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: 7795778
• 负责人: JOSEPH A. HELPERN
• 金额: $ 13.17万
• 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 2010-10-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7795778
• 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.

描述（由申请人提供）： 项目摘要：阿尔茨海默病 (AD) 是最常见的痴呆症类型，目前仅在美国就有超过 400 万人受到影响。据估计，仅将疾病发病延迟 5 年即可使疾病患病率下降 50%。因此，由于治疗或预防干预的潜在益处，在痴呆症临床出现之前识别处于痴呆症风险的人群已成为当务之急。最近，我们的实验室和其他实验室证明，在老年人达到轻度认知障碍阶段之前几年，区域性脑萎缩率就会增加。尽管这些观察结果与 AD 临床前阶段的存在一致，但造成这种观察结果的机制尚不清楚。在本提案中，我们将研究脑萎缩率、铁稳态和组织微观结构复杂性之间的关系。具体来说，我们感兴趣的是在临床相关的脑萎缩发生之前，脑铁稳态的破坏和组织微观结构复杂性的降低是否明显。为了检验这些假设，我们将对认知完整的个体、轻度认知障碍 (MCI) 受试者和轻度 AD 患者进行纵向和横断面研究。我们将使用成熟的 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：本提案要解决的问题是，AD 病理学的复杂方面是否可以给出适合定量评估的精确定义，以及这样的评估可以有助于我们了解该疾病。以无创方式纵向定量评估 AD 患者的区域脑铁稳态和组织微结构复杂性的能力具有潜在的用途：(a) 研究 AD 的发病机制，(b) 监测疾病进展，以及 (c) 帮助鉴别诊断广告。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症状前人群，帮助开发替代标记，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，这项研究的潜在影响是相当大的。