Project Summary Brain temperature regulation is crucial for neurologic function and recovery after ischemia and injury. Local brain temperature increases as small as 1-2°C significantly contribute to the extent of ischemia-induced brain damage, and dissociation of brain and body temperatures is a strong predictor of poor prognosis. While brain temperature is well-recognized as an important clinical parameter for neuroprotection, current brain thermometry has been limited to invasive temperature probes surgically implanted at a single location, making it impractical in most patient cohorts. Several magnetic resonance (MR)-based thermometry methods have been proposed and demonstrated in research environments; however, most are still limited to relative estimations of temperature and are highly vulnerable to tissue heterogeneity-related errors. Body or systemic temperature measurements are the most common surrogate, leaving brain temperature largely uncharacterized in the clinical setting. To address these gaps in our understanding of brain temperature regulation, biophysical models based on empirical data and simplified physical frameworks have been developed. Recent models have made important progress in capturing brain anatomy and vasculature, but crucial details with fundamental adherence to first principles of fluid and thermal energy transport have yet to be formulated and implemented. Treatment of blood flow even in the most sophisticated models is ad hoc and does not satisfy basic principles of momentum and energy conservation. The overall goal of this Bioengineering Research Grant R01 proposal is to develop a new approach for in vivo MR chemical shift thermometry that is complemented by a novel biophysical model of brain thermoregulation. In Aim 1 we will implement corrections to MR-derived temperature calculations that will be validated and optimized in an animal model and healthy human volunteers. Aim 2 will develop a 3D simulated model for subject-specific predictions and quantification of brain temperature. Finally, in vivo brain thermometry will be acquired in a cohort of patients with cerebrovascular disease, and injury will be incorporated into the simulated biophysical model to facilitate subject-specific brain temperature characterization in Aim 3. We anticipate these studies will enable important advances in non-invasive MR brain thermometry, facilitate evaluation of brain temperature as a prognostic biomarker, and expand our understanding of brain thermoregulation and neuroprotection for improved patient outcomes.

Project Narrative Brain temperature regulation is a crucial hemodynamic parameter particularly after ischemia or brain injury. Currently, we have limited methods to measure and predict brain temperature in the clinical setting. Our goal is to develop a new method for non-invasive brain temperature monitoring, combined with a simulated model to enable brain temperature predictions, validated in healthy volunteers and patients with chronic cerebrovascular disease.