Dataset Information

Quantitative MRI Analyses of Regional Brain Growth in Living Fetuses with Down Syndrome.

ABSTRACT: 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

SUBMITTER: Tarui T

PROVIDER: S-EPMC7029684 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Quantitative MRI Analyses of Regional Brain Growth in Living Fetuses with Down Syndrome.

Tarui Tomo T Im Kiho K Madan Neel N Madankumar Rajeevi R Skotko Brian G BG Schwartz Allie A Sharr Christianne C Ralston Steven J SJ Kitano Rie R Akiyama Shizuko S Yun Hyuk Jin HJ Grant Ellen E Bianchi Diana W DW

Cerebral cortex (New York, N.Y. : 1991) 20200101 1

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 prec ...[more]

PMID: 31264685

Similar Datasets

Project description:BackgroundCongenital heart disease (CHD) is common and is associated with impaired early brain development and neurodevelopmental outcomes, yet the exact mechanisms underlying these associations are unclear.PurposeTo utilize MRI data from a cohort of fetuses with CHD as well as typically developing fetuses to test the hypothesis that expected cerebral substrate delivery is associated with total and regional fetal brain volumes.Study typeRetrospective case-control study.PopulationThree hundred eighty fetuses (188 male), comprising 45 healthy controls and 335 with isolated CHD, scanned between 29 and 37 weeks gestation. Fetuses with CHD were assigned into one of four groups based on expected cerebral substrate delivery.Field strength/sequenceT2-weighted single-shot fast-spin-echo sequences and a balanced steady-state free precession gradient echo sequence were obtained on a 1.5 T scanner.AssessmentImages were motion-corrected and reconstructed using an automated slice-to-volume registration reconstruction technique, before undergoing segmentation using an automated pipeline and convolutional neural network that had undergone semi-supervised training. Differences in total, regional brain (cortical gray matter, white matter, deep gray matter, cerebellum, and brainstem) and brain:body volumes were compared between groups.Statistical testsANOVA was used to test for differences in brain volumes between groups, after accounting for sex and gestational age at scan. PFDR-values <0.05 were considered statistically significant.ResultsTotal and regional brain volumes were smaller in fetuses where cerebral substrate delivery is reduced. No significant differences were observed in total or regional brain volumes between control fetuses and fetuses with CHD but normal cerebral substrate delivery (all PFDR > 0.12). Severely reduced cerebral substrate delivery is associated with lower brain:body volume ratios.Data conclusionTotal and regional brain volumes are smaller in fetuses with CHD where there is a reduction in cerebral substrate delivery, but not in those where cerebral substrate delivery is expected to be normal.Evidence level3 TECHNICAL EFFICACY: Stage 3.

Project description:INTRODUCTION:Tau pathology is a major age-related event in Down syndrome with Alzheimer's disease (DS-AD). Although recently, several different Tau PET tracers have been developed as biomarkers for AD, these tracers showed different binding properties in Alzheimer disease and other non-AD tauopathies. They have not been yet investigated in tissue obtained postmortem for DS-AD cases. Here, we evaluated the binding characteristics of two Tau PET tracers (3H-MK6240 and 3H-THK5117) and one amyloid (3H-PIB) ligand in the medial frontal gyrus (MFG) and hippocampus (HIPP) in tissue from adults with DS-AD and DS cases with mild cognitive impairment (MCI) compared to sporadic AD. METHODS:Tau and amyloid autoradiography were performed on paraffin-embedded sections. To confirm respective ligand targets, adjacent sections were immunoreacted for phospho-Tau (AT8) and stained for amyloid staining using Amylo-Glo. RESULTS:The two Tau tracers showed a significant correlation with each other and with AT8, suggesting that both tracers were binding to Tau deposits. 3H-MK6240 Tau binding correlated with AT8 immunostaining but to a lesser degree than the 3H-THK5117 tracer, suggesting differences in binding sites between the two Tau tracers. 3H-THK5117, 3H-MK6240 and 3H-PIB displayed dense laminar binding in the HIPP and MFG in adult DS brains. A regional difference in Tau binding between adult DS and AD was observed suggesting differential regional Tau deposition in adult DS compared to AD, with higher THK binding density in the MFG in adult with DS compared to AD. No significant correlation was found between 3H-PIB and Amylo-Glo staining in adult DS brains suggesting that the amyloid PIB tracer binds to additional sites. CONCLUSIONS:This study provides new insights into the regional binding distribution of a first-generation and a second-generation Tau tracer in limbic and neocortical regions in adults with DS, as well as regional differences in Tau binding in adult with DS vs. those with AD. These findings provide new information about the binding properties of two Tau radiotracers for the detection of Tau pathology in adults with DS in vivo and provide valuable data regarding Tau vs. amyloid binding in adult DS compared to AD.

Project description:BackgroundReported date of last menstrual period and ultrasonography measurements are the most commonly used methods for determining gestational age in antenatal life. However, the mother cannot always determine the last menstrual period with certainty, and ultrasonography measurements are accurate only in the first trimester. We aimed to assess the ability of various biometric measurements on magnetic resonance imaging (MRI) in determining the accurate gestational age of an individual fetus in the second half of gestation.MethodsWe used MRI to scan a total of 637 fetuses ranging in age from 22 to 40 gestational weeks. We evaluated 9 standard fetal 2D biometric parameters, and regression models were fitted to assess normal fetal brain development. A stepwise linear regression model was constructed to predict gestational age, and measurement accuracy was determined in a held-out, unseen test sample (n?=?49).ResultsA second-order polynomial regression model was found to be the best descriptor of biometric measures including brain bi-parietal diameter, head circumference, and fronto-occipital diameter in relation to normal fetal growth. Normal fetuses showed divergent growth patterns for the cerebrum and cerebellum, where the cerebrum undergoes rapid growth in the second trimester, while the cerebellum undergoes rapid growth in the third trimester. Moreover, a linear model based on biometrics of brain bi-parietal diameter, length of the corpus callosum, vermis area, transverse cerebellar diameter, and cerebellar area accurately predicted gestational age in the second and third trimesters (cross-validation R2?=?0.822, p?<?0.001).ConclusionsThese results support the use of MRI biometry charts to improve MRI evaluation of fetal growth and suggest that MRI biometry measurements offer a potential estimation model of fetal gestational age in the second half of gestation, which is vital to any assessment of pregnancy, fetal development, and neonatal care.

Project description:Dandy-Walker malformation (DWM) is a common prenatally diagnosed cerebellar malformation, characterized by cystic dilatation of the fourth ventricle, upward rotation of the hypoplastic vermis, and posterior fossa enlargement with torcular elevation. DWM is associated with a broad spectrum of neurodevelopmental abnormalities such as cognitive, motor, and behavioral impairments, which cannot be explained solely by cerebellar malformations. Notably, the pathogenesis of these symptoms remains poorly understood. This study investigated whether fetal structural developmental abnormalities in DWM extended beyond the posterior fossa to the cerebrum even in fetuses without apparent cerebral anomalies. Post-acquisition volumetric fetal magnetic resonance imaging (MRI) analysis was performed in 12 fetuses with DWM and 14 control fetuses. Growth trajectories of the volumes of the cortical plate, subcortical parenchyma, cerebellar hemispheres, and vermis between 18 and 33 weeks of gestation were compared. The median (interquartile range) gestational ages at the time of MRI were 22.4 (19.4-24.0) and 23.9 (20.6-29.2) weeks in the DWM and control groups, respectively (p = 0.269). Eight of the 12 fetuses with DWM presented with associated cerebral anomalies, including hydrocephalus (n = 3), cerebral ventriculomegaly (n = 3), and complete (n = 2) and partial (n = 2) agenesis of the corpus callosum (ACC); 7 presented with extracerebral abnormalities. Chromosomal abnormalities were detected by microarray analysis in 4 of 11 fetuses with DWM, using amniocentesis. Volumetric analysis revealed that the cortical plate was significantly larger in fetuses with DWM than in controls (p = 0.040). Even without ACC, the subcortical parenchyma, whole cerebrum, cerebellar hemispheres, and whole brain were significantly larger in fetuses with DWM (n = 8) than in controls (p = 0.004, 0.025, 0.033, and 0.026, respectively). In conclusion, volumetric fetal MRI analysis demonstrated that the development of DWM extends throughout the brain during the fetal period, even without apparent cerebral anomalies.

Dataset Information

Quantitative MRI Analyses of Regional Brain Growth in Living Fetuses with Down Syndrome.

Publications

Quantitative MRI Analyses of Regional Brain Growth in Living Fetuses with Down Syndrome.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets