Over the past two decades developments in neuroimaging, especially in magnetic resonance imaging (MRI), have enabled enormous changes to be made in our knowledge and understanding of acute stroke. This knowledge is now being applied and extended in the clinical and translational research of the Stroke Neuroscience Unit at the National Institute of Neurological Disorders and Stroke. A recent advance in clinical MRI is rapid vascular imaging from the aortic arch to the circle of Willis using contrast-enhanced MR angiography (CE-MRA) and a neurovascular array. A prospective evaluation of CE-MRA has been completed and CE-MRA has been shown to be a promising method for the rapid and early detection of extracranial vascular disease. CE-MRA has been added to acute stroke MRI protocols of the NIH Stroke Program and could be of particular value for emergent decisions regarding acute stroke intervention (intravenous and intra-arterial thrombolysis), urgent surgical intervention and secondary stroke prevention. A meta-analysis comparing the accuracy of CE-MRA and time of flight MRA for the detection of carotid artery stenoses has also been completed. An assessment of the accuracy of CE-MRA using a 16 channel neurovascular array for the detection of extracranial carotid stenoses is being planned. The Principal Investigator of the Stroke Neuroscience Unit is chairing a panel that is assessing the value of MRA for the detection of extranial and intracranial vascular disease, for the Technology and Therapeutics Committee of the American Academy of Neurology.? ? In new research applications, real-time, high resolution MRI is being combined with peripheral blood markers ? of gene and protein expression and inflammation - to study patterns of stroke risk, evolution and recovery. The peripheral blood is a practical source of samples as brain tissue is rarely available in the clinical setting. In a pilot study of patients with acute ischemic stroke confirmed on neuroimaging studies, a genomic fingerprint of ischemic stroke was defined and validated in peripheral blood mononuclear cells. This work has now been extended to the identification of a gene expression signature of acute intracerebral hemorrhage from the peripheral blood. A panel of genes in the peripheral blood may also be predictive of an individual's future risk of vascular disease. The accuracy of this vascular risk gene panel is being tested by giving a group of subjects at risk of vascular disease one of 4 doses of atorvastatin for 3 months to see if dose response changes in expression of these genes can be demonstrated. The effects of atrovastatin administration on lymphocyte subsets (for example, the CD4+CD28- and the CD4+CD25+ subsets of T cells) are also being tested.? ? Future studies will involve correlation of genomic and proteomic profiles with MRI imaging patterns (for example, with reperfusion injury in Dr. Warach's section), and evaluation of their potential use for predicting stroke outcome and response to therapeutic interventions, including the e-selectin study being carried out by Dr. Hallenbeck's section. In conjunction with accurate MR imaging patterns, these approaches may give information on new cellular and pathological mechanisms involved in the etiology and response to acute stroke, allow the development of surrogate biomarkers of stroke risk and prognosis, and ultimately lead to new drug therapies or preventive vaccines.
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