Our group proposes experiments to utilize automated segmentation tools that have been utilized on Adult MRIs (see Fischl et al., Neuron 33, 1-20, 2002) to analyze a set of structural MR scans obtained from children exposed to cocaine in utero. The analysis will include both shape and contour analysis of subcortical structures, as well as the analyses of cortical structures including measurement of cortical volume, surface area, thickness, and folding pattern of the entire cortex parcellated in to specific cortical areas. By forming a collaborative imaging alliance with Dr. Barry Lester at Brown University, our proposal will be focused on studying structural MR data from cocaine and alcohol exposed 8 to 12-year-olds. Dr. Lester follows a large cohort of drug and alcohol exposed children, and is currently funded to study 60 such individuals (20 cocaine exposed, 20 alcohol exposed, 20 controls). To date he and his imaging group have collected data from 14 such individuals, which we have analyzed and provide pilot data from, thereby demonstrating the feasibility and analytic power of the proposed studies. The biologic hypotheses to be tested on the drug exposed population, supported by per preliminary data, is that cocaine and alcohol induced alterations in brain development produce specific alterations in the size and shape of particular subcortical structures, and in the volume and folding pattern of of particular cortical areas. Our study of shape analysis has initially focus on the corpus callosum, which in previous studies by others was shown to be altered in shape as a result of prenatal exposure to alcohol (Bookstein et al., Teratology, 2001). Our morphometric studies have focused on particular cortical (orbito-frontal, frontal, and anterior cingulate) and subcortical (caudate, putamen) structures that we hypothesize are specifically altered by prenatal exposure to cocaine, with resulting functional deficits in attention, reactivity, and responsivity. We additionally propose experiments to validate our automated segmentation and morphometric methods to identify cocaine and alcohol-induced differences in the size, shape and contour brain structures of exposed children. By developing and applying such tools we will not only address a clinically important problem, but we will develop methods that will be of general value to others pursuing pediatric neuroimaging studies.