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.
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