Quantitative MRI of Iron Homeostasis, Atrophy and Tissue Structure in AD Brain

AD 脑中铁稳态、萎缩和组织结构的定量 MRI

• 批准号: 7742932
• 负责人: JOSEPH A. HELPERN
• 金额: $ 2.25万
• 依托单位: NEW YORK UNIVERSITY SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-04-15 至 2012-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7742932
• 关键词: Address; Affect; Age; Alzheimer' s Disease; Anisotropy; Appearance; Atrophic; Axon; Biological Markers; Brain; Brain region; Cell Density; Cell membrane; Clinical; Complex; Cross-Sectional Studies; Dementia; Diagnosis; Differential Diagnosis; Diffusion; Diffusion Magnetic Resonance Imaging; Disease; Disease Progression; Doctor of Philosophy; Early treatment; Elderly; Evaluation; Future; Goals; Homeostasis; Image; Impaired cognition; Incidence; Individual; Intervention; Iron; Laboratories; Longitudinal Studies; Magnetic Resonance Imaging; Measurement; Measures; Medial; Monitor; Neurodegenerative Disorders; Onset of illness; Pathogenesis; Pathology; Patients; Persons; Prevalence; Quantitative Evaluations; Research Personnel; Risk; Space Perception; Staging; Structure; Surrogate Markers; Techniques; Testing; Therapeutic; Therapy Clinical Trials; Tissues; United States; Work; acronyms; brain tissue; cerebral atrophy; clinical Diagnosis; clinically relevant; density; drug discovery; frontal lobe; indexing; interest; magnetic field; mild neurocognitive impairment; novel; pre-clinical; programs

DESCRIPTION (provided by applicant): Project Summary: Alzheimer's disease (AD) is the most common type of dementia currently affecting more than 4 million people in the United States alone. It has been estimated that delaying the onset of the disease by only 5 years could result in a 50% decrease in disease prevalence. Therefore, identification of people at risk prior to the clinical appearance of dementia has become a priority due to the potential benefit from therapeutic or preventative intervention. Recently, our lab and others have demonstrated regional increased rates of cerebral atrophy several years before elderly people reach the stage known as mild cognitive impairment. Although these observations are consistent with the presence of a preclinical stage of AD, the mechanism(s) responsible for this observation are unknown. In this proposal we will investigate the relationship between cerebral atrophy rates, iron homeostasis and tissue micro structural complexity. Specifically, we are interested in whether disruption of brain iron homeostasis and reduction in tissue micro structural complexity are evident prior to the onset of clinically relevant cerebral atrophy. To test these hypotheses, we will conduct longitudinal and cross-sectional studies in cognitively intact individuals, subjects with mild cognitive impairment (MCI), and patients with mild AD. We will use well established MRI techniques (T2, T2* and DTI) along with two novel quantitative MRI techniques; Magnetic Field Correlation (MFC) imaging and Diffusional Kurtosis Imaging (OKI). Relevance: The questions to be addressed in this proposal are whether complex aspects of AD pathology can be given a precise definition suitable for quantitative evaluation, and what such an evaluation can contribute to our understanding of the disease. The ability to quantitatively assess regional brain iron homeostasis and tissue micro structural complexity in AD patients noninvasively and longitudinally has potential use in (a) studying the pathogenesis of AD, (b) monitoring disease progression, and (c) aiding in the differential diagnosis of AD. Moreover, this work will allow us to identify presymptomatic persons who are most likely to benefit from early intervention, help develop surrogate markers, accelerate drug discovery, and provide an objective, noninvasive means to monitor therapeutic trials. Given the incidence of neurodegenerative disease, the potential impact of this study is considerable.

阿尔茨海默病（AD）是目前仅在美国就影响超过400万人的最常见的痴呆类型。据估计，将该病的发病时间推迟5年就可使发病率降低50%。因此，由于治疗或预防干预的潜在益处，在痴呆症临床表现之前识别处于风险中的人已成为优先事项。最近，我们的实验室和其他人已经证明，在老年人达到轻度认知障碍的阶段之前几年，脑萎缩的区域性比率增加。尽管这些观察结果与AD临床前阶段的存在一致，但导致该观察结果的机制尚不清楚。在这个建议中，我们将探讨脑萎缩率，铁稳态和组织微结构复杂性之间的关系。具体而言，我们感兴趣的是，是否破坏脑铁稳态和减少组织微观结构的复杂性是明显的临床相关的脑萎缩发作之前。为了验证这些假设，我们将在认知功能完整的个体、轻度认知功能障碍（MCI）受试者和轻度AD患者中进行纵向和横断面研究。我们将使用完善的MRI技术（T2，T2* 和DTI）沿着两种新的定量MRI技术：磁场相关（MFC）成像和弥散峰度成像（OKI）。相关性：本提案中要解决的问题是，AD病理学的复杂方面是否可以给出适合于定量评估的精确定义，以及这种评估有助于我们了解该疾病。非侵入性和纵向定量评估AD患者局部脑铁稳态和组织微观结构复杂性的能力在以下方面具有潜在用途：（a）研究AD的发病机制，（B）监测疾病进展，和（c）辅助AD的鉴别诊断。此外，这项工作将使我们能够识别最有可能从早期干预中受益的前驱患者，帮助开发替代标记物，加速药物发现，并提供客观，非侵入性的手段来监测治疗试验。鉴于神经退行性疾病的发病率，本研究的潜在影响是相当大的。