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.
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.
Y. Lutz, A. Loewe, S. Meckel, O. Dössel, and G. Cattaneo. Combined local hypothermia and recanalization therapy for acute ischemic stroke: Estimation of brain and systemic temperature using an energetic numerical model.. In Journal of Thermal Biology, vol. 84, pp. 316-322, 2019
Local brain hypothermia is an attractive method for providing cerebral neuroprotection for ischemic stroke patients and at the same time reducing systemic side effects of cooling. In acute ischemic stroke patients with large vessel occlusion, combination with endovascular mechanical recanalization treatment could potentially allow for an alleviation of inflammatory and apoptotic pathways in the critical phase of reperfusion. The direct cooling of arterial blood by means of an intra-carotid heat exchange catheter compatible with recanalization systems is a novel promising approach. Focusing on the concept of "cold reperfusion", we developed an energetic model to calculate the rate of temperature decrease during intra-carotid cooling in case of physiological as well as decreased perfusion. Additionally, we discussed and considered the effect and biological significance of temperature decrease on resulting brain perfusion. Our model predicted a 2 °C brain temperature decrease in 8.3, 11.8 and 26.2 min at perfusion rates of 50, 30 and 10ml100g⋅min, respectively. The systemic temperature decrease - caused by the venous blood return to the main circulation - was limited to 0.5 °C in 60 min. Our results underline the potential of catheter-assisted, intracarotid blood cooling to provide a fast and selective brain temperature decrease in the phase of vessel recanalization. This method can potentially allow for a tissue hypothermia during the restoration of the physiological flow and thus a "cold reperfusion" in the setting of mechanical recanalization.
In Western countries, stroke is the third-most cause of death; 35- 55% of the survivors experience permanent disability. Mild therapeutic hypothermia (TH) showed neuroprotective effect in patients returning from cardiac arrest and is therefore assumed to decrease stroke induced cerebral damage. Recently, an intracarotid cooling sheath was developed to induce local TH in the penumbra using the cooling effect of cerebral blood flow via collaterals. Computational modeling provides unique opportunities to predict the resulting cerebral temperature without invasive procedures. In this work, we generated a simplified brain model to establish a cerebral temperature calculation using Pennes’ bio-heat equation and a 1D hemodynamics model of the cranial artery tree. In this context, we performed an extensive literature research to assign the terminal segments of the latter to the corresponding perfused tissue. Using the intracarotid cooling method, we simulated the treatment with TH for different degrees of stenosis in the middle cerebral artery (MCA) and analyzed the resulting temperature spatialtemporal distributions of the brain and the systemic body considering the influence of the collaterals on the effect of cooling.
Stroke is the third-most cause of death in developed countries. A new promising treatment method in case of an ischemic stroke is selective intracarotid blood cooling combined with mechanical artery recanalization. However, the control of the treatment requires invasive or MRI-assisted measurement of cerebral temperature. An auspicious alternative is the use of computational modeling. In this work, we extended an existing 1D hemodynamics model including the characteristics of the anterior, middle and posterior cerebral artery. Furthermore, seven ipsilateral anastomoses were additionally integrated for each hemisphere. A potential stenosis was placed into the M1 segment of the middle cerebral artery, due to the highest risk of occlusion there. The extended model was evaluated for various degrees of collateralization (“poor”, “partial” and “good”) and degrees of stenosis (0%, 50%, 75% and 99.9%). Moreover, cerebral autoregulation was considered in the model. The higher the degree of collateralization and the degree of stenosis, the higher was the blood flow through the collaterals. Hence, a patient with a good collateralization could compensate a higher degree of occlusion and potentially has a better outcome after an ischemic stroke. For a 99.9% stenosis, an increased summed mean blood flow through the collaterals of +97.7% was predicted in case of good collateralization. Consequently, the blood supply via the terminal branches of the middle cerebral artery could be compensated up to 44.4% to the physiological blood flow. In combination with a temperature model, our model of the cerebral collateral circulation can be used for tailored temperature prediction for patients to be treated with selective therapeutic hypothermia.
Y. Lutz, R. Daschner, L. Krames, A. Loewe, O. Dössel, and G. Cattaneo. Estimating Local Therapeutic Hypothermia in Case of Ischemic Stroke Using a 1D Hemodynamics Model and an Energetic Temperature Model. In 41st Annual International Conference of the IEEE Engineering in Medicine and Biology Society (EMBC), pp. 3983-3986, 2019
In Western countries, stroke is the third-most widespread cause of death. 80% of all strokes are ischemic and show a mortality rate of about 25%. Furthermore, 35-55% of affected patients retain a permanent disability. Therapeutic hypothermia (TH) could decrease inflammatory processes and the stroke-induced cerebral damage. Currently, the standard technique to induce TH is cooling of the whole body, which can cause several side effects. A novel cooling sheath uses intra-carotid blood cooling to induce local TH. Unfortunately, the control of the temporal and spatial cerebral temperature course requires invasive temperature measurements. Computational modeling could be used to predict the resulting temperature courses instead. In this work, a detailed 1D hemodynamics model of the cerebral arterial system was coupled with an energetic temperature model. For physiological conditions, 50% and 100% M1-stenoses, the temperatures in the supply area of the middle cerebral artery (MCA) and of the systemic body was analyzed. A 2K temperature decrease was reached within 10min of cooling for physiological conditions and 50% stenosis. For 100% stenosis, a significant lower cooling effect was observed, resulting in a maximum cerebral temperature decrease of 0.7K after 30min of cooling. A significant influence of collateral flow rates on the cooling effect was observed. However, regardless of the stenosis degree, the temperature decrease was strongest within the first 20min of cooling, which demonstrates the fast and effective impact of intra-carotid blood cooling.