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（由适用提供）：脑血管疾病是衰老人类痴呆症最常见的原因之一。随着西方社会的老年人口的不断增长，血管认知障碍（VCI）将在21世纪成为大量的医疗保健燃烧。磁共振成像（MRI）的最新进展正在不断降低大脑中血管异常的阈值，从而越来越了解小血管疾病和微吸收性可以累积地导致VCI。但是，MRI的功率目前受到无法将异常的MR信号与特定病变类型联系起来的限制。有效的动物模型将极大地加速诊断和治疗方法，以解决脑血管疾病。对MR异常的明确鉴定一直是研究脑A淀粉样血管病（CAA）的一个特殊问题，该疾病是一种古老的疾病，其中错误折叠的A肽积聚在脑血管壁上。研究人员已经增加了新型的成像协议来非侵入性分析CAA。但是，对于信息的迫切需要，可以解释有关患者CAA和其他血管疾病的神经影像学数据。老化的松鼠猴是一种独特的动物模型，具有天然发生的CAA，与人类的疾病高度相似。我们的研究计划的总体目标是实现这一目标，我们将首先调查带有CAA的老年松鼠猴子的独特的归档大脑样本，以及来自CAA的人类的后验证纸样本，中有强大的（7T）MRI SCANNER。这样，我们可以在最佳条件下检测到各种血管病变。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体内的一小部分老年松鼠猴子进行成像。然后，将对大脑进行显微镜检查，以明确地识别和表征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有关。这个新颖的私人模型的发现将为未来对年龄人类CAA的发病机理，诊断和治疗的非侵入性研究奠定基础。