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: 7404513
• 负责人: JOSEPH A. HELPERN
• 金额: $ 47.26万
• 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/7404513
• 关键词: Address; Affect; Age; Alzheimer' s Disease; Anisotropy; Appearance; Appendix; 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; Disruption; Doctor of Philosophy; Early Intervention; Elderly; Evaluation; Future; Goals; Homeostasis; Image; Impaired cognition; Incidence; Individual; Intervention; Invasive; Iron; Laboratories; Longitudinal Studies; Magnetic Resonance Imaging; Measurement; Measures; Medial; Monitor; Neurodegenerative Disorders; Numbers; Onset of illness; Pathogenesis; Pathology; Patients; Persons; Prevalence; Quantitative Evaluations; Rate; Research Personnel; Risk; Space Perception; Staging; Structure; Surrogate Markers; Techniques; Testing; Therapeutic; Therapy Clinical Trials; Tissues; United States; Work; 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.

描述（申请人提供）：项目摘要：阿尔茨海默氏病（AD）是目前仅影响美国超过400万人的最常见痴呆症类型。据估计，将疾病的发作延迟5年可能会导致疾病患病率降低50％。因此，由于治疗或预防性干预的潜在益处，在痴呆症临床出现之前对处于危险的人的识别已成为优先事项。最近，我们的实验室和其他实验室表明，在老年人达到被称为轻度认知障碍的阶段，大脑萎缩率提高。尽管这些观察结果与AD的临床前阶段的存在一致，但负责该观察结果的机制尚不清楚。在此提案中，我们将研究脑萎缩率，铁稳态和组织微结构复杂性之间的关系。具体而言，我们对在临床相关的脑萎缩开始之前是否明显显现出脑铁稳态的破坏和组织微结构复杂性的降低感兴趣。为了检验这些假设，我们将对认知完整个体，轻度认知障碍（MCI）和轻度AD患者进行纵向和横断面研究。我们将使用良好的MRI技术（T2，T2*和DTI）以及两种新颖的定量MRI技术。磁场相关（MFC）成像和扩散峰度成像（OKI）。相关性：本提案中要解决的问题是，是否可以为AD病理学的复杂方面提供适合定量评估的精确定义，以及这种评估可以有助于我们对疾病的理解。定量评估AD患者的区域铁稳态和组织微结构复杂性的能力无创和纵向具有潜在的用途（a）研究AD的发病机理，（b）监测疾病进展，以及（c）在AD的鉴别诊断中有助于（c）。此外，这项工作将使我们能够确定最有可能从早期干预中受益，有助于开发替代标记，加速药物发现并提供客观的无创方法来监测治疗试验的人。鉴于神经退行性疾病的发生率，这项研究的潜在影响很大。