Cerebral small vessel disease: Enhancing the diagnostic precision of MRI

脑小血管疾病：提高 MRI 的诊断精度

• 批准号: 8325607
• 负责人: LARY C WALKER
• 金额: $ 22万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-09-01 至 2014-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8325607
• 关键词: Address; Affect; Aging; Alzheimer' s Disease; Amyloid; Animal Model; Archives; Autopsy; Awareness; Biological Markers; Blood; Blood Vessels; Brain; Cerebral Amyloid Angiopathy; Cerebrovascular Disorders; Cerebrum; Characteristics; Cognition; Data; Dementia; Detection; Diabetic Angiopathies; Diagnosis; Diagnostic; Disease; Elderly; Foundations; Functional disorder; Future; Goals; Healthcare; Histologic; Human; Image; Impaired cognition; Individual; Infarction; Inflammation; Investigation; Lead; Lesion; Life; Link; Magnetic Resonance Imaging; Modeling; Molecular; Multi-Infarct Dementia; Pathogenesis; Pathologic; Pathology; Patients; Peptides; Population; Primates; Process; Protocols documentation; Research; Research Personnel; Risk; Risk Factors; Role; Saimiri; Sampling; Scanning; Signal Transduction; Smooth Muscle; Societies; Specificity; Staging; System; Therapeutic; Tissue Sample; Vascular Diseases; aged; aging brain; base; cohort; improved; in vivo; neuroimaging; new therapeutic target; nonhuman primate; novel; post stroke; programs; white matter change

DESCRIPTION (provided by applicant): Cerebrovascular disease is one of the most common causes of dementia in aging humans. With the growing elderly population in Western societies, vascular cognitive impairment (VCI) will become a significant healthcare burden in the 21st century. Recent advances in magnetic resonance imaging (MRI) are continually lowering the threshold for detection of vascular anomalies in the brain, leading to a growing awareness that small vessel disease and microinfarcts can cumulatively lead to VCI. However, the power of MRI currently is limited by the inability to link anomalous MR signals unambiguously to specific lesion types. Valid animal models would greatly accelerate diagnostic and therapeutic approaches to cerebrovascular disease. The explicit identification of MR anomalies has been a particular problem in investigating cerebral A¿-amyloid angiopathy (CAA), a disease of the elderly in which misfolded A¿ peptide accumulates in the walls of brain blood vessels. Investigators have increasingly employed novel imaging protocols to analyze CAA non-invasively. However, there is a critical need for information that will enable the interpretation of neuroimaging data on CAA and other vascular disorders in patients. The aged squirrel monkey is a unique animal model of naturally occurring CAA that is highly similar to the disorder in humans. The overarching goal of our research program is to clarify the role of CAA in vascular dysfunction and cognitive decline in the elderly. The objective of this proposal is to employ this exceptional primate model to optimize the power of MRI to non-invasively identify and characterize CAA-related lesions in living patients. To achieve this goal, we first will investigate a unique sample of archived brains from aged squirrel monkeys with CAA, along with postmortem tissue samples from humans with CAA, in a powerful (7T) MRI scanner. In this way, we can detect a variety of vascular lesions under optimal conditions. Next, we will use the information gained from these ex vivo imaging studies to image a small cohort of aged squirrel monkeys in vivo. The brains then will be examined microscopically to identify and characterize the MRI anomalies unambiguously, and to determine the cellular and molecular features of the lesions. We predict that MRI signal anomalies will be linked to specific histopathological indicators of CAA and associated lesions. The findings from this novel primate model will establish a foundation for future non-invasive studies of the pathogenesis, diagnosis and treatment of CAA in aged humans.

描述（由申请人提供）：脑血管疾病是老年人痴呆症的最常见原因之一。随着西方社会老年人口的不断增长，血管性认知功能障碍（VCI）将成为21世纪世纪的重大医疗负担。磁共振成像（MRI）的最新进展不断降低检测脑血管异常的阈值，导致越来越多的人意识到小血管疾病和微梗死可累积导致VCI。然而，MRI的能力目前受到无法将异常MR信号明确地与特定病变类型联系起来的限制。有效的动物模型将大大加快脑血管疾病的诊断和治疗。明确识别MR异常一直是研究脑A-淀粉样血管病（CAA）的一个特殊问题，CAA是一种老年人疾病，其中错误折叠的A肽积聚在脑血管壁中。研究人员越来越多地采用新的成像协议来分析CAA的非侵入性。然而，有一个关键的信息，这将使解释CAA和其他血管疾病的患者的神经影像学数据的需求。老年松鼠猴是一种独特的自然发生CAA的动物模型，与人类的疾病高度相似。我们研究计划的首要目标是阐明CAA在老年人血管功能障碍和认知能力下降中的作用。该提案的目的是采用这种特殊的灵长类动物模型来优化MRI的能力，以非侵入性地识别和表征活体患者中的CAA相关病变。为了实现这一目标，我们首先将在一个强大的（7 T）MRI扫描仪中研究一个独特的存档大脑样本，来自患有CAA的老年松鼠猴，沿着来自患有CAA的人类的死后组织样本。通过这种方式，我们可以在最佳条件下检测各种血管病变。接下来，我们将使用从这些离体成像研究中获得的信息来对一小群老年松鼠猴进行体内成像。然后对大脑进行显微镜检查，以明确识别和表征MRI异常，并确定病变的细胞和分子特征。我们预测MRI信号异常将与CAA和相关病变的特定组织病理学指标相关。这一新的灵长类动物模型的研究结果将为未来老年人CAA的发病机制、诊断和治疗的非侵入性研究奠定基础。