Abstract 691: Simulating TTFields-induced temperature changes within a patient’s brain - a proof of concept study

Abstract

Abstract Introduction: TTFields is an antimitotic cancer treatment that utilizes low intensity (1-3 V/cm) alternating electric fields in the intermediate frequency (100-300 kHz) that are delivered in two orthogonal directions using 2 pairs of transducer arrays. TTFields are currently approved for Glioblastoma Multiforme (GBM). Preclinical studies show that the effect of TTFields is intensity-dependent with a therapeutic threshold of 1 V/cm, and that as the intensity rises so does the efficacy. However, delivery of high field intensities could result in temperature increases within the body that lead to thermal damage to tissue. In practice, during treatment with TTFields, tissue heating is limited by a closed loop that adjusts the delivery of TTFields to ensure that skin temperature remains within the safety limits. Since heating limits the intensity at which TTFields is delivered, accurate models of tissue heating during TTFields therapy could provide insights into new approaches for the delivery of TTFields. Since measuring the temperature spatial distribution within a patient’s brain is extremely challenging, simulating the heat flow within the head during treatment is a more practical approach. Here, we present preliminary results from a study aimed at developing a valid computational model of heat transfer in the head during TTFields therapy. Method: A realistic computational head model of a healthy male was used in this study. Virtual transducer arrays were placed on the head. To simulate the delivery of TTFields to the brain, we used ZMT's Sim4Life v4.0 electro-quasi-static solver. The results of the electric field simulation were then used as heat source for the heat simulation. The heat simulation solves the Pennes bio-heat model, taking into account tissue heat capacity and conductivity, and also accounting for heat convection through blood perfusion. Sensitivity analysis was performed to establish the sensitivity of the temperature distribution within the brain to the thermal properties of the various tissue types. Results: Average temperatures within the brain tissue were well below 38° C for all simulations. Temperature distributions within the brain were highly sensitive to the perfusion coefficient assigned to the cerebrospinal fluid as well as other tissues.Conclusions: We have established a computational framework for investigating heat transfer in the brain during TTFields therapy. Further work is needed to correctly establish the thermal properties of the various tissue types. This may require experimental measurements in which the heat transfer model is fine-tuned and validated. Citation Format: Ariel Naveh, Ze'ev Bomzon. Simulating TTFields-induced temperature changes within a patient’s brain - a proof of concept study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 691.