Abstract:

Therapeutic hypothermia (TH) is an approved neuroproctetive treatment to reduce neurological morbidity and mortality after hypoxic-ischemic damage related to cardiac arrest and neonatal asphyxia. Also in the treatment of acute ischemic stroke (AIS), which in Western countries still shows a very high mortality rate of about 25 %, selective mild TH by means of Targeted Temperature Management (TTM) could potentially decrease final infarct volume. In this respect, a novel intracarotid blood cooling catheter system has recently been developed, which allows for combined carotid blood cooling and mechanical thrombectomy (MT) and aims at selective mild TH in the affected ischemic brain (core and penumbra). Unfortunately, so far direct measurement and control of cooled cerebral temperature requires invasive or elaborate MRI-assisted measurements. Computational modeling provides unique opportunities to predict the resulting cerebral temperatures on the other hand. In this work, a simplified 3D brain model was generated and coupled with a 1D hemodynamics model to predict spatio-temporal cerebral temperature profiles using finite element modeling. Cerebral blood and tissue temperatures as well as the systemic temperature were analyzed for physiological conditions as well as for a middle cerebral artery (MCA) M1 occlusion. Furthermore, vessel recanalization and its effect on cerebral temperature was analyzed. The results show a significant influence of collateral flow on the cooling effect and are in accordance with experimental data in animals. Our model predicted a possible neuroprotective temperature decrease of 2.5 ℃ for the territory of MCA perfusion after 60 min of blood cooling, which underlines the potential of the new device and the use of TTM in case of AIS.

Abstract:

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.