A practical, clinically-focused endovascular cooling system for neuroprotection in acute ischemic stroke

About This Grant

PROJECT SUMMARY/ABSTRACT Ischemic stroke represents the second leading cause of death worldwide, and the direct costs of stroke are approximately $71.6 billion. These costs are disproportionately driven by patients with large vessel occlusions (LVO). Recent advances in urgent thrombectomy (clot removal) have led to improved outcomes, yet more than 50% of patients fail to achieve good functional outcomes even in the most recent trials. Developing neuroprotectants in order to mitigate neuronal injury immediately following the ischemic event is now a primary focus for researchers in this area. Among numerous proposed neuroprotectant strategies, hypothermia, or brain cooling, remains the most promising. Numerous previous investigators have proposed selective brain cooling of the brain only rather than full-body cooling, especially in conjunction with thrombectomy procedures since the access catheters to the carotid arteries are already in place and could be utilized to selectively cool the brain immediately after clot removal. These selective cooling approaches use the indwelling procedural catheters either for infusion of cold saline directly into the intracranial blood flow or cold saline to cool flowing blood as it passes along an indwelling catheter wall. Both of these approaches are limited by the cold saline's inherent warming as it travels to the target location. Also, saline will cause both fluid overload as well as dilution of oxygen- rich blood. Further, the devices being developed are not similar to the modern, high- performance catheters currently in use in thrombectomy procedures, which likely will limit their use. The long-term goal of this research and development proposal is to enable an advanced cooling system that targets the practitioners---neurointerventionalists, neurointensive care physicians, and perfusionists--- to provide them with a state-of-the-art cooling catheter system that focuses on ease of use rather than engineering principles, yet enables speed, depth, and duration of cooling superior to any other device. The first Specific Aim of this R21 proposal involves the design, construction, and bench-testing of a coaxial infusion catheter. Milestones for this Aim will include both heat transfer and mechanical design metrics as well as in vitro tests assessing the efficacy and safety of our catheter on the bench. Aim 2 will assess efficacy and safety in leading preclinical in vivo models. The research plan will include placement of the device in the carotid arteries in swine and measuring the speed, depth, and duration of parenchymal cooling. If successful, this research program will improve the neurological function of patients suffering from large vessel occlusion acute ischemic stroke by protecting brain tissue that would otherwise not be salvaged.