Multimodal MRI Studies of Brain Structure and Function in PDD and AD

描述(由申请人提供)： 摘要：在K02年度独立科学家职业发展奖中，候选人寻求以其在功能和结构神经成像方面的背景为基础，并使用多模式神经成像来了解认知障碍的演变，如帕金森氏病痴呆(PDD)和阿尔茨海默病(AD)。K02将为候选人的研究和职业发展活动提供受保护的时间，这些活动将增强他的成像专业知识的临床适用性，并确保在负责任的人类受试者研究中取得卓越表现。建议的项目使用多模式磁共振成像(MRI)来检查PDD和AD患者与老年对照组相比大脑结构和功能的差异。这项研究的总体目标是更好地了解大脑区域对突触核蛋白和淀粉样蛋白病理的选择性易感性，并了解痴呆症的认知缺陷如何与大脑结构和电路的潜在损害有关。具体地说，临床和神经心理学特征的对照组和患有PDD和AD的受试者将接受大约30分钟的基线和随访静息MRI方案，该方案将允许以下测量：1)皮质和皮质下结构的区域体积，2)使用基于概率图谱的扩散张量束成像确定的区域中的白质完整性，3)默认网络的解剖定义区域内的功能连通性，以及4)使用序列图像数据集的非线性配准的皮质和皮质下结构体积的间隔变化。高吞吐量处理流可以有效地捕获从每个程序获得的结构测量，候选人的实验室还增加了功能连通性分析方面的专业知识。因此，拟议的研究将使人们能够对神经退行性疾病的结构和功能后果有新的见解。 公共卫生相关性： 叙述：这项拟议的研究旨在通过非侵入性脑成像提高对痴呆症对大脑结构影响的理解。这些信息可能有助于研究人员评估针对不同痴呆症原因而设计的新疗法的疾病修改效果。脑结构的快速定量评估在临床环境中可能是实用的，以帮助临床医生对神经退行性疾病做出更早和更准确的诊断。

DESCRIPTION (provided by applicant): ABSTRACT: In this K02 Independent Scientist Career Development Award, the candidate seeks to build upon his background in functional and structural neuroimaging and use multimodal neuroimaging to understand the evolution of cognitive disorders, such as Parkinson's disease dementia (PDD) and Alzheimer's disease (AD). The K02 will provide the candidate protected time for research and career development activities that will enhance the clinical applicability of his imaging expertise and assure excellence in the responsible conduct of human subject research. The proposed projects use multimodal magnetic resonance imaging (MRI) to examine structural and functional differences in the brains of patients with PDD and AD relative to elderly controls. The overall goal of the research is to better understand the selective vulnerability of brain regions to synuclein and amyloid pathology and to understand how cognitive deficits in dementia relate to underlying damage in brain structure and circuitry. Specifically, clinically and neuropsychologically characterized controls and subjects with PDD and AD will undergo a baseline and followup resting MRI protocol of around 30 minutes that will allow the following measurements: 1) regional volume of cortical and subcortical structures, 2) white matter integrity in tracts identified using probabilistic atlas-based diffusion tensor tractography, 3) functional connectivity within anatomically-defined regions of the default network, and 4) interval change in volume of cortical and subcortical structures using nonlinear registration of serial image datasets. High throughput processing streams are in place for efficiently capturing the structural measures obtained from each procedure, and the candidate's laboratory has added expertise in functional connectivity analysis. Thus, the proposed research will allow new insight into the structural and functional consequences of neurodegenerative disease. PUBLIC HEALTH RELEVANCE: NARRATIVE: The proposed research aims to improve understanding of the effects of dementia on brain structure using noninvasive brain imaging. Such information may help researchers evaluate disease-modifying effects of new therapies designed to target different causes of dementia. Rapid quantitative assessment of brain structure might be practical in the clinical setting to assist clinicians in making earlier and more accurate diagnoses of neurodegenerative diseases.