50 in 55%. There were no statistically significant differences between study groups in NC function or IHDS results (P>0.27 all observations). PRMQ scores were significantly higher (42 versus 35, P = 0.02) and MRS BG inflammatory-metabolites (choline- and myo-inositol- to creatine ratios) were significantly greater in Group 1 versus Group 2 (0.83 versus 0.63, P = 0.02 and 3.43 versus 3.03.P = 0.09 respectively). No significant association between PRMQ score and MRS metabolites was observed (P = 0.89). CONCLUSION: Statistically significant differences in cerebral function parameters were observed in PaHIV young adults compared to a well-matched control population. The cognitive deficit observed, in memory, rather than fine motor function, differs from the cerebral impairment often reported in HIV-infected adults.

Thalamocortical Connectivity Predicts Cognition in Children Born Preterm.

Thalamocortical connections are: essential for brain function, established early in development, and significantly impaired following preterm birth. Impaired cognitive abilities in preterm infants may be related to disruptions in thalamocortical connectivity. The aim of this study was to test the hypothesis: thalamocortical connectivity in the preterm brain at term-equivalent is correlated with cognitive performance in early childhood. We examined 57 infants who were born <35 weeks gestational age (GA) and had no evidence of focal abnormality on magnetic resonance imaging (MRI). Infants underwent diffusion MRI at term and cognitive performance at 2 years was assessed using the Bayley III scales of Infant and Toddler development. Cognitive scores at 2 years were correlated with structural connectivity between the thalamus and extensive cortical regions at term. Mean thalamocortical connectivity across the whole cortex explained 11% of the variance in cognitive scores at 2 years. The inclusion of GA at birth and parental socioeconomic group in the model explained 30% of the variance in subsequent cognitive performance. Identifying impairments in thalamocortical connectivity as early as term equivalent can help identify those infants at risk of subsequent cognitive delay and may be useful to assess efficacy of potential treatments at an early age.

T2* relaxometry of fetal brain at 1.5 Tesla using a motion tolerant method.

PURPOSE: The aim of this study was to determine T2* values for the fetal brain in utero and to compare them with previously reported values in preterm and term neonates. Knowledge of T2* may be useful for assessing brain development, brain abnormalities, and for optimizing functional imaging studies. METHODS: Maternal respiration and unpredictable fetal motion mean that conventional multishot acquisition techniques used in adult T2* relaxometry studies are not practical. Single shot multiecho echo planar imaging was used as a rapid method for measuring fetal T2* by effectively freezing intra-slice motion. RESULTS: T2* determined from a sample of 24 subjects correlated negatively with gestational age with mean values of 220 ms (±45) for frontal white matter, 159 ms (±32) for thalamic gray matter, and 236 ms (±45) for occipital white matter. CONCLUSION: Fetal T2* values are higher than those previously reported for preterm neonates and decline with a consistent trend across gestational age. The data suggest that longer than usual echo times or direct T2* measurement should be considered when performing fetal fMRI to reach optimal BOLD sensitivity.

Resting State fMRI in the moving fetus: a robust framework for motion, bias field and spin history correction.

There is growing interest in exploring fetal functional brain development, particularly with Resting State fMRI. However, during a typical fMRI acquisition, the womb moves due to maternal respiration and the fetus may perform large-scale and unpredictable movements. Conventional fMRI processing pipelines, which assume that brain movements are infrequent or at least small, are not suitable. Previous published studies have tackled this problem by adopting conventional methods and discarding as much as 40% or more of the acquired data. In this work, we developed and tested a processing framework for fetal Resting State fMRI, capable of correcting gross motion. The method comprises bias field and spin history corrections in the scanner frame of reference, combined with slice to volume registration and scattered data interpolation to place all data into a consistent anatomical space. The aim is to recover an ordered set of samples suitable for further analysis using standard tools such as Group Independent Component Analysis (Group ICA). We have tested the approach using simulations and in vivo data acquired at 1.5 T. After full motion correction, Group ICA performed on a population of 8 fetuses extracted 20 networks, 6 of which were identified as matching those previously observed in preterm babies.

Development of the optic radiations and visual function after premature birth.

INTRODUCTION: Visual impairment in preterm infants at term equivalent age (TEA) is associated with impaired microstructural development in the optic radiation, measured as reduced fractional anisotropy (FA) by Diffusion Tensor Imaging (DTI). We tested the hypothesis that these abnormalities develop during the late preterm period. METHODS: DTI was performed in 53 infants born at a median (range) of 30(+1) (25(+4)-34(+6)) weeks post-menstrual age (PMA), 22 of whom were imaged twice. RESULTS: FA in the optic radiation at TEA was related to: visual function (p = .003); PMA at birth (p = .015); and PMA at scan (p = .008); while a significant interaction between PMA at birth and scan (p = .019) revealed an effect of the period of premature extra-uterine life additional to the degree of prematurity. We explored this further in a sub-group of 22 infants who were studied twice. FA increased from mean (95% CI) .174 (.164-.176) on the first image at 32(+5) (29(+5)-36) weeks PMA, to .198 (.190-.206) on the second image at 40(+6) (39(+2)-46) weeks PMA. Visual function was not predicted by FA on the images obtained in the early neonatal period, but was significantly related to the rate of increase in FA between scans (p = .027) and to FA on the second image (p = .015). CONCLUSION: Microstructural maturation during the late preterm period is thus required for normal visual function, suggesting that interventions applied after 30 weeks PMA might reduce impairment in preterm infants.

Cortical overgrowth in fetuses with isolated ventriculomegaly.

Mild cerebral ventricular enlargement is associated with schizophrenia, autism, epilepsy, and attention-deficit/hyperactivity disorder. Fetal ventriculomegaly is the most common central nervous system (CNS) abnormality affecting 1% of fetuses and is associated with cognitive, language, and behavioral impairments in childhood. Neurodevelopmental outcome is partially predictable by the 2-dimensional size of the ventricles in the absence of other abnormalities. We hypothesized that isolated fetal ventriculomegaly is a marker of altered brain development characterized by relative overgrowth and aimed to quantify brain growth using volumetric magnetic resonance imaging (MRI) in fetuses with isolated ventriculomegaly. Fetal brain MRI (1.5 T) was performed in 60 normal fetuses and 65 with isolated ventriculomegaly, across a gestational age range of 22-38 weeks. Volumetric analysis of the ventricles and supratentorial brain structures was performed on 3-dimensional reconstructed datasets. Fetuses with isolated ventriculomegaly had increased brain parenchyma volumes when compared with the control cohort (9.6%, P < 0.0001) with enlargement restricted to the cortical gray matter (17.2%, P = 0.002). The extracerebral cerebrospinal fluid and third and fourth ventricles were also enlarged. White matter, basal ganglia, and thalamic volumes were not significantly different between cohorts. The presence of relative cortical overgrowth in fetuses with ventriculomegaly may represent the neurobiological substrate for cognitive, language, and behavioral deficits in these children.

Myo-inositol metabolism in appropriately grown and growth-restricted fetuses: a proton magnetic resonance spectroscopy study.

OBJECTIVE: Myo-inositol (Myo-ins) is a marker of neuroglial cells, being present in the astrocytes of brain tissue, but also functions as an osmolyte. Numbers of astrocytes are known to increase following injury to the brain. Growth-restricted fetuses are at increased risk of later neurodevelopmental impairments even in the absence of overt lesions and despite preserved/increased cerebral blood flow. This study aims to investigate brain Myo-ins metabolism in fetuses with intrauterine growth restriction (IUGR) and evidence of cerebral redistribution using magnetic resonance spectroscopy (MRS) at a short echo time. STUDY DESIGN: Biometry and Doppler assessment of blood flow was assessed using ultrasound in 28 fetuses with IUGR and 47 appropriately grown control subjects. MRI was used to exclude overt brain injury. Proton magnetic resonance spectroscopy of the fetal brain was then performed at an echo time of 42 ms to examine the Myo-ins:Choline (Cho), Myo-ins:Creatine (Cr) and Cho:Cr ratios. RESULTS: No alterations in brain Myo-ins:Cho, Myo-ins:Cr or Cho:Cr ratios were detected between appropriately grown and growth restricted fetuses. CONCLUSIONS: IUGR is not associated with a measureable difference in brain myo-inositol ratios. This may be due to the protective effects of preserved cerebral blood flow in growth restriction and comparable astrocyte numbers when compared to controls.

Multidimensional analysis of fetal posterior fossa in health and disease.

Fetal magnetic resonance imaging (MRI) is now routinely used to further investigate cerebellar malformations detected with ultrasound. However, the lack of 2D and 3D biometrics in the current literature hinders the detailed characterisation and classification of cerebellar anomalies. The main objectives of this fetal neuroimaging study were to provide normal posterior fossa growth trajectories during the second and third trimesters of pregnancy via semi-automatic segmentation of reconstructed fetal brain MR images and to assess common cerebellar malformations in comparison with the reference data. Using a 1.5-T MRI scanner, 143 MR images were obtained from 79 normal control and 53 fetuses with posterior fossa abnormalities that were grouped according to the severity of diagnosis on visual MRI inspections. All quantifications were performed on volumetric datasets, and supplemental outcome information was collected from the surviving infants. Normal growth trajectories of total brain, cerebellar, vermis, pons and fourth ventricle volumes showed significant correlations with 2D measurements and increased in second-order polynomial trends across gestation (Pearson r, p < 0.05). Comparison of normal controls to five abnormal cerebellum subgroups depicted significant alterations in volumes that could not be detected exclusively with 2D analysis (MANCOVA, p < 0.05). There were 15 terminations of pregnancy, 8 neonatal deaths, and a spectrum of genetic and neurodevelopmental outcomes in the assessed 24 children with cerebellar abnormalities. The given posterior fossa biometrics enhance the delineation of normal and abnormal cerebellar phenotypes on fetal MRI and confirm the advantages of utilizing advanced neuroimaging tools in clinical fetal research.