Pathological basis of MRS and DTI changes in neurodegenerative dementia

描述（由申请方提供）：年龄相关认知下降、轻度认知障碍（MCI）和痴呆的最常见神经退行性病变是阿尔茨海默病（AD）和路易体病（LBD）病变。来自质子磁共振波谱（MRS）和扩散张量MRI（DTI）的证据表明，这些技术在细胞或分子水平上对神经退行性疾病过程中的早期事件敏感。这些MR标记物可能对萎缩前的退行性变化更敏感，并可提供结构MRI的额外信息，特别是在病程早期。虽然最近在临床诊断的患者的研究结果是有希望的，MRS和DTI改变在神经退行性痴呆的病理基础还没有得到很好的理解。我们的目标是验证MRS和DTI测量作为AD和LBD病理学的替代标志物，因为它们是老年人群中最常见的神经退行性变化。我们的目标是确定与成对螺旋丝（PHF）-tau、淀粉样蛋白-β和α-突触核蛋白介导的病理相关的特定皮质区域和白色物质束中死前MRS和DTI变化的生物学相关性。总体目标是将MR标志物转化为AD和LBD病理的临床有效指标。将使用基于ROI的定量方法确定与死后PHF-tau、淀粉样蛋白-b和α-突触核蛋白介导的神经退行性病理学相关的死前MRS和DTI变化，以将死前成像与死后组织学相关联。最后，我们将MRS和DTI标记物转化为临床有效的病理严重程度的措施。

DESCRIPTION (provided by applicant): The most common neurodegenerative pathologies underlying age associated cognitive decline, mild cognitive impairment (MCI) and dementia are Alzheimer's disease (AD) and Lewy body disease (LBD) pathologies. Evidence from proton MR Spectroscopy (MRS) and diffusion tensor MRI (DTI) suggest that these techniques are sensitive to early events in the neurodegenerative disease process at the cellular or molecular level. These MR markers may be more sensitive to degenerative changes preceding atrophy, and may provide additional information over structural MRI especially early in the disease course. Although the recent findings in clinically diagnosed patients are promising, the pathologic underpinnings of MRS and DTI alterations in neurodegenerative dementia are not well understood. Our goal is to validate MRS and DTI measures as surrogate markers of AD and LBD pathologies, because they are the most common neurodegenerative changes found in the elderly population. Our objective is to identify the biological correlates of antemortem MRS and DTI changes in specific cortical regions and white matter tracts associated with the paired helical filament (PHF)-tau, amyloid-� and alpha-synuclein mediated pathology. The overarching goal is to translate the MR markers into clinically valid measures of AD and LBD pathologies. The antemortem MRS and DTI changes associated with postmortem PHF-tau, amyloid-b and alpha-synuclein mediated neurodegenerative pathology will be identified using ROI-based quantitative methods for correlating antemortem imaging with postmortem histology. Finally, we will translate MRS and DTI markers to clinically valid measures of pathological severity.