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

描述(由申请人提供)：这份为期两年的附属拨款申请旨在解决亨廷顿病(HD)，这是一种遗传性和进行性神经疾病，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，了解受影响脑区早期的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质的皮质-纹状体白质通路是HD运动功能症状学的关键。然而，目前弥散磁共振成像的分析方法不足以正确地描述HD引起的这一通路的病理变化。因此，这项辅助拨款申请的目的是将我们的新型高级扩散磁共振生物标记物和分析方法对准皮质-纹状体通路。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出白质束退变和运动功能障碍之间的关系。这将有助于加深我们对HD运动退化的神经病理基础的理解。这项拨款提案的核心是Predicate-HD数据库。此数据集包含大脑成像数据和一组全面的临床相关性，这些数据来自于大量患有先兆HD的个体样本，他们被选中以允许从HD的最早症状开始追踪HD症状。这项建议将把Predicate-HD的优势与我们尖端的神经成像技术结合起来，该技术可以检测和测量几种新型的脑白质组织的结构和生理特性。因此，这项资助的主要创新是使用我们的扩散磁共振数据分析的新方法，在体内表征HD患者皮质-纹状体通路的白质连接中发生的变化。结合应用，这些新方法将不仅有能力量化白质的病理变化，而且还能够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性前HD的了解，并将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.