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: 9157583
• 负责人: Richard Leigh
• 金额: $ 58.53万
• 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/9157583
• 关键词: Acute; Adverse effects; Aftercare; Big Data; Biological Markers; Blood - brain barrier anatomy; Blood Vessels; Blood flow; Brain; Brain hemorrhage; Brain imaging; Cerebral Ischemia; Cerebrovascular Circulation; Cerebrovascular Disorders; Cerebrum; Chronic; Clinical Trials; Collaborations; Contrast Media; Data; Data Analyses; Databases; Dementia; Development; Diagnosis; Disease; Disease Progression; Dose; Edema; Evolution; Extravasation; Functional disorder; Gadolinium; Goals; Hemorrhage; Human; Infarction; Inflammation; Infusion procedures; Intracranial Hemorrhages; Intramural Research Program; Intravenous; Ischemia; Ischemic Stroke; Knowledge; Link; Magnetic Resonance Imaging; Manuscripts; Measures; Methodology; Methods; Mission; Modeling; Monitor; Morbidity - disease rate; National Institute of Neurological Disorders and Stroke; Natural History; Pathologic; Pathology; Patients; Pattern; Performance; Permeability; Phase; Physiology; Play; Population; Property; Reperfusion Therapy; Review Literature; Risk; Risk Factors; Role; Safety; Signal Transduction; Source; Stroke; Target Populations; Testing; Therapeutic; Thrombolytic Therapy; Time; Tissues; United States National Institutes of Health; Universities; Vascular Cognitive Impairment; Vascular Diseases; Weight; Work; acute stroke; arm; base; brain tissue; cerebrovascular; demographics; experience; functional outcomes; gadolinium oxide; imaging modality; improved; insight; migration; mortality; new therapeutic target; open label; response; restoration; thrombolysis; white matter

The mission of the Neuro Vascular Brain Imaging (NVBI) Unit is to leverage the vast information provided by magnetic resonance imaging (MRI) to alleviate the morbidity and mortality associated with cerebrovascular disease. This is done by finding ways to use MRI to better understand pathologic states, improve diagnosis, guide treatment, monitor response to therapy, identify new therapeutic targets, and develop new therapies. The NVBI is part of the Stroke Branch of the NINDS Intramural Research Program. The Stroke Branch has been conducting a Natural History Study of Acute Stroke for more than a decade. This study has guided our knowledge of how MRI can identify brain tissue at risk of infarction and understand the role that restoration of blood flow plays in improved functional outcome in patients suffering from an ischemic stroke. This classic model for using MRI as a biomarker to guide therapy is now being expanded to incorporate the use of MRI as a measure of core stability. The core stability model focuses on whether a treatment can be safely administered rather than trying to estimate the potential for benefit. Such an approach can be beneficial in situations where all of the potential benefits of a therapy have not been fully elucidated. The core stability model is predicated on the notion that we can use MRI to identify those patients whose core infarct is stable enough to receive a particular therapy without suffering treatment related side effects. The typical example of an unstable core is the infarct that undergoes hemorrhagic transformation after treatment with thrombolysis. The NVBI has been focused on developing a new model of core stability. This model involves measuring the integrity of the blood brain barrier (BBB). The NVBI has shown, by analyzing data collected through the NIH Natural History Study, that increasing disruption of the BBB of the core infarct is associated with an increasing risk of intracranial hemorrhage (ICH) in patients receiving intravenous thrombolysis (Leigh et al., Stroke, 2014). Through collaboration with a large multicenter clinical trial, this result has been replicated for stroke patients receiving endovascular therapy (manuscript in prep). The method developed by the NVBI to measure BBB integrity uses an existing MRI sequence that is typically acquired to measure blood flow. However this sequence is also sensitive to leakage of gadolinium (MRI contrast agent) through the BBB. By modeling the recorded signal as reflecting both intravascular and extravascular gadolinium, these two components can be separated, and BBB permeability can be estimated. The advantage of this methodology is that since it uses an existing MR sequence, it is widely applicable and can be applied retrospectively. Over the past fiscal year, the NVBI has undertaken the big data project of retrospectively calculating the BBB permeability for MRIs collected as part of the NIH Natural History Study. This has created a window into a pathophysiology that was previously overlooked. In addition to the BBB changes associated with the core infarct, a new appreciation of BBB associated with chronic vascular disease has been recognized. Chronic cerebrovascular disease has been linked to vascular cognitive impairment and dementia. Using this new methodology to analyze chronic cerebrovascular disease in the Natural History database has led to a better characterization of the changing patterns of BBB disruption in relation to risk factors, demographics, disease progression, and response to therapy. In addition to studying BBB disruption of acute and chronic ischemia, the NVBI has been working on new types of MRI sequences and new types of therapeutics. In the coming fiscal year, we hope to continue to branch out in these directions to further our mission of reducing the morbidity and mortality associated with cerebrovascular disease.

神经血管脑成像（NVBI）部门的使命是利用磁共振成像（MRI）提供的大量信息来降低与脑血管疾病相关的发病率和死亡率。 这是通过寻找使用MRI的方法来更好地了解病理状态，改善诊断，指导治疗，监测对治疗的反应，确定新的治疗靶点和开发新的治疗方法来实现的。 NVBI是NINDS校内研究计划中风分支的一部分。 中风分支十多年来一直在进行急性中风的自然史研究。 这项研究指导我们了解MRI如何识别有梗死风险的脑组织，并了解血流恢复在改善缺血性卒中患者功能结局中的作用。 这种使用MRI作为生物标志物来指导治疗的经典模型现在正在扩展，以将MRI作为核心稳定性的衡量标准。 核心稳定性模型关注的是治疗是否可以安全地进行，而不是试图估计潜在的获益。 这种方法在治疗的所有潜在益处尚未完全阐明的情况下可能是有益的。 核心稳定性模型是基于这样的概念，即我们可以使用MRI来识别那些核心梗死足够稳定以接受特定治疗而不遭受治疗相关副作用的患者。 不稳定核心的典型例子是溶栓治疗后发生出血性转化的梗死。 NVBI一直致力于开发一种新的核心稳定性模型。 该模型涉及测量血脑屏障（BBB）的完整性。 通过分析NIH自然史研究收集的数据，NVBI已经表明，在接受静脉溶栓的患者中，核心梗死的BBB破坏的增加与颅内出血（ICH）风险的增加相关（Leigh et al.，Stroke，2014）。 通过与一项大型多中心临床试验的合作，该结果已在接受血管内治疗的卒中患者中得到复制（手稿准备中）。 NVBI开发的测量BBB完整性的方法使用了现有的MRI序列，该序列通常用于测量血流。 然而，该序列也对钆（MRI造影剂）通过BBB的泄漏敏感。 通过将记录的信号建模为反映血管内和血管外钆，可以分离这两个分量，并且可以估计BBB渗透性。 这种方法的优点是，由于它使用现有的MR序列，因此它适用广泛，并且可以回顾性应用。 在过去的一个财政年度，NVBI开展了大数据项目，回顾性地计算了作为NIH自然历史研究一部分收集的MRI的BBB渗透性。 这为以前被忽视的病理生理学打开了一扇窗户。 除了与核心梗死相关的血脑屏障变化外，还认识到血脑屏障与慢性血管疾病相关。 慢性脑血管病与血管性认知障碍和痴呆有关。 使用这种新的方法来分析自然史数据库中的慢性脑血管疾病，可以更好地描述与风险因素，人口统计学，疾病进展和治疗反应相关的BBB破坏变化模式。 除了研究急性和慢性缺血的血脑屏障破坏外，NVBI一直在研究新型MRI序列和新型治疗方法。 在下一个财政年度，我们希望继续在这些方向上开展分支工作，以进一步履行我们的使命，降低与脑血管疾病有关的发病率和死亡率。