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

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。中风分支进行急性中风的自然史研究已经有十多年了。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（Leigh等人，神经病学，2016）。 进一步的分析已经改进了该模型以区分缓解可逆性和局灶性严重BBB破坏（Replikins等人，Stroke，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）相关的BBB破坏的能力。 对卒中自然史研究的系列MRI扫描的检查表明，在白色高信号患者中，血脑屏障可以长期开放，这表明它可能是认知能力下降的前兆。 NVBI目前正在开发一种方案，该方案将绘制BBB破坏和白色物质高强度之间的关系。 除了使用MRI测量BBB完整性外，NVBI还一直在研究使用MRI测量大脑pH值的方法。pH加权MRI的使用具有提供对缺血性损伤的细胞反应的最直接生物标志物的潜力（Leigh等人，JCBFM，2017）。与约翰霍普金斯大学的研究合作，NVBI已经实施了一种用于处理定量的pH加权MRI的新方法（Heo等人，Mag Res Med，2017）。 在下一个财政年度，NVBI将继续在这些方向上开展分支工作，以进一步实现我们降低脑血管疾病相关发病率和死亡率的使命。

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.