Impact of Quantitative Perfusion Deficits on Endothelial Dysfunction During Endovascular Thrombectomy in Large Vessel Ischemic Stroke

TITLE: Impact of Quantitative Perfusion Deficits on Endothelial Dysfunction During Endovascular Thrombectomy in Large Vessel Ischemic Stroke SNIS Foundation Fellow/Young Investigator Research Grant Principle Investigator: David L Dornbos III, MD ABSTRACT As endovascular intervention for large vessel acute ischemic stroke continues to expand, advanced imaging modalities and a better understanding of imaging findings are clearly needed to aid in patient selection and prognostication of post-thrombectomy outcomes. After our recent validation of a novel cone beam CT perfusion scan, this proposal will allow fusion of perfusion imaging with intra-procedural angiograms to identify precise location of intracranial blood sampling during thrombectomy in a quantifiable way. We will test the hypothesis that perfusion imaging-directed intracranial blood sampling will elucidate underlying mechanisms of endothelial dysfunction, thrombotic activation, and early immune response in ischemic core and penumbral territory during acute ischemic stroke. Inflammatory and immune markers (microglial activators, chemokines, transmembrane proteins, complement factors), in addition to markers of thrombotic activation (von Willebrand factor, platelet glycoprotein 1b [GP1b]), will be analyzed in their relation to quantitative perfusion deficit. Further, flow cytometry on intracranial blood samples will be performed to assess the neuroinflammatory and pro-thrombotic intravascular environment (neutrophils, monocytes, T cells, platelets, microthrombi) in regions of perfusion that correlate with ischemic core, penumbra, or normal tissue. This study will be the first of its kind to directly assess differences in ischemic core tissue and penumbra regions through direct sampling and analysis in human subjects. Ultimately, we expect the findings from this study to unlock two pivotal domains for endovascular neurosurgery and stroke science. First, this study will provide an in depth understanding of the molecular and cellular underpinnings of non-contrast CT, CT perfusion, and MR imaging, providing a more robust understanding of what is being visually assessed and used to guide patient management. Second, through better understanding of the pathologic differences in ischemic territories in comparison to penumbra regions, we anticipate identification of innovative neuroprotective interventions targeted at penumbra-specific mechanisms.