Automatic Cerebellar MRI Labeling In Health and Disease

描述(由申请人提供)：小脑功能障碍与多种疾病有关，这些疾病的发病率很高，但治疗不充分。中风、肿瘤、感染、自身免疫性疾病、药物副作用和慢性酒精中毒都会影响小脑，以及更具体的小脑疾病，如橄榄桥脑小脑变性和小脑性共济失调。通过对小脑性共济失调的研究，我们将能够在小脑萎缩的模式与运动和认知缺陷的模式之间建立精确的联系。最终，在临床评估中观察到小脑变性的功能影响时，将有可能预测其功能影响，从而建议适当的靶向治疗。先前的研究已经使小脑区域萎缩的自动分析成为可能，这是一项以前手动执行的任务。拟议的研究将推进这一能力，包括使用多模式成像数据对小脑及其附近区域的白质和灰质进行联合、自动分割和分析。具体地说，我们将：1)使用多模式图像实施和优化小脑及其附近的灰质和白质分割方法；2)开发方法来量化个体的局部小脑形状，并定义不同人群的统计形状差异；3)对灰质和白质结构进行初步研究，并将其与运动和认知功能表现联系起来。将测试与SCA2、SCA3和SCA6的退变模式和相应的功能缺陷相关的特定假设，并将产生包含正常和共济失调受试者的低维形状空间上的功能评分的初步地形图。这一新的能力将产生一个新的小脑功能分期图，用于诊断、预后和治疗评估。拟议研究的总体目标是开发自动图像和统计分析方法，可以分析由于小脑功能障碍而导致的人群和个人的萎缩模式以及相关的运动和认知障碍。开发的方法将作为开放源码软件在先前建立的、已经在NITRC网站上提供的非常广泛的软件集合中提供。我们受试者的统计地图集也将与软件一起提供，以便在这一空间内定位个人，并根据新的数据收集生成新的地图集。通过我们在技术开发方面的努力以及我们的试点研究展示了这种分析方法的实用性，许多实验室将有可能在各种疾病中发现与小脑有关的新发现。这样的研究可以为小脑疾病带来新的治疗方法，并对那些患有共济失调和其他小脑受累的疾病的患者进行有针对性的治疗。 公共卫生相关性： 小脑功能障碍可由中风、肿瘤、感染、自身免疫性疾病、药物副作用、慢性酒精中毒和遗传缺陷引起。本研究侧重于小脑性共济失调的研究，以便将特定的组织丢失模式与协调、步态、言语、眼球运动和认知等功能的相应丧失联系起来。这项研究中开发的计算机方法将为研究人员和临床医生提供关于小脑疾病对个人和群体的物理影响的新信息，以便更好地监测当前的治疗方法，并帮助开发新的治疗方法。

DESCRIPTION (provided by applicant): Dysfunction of the cerebellum is associated with a wide variety of diseases that have significant morbidity yet inadequate therapy. Strokes, tumors, infection, autoimmune disease, medication side effects, and chronic alcoholism can all affect the cerebellum, as can more specific diseases of the cerebellum such as olivopontine cerebellar degeneration and cerebellar ataxia. Through the study of cerebellar ataxia, which involves pronounced atrophy in distinct patterns associated with specific genetic defects, we will be able to establish precise relationships between patterns of cerebellar atrophy and patterns of motor and cognitive deficits. Eventually, it will become possible to predict the functional impacts of cerebellar degeneration when observed in clinical assessments and thereby to suggest appropriate targeted therapies. Prior research has enabled automated analysis of regional atrophy in the cerebellum, a task that had previously been carried out manually. The proposed research will advance this capability to include joint, automated segmentation and analysis of both white matter and gray matter in cerebellum and nearby regions using multimodal imaging data. Specifically, we will: 1) Implement and optimize gray matter and white matter segmentation methods in the cerebellum and vicinity using multimodal images; 2) Develop methods to quantify regional cerebellar shapes in individuals and to define statistical shape variation across populations; 3) Carry out a pilot study on gray matter and white matter structure and relate these to motor and cognitive functional performance. Specific hypotheses related to patterns of degeneration and corresponding functional deficits in SCA2, SCA3, and SCA6 will be tested, and a preliminary map of the topography of functional scores on a low- dimensional shape space incorporating normal and ataxia subjects will be produced. This new capability will yield a novel staging chart for cerebellar function for use in diagnosis, prognosis, and treatment assessment. The overall goal of the proposed research is to develop automated image and statistical analysis methods that can analyze the patterns of atrophy and associated motor and cognitive deficits in populations and individuals due to cerebellar dysfunction. Methods that are developed will be made available as open source software within a previously established and very extensive software collection already available on the NITRC website. The statistical atlas of our subjects will also be made available together with software for positioning individuals within this space and for generating new atlases on new data collections. Through our efforts in technology development as well as our pilot study demonstrating utility of this analytic approach, new discoveries related to the cerebellum in diverse diseases carried out by many labs will become possible. Such investigations can then lead to new treatments for cerebellar disease and to targeted therapies in those suffering from ataxia and other diseases with cerebellum involvement. PUBLIC HEALTH RELEVANCE: Project Narrative Dysfunction of the cerebellum can be caused by strokes, tumors, infection, autoimmune disease, medication side effects, chronic alcoholism, and genetic defects. This research focuses on the study of cerebellar ataxia in order to relate specific patterns of tissue loss to corresponding losses in functions such as coordination, gait, speech, eye movement, and cognition. The computer methods developed in this research will provide researchers and clinicians new information about the physical effects of cerebellar disease in individuals and groups of people in order to better monitor current treatments and to help develop new treatments.