Early alterations in cortical and cerebellar regional brain growth in Down Syndrome: An in vivo fetal and neonatal MRI assessment.
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ABSTRACT:
SUBMITTER: Patkee PA
PROVIDER: S-EPMC6938981 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Down syndrome (DS) is the most common genetic cause of developmental disabilities. Advanced analysis of brain magnetic resonance imaging (MRI) has been used to find brain abnormalities and their relationship to neurocognitive impairments in children and adolescents with DS. Because genetic factors affect brain development in early fetal life, there is a growing interest in analyzing brains from living fetuses with DS. In this study, we investigated regional sulcal folding depth as well as global cortical gyrification from fetal brain MRIs. Nine fetuses with DS (29.1 ± 4.24 gestational weeks [mean ± standard deviation]) were compared with 17 typically developing [TD] fetuses (28.4 ± 3.44). Fetuses with DS showed lower whole-brain average sulcal depths and gyrification index than TD fetuses. Significant decreases in sulcal depth were found in bilateral Sylvian fissures and right central and parieto-occipital sulci. On the other hand, significantly increased sulcal depth was shown in the left superior temporal sulcus, which is related to atypical hemispheric asymmetry of cortical folding. Moreover, these group differences increased as gestation progressed. This study demonstrates that regional sulcal depth is a sensitive marker for detecting alterations of cortical development in DS during fetal life, which may be associated with later neurocognitive impairment.
| S-EPMC7786357 | biostudies-literature
Project description:The cerebellum is a complex system with distinct cortical laminar organization. Alterations in cerebellar microstructure are common and associated with many factors such as genetics, cancer and ageing. Diffusion MRI (dMRI) provides a non-invasive tool to map the brain structural organization, and the recently proposed diffusion-time (td )-dependent dMRI further improves its capability to probe the cellular and axonal/dendritic microstructures by measuring water diffusion at multiple spatial scales. The td -dependent diffusion profile in the cerebellum and its utility in detecting cerebellar disorders, however, are not yet elucidated. Here, we first deciphered the spatial correspondence between dMRI contrast and cerebellar layers, based on which the cerebellar layer-specific td -dependent dMRI patterns were characterized in both euploid and Ts65Dn mice, a mouse model of Down syndrome. Using oscillating gradient dMRI, which accesses diffusion at short td 's by modulating the oscillating frequency, we detected subtle changes in the apparent diffusivity coefficient of the cerebellar internal granular layer and Purkinje cell layer of Ts65Dn mice that were not detectable by conventional pulsed gradient dMRI. The detection sensitivity of oscillating gradient dMRI increased with the oscillating frequency at both the neonatal and adult stages. The td -dependence, quantified by ΔADC map, was reduced in Ts65Dn mice, likely associated with the reduced granule cell density and abnormal dendritic arborization of Purkinje cells as revealed from histological evidence. Our study demonstrates superior sensitivity of short-td diffusion using oscillating gradient dMRI to detect cerebellar microstructural changes in Down syndrome, suggesting the potential application of this technique in cerebellar disorders.
| S-EPMC8063586 | biostudies-literature
Project description:Background and purposeRecent data suggest that early symptoms may be related to cortex alterations in CADASIL (Cerebral Autosomal-Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy), a monogenic model of cerebral small vessel disease (SVD). The aim of this study was to investigate cortical alterations using both high-resolution T2* acquisitions obtained with 7 Tesla MRI and structural T1 images with 3 Tesla MRI in CADASIL patients with no or only mild symptomatology (modified Rankin's scale ?1 and Mini Mental State Examination (MMSE) ?24).MethodsComplete reconstructions of the cortex using 7 Tesla T2* acquisitions with 0.7 mm isotropic resolution were obtained in 11 patients (52.1±13.2 years, 36% male) and 24 controls (54.8±11.0 years, 42% male). Seven Tesla T2* within the cortex and cortical thickness and morphology obtained from 3 Tesla images were compared between CADASIL and control subjects using general linear models.ResultsMMSE, brain volume, cortical thickness and global sulcal morphology did not differ between groups. By contrast, T2* measured by 7 Tesla MRI was significantly increased in frontal, parietal, occipital and cingulate cortices in patients after correction for multiple testing. These changes were not related to white matter lesions, lacunes or microhemorrhages in patients having no brain atrophy compared to controls.ConclusionsSeven Tesla MRI, by contrast to state of the art post-processing of 3 Tesla acquisitions, shows diffuse T2* alterations within the cortical mantle in CADASIL whose origin remains to be determined.
| S-EPMC4148432 | biostudies-literature
Project description:Neuroimaging studies have revealed that disturbances in network organization of key brain regions may underlie cognitive and emotional dysfunction in posttraumatic stress disorder (PTSD). Examining both brain structure and function in the same population may further our understanding of network alterations in PTSD. We used tensor-based morphometry (TBM) and intrinsic connectivity distribution (ICD) to identify regions of altered volume and functional connectivity in unmedicated individuals with PTSD (n=21) and healthy comparison (HC) participants (n=18). These regions were then used as seeds for follow-up anatomical covariance and functional connectivity analyses. Smaller volume in the cerebellum and weaker structural covariance between the cerebellum seed and middle temporal gyrus were observed in the PTSD group. Individuals with PTSD also exhibited lower whole-brain connectivity in the cerebellum, dorsolateral prefrontal cortex (dlPFC) and medial prefrontal cortex (mPFC). Functional connectivity in the cerebellum and grey matter volume in the dlPFC were negatively correlated with PTSD severity as measured by the DSM-5 PTSD checklist (PCL-5; r= -.0.77, r=-0.79). Finally, seed connectivity revealed weaker connectivity within nodes of the central executive network (right and left dlPFC), and between nodes of the default mode network (mPFC and cerebellum) and the supramarginal gyrus, in the PTSD group. We demonstrate structural and functional alterations in PTSD converging on the PFC and cerebellum. Whilst PFC alterations are relatively well established in PTSD, the cerebellum has not generally been considered a key region in PTSD. Our findings add to a growing evidence base implicating cerebellar involvement in the pathophysiology of PTSD.
| S-EPMC6054445 | biostudies-literature
Project description:Background and purposeTraditional methods of dating a pregnancy based on history or sonographic assessment have a large variation in the third trimester. We aimed to assess the ability of various quantitative measures of brain cortical folding on MR imaging in determining fetal gestational age in the third trimester.Materials and methodsWe evaluated 8 different quantitative cortical folding measures to predict gestational age in 33 healthy fetuses by using T2-weighted fetal MR imaging. We compared the accuracy of the prediction of gestational age by these cortical folding measures with the accuracy of prediction by brain volume measurement and by a previously reported semiquantitative visual scale of brain maturity. Regression models were constructed, and measurement biases and variances were determined via a cross-validation procedure.ResultsThe cortical folding measures are accurate in the estimation and prediction of gestational age (mean of the absolute error, 0.43 ± 0.45 weeks) and perform better than (P = .024) brain volume (mean of the absolute error, 0.72 ± 0.61 weeks) or sonography measures (SDs approximately 1.5 weeks, as reported in literature). Prediction accuracy is comparable with that of the semiquantitative visual assessment score (mean, 0.57 ± 0.41 weeks).ConclusionsQuantitative cortical folding measures such as global average curvedness can be an accurate and reliable estimator of gestational age and brain maturity for healthy fetuses in the third trimester and have the potential to be an indicator of brain-growth delays for at-risk fetuses and preterm neonates.
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Project description:The morphology of axonal and dendritic arbors in the immature cerebral cortex influences the degree of anisotropy in water diffusion. This enables cortical maturation to be monitored by the noninvasive technique of diffusion tensor magnetic resonance imaging (DTI). Herein, we utilized DTI of postmortem ferret brain to quantify regional and temporal patterns in cortical maturation. We found that diffusion anisotropy within the isocortex decreases over the first month of life, coinciding closely in time with expansion of axonal and dendritic cellular processes of pyramidal neurons. Regional patterns consist of differences between allocortex and isocortex, a regional anisotropy gradient that closely parallels the transverse neurogenetic gradient, and differences between primary and nonprimary isocortical areas. By combining the temporal and regional factors, the isocortical developmental gradient magnitude corresponds to a 5-day difference in maturity between relatively developed rostral/caudal isocortex at the gradient source and less mature isocortex at the occipital pole. Additionally, the developmental trajectory of primary areas precedes nonprimary areas by 2.7 days. These quantitative estimates coincide with previous histological studies of ferret development. Similarities in cerebral cortical diffusion anisotropy observed between ferret and other species suggest the framework developed here is of general potential relevance.
| S-EPMC2774393 | biostudies-other
Project description:Epidemiological studies report associations between early-life exposure to persistent organic pollutants (POPs) and impaired metabolic homeostasis in adulthood. We investigated the impact of early-life exposure to low-dose 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD or 'dioxin') on the establishment of β-cell area during the perinatal period, as well as β-cell health and glucose homeostasis later in life. Adult female mice were injected with either corn oil (CO; vehicle control) or TCDD (20 ng/kg/day) 2×/week throughout mating, pregnancy, and lactation; offspring were thus indirectly exposed to maternal TCDD in utero and during lactation, with pollutant exposure ending at weaning. All offspring were maintained on chow diet from weaning until 12-17 weeks of age, after which a subset of CO- and TCDD-exposed offspring were transferred to a 45% high fat diet (HFD) as a metabolic stressor for an additional 10 weeks. TCDD significantly upregulated cytochrome P450 1a1 (Cyp1a1) gene expression in offspring pancreas at birth and weaning, indicating that maternal TCDD directly reaches the developing pancreas. TCDD-exposed pups were transiently hypoglycemic at birth and females were born with reduced % β-cell area, which persisted into adulthood. Early-life TCDD exposure had no persistent long-term effects on glucose homeostasis in chow-fed offspring, but when transferred to HFD, TCDD-exposed female offspring had a delayed onset of HFD-induced hyperglycemia, more pronounced HFD-induced hyperinsulinemia, and increase % PCNA+ β-cells compared with CO-exposed female offspring. This study demonstrates that early-life exposure of mice to TCDD has modest effects on metabolic health in chow-fed offspring but alters metabolic adaptability to HFD feeding in females.
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Project description:Structural asymmetries and sexual dimorphism of the human cerebral cortex have been identified in newborns, infants, children, adolescents, and adults. Some of these findings were linked with cognitive and neuropsychiatric disorders, which have roots in altered prenatal brain development. However, little is known about structural asymmetries or sexual dimorphism of transient fetal compartments that arise in utero. Thus, we aimed to identify structural asymmetries and sexual dimorphism in the volume of transient fetal compartments (cortical plate [CP] and subplate [SP]) across 22 regions. For this purpose, we used in vivo structural T2-weighted MRIs of 42 healthy fetuses (16.43-36.86 gestational weeks old, 15 females). We found significant leftward asymmetry in the volume of the CP and SP in the inferior frontal gyrus. The orbitofrontal cortex showed significant rightward asymmetry in the volume of CP merged with SP. Males had significantly larger volumes in regions belonging to limbic, occipital, and frontal lobes, which were driven by a significantly larger SP. Lastly, we did not observe sexual dimorphism in the growth trajectories of the CP or SP. In conclusion, these results support the hypothesis that structural asymmetries and sexual dimorphism in relative volumes of cortical regions are present during prenatal brain development.
| S-EPMC7132947 | biostudies-literature
Project description:Down syndrome (DS) is the most common liveborn autosomal chromosomal anomaly and is a major cause of developmental disability. Atypical brain development and the resulting intellectual disability originate during the fetal period. Perinatal interventions to correct such aberrant development are on the horizon in preclinical studies. However, we lack tools to sensitively measure aberrant structural brain development in living human fetuses with DS. In this study, we aimed to develop safe and precise neuroimaging measures to monitor fetal brain development in DS. We measured growth patterns of regional brain structures in 10 fetal brains with DS (29.1 ± 4.2, weeks of gestation, mean ± SD, range 21.7~35.1) and 12 control fetuses (25.2 ± 5.0, range 18.6~33.3) using regional volumetric analysis of fetal brain MRI. All cases with DS had confirmed karyotypes. We performed non-linear regression models to compare fitted regional growth curves between DS and controls. We found decreased growth trajectories of the cortical plate (P = 0.033), the subcortical parenchyma (P = 0.010), and the cerebellar hemispheres (P < 0.0001) in DS compared to controls. This study provides proof of principle that regional volumetric analysis of fetal brain MRI facilitates successful evaluation of brain development in living fetuses with DS.
| S-EPMC7029684 | biostudies-literature
Project description:This study aimed to validate a fully automatic method to quantify knee-extensor muscle volume and exercise-induced hypertrophy. By using a magnetic resonance imaging-based fat-water separated two-point Dixon sequence, the agreement between automated and manual segmentation of a specific ~15-cm region (partial volume) of the quadriceps muscle was assessed. We then explored the sensitivity of the automated technique to detect changes in both complete and partial quadriceps volume in response to 8 weeks of resistance training in 26 healthy men and women. There was a very strong correlation (r?=?0.98, P?<?0.0001) between the manual and automated method for assessing partial quadriceps volume, yet the volume was 9.6% greater with automated compared with manual analysis (P?<?0.0001, 95% limits of agreement -93.3?±?137.8?cm3). Partial muscle volume showed a 6.0?±?5.0% (manual) and 4.8?±?8.3% (automated) increase with training (P?<?0.0001). Similarly, the complete quadriceps increased 5.1?±?5.5% with training (P?<?0.0001). The intramuscular fat proportion decreased (P?<?0.001) from 4.1% to 3.9% after training. In conclusion, the automated method showed excellent correlation with manual segmentation and could detect clinically relevant magnitudes of exercise-induced muscle hypertrophy. This method could have broad application to accurately measure muscle mass in sports or to monitor clinical conditions associated with muscle wasting and fat infiltration.
| S-EPMC7010694 | biostudies-literature