Selective brain cooling monitored by CT perfusion as adjuvant therapy in a porcine model of severe ischemic stroke

Abstract

Despite the advances in ischemic stroke treatment, not all patients are eligible for or fully recovered after recanalization therapies. Therapeutic hypothermia could be adjuvant therapy that optimizes the beneficial effect of reperfusion. While conventional whole-body cooling has severe adverse effects, selective brain cooling has emerged as an attractive alternative. However, clinical application is limited by the lack of optimal delivery methods and unknown treatment parameters. Optimal parameters may depend on injury levels and monitoring cerebral perfusion may provide valuable information. Here, we show that selective brain cooling via our in-house developed Vortex tube IntraNasal Cooling Instrument (VINCI), even with a clinically relevant delay in treatment, can attenuate subacute injuries in animals with severe ischemic stroke. The treatment responses of selective brain cooling were characterized by CT Perfusion (CTP). The predicted lesion volume by CTP matched the true infarct volume by histology when the brain temperature was decreased by 5{degrees}C from normothermia. More importantly, we found that global hyperemia (high cerebral blood flow) before rewarming could be an early manifestation of poor treatment outcomes. Altogether, our study shows that VINCI-enabled brain cooling could be guided by CTP imaging as adjuvant therapy for severe ischemic stroke. This work lays the groundwork toward individualized selective brain cooling. Significance StatementNot all patients suffering from ischemic stroke are eligible or fully recovered after recanalization therapies. Therapeutic hypothermia could be an adjuvant therapy, but the clinical application is hindered by the delivery methods. The optimum treatment depth and duration are also unknown, and they may depend on the injury level. We developed a non-invasive selective brain cooling device, Vortex tube IntraNasal Cooling Instrument (VINCI). The treatment responses were characterized by CT Perfusion (CTP). Global hyperemia (high cerebral blood flow) was identified and could be an early manifestation of poor treatment outcomes. Our work shows that VINCI-enabled brain cooling could be guided by CTP imaging as adjuvant therapy for ischemic stroke. This work also lays the groundwork toward individualized selective brain cooling.