Using MRI to Understand Disease States that Occur at the Interface of the Brain and the Cerebral Circulation

使用 MRI 了解大脑和脑循环接口处发生的疾病状态

• 批准号: 10256467
• 负责人: Richard Leigh
• 金额: $ 68.85万
• 依托单位: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10256467
• 关键词: Acute; Blood - brain barrier anatomy; Blood Vessels; Brain; Brain imaging; Cell Communication; Cells; Cellular Structures; Cerebral Ischemia; Cerebrovascular Circulation; Cerebrovascular Disorders; Chronic; Cognition; Cohort Studies; Complex; Dementia; Diagnosis; Disease; Enrollment; Goals; Impaired cognition; Lesion; Light; Link; Magnetic Resonance Imaging; Measures; Mission; Monitor; Morbidity - disease rate; Natural History; Pathogenesis; Pathologic; Patients; Populations at Risk; Protocols documentation; Recording of previous events; Research; Risk; Stroke; Time; White Matter Hyperintensity; blood-brain barrier disruption; cohort; experience; imaging biomarker; imaging modality; improved; mortality; neurovascular; new therapeutic target; novel; novel marker; novel therapeutics; post stroke; prevent; response; stroke patient; vascular cognitive impairment and dementia

The Neuro Vascular Brain Imaging (NVBI) unit studies pathologic states that occur at the interface between blood vessels and the brain. This encompasses acute cerebral ischemia caused by an occluded blood vessel as well as chronic cerebral ischemia that can be associated with dementia. Specifically, the NVBI unit is investigating why some patients who have had a stroke subsequently develop cognitive decline and dementia in association with changes on their MRI. This phenomenon is being studied in protocol 18-N-0020, The Natural History of Blood-Brain Barrier Disruption in Stroke Patients with White Matter Hyperintensities (A Cohort Study). This study is currently enrolling and is listed on https://clinicaltrials.gov/ct2/show/NCT03366129. It has long been known that changes seen on MRI, often referred to as white matter hyperintensities (WMH), are a hallmark for vascular cognitive impairment and dementia (VCID). However, it is not fully understood why these lesions develop, and thus we do not currently have a way to stop their progression. It is clear that progression (expansion) of WMH is associated with worsening cognition. The NVBI is studying what causes WMH to progress. Specifically, a novel biomarker for imaging the bloods-brain barrier (BBB) is being employed to determine if disruption of the BBB precedes the progression of WMH. The BBB results from a complex interaction of cells and cell structures and serves as the gateway between the blood vessels and the brain. When it becomes dysfunctional, cells and molecules can enter the brain that otherwise would not cross the BBB; additionally, a dysfunctional BBB may prevent facilitated transport out of the brain. The primary objective of our research is to determine if patients with a history of previous stroke and WMH on MRI will experience progression of their WMH in a manner that can be predicted by disruption of their BBB detected using MRI prior to the progression. This would allow us to identify patients at risk for cognitive decline and may shed light on its mechanisms which could help identify targets for treatment. By elucidating the genesis of WMH, we aim to reduce the morbidity and mortality associated with cerebrovascular disease.

神经血管脑成像（NVBI）单位研究发生在血管和大脑之间的界面的病理状态。这包括由闭塞的血管引起的急性脑缺血以及可能与痴呆相关的慢性脑缺血。具体来说，NVBI部门正在调查为什么一些中风患者随后会出现认知能力下降和痴呆，这与他们的MRI变化有关。在方案18-N-0020“白色高信号卒中患者血脑屏障破坏的自然史（一项队列研究）”中对该现象进行了研究。本研究目前正在招募，并在https://clinicaltrials.gov/ct2/show/NCT03366129上列出。 人们早就知道，在MRI上看到的变化，通常被称为白色高信号（WMH），是血管性认知障碍和痴呆（VCID）的标志。然而，目前还不完全清楚这些病变发生的原因，因此我们目前没有办法阻止其进展。很明显，WMH的进展（扩展）与认知恶化有关。 NVBI正在研究是什么原因导致WMH进步。具体来说，一种用于血脑屏障（BBB）成像的新生物标志物被用于确定BBB的破坏是否先于WMH的进展。血脑屏障由细胞和细胞结构的复杂相互作用产生，并作为血管和大脑之间的通道。当它变得功能障碍时，细胞和分子可以进入大脑，否则不会穿过BBB;此外，功能障碍的BBB可能会阻止从大脑中运输出来。 我们研究的主要目的是确定既往有卒中史且MRI显示WMH的患者是否会经历WMH进展，其进展方式可通过在进展前使用MRI检测到的BBB破坏来预测。这将使我们能够识别有认知能力下降风险的患者，并可能揭示其机制，这可能有助于确定治疗目标。通过阐明WMH的发生机制，我们的目标是降低与脑血管疾病相关的发病率和死亡率。