Cerebellar Structure and Function Studies in Very Early Abstinence

早期禁欲中的小脑结构和功能研究

• 批准号: 9268635
• 负责人: George Fein
• 金额: $ 42.32万
• 依托单位: NEUROBEHAVIORAL RESEARCH, INC.
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-07-01 至 2019-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9268635
• 关键词: Abstinence; Affect; Affective; Age; Alcohol abuse; Alcohol consumption; Alcoholism; Alcohols; Algorithms; Anatomy; Anterior; Appearance; Atlases; Atrophic; Attention; Behavior; Brain; Brain region; Cerebellar vermis structure; Cerebellum; Cerebrum; Chronic; Clinical; Computer software; Controlled Study; Data; Equilibrium; Gait; Gender; Gold; Grant; Human; Image; Image Analysis; Impaired cognition; Impairment; Inpatients; Intramural Research Program; Knowledge; Label; Language; Lateral; Lobule; Magnetic Resonance Imaging; Manuals; Measurement; Measures; Medical Imaging; Methodology; Methods; Modeling; Motion; Motor; Movement; National Institute on Alcohol Abuse and Alcoholism; Participant; Pathology; Patients; Pattern; Phase; Problem Solving; Protocols documentation; Recovery; Resolution; Scanning; Shapes; Short-Term Memory; Small Business Innovation Research Grant; Structural defect; Structure; Surface; Testing; Time; Treatment Protocols; United States National Institutes of Health; Validity and Reliability; Visuospatial; Work; alcohol effect; alcohol exposure; base; brain volume; clinically significant; cognitive task; cognitive testing; cohort; executive function; high resolution imaging; imaging study; in vivo; motor impairment; neuroimaging; neuropathology; novel; problem drinker; prospective; public health relevance; skills; tool

 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.

 描述（由申请人提供）：小脑萎缩（特别是涉及小脑蚓部前上）是长期危险饮酒对大脑结构最显着且具有临床意义的病态影响之一。以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，并且蚓部外侧边界不明显，这给自动分割算法带来了特殊的挑战。在 SBIR 第一阶段资助下，我们 (NRI) 开发了一种基于主动外观建模 (AAM) 的小脑半球和蚓部分割新算法，该算法使用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方面的最新进展，获得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早期戒酒期间的小脑体积恢复。我们还建议研究小脑回路如何导致酒精中毒的认知和运动障碍。方法：将在治疗开始时和住院治疗结束时对 112 名因住院治疗方案入院的 NIAAA 酗酒者进行研究，使用分辨率为 0.7 mm3 的全脑（包括小脑）结构成像，使用前瞻性运动跟踪、步态和平衡的 Fregly 评估以及受小脑损伤影响的能力的认知评估进行运动校正。年龄和性别可比较的对照将使用相同的方案进行研究。将从酗酒者和对照组的子集获得小脑蚓部和小叶（30 个包裹）的专家手动描绘，用于开发高分辨率统计形状模型和概率图集，这将使我们能够使用 AAM 方法结合非刚性配准小脑图集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中进行验证，然后用于量化所有参与者的小脑亚结构体积。将在酒精组中比较治疗结束和治疗进入测量，以评估早期戒酒期间小脑结构和功能的恢复情况，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，以估计酒精相关损害的程度。我们还将通过检查构成脑小脑回路节点的大脑区域之间的相关模式来确定小脑回路的破坏是否是酗酒者认知和运动障碍的基础，然后使用多个区域脑容量来预测小脑回路所促进的认知和运动功能测试的分数，并且已知在酗酒者中会受到损害。