Abstract WP311: Novel Computational Framework for Modelling the Effects of Temperature on Survival Time in Ischemic Stroke

Abstract

Introduction: The detrimental influence of cerebral hyperthermia is well known, with notably deleterious effects in the ischemic brain, where even mild increases (<1°C) may rapidly potentiate ischemic injury. Experimental models of ischemic hyperthermia are undermined by the lack of pragmatic means for temporally- and spatially-resolved, direct cerebral thermometry. Computational models of cerebrovascular ischemia are well-suited to such exploration, and the use of digital phantoms for sophisticated biophysical modeling has been facilitated by emergent hardware, software, and computational solutions. We present a realistic computational environment for the simulation of thermal disturbance in cerebrovascular ischemia, permitting multiscale demonstration of hemodynamic, metabolic, and thermal aberrations in ischemic brain Methods: A multi-tissue biophysical numerical model of the human head and brain was extended to incorporate the dynamics of nutritive flow, metabolic need, tissue heating, and cytotoxicity. By restricting perfusion in a region of brain using a rudimentary representation of vascularization, we could quantify tissue heating arising from impaired radiative cooling, and time-dependent cell death. The procedure was iterated with an expected proportionality between temperature and metabolic rate Results: Fig 1 demonstrates simulated hypoperfusion affecting one hemisphere with resultant cerebral hyperthermia arising from impaired countercurrent heat exchange. Incorporating the effects of hyperthermia upon metabolic demand, the downward influence of heating on survivability is apparent, with ~30-minute acceleration to cytotoxicity. Conclusion: We present a combined model for tissue physiology and survival time following ischemic stroke using a multi-tissue model of whole-head bio-thermodynamics to examine effects of critical temperature disturbance on predicted tissue survival time.