Arterial input function Independent Measures of Perfusion with Physics Driven Models

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ABSTRACT Acute Ischemic Stroke (AIS) affects approximately 700,000 patients each year in the United States. [Benjamin EJ 2019, Circulation] Though the introduction of intravenous thrombolytics improved patient outcomes, the development of effective treatment regimens with mechanical thrombectomy has significantly altered the clinical management of AIS patients, especially when appropriate patients are selected for intervention. The current treatment selection approaches utilize patient specific data heavily relies on quantitative neuroimaging approaches, derived from either Computer Tomography (CT), or to a lesser extent magnetic resonance imaging (MRI). CT, with its relative availability within the US, has been the primary modality used for stroke patient triage. Brain perfusion imaging has been central to the evaluation of the ischemic penumbra and infarct core enabling precision in patient selection for intra-arterial thrombolysis. Typically dynamic CT perfusion scans with repeated scans 40 to 60 time points with the administration of iodinated contrast are obtained upon the arrival in the emergency room. These images are automatically or semi-automatically post-processed into perfusion metrics, using a number of FDA approved software packages. These packages all essentially rely on a similar post-processing pathway for the dynamically acquired images, consisting of motion correction, arterial input function selection and some form of deconvolution post-processing. A set of perfusion maps are generated, typically including cerebral blood flow (CBF), cerebral blood volume (CBV), mean transit time (MTT) and time to the maximum contrast concentration (Tmax). The software packages then apply thresholds to the CBF and Tmax maps to generate a presumed ischemic “core” from the CBF and “penumbra” from the Tmax. However, the dependence of these values on the arterial input function (AIF) selected has resulted in extensive efforts to automate AIF selection, or explore systematic methods to produce local AIFs to improve perfusion measurements. Defining a perfusion metric that is independent of AIF selection could substantially improve stroke perfusion analysis, and reduce patient radiation exposure. The goal of this study is to evaluate a physics based model of cerebral perfusion for evaluating perfusion parameters from CT perfusion modalities. The critical requirements of the new technique include independence from AIF selection, quantitative and stable measurements of perfusion that are clinically relevant and predictive of stroke outcomes.