R01NS125635

Quantitative model-based ESUS reclassification using cardiac and cerebral vessel wall MRI - Quantitative model-based ESUS reclassification using cardiac and cerebral vessel wall MRI.

Stroke is a major cause of death and the leading cause of permanent disability worldwide. Ischemic stroke is the dominant stroke variety, representing approximately 80+% of strokes in the United States.

Defining the specific underlying pathophysiology of ischemic strokes is critical for personalized secondary prevention treatments with the goal of minimizing the risk of recurrent events. However, even with extensive diagnostic workup in current clinical practice, a large portion of ischemic strokes are classified as embolic stroke of undetermined source (ESUS), leaving these patients without optimal treatment tailored to their specific pathophysiology.

Recent literature has demonstrated that among subjects diagnosed with ESUS, there may be under-detected lesions of atherosclerosis in intra/extracranial arteries or cardiac pathology on a path towards atrial fibrillation, a so-called "atrial cardiopathy". This implies that there are opportunities to improve the sensitivity and accuracy of etiologic diagnosis to reduce ischemic strokes classified into the ESUS category, allowing for more targeted, personalized secondary prevention measures.

New developments in magnetic resonance imaging (MRI) of intra/extracranial atherosclerosis and atrial cardiopathy may provide new opportunities to detect these currently under-detected lesions and allow reclassification of ESUS patients into large-artery atherosclerosis or cardioembolic categories leading to focused treatment strategies.

However, there are still significant challenges to using these imaging methods in practice: 1) specialized vessel wall and cardiac MRI (ESUS-imaging) and image analysis algorithms need to be integrated into the standard of care workflow of stroke patients; 2) a model-based analysis will be needed that combines new findings from ESUS-imaging and findings from existing clinical workup so that new "risk features (RFS)" can be defined for reclassification; and 3) the impact of using these RFS on stroke subtype reclassification needs to be studied prospectively.

In this proposal, we plan to develop a model-based analysis focused on ESUS-imaging and test the hypothesis that among acute ischemic stroke subjects diagnosed as ESUS under current clinical workup, a new set of RFS drawn from ESUS-imaging will allow reclassification of a subset of ESUS into large-artery atherosclerosis or cardioembolic categories.

The specific aims will: 1) establish new vessel wall and cardiac MRI (ESUS-imaging) and image analysis techniques; 2) develop a multiparametric statistical model that combines information from the standard stroke workup and new ESUS-imaging to identify a set of RFS that can reclassify ischemic stroke etiology; and 3) evaluate the impact of the model on ischemic stroke subtype reclassification.

If successful, this proposal will help to establish a clinical workflow that includes ESUS-imaging in ischemic stroke workup and provide a model-based algorithm to assist in future stroke subtype classification.

University Of Washington

(1) TO SUPPORT EXTRAMURAL RESEARCH FUNDED BY THE NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE (NINDS) INCLUDING: BASIC RESEARCH THAT EXPLORES THE FUNDAMENTAL STRUCTURE AND FUNCTION OF THE BRAIN AND THE NERVOUS SYSTEM, RESEARCH TO UNDERSTAND THE CAUSES AND ORIGINS OF PATHOLOGICAL CONDITIONS OF THE NERVOUS SYSTEM WITH THE GOAL OF PREVENTING THESE DISORDERS, RESEARCH ON THE NATURAL COURSE OF NEUROLOGICAL DISORDERS, IMPROVED METHODS OF DISEASE PREVENTION, NEW METHODS OF DIAGNOSIS AND TREATMENT, DRUG DEVELOPMENT, DEVELOPMENT OF NEURAL DEVICES, CLINICAL TRIALS, AND RESEARCH TRAINING IN BASIC, TRANSLATIONAL AND CLINICAL NEUROSCIENCE. THE INSTITUTE IS THE LARGEST FUNDER OF BASIC NEUROSCIENCE IN THE US AND SUPPORTS RESEARCH ON TOPICS INCLUDING BUT NOT LIMITED TO: DEVELOPMENT OF THE NERVOUS SYSTEM, INCLUDING NEUROGENESIS AND PROGENITOR CELL BIOLOGY, SIGNAL TRANSDUCTION IN DEVELOPMENT AND PLASTICITY, AND PROGRAMMED CELL DEATH, SYNAPSE FORMATION, FUNCTION, AND PLASTICITY, LEARNING AND MEMORY, CHANNELS, TRANSPORTERS, AND PUMPS, CIRCUIT FORMATION AND MODULATION, BEHAVIORAL AND COGNITIVE NEUROSCIENCE, SENSORIMOTOR LEARNING, INTEGRATION AND EXECUTIVE FUNCTION, NEUROENDOCRINE SYSTEMS, SLEEP AND CIRCADIAN RHYTHMS, AND SENSORY AND MOTOR SYSTEMS. IN ADDITION, THE INSTITUTE SUPPORTS BASIC, TRANSLATIONAL AND CLINICAL STUDIES ON A NUMBER OF DISORDERS OF THE NERVOUS SYSTEM INCLUDING (BUT NOT LIMITED TO): STROKE, TRAUMATIC INJURY TO THE BRAIN, SPINAL CORD AND PERIPHERAL NERVOUS SYSTEM, NEURODEGENERATIVE DISORDERS, MOVEMENT DISORDERS, BRAIN TUMORS, CONVULSIVE DISORDERS, INFECTIOUS DISORDERS OF THE BRAIN AND NERVOUS SYSTEM, IMMUNE DISORDERS OF THE BRAIN AND NERVOUS SYSTEM, INCLUDING MULTIPLE SCLEROSIS, DISORDERS RELATED TO SLEEP, AND PAIN. PROGRAMMATIC AREAS, WHICH ARE PRIMARILY SUPPORTED BY THE DIVISION OF NEUROSCIENCE, ARE ALSO SUPPORTED BY THE DIVISION OF EXTRAMURAL ACTIVITIES, THE DIVISION OF TRANSLATIONAL RESEARCH, THE DIVISION OF CLINICAL RESEARCH, THE OFFICE OF TRAINING AND WORKFORCE DEVELOPMENT, THE OFFICE OF PROGRAMS TO ENHANCE NEUROSCIENCE WORKFORCE DEVELOPMENT, AND THE OFFICE OF INTERNATIONAL ACTIVITIES. (2) TO EXPAND AND IMPROVE THE SMALL BUSINESS INNOVATION RESEARCH (SBIR) PROGRAM, TO INCREASE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT, TO INCREASE SMALL BUSINESS PARTICIPATION IN FEDERAL RESEARCH AND DEVELOPMENT, AND TO FOSTER AND ENCOURAGE PARTICIPATION OF SOCIALLY AND ECONOMICALLY DISADVANTAGED SMALL BUSINESS CONCERNS AND WOMEN-OWNED SMALL BUSINESS CONCERNS IN TECHNOLOGICAL INNOVATION. TO UTILIZE THE SMALL BUSINESS TECHNOLOGY TRANSFER (STTR) PROGRAM, TO STIMULATE AND FOSTER SCIENTIFIC AND TECHNOLOGICAL INNOVATION THROUGH COOPERATIVE RESEARCH AND DEVELOPMENT CARRIED OUT BETWEEN SMALL BUSINESS CONCERNS AND RESEARCH INSTITUTIONS, TO FOSTER TECHNOLOGY TRANSFER BETWEEN SMALL BUSINESS CONCERNS AND RESEARCH INSTITUTIONS, TO INCREASE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT, AND TO FOSTER AND ENCOURAGE PARTICIPATION OF SOCIALLY AND ECONOMICALLY DISADVANTAGED SMALL BUSINESS CONCERNS AND WOMEN-OWNED SMALL BUSINESS CONCERNS IN TECHNOLOGICAL INNOVATION.

93.853 - Extramural Research Programs in the Neurosciences and Neurological Disorders

National Institute of Neurological Disorders and Stroke (NNDS) [HHS - NIH]

Seattle, Washington 981094725 United States

Single Zip Code

NIH Research Project Grant (Parent R01 Clinical Trial Not Allowed) (PA-20-185)

Amendment Since initial award the total obligations have increased 282% from $797,438 to $3,048,621.