Using diffusion anisotropy to study cerebral cortical gray matter development

Diffusion-weighted magnetic resonance imaging (diffusion MRI) is being used to characterize morphological development of cells within developing cerebral cortical gray matter. Abnormal morphology is a shared characteristic of cerebral cortical neurons for many neurodevelopmental disorders, and therefore diffusion MRI is potentially of high value for monitoring growth-related anatomical changes of relevance to brain function. Here, the theoretical framework for analyzing diffusion MRI data is summarized. An overview of quantitative methods for validating the interpretations of diffusion MRI data using light microscopy is then presented. These theoretical modeling and validation methods have been used to precisely characterize changes in water diffusion anisotropy with development in the context of several animal model systems. Further, in diffusion MRI studies of several preclinical models of neurodevelopmental disorders, the ability is demonstrated of diffusion MRI to detect abnormal morphological neural development. These animal model studies are reviewed along with recent initial efforts to translate the findings into an approach for studies of human subjects. This body of data indicates that diffusion MRI has the requisite sensitivity to detect abnormal cellular development in the context of several models of neurodevelopmental disorders, and therefore may provide a new strategy for detecting abnormalities in early stages of brain development in humans.