Acute ischemic stroke is a major health problem in Western countries with a high mortality rate and a high risk for permanent disabilities. In 2018, a cohort study with 113 patients showed a preliminary evidence of neuroprotective effect of selective therapeutic hypothermia. In that study, intra- arterial, time-limited blood cooling by means of infusion of cold saline in combination with endovascular mechanical thrombectomy significantly reduced the final infarct volume. A recently developed catheter system enables to combine endovascular blood cooling and thrombectomy using the same endovascular access. By using the penumbral perfusion via leptomeningeal collaterals, the catheter aims at enabling a cold reperfusion, which mitigates the risk of a reperfusion injury. However, cerebral circulation is highly patient-specific and can vary greatly. Since direct measurement of remaining perfusion and temperature decrease induced by the catheter is not possible without additional harm to the patient, computational modeling provides an alternative to gain knowledge about resulting cerebral temperature decrease. In this work, we present a brain temperature model with a realistic division into gray and white matter and consideration of spatially resolved perfusion. Furthermore, it includes detailed anatomy of cerebral circulation with possibility of personalizing on base of real patient anatomy. For evaluation of catheter performance in terms of cold reperfusion and to analyze its general performance, we calculated the decrease in brain temperature in case of a large vessel occlusion in the middle cerebral artery (MCA) for different scenarios of cerebral arterial anatomy. Congenital arterial variations in the circle of Willis had a distinct influence on the cooling effect and the resulting spatial temperature distribution before vessel recanalization. Independent of the branching configurations, the model predicted a cold reperfusion due to a strong temperature decrease after recanalization (1.4-2.2°C after 25min of cooling, recanalization after 20min of cooling). Our model illustrates the effectiveness of endovascular cooling in combination with mechanical thrombectomy and serves as an adequate substitute for temperature measurement in a clinical setting in assence of direct intraparenchymal temperature probes.
Y. Lutz. Modeling of the Human Brain to Predict Spatial and Temporal Temperature Profiles for the Selective Hypothermia Treatment of an Ischemic Stroke. Dissertation. 2020
Acute ischemic stroke is a major health problem due to its high mortality rate and high residual risk for permanent disabilities. Targeted temperature management in terms of hypothermia is known to have neuroprotective effects and can potentially reduce the cerebral harm caused by an acute ischemic stroke. Nevertheless, available clinical studies show that the efficacy depends on various factors such as the timing, duration, and depth of hypothermia. In this context, selective brain hypothermia by means of endovascular blood cooling and the combination with mechanical thrombectomy appears to be especially promising. A novel catheter system enables the direct combination of endovascular blood cooling and thrombectomy using the same endovascular access. In this context, a prereperfusion cooling of penumbral tissue by cold leptomeningeal collateral blood flow might mitigate the risk of a reperfusion injury. However, direct measurements of blood temperature in the penumbra and temperature decrease induced by the novel catheter is not possible without additional harm to the patient. Additionally, cerebral circulation varies distinctly between patients and can influence the cooling conditions. A computational model can provide an alternative to temperature measurements and can help to gain knowledge about influences on the catheter's cooling performance. This work presents the development of a brain temperature model that is based on a realistic 3D brain geometry. Divided into gray and white matter, the geometry considers spatially resolved blood perfusion rates. To account for realistic spatial blood perfusion, a detailed hemodynamics model of the cerebral arterial anatomy was coupled. The hemodynamics model includes the possibility of personalizing based on real patient anatomy. For the evaluation of the catheter's performance, a complete right middle cerebral artery occlusion was simulated for different scenarios of cerebral arterial anatomy. The model predicted a distinct influence of congenital arterial variations in the circle of Willis on the cooling capacity and on the resulting spatial temperature distribution before vessel recanalization. Nevertheless, the model showed a possible cold reperfusion in the penumbra due to a strong increase in cooling performance after the recanalization (-1.4-2.2\,∘C 25\,min after the start of cooling, recanalization 20\,min after the start of cooling). This steep decrease in temperature was independent of the cerebral arterial anatomy. The developed model proves the effectiveness of endovascular blood cooling in combination with mechanical thrombectomy. Moreover, the model can contribute to the identification of possible influencing factors in the therapy of acute ischemic stroke with targeted temperature management, which is a timely and highly relevant topic as similar data can hardly be obtained by studying stroke cases in clinics.