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.
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