Stroke is the fifth largest cause of death and a leading cause of long-term disability among adults in the United States. More than 300 neuroprotective and thrombolytic drug candidates for ischemic stroke have failed in clinical trials between 1995 and 2015, raising concerns regarding the efficacy of preclinical studies. Our long- term goal is to improve the value of animal models of ischemic stroke and accelerate the path of the most efficacious treatments to clinical trials with reduced failure rates and associated costs. The goal of this SBIR proposal is to demonstrate the utility of a wireless optical imaging instrument for providing an in vivo estimate of brain ischemia. Such knowledge will reduce inconsistency in animal models of ischemic stroke and enable longitudinal assessment of treatmentsÂ’ efficacy. At Barati Medical, LLC, we have developed a miniaturized, wireless near infrared spectroscopy (NIRS) prototype for noninvasive monitoring of cerebral oxygenation parameters, i.e. deoxyhemoglobin (Hb) and oxyhemoglobin (HbO2), in rats. In a preliminary study, our prototype detected a twofold reduction in cerebral oxygenation during deep anesthesia relative to light anesthesia in a male rat. The product of this proposal will be a cost-effective, miniaturized, wireless NIRS platform for the measurement of cerebral oxygenation in small lab animals, which enables in vivo, longitudinal assessment of brain injury models and treatmentsÂ’ efficacy. Our innovation centers on the utility of a cost-effective NIRS solution in predicting the infarct volume after procedures of middle cerebral artery occlusion (MCAO) in freely moving animals. No other in vivo measure is readily available that accurately predicts infarct volume or behavioral deficit. Our Specific Aims are to refine the NIRS prototype, demonstrate the feasibility of the NIRS device in predicting behavioral deficits and infarct volume at 48h after ischemic stroke, and show the feasibility of continuous, long- term measurement of cerebral oxygenation during the subacute phase of ischemic stroke in rats.
Public Health Relevance Statement: PROJECT NARRATIVE Clinical trials of drugs for acute ischemic stroke fail because of poor quality animal studies. We propose an imaging device that works based on light absorption by the brain for the use in ratsÂ’ models of stroke. Our device will refine stroke studies and improve translation of treatments.
NIH Spending Category: Bioengineering; Biomedical Imaging; Brain Disorders; Cerebrovascular; Hematology; Networking and Information Technology R&D (NITRD); Neurosciences; Stroke
Project Terms: absorption; Acute; Adult; Anesthesia procedures; Animal Model; Animals; base; Behavioral; Biomedical Research; Biotechnology; Blood flow; Brain; Brain Infarction; Brain Injuries; Brain Ischemia; Cause of Death; Cerebral cortex; Cerebral Infarction; cerebral oxygenation; Cerebrovascular Circulation; Clinical Trials; cost; cost effective; Data; data acquisition; deoxyhemoglobin; Development; Devices; disability; drug candidate; Evaluation; Failure; Feedback; Fiber Optics; Fibrinolytic Agents; Goals; Gold; Hour; Image; Imagery; Imaging Device; improved; in vivo; Infarction; Injury; innovation; instrument; Ischemia; Ischemic Stroke; Knowledge; Laser-Doppler Flowmetry; Letters; Licensing; Light; Linear Regressions; Liquid substance; Location; Longitudinal Studies; Magnetic Resonance Imaging; male; Measurement; Measures; Medical; Middle Cerebral Artery Occlusion; miniaturize; minimally invasive; Modeling; Monitor; Mus; Near-Infrared Spectroscopy; Neurologic; Neuroprotective Agents; Noise; non-invasive monitor; optical imaging; Optics; Oryctolagus cuniculus; Oxyhemoglobin; Penetration; Pharmaceutical Preparations; Phase; pre-clinical; Pre-Clinical Model; preclinical efficacy; preclinical study; Procedures; Property; prototype; Rattus; Reaction; Reperfusion Therapy; Research; Secure; sensor; Signal Transduction; Skin; Small Business Innovation Research Grant; Source; Stroke; stroke model; System; technological innovation; Technology; Testing; Therapeutic; Time; Tissues; tool; Translations; Treatment Efficacy; United States; user-friendly; Wireless Technology; Work
