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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

基本信息

批准号：
10915994
负责人：
Richard Leigh
金额：
$ 46.28万
依托单位：
NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE
依托单位国家：
美国
项目类别：
财政年份：
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/10915994
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 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 Structure Techniques Time Tissues Vascular Cognitive Impairment Water Movements White Matter Hyperintensity blood vessel occlusion blood-brain barrier disruption cohort experience imaging biomarker improved mortality neurovascular new therapeutic target novel novel therapeutics participant enrollment post stroke prevent processing speed response to injury stroke patient treatment response vascular cognitive impairment and dementia vasogenic edema white matter white matter injury

项目摘要

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)单元研究发生在血管和大脑之间的界面上的病理状态。这包括由闭塞的血管引起的急性脑缺血，以及可能与痴呆症相关的慢性脑缺血。具体地说，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症，这与他们的MRI变化有关。这一现象正在18-N-0020方案《中风患者血脑屏障破坏的自然史》(队列研究)中进行研究。这项研究目前正在注册中，并在https://clinicaltrials.gov/ct2/show/NCT03366129.上列出人们早就知道，MRI上看到的变化，通常被称为白质高信号(WMH)，是血管性认知障碍和痴呆(VCID)的标志。然而，目前还不完全了解这些病变发生的原因，因此我们目前还没有办法阻止它们的进展。很明显，WMH的进展(扩大)与认知能力的恶化有关。 NVBI正在研究是什么导致WMH使用新的成像生物标记物进行进展。血脑屏障(BBB)成像被用来确定血脑屏障的破坏是否先于WMH的进展。血脑屏障是细胞和细胞结构复杂相互作用的结果，是血管和大脑之间的门户。当它功能失调时，细胞和分子可以进入大脑，否则它们就不会穿过血脑屏障；此外，功能失调的血脑屏障可能会阻止促进运输离开大脑。使用弥散张量成像(DTI)也在研究脑白质微结构损伤。DTI是一种非侵入性技术，它测量细胞外空间中水运动的方向和大小。DTI不仅能反映脑白质微结构退化等永久性改变，还能反映对损伤的一过性反应，如血管源性水肿。DTI变化先于WMH，全局测量与认知加工速度更紧密地联系在一起。DTI对卒中的急性微结构改变和导致WMH和血管认知损害的慢性改变都很敏感。我们研究的主要目的是确定有既往中风病史和MRI上WMH的患者是否会经历WMH的进展，这种进展可以通过他们的血脑屏障的破坏和/或在进展之前使用MRI检测到的微结构的变化来预测。这将使我们能够识别有认知能力下降风险的患者，并可能阐明其机制，这可能有助于确定治疗的目标。通过阐明WMH的发病机制，我们旨在降低与脑血管疾病相关的发病率和死亡率。

项目成果

期刊论文数量（22）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Routine use of FLAIR-negative MRI in the treatment of unknown onset stroke.

DOI：
10.1016/j.jstrokecerebrovasdis.2020.105093
发表时间：
2020-09
期刊：
JOURNAL OF STROKE & CEREBROVASCULAR DISEASES
影响因子：
2.5
作者：
Adil, Malik M.;Luby, Marie;Lynch, John K.;Hsia, Amie W.;Kalaria, Chandni P.;Nadareishvili, Zurab;Latour, Lawrence L.;Leigh, Richard
通讯作者：
Leigh, Richard

Post-stroke blood-brain barrier disruption predicts poor outcome in patients enrolled in the ACTION study.

中风后血脑屏障破坏预示着参加 ACTION 研究的患者预后不佳。

DOI：
10.1111/jon.12862
发表时间：
2021
期刊：
Journal of neuroimaging : official journal of the American Society of Neuroimaging
影响因子：
0
作者：
Leigh,Richard;Hitomi,Emi;Hutchison,RMatthew;Elkins,Jacob
通讯作者：
Elkins,Jacob

Not-So-Normal-Appearing White Matter.

看起来不太正常的白质。

DOI：
10.1212/wnl.0000000000012405
发表时间：
2021
期刊：
Neurology
影响因子：
9.9
作者：
Leigh,Richard;Luby,Marie
通讯作者：
Luby,Marie

Estimating Perfusion Deficits in Acute Stroke Patients Without Perfusion Imaging.

DOI：
10.1161/strokeaha.121.038101
发表时间：
2022-11
期刊：
Stroke
影响因子：
8.3
作者：
通讯作者：

Early Change in Stroke Size Performs Best in Predicting Response to Therapy.

DOI：
10.1159/000477945
发表时间：
2017
期刊：
Cerebrovascular diseases (Basel, Switzerland)
影响因子：
0
作者：
Simpkins AN;Dias C;Norato G;Kim E;Leigh R;NIH Natural History of Stroke Investigators
通讯作者：
NIH Natural History of Stroke Investigators