Cerebellar Structure and Function Studies in Very Early Abstinence

 描述(申请人提供)：小脑萎缩(尤其是累及小脑前上丘疹)是慢性危险饮酒对大脑结构最显著和临床上最显著的病态影响之一。之前关于酒精对小脑影响的磁共振成像(MRI)研究依赖于手动勾画，因为小脑的解剖结构，叶层比标准图像分辨率更窄，侧疣边界模糊，对自动分割算法提出了特别的挑战。在SBIR第一阶段的资助下，我们(NRI)开发了一种基于主动外观建模(AAM)的新算法，该算法利用人类专家用于推断医学图像中对象边界的形状、图像强度和形状间关系的先验知识。通过利用前瞻性运动跟踪和校正方面的最新进展，我们可以获得更高分辨率和更高质量的小脑图像，我们建议扩展和优化我们的小脑分割软件，将小脑分割成30个子结构，然后使用我们的软件来表征活跃酗酒者的小脑体积和非常早期戒酒期间的小脑体积恢复。我们还建议调查大脑小脑回路如何在酒精中毒的认知和运动障碍中起作用。方法：112名因住院治疗方案而进入NIAAA的酗酒患者将在治疗开始时和住院治疗结束时进行研究，使用前瞻性运动跟踪、步态和平衡的Fregly评估以及对受小脑损伤影响的能力的认知评估，对0.7mm3分辨率的全脑(包括小脑)结构成像进行校正。年龄和性别可比较的对照将按照相同的方案进行研究。将从酒精患者和对照的子集获得小脑蠕虫和小叶(30个包)的专家手工描绘，用于开发高分辨率统计形状模型和概率图谱，这将使我们能够使用AAM方法结合非刚性配准到小脑图谱来优化我们的小脑分割。我们的算法将通过手动标记的重测图像在酗酒者和对照组上得到验证，然后用于量化所有参与者的小脑亚结构体积。在酗酒组中，将比较治疗结束和治疗开始措施，以评估非常早期戒酒期间小脑结构和功能的恢复，并将治疗开始和结束时的酒精数据与对照组的数据进行比较，以估计与酒精相关的损害的程度。我们还将通过检查组成电路节点的大脑区域之间的相互关系模式，然后使用多个区域的大脑体积来预测认知和运动功能测试中的分数，这些测试由脑小脑电路辅助，并已知在酗酒者中受损，从而确定大脑小脑电路中断是否导致酒精中毒患者的认知和运动障碍。

 DESCRIPTION (provided by applicant): Cerebellar shrinkage (especially involving the anterior superior cerebellar vermis) is among the most salient and clinically significant morbid effects of chronic hazardous alcohol consumption on brain structure. Previous magnetic resonance imaging (MRI) studies of alcohol's effect on the cerebellum relied on manual delineation, because cerebellar anatomy, with foliations narrower than standard image resolution and indistinct lateral vermis boundaries, poses particular challenges for automated segmentation algorithms. Under an SBIR Phase I grant, we (NRI) developed a novel algorithm for segmentation of the cerebellar hemispheres and vermis based on Active Appearance Modeling (AAM), which uses the prior knowledge of shape, image intensities and inter-shape relationships that human experts use to infer object boundaries in medical images. By taking advantage of recent advances in prospective motion tracking and correction that allow the acquisition of higher resolution and better quality cerebellar images, we propose to extend and optimize our cerebellar segmentation software to parcellate the cerebellum into 30 substructures, then to use our software to characterize cerebellar volumes in active alcoholics and cerebellar volume recovery during very early abstinence. We also propose to investigate how cerebrocerebellar circuits contribute to cognitive and motor impairment in alcoholism. Methods: 112 alcoholics admitted to the NIAAA for inpatient treatment protocols will be studied at treatment entry and at the end of inpatient treatment with whole brain (including cerebellar) structural imaging at 0.7 mm3 resolution corrected for movement using prospective motion tracking, the Fregly assessment of gait and balance, and cognitive assessment of abilities shown to be affected by cerebellar damage. Age and gender comparable controls will be studied with the same protocols. Expert manual delineation of cerebellar vermis and lobules (30 parcels) will be obtained from a subset of alcoholics and controls for use in developing a high-resolution statistical shape model and probabilistic atlas, which will allow us to optimize our cerebellar segmentation using the AAM approach combined with non-rigid registration to a cerebellar atlas. Our algorithm will be validated on alcoholics and controls with manually labeled test-retest images, then used to quantify cerebellar substructure volume on all participants. End of treatment and treatment entry measures will be compared in the alcoholic group to assess recovery of cerebellar structure and function during very early abstinence, and alcoholic data at the beginning and end of treatment will be compared to data from controls to estimate the magnitude of the alcohol-related damage. We will also determine whether disruption of the cerebrocerebellar circuit underlies cognitive and motor impairment in alcoholism by examining the correlational patterns between brain regions that comprise nodes of the circuit, followed by using multiple regional brain volumes to predict scores on tests of cognitive and motor functions subserved by the cerebrocerebellar circuit and known to be impaired in alcoholics.