Candidate goals and career development plan: The candidate is a neurologist with a long-term goal of becoming an independent investigator in patient-oriented research with clinical responsibilities in an academic medical center. The candidate has learned basic skills in the use of positron emission tomography (PET) for cerebral hemodynamic and metabolic measurements. This award will secure the dedicated time and guidance needed to develop the foundation of knowledge and skills required for successful long-term investigation. This foundation will be built over the proposed five years of the award by: 1) Gaining a deeper understanding of cerebrovascular pathophysiology and the use of PET for its study. Specifically, the candidate will expand current knowledge to use different and more complicated imaging techniques and will learn compartmental modeling and analysis. 2) The learning of advanced skills in the application of PET techniques through participation as a member of the coordinating center of a multicenter randomized trial of surgical revascularization in carotid occlusion (Carotid Occlusion Surgery Study, COSS) that utilizes PET for patient selection. 3) Receiving training in clinical trial design, biostatistics, and the responsible conduct of research using human subjects. Environment: The environment is unique in the availability of both PET and MRI expertise and technology and in its capability to support measurements of physiologic parameters in acutely ill patients. The candidate's sponsor is well recognized as an independent investigator of cerebrovascular pathophysiology using PET. Research proposal: The primary Aim is to investigate the mechanisms of secondary injury in acute intracerebral hemorrhage (ICH). Experimental data have established that secondary injury occurs after ICH and that ischemia, edema, and toxic effects of blood components play a role. Other than the clear effect of hemorrhage extension on outcome, clinical data regarding these potential mechanisms of secondary injury are scarce and conflicting. The primary null hypotheses to be tested are that: 1) Brain swelling does not occur in the first week after ICH, 2) blood-brain barrier permeability is intact in the first week after ICH and 3) the area of damaged cortical neurons does not enlarge in the absence of hematoma enlargement within the first week after ICH. These hypotheses will be tested using sequential PET or MRI studies in 60 patients with acute ICH.
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