Publications by authors named "Colin Studholme"

Article Synopsis
  • Adequate nutrition during pregnancy is essential for fetal brain development, and low protein intake can lead to neurological issues in offspring, which is a major global health concern.
  • A study using rhesus macaques showed that reduced maternal protein levels led to structural brain abnormalities and decreased gray matter volume, particularly in areas important for motor control.
  • Although significant brain changes were observed through MRI, early behavioral tests at 1 month showed only minor effects, suggesting that the impacts of protein reduction may not immediately translate to behavior.
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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.

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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.

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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.

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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.

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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.

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Article Synopsis
  • Reconstruction of fetal brain white matter connectivity using in utero diffusion-weighted MRI has challenges like subject movement, small anatomy, and low image quality.
  • An automated method enhances the reliability and completeness of extracting brain tracts by focusing on streamline tractography patterns and is specifically designed for fetal imaging.
  • The approach successfully reconstructs the corpus callosum while minimizing errors and misleading connections in the imaging process.
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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.

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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.

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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.

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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.

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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.

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Article Synopsis
  • The placenta plays a crucial role in fetal development, and problems with its function can lead to insufficient oxygen and nutrient delivery to the fetus, resulting in growth restrictions and neurodevelopmental issues.
  • In a study involving pregnant Rhesus macaques, researchers identified intrauterine growth restriction (IUGR) and abnormal brain development in one fetus using advanced imaging techniques like Doppler ultrasound and DCE-MRI.
  • The findings indicate that these imaging methods may help detect placental insufficiency and potential fetal neural problems early on, potentially preventing serious complications during pregnancy and after birth.
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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 measurements of water diffusion anisotropy in the fetal brain.

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Article Synopsis
  • Scientists studied how the Zika virus affected a baby monkey's brain when its mom was infected.
  • The baby developed brain damage in specific areas within 10 days after the infection.
  • This study helps researchers better understand Zika's effects on the brain, which can help find better treatments.
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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 mm isotropic resolution from a sequence of multiple time points, together with 1.

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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.

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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.

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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.

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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.

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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.

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Background: Cerebellar hypoplasia is a common problem in preterm infants and infants suffering from intraventricular hemorrhage (IVH). To evaluate the effects of IVH on cerebellar growth and development, we used a neonatal rabbit model of systemic glycerol to produce IVH.

Methods: New Zealand White rabbit kits were surgically delivered 2 d preterm and treated with intraperitoneal glycerol (3.

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Article Synopsis
  • This paper introduces a new technique for correcting intensity inhomogeneity in fMRI studies, particularly when subjects are in motion.
  • The method utilizes multiple images captured during motion to avoid relying on fixed tissue models, allowing for a more adaptable analysis of the bias field.
  • Evaluations show that this new approach outperforms existing methods, demonstrating its effectiveness in both simulated and actual fMRI scenarios involving motion.
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In the context of medical imaging, super-resolution (SR) is currently a promising post-processing technique to increase the image resolution. However, although many SR methods have been proposed in the literature, the gain of this type of approach in a real situation has not been precisely quantified. In this work, we evaluate image acquisition protocols and SR algorithms using in-vivo brain MR data as gold standard.

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A crucial step in studying brain connectivity is the definition of the Regions Of Interest (ROI's) which are considered as nodes of a network graph. These ROI's identified in structural imaging reflect consistent functional regions in the anatomies being compared. However in serial studies of the developing fetal brain such functional and associated structural markers are not consistently present over time.

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