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: 10688934
• 负责人: Richard Leigh
• 金额: $ 82.58万
• 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/10688934
• 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; Cognitive; Cohort Studies; Complex; Dementia; Development; Diagnosis; Diffusion Magnetic Resonance Imaging; Disease; Enrollment; Extracellular Space; Goals; Image; Impaired cognition; Injury; 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; Serial Magnetic Resonance Imaging; Stroke; Techniques; Time; Tissues; Vascular Cognitive Impairment; Water Movements; White Matter Hyperintensity; blood-brain barrier disruption; cohort; experience; imaging biomarker; improved; mortality; neurovascular; new therapeutic target; novel; novel therapeutics; post stroke; prevent; processing speed; response to injury; stroke patient; treatment response; vascular cognitive impairment and dementia; vasogenic edema; white matter; white matter injury

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 using novel imaging biomarkers. Blood-brain barrier (BBB) imaging 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. Microstructural white matter injury is also being studied using diffusion tensor imaging (DTI). DTI is a noninvasive technique that measures the direction and magnitude of water movement in the extracellular space. DTI can reflect transient response to injury such as vasogenic edema in addition to more permanent changes such as white matter microstructural degradation. DTI changes precede WMH, and global meausures are more closely linked to cognitive processing speed. DTI is sensitive to both the acute microstructural tissue changes in stroke and the chronic changes that contribute to WMH and vascular cognitive impairment. 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 and/or changes in microstructure 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正在使用新的成像生物标志物研究导致WMH进展的原因。血脑屏障（BBB）成像正在被用来确定是否破坏的BBB之前的进展WMH。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。 微结构白色物质损伤也正在使用扩散张量成像（DTI）进行研究。弥散张量成像是一种非侵入性的技术，可以测量细胞外间隙中水分运动的方向和幅度。DTI可以反映短暂的反应损伤，如血管源性水肿，除了更永久的变化，如白色物质的微结构退化。DTI变化先于WMH，全局测量与认知处理速度更密切相关。DTI对脑卒中的急性微结构变化和导致WMH和血管性认知障碍的慢性变化都很敏感。 我们研究的主要目的是确定既往有卒中史且MRI显示WMH的患者是否会以可通过BBB破坏和/或在进展前使用MRI检测到的微结构变化预测的方式经历WMH进展。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。