Synergistic advancements in MR thermometry and predictive thermal modeling towards improved characterization of human brain temperature

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.