Nests of dividing neuroblasts sustain interneuron production for the developing human brain.

The human cortex contains inhibitory interneurons derived from the medial ganglionic eminence (MGE), a germinal zone in the embryonic ventral forebrain. How this germinal zone generates sufficient interneurons for the human brain remains unclear. We found that the human MGE (hMGE) contains nests of proliferative neuroblasts with ultrastructural and transcriptomic features that distinguish them from other progenitors in the hMGE. When dissociated hMGE cells are transplanted into the neonatal mouse brain, they reform into nests containing proliferating neuroblasts that generate young neurons that migrate extensively into the mouse forebrain and mature into different subtypes of functional interneurons. Together, these results indicate that the nest organization and sustained proliferation of neuroblasts in the hMGE provide a mechanism for the extended production of interneurons for the human forebrain.

Motion corrected MRI differentiates male and female human brain growth trajectories from mid-gestation.

It is of considerable scientific, medical, and societal interest to understand the developmental origins of differences between male and female brains. Here we report the use of advances in MR imaging and analysis to accurately measure global, lobe and millimetre scale growth trajectory patterns over 18 gestational weeks in normal pregnancies with repeated measures. Statistical modelling of absolute growth trajectories revealed underlying differences in many measures, potentially reflecting overall body size differences. However, models of relative growth accounting for global measures revealed a complex temporal form, with strikingly similar cortical development in males and females at lobe scales. In contrast, local cortical growth patterns and larger scale white matter volume and surface measures differed significantly between male and female. Many proportional differences were maintained during neurogenesis and over 18 weeks of growth. These indicate sex related sculpting of neuroanatomy begins early in development, before cortical folding, potentially influencing postnatal development.

In utero MRI identifies consequences of early-gestation alcohol drinking on fetal brain development in rhesus macaques.

One factor that contributes to the high prevalence of fetal alcohol spectrum disorder (FASD) is binge-like consumption of alcohol before pregnancy awareness. It is known that treatments are more effective with early recognition of FASD. Recent advances in retrospective motion correction for the reconstruction of three-dimensional (3D) fetal brain MRI have led to significant improvements in the quality and resolution of anatomical and diffusion MRI of the fetal brain. Here, a rhesus macaque model of FASD, involving oral self-administration of 1.5 g/kg ethanol per day beginning prior to pregnancy and extending through the first 60 d of a 168-d gestational term, was utilized to determine whether fetal MRI could detect alcohol-induced abnormalities in brain development. This approach revealed differences between ethanol-exposed and control fetuses at gestation day 135 (G135), but not G110 or G85. At G135, ethanol-exposed fetuses had reduced brainstem and cerebellum volume and water diffusion anisotropy in several white matter tracts, compared to controls. Ex vivo electrophysiological recordings performed on fetal brain tissue obtained immediately following MRI demonstrated that the structural abnormalities observed at G135 are of functional significance. Specifically, spontaneous excitatory postsynaptic current amplitudes measured from individual neurons in the primary somatosensory cortex and putamen strongly correlated with diffusion anisotropy in the white matter tracts that connect these structures. These findings demonstrate that exposure to ethanol early in gestation perturbs development of brain regions associated with motor control in a manner that is detectable with fetal MRI.

Automatic, Age Consistent Reconstruction of the Corpus Callosum Guided by Coherency From In Utero Diffusion-Weighted MRI.

Reconstruction of white matter connectivity in the fetal brain from in utero diffusion-weighted magnetic resonance imaging (MRI) faces many challenges, including subject motion, small anatomical scale, and limited image resolution and signal. These issues are compounded by the need to track significant changes in structural connectivity throughout development. We present an automated method for improved reliability and completeness of tract extraction across a wide range of gestational ages, based on the geometry of coherent patterns in streamline tractography, and apply it to the reconstruction of the corpus callosum. This method, focused specifically at addressing the challenges of fetal brain imaging, avoids depending on a tractography atlas, and handles variations in size, shape, and tissue properties of developing brains, both between subjects and across ages. Although tractography from in utero MRI generally suffers from a significant number of misleading and missing pathways, we demonstrate the feasibility of extracting the coherent bundle of the corpus callosum while avoiding inappropriate diversions into other tracts.

Anatomical and diffusion MRI brain atlases of the fetal rhesus macaque brain at 85, 110 and 135 days gestation.

Recent advances in image reconstruction techniques have enabled high resolution MRI studies of fetal brain development in human subjects. Rhesus macaques (Macaca mulatta) are valuable animal models for use in studies of fetal brain development due to the similarities between this species and humans in brain development and anatomy. There is a need to develop fetal brain templates for the rhesus macaque to facilitate the characterization of the normal brain growth trajectory and departures from this trajectory in rhesus models of neurodevelopmental disorders. Here we have developed unbiased population-based anatomical T2-weighted, fractional anisotropy (FA) and apparent diffusion coefficient (ADC) templates for fetal brain from MR images scanned at 3 time points over the second and third trimesters of the 168 day gestational term. Specifically, atlas images are constructed for brains at gestational ages of 85 days (G85, N = 18, 9 females), 110 days (G110, N = 10, 7 females) and 135 days (G135, N = 16, 7 females). We utilized this atlas to perform segmentation of fetal brain MR images and fetal brain volumetric and microstructure analysis. The T2-weighted template images facilitated characterization of the growth within six fetal brain regions. The template images of diffusion tensor indices provided information related to the maturation of white matter tracts. These growth trajectories are referenced to human studies of fetal brain development. Similarities in the temporal and regional patterns of brain growth over the corresponding periods of central nervous system development are identified between the two species. Atlas images are available online as a reference for registration, reconstruction, segmentation, and for longitudinal analysis of early fetal brain growth over this unique time window.

Challenges and Opportunities in Connectome Construction and Quantification in the Developing Human Fetal Brain.

The white matter structure of the human brain undergoes critical developmental milestones in utero, which we can observe noninvasively using diffusion-weighted magnetic resonance imaging. In order to understand this fascinating developmental process, we must establish the variability inherent in such a challenging imaging environment and how measurable quantities can be transformed into meaningful connectomes. We review techniques for reconstructing and studying the brain connectome and explore promising opportunities for in utero studies that could lead to more accurate measurement of structural properties and allow for more refined and insightful analyses of the fetal brain. Opportunities for more sophisticated analyses of the properties of the brain and its dynamic changes have emerged in recent years, based on the development of iterative techniques to reconstruct motion-corrupted diffusion-weighted data. Although reconstruction quality is greatly improved, the treatment of fundamental quantities like edge strength requires careful treatment because of the specific challenges of imaging in utero. There are intriguing challenges to overcome, from those in analysis due to both imaging limitations and the significant changes in structural connectivity, to further image processing to address the specific properties of the target anatomy and quantification into a developmental connectome.

Plasma cholesterol levels and brain development in preterm newborns.

BACKGROUND: To assess whether postnatal plasma cholesterol levels are associated with microstructural and macrostructural regional brain development in preterm newborns. METHODS: Sixty preterm newborns (born 24-32 weeks gestational age) were assessed using MRI studies soon after birth and again at term-equivalent age. Blood samples were obtained within 7 days of each MRI scan to analyze for plasma cholesterol and lathosterol (a marker of endogenous cholesterol synthesis) levels. Outcomes were assessed at 3 years using the Bayley Scales of Infant Development, Third Edition. RESULTS: Early plasma lathosterol levels were associated with increased axial and radial diffusivities and increased volume of the subcortical white matter. Early plasma cholesterol levels were associated with increased volume of the cerebellum. Early plasma lathosterol levels were associated with a 2-point decrease in motor scores at 3 years. CONCLUSIONS: Higher early endogenous cholesterol synthesis is associated with worse microstructural measures and larger volumes in the subcortical white matter that may signify regional edema and worse motor outcomes. Higher early cholesterol is associated with improved cerebellar volumes. Further work is needed to better understand how the balance of cholesterol supply and endogenous synthesis impacts preterm brain development, especially if these may be modifiable factors to improve outcomes.

Congenital Zika virus infection as a silent pathology with loss of neurogenic output in the fetal brain.

Zika virus (ZIKV) is a flavivirus with teratogenic effects on fetal brain, but the spectrum of ZIKV-induced brain injury is unknown, particularly when ultrasound imaging is normal. In a pregnant pigtail macaque (Macaca nemestrina) model of ZIKV infection, we demonstrate that ZIKV-induced injury to fetal brain is substantial, even in the absence of microcephaly, and may be challenging to detect in a clinical setting. A common and subtle injury pattern was identified, including (i) periventricular T2-hyperintense foci and loss of fetal noncortical brain volume, (ii) injury to the ependymal epithelium with underlying gliosis and (iii) loss of late fetal neuronal progenitor cells in the subventricular zone (temporal cortex) and subgranular zone (dentate gyrus, hippocampus) with dysmorphic granule neuron patterning. Attenuation of fetal neurogenic output demonstrates potentially considerable teratogenic effects of congenital ZIKV infection even without microcephaly. Our findings suggest that all children exposed to ZIKV in utero should receive long-term monitoring for neurocognitive deficits, regardless of head size at birth.

Novel Detection of Placental Insufficiency by Magnetic Resonance Imaging in the Nonhuman Primate.

The placenta is a vital organ necessary for healthy fetal development. Placental insufficiency creates an in utero environment where the fetus is at risk of insufficient oxygen or nutrient exchange. This is primarily caused by impairment of either maternal or fetal circulation or vascular thrombosis such as placental infarction. As a result of placental dysfunction, affected fetuses may be growth restricted, neurologically impaired, and at risk of increased morbidity and mortality. In a cohort of 4 pregnant Rhesus macaques, we describe antenatal detection of naturally occurring intrauterine growth restriction (IUGR) and aberrant fetal neurodevelopment in 1 animal. Abnormal growth parameters were detected by Doppler ultrasound, and vascular insufficiency in the intervillous space was characterized by dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). Furthermore, placental oxygen reserve was shown to be reduced compared to control animals by measurements of placental water T2*. To characterize the effects of IUGR on fetal brain development, T2 and diffusion anisotropy images of the fetal brain were acquired in utero. Reduced brain volume and cerebral cortical surface area were apparent macroscopically. Microstructural abnormalities within the developing white matter and cerebral cortex were also observed through analysis of water diffusion anisotropy. After delivery by cesarean section, pathological examination confirmed placental insufficiency with hypoxia. These findings exemplify how DCE-MRI and T2*-based measurements of blood oxygenation within the placenta can provide noninvasive imaging methods for assessing in vivo placental health to potentially identify pregnancies affected by placental insufficiency and abnormal fetal neurodevelopment prior to the onset of fetal and neonatal distress.

Postnatal polyunsaturated fatty acids associated with larger preterm brain tissue volumes and better outcomes.

BackgroundHuman studies investigating the link between postnatal polyunsaturated fatty acids and preterm brain growth are limited, despite emerging evidence of potential effects on outcomes.MethodsSixty preterm neonates <32 weeks gestational age with magnetic resonance imaging (MRI) scanning at near-birth and near-term age were assessed for brain tissue volumes, including cortical gray matter, white matter, deep gray matter, cerebellum, brainstem, and ventricular cerebrospinal fluid. Red blood cell fatty acid content was evaluated within 1 week of each MRI scan. Neurodevelopmental outcome at 30-36 months corrected age was assessed.ResultsAdjusting for potential confounders, higher near-birth docosahexaenoic acid levels are associated with larger cortical gray matter, deep gray matter, and brainstem volumes and higher near-term levels with larger deep gray matter, cerebellar, and brainstem volumes at near-term age; lower near-birth linoleic acid levels are correlated with larger white matter volume at near-term age. By 30-36 months corrected age, larger cortical and deep gray matter, cerebellar, and brainstem volumes by term age are associated with improved language scores and larger cerebellar and brainstem volumes with improved motor scores.ConclusionSpecific polyunsaturated fatty acid levels have differential and time-dependent associations with brain region growth. Larger brain volumes are associated with improved outcomes at preschool age.

Gyri of the human parietal lobe: Volumes, spatial extents, automatic labelling, and probabilistic atlases.

Accurately describing the anatomy of individual brains enables interlaboratory communication of functional and developmental studies and is crucial for possible surgical interventions. The human parietal lobe participates in multimodal sensory integration including language processing and also contains the primary somatosensory area. We describe detailed protocols to subdivide the parietal lobe, analyze morphological and volumetric characteristics, and create probabilistic atlases in MNI152 stereotaxic space. The parietal lobe was manually delineated on 3D T1 MR images of 30 healthy subjects and divided into four regions: supramarginal gyrus (SMG), angular gyrus (AG), superior parietal lobe (supPL) and postcentral gyrus (postCG). There was the expected correlation of male gender with larger brain and intracranial volume. We examined a wide range of anatomical features of the gyri and the sulci separating them. At least a rudimentary primary intermediate sulcus of Jensen (PISJ) separating SMG and AG was identified in nearly all (59/60) hemispheres. Presence of additional gyri in SMG and AG was related to sulcal features and volumetric characteristics. The parietal lobe was slightly (2%) larger on the left, driven by leftward asymmetries of the postCG and SMG. Intersubject variability was highest for SMG and AG, and lowest for postCG. Overall the morphological characteristics tended to be symmetrical, and volumes also tended to covary between hemispheres. This may reflect developmental as well as maturation factors. To assess the accuracy with which the labels can be used to segment newly acquired (unlabelled) T1-weighted brain images, we applied multi-atlas label propagation software (MAPER) in a leave-one-out experiment and compared the resulting automatic labels with the manually prepared ones. The results showed strong agreement (mean Jaccard index 0.69, corresponding to a mean Dice index of 0.82, average mean volume error of 0.6%). Stereotaxic probabilistic atlases of each subregion were obtained. They illustrate the physiological brain torque, with structures in the right hemisphere positioned more anteriorly than in the left, and right/left positional differences of up to 10 mm. They also allow an assessment of sulcal variability, e.g. low variability for parietooccipital fissure and cingulate sulcus. Illustrated protocols, individual label sets, probabilistic atlases, and a maximum-probability atlas which takes into account surrounding structures are available for free download under academic licences.

Complementary cortical gray and white matter developmental patterns in healthy, preterm neonates.

Preterm birth is associated with brain injury and altered cognitive development. However, the consequences of extrauterine development are not clearly distinguished from perinatal brain injury. Therefore, we characterized cortical growth patterns from 30 to 46 postmenstrual weeks (PMW) in 27 preterm neonates (25-32 PMW at birth) without detectable brain injury on magnetic resonance imaging. We introduce surface-based morphometric descriptors that quantify radial (thickness) and tangential (area) change rates. Within a tensor-based morphometry framework, we use a temporally weighted formulation of regression to simultaneously model local age-related changes in cortical gray matter (GM) and underlying white matter (WM) mapped onto the cortical surface. The spatiotemporal pattern of GM and WM development corresponded to the expected gyrification time course of primary sulcal deepening and branching. In primary gyri, surface area and thickness rates were below average along sulcal pits and above average on gyral banks and crests in both GM and WM. Above average surface area rates in GM corresponded to emergence of secondary and tertiary folds. These findings map the development of neonatal cortical morphometry in the context of extrauterine brain development using a novel approach. Future studies may compare this developmental trajectory to preterm populations with brain injury. Hum Brain Mapp 38:4322-4336, 2017. © 2017 Wiley Periodicals, Inc.

Folding, But Not Surface Area Expansion, Is Associated with Cellular Morphological Maturation in the Fetal Cerebral Cortex.

Altered macroscopic anatomical characteristics of the cerebral cortex have been identified in individuals affected by various neurodevelopmental disorders. However, the cellular developmental mechanisms that give rise to these abnormalities are not understood. Previously, advances in image reconstruction of diffusion magnetic resonance imaging (MRI) have made possible high-resolution in utero measurements of water diffusion anisotropy in the fetal brain. Here, diffusion anisotropy within the developing fetal cerebral cortex is longitudinally characterized in the rhesus macaque, focusing on gestation day (G85) through G135 of the 165 d term. Additionally, for subsets of animals characterized at G90 and G135, immunohistochemical staining was performed, and 3D structure tensor analyses were used to identify the cellular processes that most closely parallel changes in water diffusion anisotropy with cerebral cortical maturation. Strong correlations were found between maturation of dendritic arbors on the cellular level and the loss of diffusion anisotropy with cortical development. In turn, diffusion anisotropy changes were strongly associated both regionally and temporally with cortical folding. Notably, the regional and temporal dependence of diffusion anisotropy and folding were distinct from the patterns observed for cerebral cortical surface area expansion. These findings strengthen the link proposed in previous studies between cellular-level changes in dendrite morphology and noninvasive diffusion MRI measurements of the developing cerebral cortex and support the possibility that, in gyroencephalic species, structural differentiation within the cortex is coupled to the formation of gyri and sulci.SIGNIFICANCE STATEMENT Abnormal brain morphology has been found in populations with neurodevelopmental disorders. However, the mechanisms linking cellular level and macroscopic maturation are poorly understood, even in normal brains. This study contributes new understanding to this subject using serial in utero MRI measurements of rhesus macaque fetuses, from which macroscopic and cellular information can be derived. We found that morphological differentiation of dendrites was strongly associated both regionally and temporally with folding of the cerebral cortex. Interestingly, parallel associations were not observed with cortical surface area expansion. These findings support the possibility that perturbed morphological differentiation of cells within the cortex may underlie abnormal macroscopic characteristics of individuals affected by neurodevelopmental disorders.

3D in utero quantification of T2* relaxation times in human fetal brain tissues for age optimized structural and functional MRI.

PURPOSE: Maximization of the blood oxygen level-dependent (BOLD) functional MRI (fMRI) contrast requires the echo time of the MR sequence to match the T2* value of the tissue of interest, which is expected to be higher in the fetal brain compared with the brain of a child or an adult. METHODS: T2* values of the cortical plate/cortical gray matter tissue in utero in healthy fetuses from mid-gestation onward (20-36 gestational weeks) were measured using 3D T2* maps calculated from 2D dual-echo T2*-weighted data corrected for between-slice motion and reconstructed in 1.0 mm3 isotropic resolution from a sequence of multiple time points, together with 1.0 mm3 isotropic resolution T2-weighted structural data. RESULTS: Mean T2* relaxation times of the cortical tissue were about twice as high as those reported previously in adults. In a supporting experiment applying single seed analysis, default mode and auditory networks appeared better localized and less noisy while using an echo time of 100 ms versus 43 ms. The results of the previous study reporting a trend for T2* values to decrease with fetal age were reproduced and extended to include cortical tissues and subjects in earlier gestation (20-26 gestational weeks). CONCLUSION: The first measurement of T2* values in fetal cortical tissues suggested the appropriate echo time range for fetal BOLD fMRI protocol optimization to be 130-190 ms. Magn Reson Med 78:909-916, 2017. © 2016 International Society for Magnetic Resonance in Medicine.

Fetal brain lesions after subcutaneous inoculation of Zika virus in a pregnant nonhuman primate.

We describe the development of fetal brain lesions after Zika virus (ZIKV) inoculation in a pregnant pigtail macaque. Periventricular lesions developed within 10 d and evolved asymmetrically in the occipital-parietal lobes. Fetal autopsy revealed ZIKV in the brain and significant cerebral white matter hypoplasia, periventricular white matter gliosis, and axonal and ependymal injury. Our observation of ZIKV-associated fetal brain lesions in a nonhuman primate provides a model for therapeutic evaluation.

Detecting default mode networks in utero by integrated 4D fMRI reconstruction and analysis.

Recently, there has been considerable interest, especially for in utero imaging, in the detection of functional connectivity in subjects whose motion cannot be controlled while in the MRI scanner. These cases require two advances over current studies: (1) multiecho acquisitions and (2) post processing and reconstruction that can deal with significant between slice motion during multislice protocols to allow for the ability to detect temporal correlations introduced by spatial scattering of slices into account. This article focuses on the estimation of a spatially and temporally regular time series from motion scattered slices of multiecho fMRI datasets using a full four-dimensional (4D) iterative image reconstruction framework. The framework which includes quantitative MRI methods for artifact correction is evaluated using adult studies with and without motion to both refine parameter settings and evaluate the analysis pipeline. ICA analysis is then applied to the 4D image reconstruction of both adult and in utero fetal studies where resting state activity is perturbed by motion. Results indicate quantitative improvements in reconstruction quality when compared to the conventional 3D reconstruction approach (using simulated adult data) and demonstrate the ability to detect the default mode network in moving adults and fetuses with single-subject and group analysis. Hum Brain Mapp 37:4158-4178, 2016. © 2016 Wiley Periodicals, Inc.

Smaller Cerebellar Growth and Poorer Neurodevelopmental Outcomes in Very Preterm Infants Exposed to Neonatal Morphine.

OBJECTIVE: To examine the relationship between morphine exposure and growth of the cerebellum and cerebrum in very preterm neonates from early in life to term-equivalent age, as well as to examine morphine exposure and brain volumes in relation to neurodevelopmental outcomes at 18 months corrected age (CA). STUDY DESIGN: A prospective cohort of 136 very preterm neonates (24-32 weeks gestational age) was serially scanned with magnetic resonance imaging near birth and at term-equivalent age for volumetric measurements of the cerebellum and cerebrum. Motor outcomes were assessed with the Peabody Developmental Motor Scales, Second Edition and cognitive outcomes with the Bayley Scales of Infant and Toddler Development, Third Edition at 18 months CA. Generalized least squares models and linear regression models were used to assess relationships between morphine exposure, brain volumes, and neurodevelopmental outcomes. RESULTS: A 10-fold increase in morphine exposure was associated with a 5.5% decrease in cerebellar volume, after adjustment for multiple clinical confounders and total brain volume (P = .04). When infants exposed to glucocorticoids were excluded, the association of morphine was more pronounced, with an 8.1% decrease in cerebellar volume. Morphine exposure was not associated with cerebral volume (P = .30). Greater morphine exposure also predicted poorer motor (P < .001) and cognitive outcomes (P = .006) at 18 months CA, an association mediated, in part, by slower brain growth. CONCLUSIONS: Morphine exposure in very preterm neonates is independently associated with impaired cerebellar growth in the neonatal period and poorer neurodevelopmental outcomes in early childhood. Alternatives to better manage pain in preterm neonates that optimize brain development and functional outcomes are urgently needed.

Patch-based augmentation of Expectation-Maximization for brain MRI tissue segmentation at arbitrary age after premature birth.

Accurate automated tissue segmentation of premature neonatal magnetic resonance images is a crucial task for quantification of brain injury and its impact on early postnatal growth and later cognitive development. In such studies it is common for scans to be acquired shortly after birth or later during the hospital stay and therefore occur at arbitrary gestational ages during a period of rapid developmental change. It is important to be able to segment any of these scans with comparable accuracy. Previous work on brain tissue segmentation in premature neonates has focused on segmentation at specific ages. Here we look at solving the more general problem using adaptations of age specific atlas based methods and evaluate this using a unique manually traced database of high resolution images spanning 20 gestational weeks of development. We examine the complimentary strengths of age specific atlas-based Expectation-Maximization approaches and patch-based methods for this problem and explore the development of two new hybrid techniques, patch-based augmentation of Expectation-Maximization with weighted fusion and a spatial variability constrained patch search. The former approach seeks to combine the advantages of both atlas- and patch-based methods by learning from the performance of the two techniques across the brain anatomy at different developmental ages, while the latter technique aims to use anatomical variability maps learnt from atlas training data to locally constrain the patch-based search range. The proposed approaches were evaluated using leave-one-out cross-validation. Compared with the conventional age specific atlas-based segmentation and direct patch based segmentation, both new approaches demonstrate improved accuracy in the automated labeling of cortical gray matter, white matter, ventricles and sulcal cortical-spinal fluid regions, while maintaining comparable results in deep gray matter.

Characterization of Laminar Zones in the Mid-Gestation Primate Brain with Magnetic Resonance Imaging and Histological Methods.

Distinct populations of progenitor and postmitotic neural and glial cells are stratified in the fetal primate brain across developmentally transient tissue zones between the ventricular and pial surfaces. These zones were originally identified by light microscopy. However, it has subsequently been shown that various forms of magnetic resonance image (MRI) contrast can be used to distinguish layers of developing neural tissue in ex vivo, as well as in vivo (including in utero) conditions. Here we compare mid-gestation rhesus macaque tissue zones identified using histological techniques to ex vivo as well as in utero MRI performed on the same brains. These data are compared to mid-gestation fetal human brain MRI results, obtained in utero. We observe strong similarity between MRI contrast in vivo and post mortem, which facilitates interpretation of in utero images based on the histological characterization performed here. Additionally, we observe differential correspondence between the various forms of ex vivo MRI contrast and microscopy data, with maps of the water apparent diffusion coefficient providing the closest match to histologically-identified lamina of the nonhuman primate brain. Examination of histology and post mortem MRI helps to provide a better understanding of cytoarchitectrual characteristics that give rise to in utero MRI contrast.

Mapping the developing human brain in utero using quantitative MR imaging techniques.

Magnetic resonance imaging of the human fetal brain has been a clinical tool for many years and provides valuable additional information to compliment more common ultrasound studies. Advances in both MRI acquisition and post processing over the last 10 years have enabled full 3D imaging and the accurate combination of data acquired in different head positions to create improved geometric integrity, tissue contrast, and resolution. This research is now motivating the development of new quantitative MRI-based techniques for clinical imaging that can more accurately characterize brain development and detect abnormalities. In this article, we will review some of the key areas that are driving changes in our understanding of fetal brain growth using quantitative measures derived from in utero MRI and the possible directions for its increased use in improving the evaluation of pregnancies and the accurate characterization of abnormal brain growth.