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Biomedical subjects

Paul Yarowsky

Publications and source records attributed to Paul Yarowsky.

6 recordsLinked to original sources

White and gray matter development in human fetal, newborn and pediatric brains.

Brain anatomy is characterized by dramatic growth from the end of the second trimester through the neonatal stage. The characterization of normal axonal growth of the white matter tracts has not been well-documented to date and could provide important clues to understanding the extensive inhomogeneity of white matter injuries in cerebral palsy (CP) patients. However, anatomical studies of human brain development during this period are surprisingly scarce and histology-based atlases have become available only recently. Diffusion tensor magnetic resonance imaging (DTMRI) can reveal detailed anatomy of white matter. We acquired diffusion tensor images (DTI) of postmortem fetal brain samples and in vivo neonates and children. Neural structures were annotated in two-dimensional (2D) slices, segmented, measured, and reconstructed three-dimensionally (3D). The growth status of various white matter tracts was evaluated on cross-sections at 19-20 gestational weeks, and compared with 0-month-old neonates and 5- to 6-year-old children. Limbic, commissural, association, and projection white matter tracts and gray matter structures were illustrated in 3D and quantitatively characterized to assess their dynamic changes. The overall pattern of the time courses for the development of different white matter is that limbic fibers develop first and association fibers last and commissural and projection fibers are forming from anterior to posterior part of the brain. The resultant DTMRI-based 3D human brain data will be a valuable resource for human brain developmental study and will provide reference standards for diagnostic radiology of premature newborns.

Adult↗

Spatiotemporal maturation patterns of murine brain quantified by diffusion tensor MRI and deformation-based morphometry.

Highly heterogeneous spatiotemporal patterns of maturation of the murine brain during the first 80 postnatal days were examined by high-dimensional deformation-based morphometry applied to high-resolution diffusion tensor MRIs. The maturation profile revealed a sharp contrast between tissue anisotropy changes in the cortex and in major white-matter fibers. Radially oriented tissue anisotropy was measured during the first postnatal week in cortical regions, reflecting the underlying columnar organization of the cortex. Subsequently, tissue anisotropy reduced rapidly, potentially reflecting the growth of randomly oriented dendritic trees that reduce tissue coorientation. Distinct anisotropy patterns were also observed along layer I of the cortex and were attributed to thin fibers oriented parallel to the outer surface. Last, spatially complex patterns of maturation were measured in all major axonal pathways and in the hippocampus, caudate putamen, and cerebellum. This analysis provides a framework for quantifying normative maturation patterns against which phenotypes of mice of different genetic and environmental backgrounds can be contrasted.

Age Factors↗

Mapping postnatal mouse brain development with diffusion tensor microimaging.

While mouse brain development has been extensively studied using histology, quantitative characterization of morphological changes is still a challenging task. This paper presents how developing brain structures can be quantitatively characterized with magnetic resonance diffusion tensor microimaging coupled with techniques of computational anatomy. High resolution diffusion tensor images of ex vivo postnatal mouse brains provide excellent contrasts to reveal the evolutions of mouse forebrain structures. Using anatomical landmarks defined on diffusion tensor images, tissue level growth patterns of mouse brains were quantified. The results demonstrate the use of these techniques to three-dimensionally and quantitatively characterize brain growth.

Algorithms↗

Magnetic resonance diffusion tensor microimaging reveals a role for Bcl-x in brain development and homeostasis.

A new technique based on diffusion tensor imaging and computational neuroanatomy was developed to efficiently and quantitatively characterize the three-dimensional morphology of the developing brains. The technique was used to analyze the phenotype of conditional Bcl-x knock-out mice, in which the bcl-x gene was deleted specifically in neurons of the cerebral cortex and hippocampus beginning at embryonic day 13.5 as cells became postmitotic. Affected brain regions and associated axonal tracts showed severe atrophy in adult Bcl-x-deficient mice. Longitudinal studies revealed that these phenotypes are established by regressive processes that occur primarily during the first postnatal week, whereas neurogenesis and migration showed no obvious abnormality during embryonic stages. Specific families of white matter tracts that once formed normally during the embryonic stages underwent dramatic degeneration postnatally. Thus, this technique serves as a powerful tool to efficiently localize temporal and spatial manifestation of morphological phenotype.

Animals↗

Detection of amyloid plaques in mouse models of Alzheimer's disease by magnetic resonance imaging.

We performed three-dimensional, high-resolution magnetic resonance imaging (MRI) of fixed mouse brains to determine whether MRI can detect amyloid plaques in transgenic mouse models of Alzheimer's disease. Plaque-like structures in the cortex and hippocampus could be clearly identified in T2-weighted images with an image resolution of 46 microm x 72 microm x 72 microm. The locations of plaques were confirmed in coregistration studies comparing MR images with Congo red-stained histological results. This technique is quantitative, less labor-intensive compared to histology, and is free from artifacts related to sectioning process (deformation and missing tissues). It enabled us to study the distribution of plaques in the entire brain in 3D. The results of this study suggest that this method may be useful for assessing treatment efficacy in mouse models of Alzheimer's disease (AD).

Alzheimer Disease↗

Three-dimensional anatomical characterization of the developing mouse brain by diffusion tensor microimaging.

Investigation of three-dimensional (3D) morphometry of developing brains has been hindered by a lack of imaging modalities that can monitor the 3D evolution of various anatomical structures without sectioning and staining processes. In this study, we combined magnetic resonance microimaging and diffusion tensor imaging techniques to accomplish such visualization. The application of this approach to developing mouse embryos revealed that it could clearly delineate early critical structures such as neuroepithelium, cortical plate, and various axonal structures, and follow their developmental evolution. The technique was applied to the study of the Netrin-1 mutant, allowing verification of its anatomical phenotype.

Animals↗