Cerebellar Structure and Function Studies in Very Early Abstinence

 描述（由申请人提供）：小脑萎缩（特别是累及小脑前上级蚓部）是慢性有害酒精摄入对大脑结构最显著和临床显著的病态影响之一。先前关于酒精对小脑影响的磁共振成像（MRI）研究依赖于手动描绘，因为小脑解剖结构的叶状结构比标准图像分辨率窄，并且侧蚓部边界不清楚，这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）的小脑半球和小脑蚓部分割的新算法，该算法使用了人类专家用来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的最新进展，允许采集更高分辨率和更好质量的小脑图像，我们建议扩展和优化我们的小脑分割软件，将小脑包裹成30个子结构，然后使用我们的软件来表征活跃的酗酒者小脑体积和小脑体积恢复在非常早期的禁欲。我们还建议调查小脑神经回路如何有助于酒精中毒的认知和运动障碍。研究方法：将在治疗开始时和住院治疗结束时对112名因住院治疗方案而进入NIAAA的酗酒者进行研究，使用前瞻性运动跟踪、步态和平衡的Fregly评估以及显示受小脑损伤影响的能力的认知评估，以0.7 mm3分辨率进行全脑（包括小脑）结构成像。年龄和性别相当的对照将采用相同的方案进行研究。小脑蚓部和小叶（30个包裹）的专家手动描绘将从酗酒者和对照组的子集中获得，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方法结合小脑图谱的非刚性配准来优化我们的小脑分割。我们的算法将验证酗酒者和控制手动标记的重测图像，然后用于量化所有参与者的小脑子结构体积。将在酒精组中比较治疗结束和治疗进入测量，以评估在极早期戒断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，以估计酒精相关损伤的程度。我们还将确定是否中断的小脑回路的认知和运动障碍的酗酒通过检查大脑区域之间的相关模式，包括节点的电路，然后使用多个区域的脑容量来预测分数的认知和运动功能的测试subserved由小脑回路和已知的酗酒者受损。

 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.