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: 9569203
• 负责人: Richard Leigh
• 金额: $ 79.35万
• 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/9569203
• 关键词: Acute; Adverse effects; Aftercare; Biological Markers; Blood - brain barrier anatomy; Blood Vessels; Blood flow; Brain; Brain hemorrhage; Brain imaging; Cerebral Infarction; Cerebral Ischemia; Cerebrovascular Circulation; Cerebrovascular Disorders; Cerebrum; Chronic; Clinical; Clinical Trials; Collaborations; Data Analyses; Development; Diagnosis; Disease; Edema; Evolution; Functional disorder; Goals; Hemorrhage; Human; Impaired cognition; Infarction; Inflammatory; Intracranial Hemorrhages; Intramural Research Program; Intravenous; Ischemic Stroke; Knowledge; Lead; MRI Scans; Magnetic Resonance Imaging; Measures; Methodology; Methods; Mission; Modeling; Monitor; Morbidity - disease rate; National Institute of Neurological Disorders and Stroke; Natural History; Neurology; Pathologic; Pathology; Patients; Pattern; Phase; Physiology; Play; Property; Protocols documentation; Reperfusion Therapy; Research; Risk; Risk Factors; Role; Severities; Stroke; Therapeutic Intervention; Thrombolytic Therapy; Time; Tissues; United States National Institutes of Health; Universities; Vascular Dementia; White Matter Hyperintensity; acute stroke; brain tissue; cerebrovascular; clinically relevant; clinically significant; functional outcomes; imaging modality; improved; insight; mortality; neurovascular; new therapeutic target; novel therapeutics; patient population; predictive marker; 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 (Leigh et al., Neurology, 2016). Further analysis has refined the model to differentiate between defuse reversible and focal severe BBB disruption (Simpkins et al., Stroke, 2016). This research has also lead to the ability to track BBB disruption associated with chronic cerebrovascular disease such as vascular dementia. Examination of serial MRI scans from the Natural History of Stroke Study has demonstrated that the BBB can be chronically open in patients with white matter hyperintensities suggesting it may represent a precursor to cognitive decline. The NVBI is currently developing a protocol that will chart the relationship between BBB disruption and white matter hyperintensities. In addition to using MRI to measure BBB integrity, the NVBI has also been investigating methods for using MRI to measure pH in the brain. The use of pH-weighted MRI has the potential to provide the most direct biomarker of cellular response to ischemic insult (Leigh et al., JCBFM, 2017). In collaboration with research at Johns Hopkins University, the NVBI has implemented a new methodology for processing pH-weighted MRI that is quantitative (Heo et al., Mag Res Med, 2017). In the coming fiscal year, the NVBI will 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)单位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。这是通过寻找利用核磁共振更好地了解病理状态、改进诊断、指导治疗、监测治疗反应、确定新的治疗靶点和开发新的治疗方法来实现的。 NVBI是NINDS血管内研究计划卒中分支的一部分。中风分部十多年来一直在进行一项关于急性中风的自然历史研究。这项研究指导了我们对MRI如何识别有脑梗塞风险的脑组织以及了解血流恢复在改善缺血性中风患者功能结局中的作用的知识。 将核磁共振作为生物标记物来指导治疗的这一经典模式现在正在扩展，以纳入核磁共振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实施，而不是试图估计受益的可能性。在治疗的所有潜在益处尚未完全阐明的情况下，这种方法可能是有益的。核心稳定性模型是基于这样一个概念，即我们可以使用MRI来识别核心梗塞足够稳定的患者，以便接受特定的治疗，而不会出现与治疗相关的副作用。不稳定核心的典型例子是在溶栓治疗后经历出血性转化的梗塞。 NVBI一直专注于开发一种新的核心稳定模式。该模型包括测量血脑屏障(BBB)的完整性。NVBI通过分析通过NIH自然病史研究收集的数据表明，在接受静脉溶栓治疗的患者中，核心梗塞的血脑屏障的日益破坏与颅内出血(ICH)风险的增加相关(Leigh等人，中风，2014)。通过与一项大型多中心临床试验的合作，这一结果已经在接受血管内治疗的中风患者中得到复制(Leigh等人，神经学，2016)。进一步的分析改进了该模型，以区分化解可逆性和局灶性严重的BBB干扰(Simpkins等人，中风，2016)。 这项研究还导致了追踪与慢性脑血管疾病(如血管性痴呆症)相关的血脑屏障中断的能力。对中风自然史研究的一系列MRI扫描的检查表明，在脑白质高信号的患者中，血脑屏障可以长期开放，这表明它可能是认知能力下降的先兆。NVBI目前正在开发一种方案，该方案将绘制出血脑屏障中断和白质高强度之间的关系。 除了使用核磁共振测量血脑屏障的完整性外，NVBI还一直在研究使用核磁共振测量大脑pH值的方法。PH加权MRI的使用有可能提供细胞对缺血性损伤反应的最直接生物标记物(Leigh等人，JCBFM，2017)。NVBI与约翰·霍普金斯大学的研究合作，实施了一种处理pH加权MRI的新方法，这种方法是定量的(Heo等人，Mag res Med，2017)。 在下一财年，NVBI将继续向这些方向扩展，以推进我们降低与脑血管疾病相关的发病率和死亡率的使命。