An Imaging Repository for the Cerebrovascular Disease Knowledge Portal (iCDKP) - PROJECT ABSTRACT Stroke is the world’s second-leading cause of death. By 2030 an estimated 122.4 million people world-wide will be affected while stroke-related medical costs in the US alone are projected to exceed $180 billion. Furthermore, stroke itself is only the most acute manifestation of cerebrovascular disease, which also causes chronic progressive deterioration in brain function, including vascular contributions to cognitive impairment and dementia (VCID). Despite a pressing need for novel treatments, the precise biological pathways that lead to brain ischemia and hemorrhage, the response of the brain to injury, and the brain’s capacity for recovery remain poorly understood. Imaging provides crucial and quantifiable measures of these processes. Without imaging it is impossible to characterize the location of the brain affected, quantity of brain tissue involved, or amount of brain swelling/edema. Furthermore, serial images of the same patient over time capture dynamic physiology such as infarct growth or hemorrhage growth, which are both crucial to studying injury and recovery. The International Stroke Genetics Consortium (ISGC) was founded to harness human genetics to identify novel biological pathways that can ultimately lead to effective treatments for stroke. Indeed, candidate drug treatments supported by evidence from human genetics are substantially more likely to achieve FDA approval. The ISGC’s commitment to large harmonized data sets, open data sharing and collaborative culture has led to the discovery of all of the robustly supported risk genes for common forms of stroke to date, many of which are already being studied as the basis for novel treatments. In 2017 the ISGC launched the Cerebrovascular Disease Knowledge Portal (CDKP) (R24NS092983) to share genetic data freely with the research community in a manner adherent to FAIR Data Principles. A major limitation of this resource is the absence of brain images. For this proposed biomedical data repository cooperative agreement (U24) we will aggregate brain imaging and genetic data according to FAIR data principles from an estimated 30,000 individuals with stroke and share these data according to FAIR data principles. Building on the established Stroke Neuro-Imaging Phenotype Repository (SNIPR) at Washington University, our program will transform the CDKP into the imaging CDKP (iCDKP), providing the global community with a single FAIR access point to genetic, phenotypic, and imaging data. Milestone-driven aims will: 1) Aggregate high value stroke imaging datasets from across the international investigator community; 2) Implement FAIR data sharing practices and procedures; 3) Engage the research community with repository. Our team, led by the PIs for CDKP and SNIPR is well-situated to execute this project given that we have developed this proposal in consultation with the international stroke research community to ensure broad support and maximum response to their anticipated needs.