Structural MR Analyses of Drug Exposed Brains

我们的小组提出了利用自动分割工具的实验，这些工具已用于成人 MRI（参见Fischl等人，Neuron 33，1-20，2002），以分析从以下获得的一组结构MR扫描： 在子宫内接触可卡因的孩子分析将包括形状和轮廓分析， 皮质下结构，以及皮质结构的分析，包括皮质 体积、表面积、厚度和包裹在特定皮质中的整个皮质的折叠模式 地区通过与布朗大学的巴里莱斯特博士建立一个合作成像联盟，我们的提议将 重点研究8至12岁接触可卡因和酒精的儿童的结构MR数据。李斯特博士 跟踪了一个大的药物和酒精暴露的儿童队列，目前正在资助研究60个这样的 （20名可卡因暴露者，20名酒精暴露者，20名对照者）。到目前为止，他和他的成像小组已经 从14个这样的人收集的数据，我们已经分析，并提供试点数据，从而 证明了拟议研究的可行性和分析能力。生物学假设是 根据初步数据，对毒品暴露人群进行的测试表明，可卡因和酒精 在大脑发育中诱导的改变产生特定的大小和形状的变化， 皮质下结构，以及特定皮质区域的体积和折叠模式。我们研究 形状分析最初集中在胼胝体上，在其他人的先前研究中， 由于产前暴露于酒精而改变形状（Bookstein等人，畸形学，2001年）。我们 形态测量学研究集中在特定的皮质（眶额、额和前扣带）， 皮质下（尾状核，壳核）结构，我们假设是专门改变产前暴露 可卡因，导致注意力，反应性和反应性的功能缺陷。我们还建议 实验来验证我们的自动分割和形态测量方法，以识别可卡因和 酒精引起的暴露儿童大脑结构大小、形状和轮廓的差异。通过 开发和应用这些工具，我们不仅可以解决临床上的重要问题， 开发出对其他从事儿科神经影像学研究的人具有普遍价值的方法。

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.