Characterization of White Matter in Huntington's Disease Using Diffusion MRI

描述（由申请人提供）：这项为期两年的辅助资助申请针对亨廷顿舞蹈病（HD），这是一种遗传性进行性神经系统疾病，其特征是运动、认知和行为功能逐渐下降。目前还没有治愈HD的方法，在受影响的大脑区域的早期阶段了解疾病进展对于开发新的治疗干预措施非常重要。最近的研究发现，连接纹状体和运动皮层的皮质-纹状体白质通路是HD运动功能症状学的关键。然而，目前的扩散MRI分析方法不足以正确表征HD诱导的该通路的病理变化。因此，这项辅助拨款申请的目的是针对我们新颖的先进弥散MRI生物标志物和皮质纹状体通路的分析方法。通过将这些新的生物标志物检测到的异常与皮质纹状体束的特定部分联系起来，将有可能精确地绘制白质束变性和运动功能障碍之间的关系。这将有助于提高我们对HD运动退化的神经病理学基础的理解。这项拨款提案的核心是PREDICT-HD数据库。该数据集包含脑成像数据和一套全面的临床相关性，这些数据来自于一个非常大的样本，这些样本来自于表现前（前驱）HD患者，这些样本被选中，以便从最早的症状开始追踪HD症状。该提案将结合PREDICT-HD的优势和我们尖端的神经成像技术，该技术可以检测和测量白质组织的几种新型结构和生理特性。因此，这项资助的主要创新是使用我们的扩散MRI数据分析的新方法来表征HD患者皮质纹状体通路白质连接中发生的变化。将这些新方法结合起来，不仅可以量化白质的病理变化，还可以将这些变化的纵向演变与特定运动功能障碍的演变联系起来。这些生物标志物将增强对显前HD的理解，并使更好地监测疾病进展和针对潜在的早期治疗成为可能。

DESCRIPTION (provided by applicant): This ancillary grant application for two years of funding addresses Huntington's disease (HD), a genetic and progressive neurological disorder characterized by a gradual decline in motor, cognitive and behavioral functions. No cure for HD currently exists, and an understanding of disease progression at early stages in the affected brain areas is important for the development of new therapeutic interventions. Recent research has identified the cortico-striatal white matter pathway, which connects the striatum to the motor cortex, as key to HD motor function symptomatology. Current methods of analysis in diffusion MRI, however, are insufficient to properly characterize the pathological changes in this pathway induced by HD. The purpose of this ancillary grant application is therefore to target our novel advanced diffusion MRI biomarkers and analysis methods to the cortico-striatal pathway. By associating abnormalities detected with these novel biomarkers to specific parts of the cortico-striatal tract, it will be possible to precisely map the relationship between white matter tract degeneration and motor dysfunction. This will help advance our understanding of the neuropathological basis of motor deterioration in HD. At the center of this grant proposal is the PREDICT-HD database. This dataset contains brain imaging data and a comprehensive set of clinical correlates from a very large sample of individuals with pre-manifest (prodromal) HD, who were selected to allow for tracing HD symptomatology from its very earliest signs. This proposal will combine the strengths of PREDICT-HD with our cutting-edge neuroimaging technology, which detects and measures several novel types of structural and physiological properties of white matter tissue. The principal innovation in this grant is therefore the use of our novel methods of analysis of diffusion MRI data to characterize in vivo the changes occurring in the white matter connections of the cortico-striatal pathways in HD. Applied together, these new methods will have the ability to not only to quantify pathological changes in white matter, but also to correlate the longitudinal evolution of these changes to the evolution of specific motor dysfunctions. These biomarkers will enhance understanding of pre-manifest HD and will make possible the ability to better monitor disease progression and to target potential early treatments.