Project Summary The importance of brain temperature for neuroprotection and recovery after trauma cannot be understated. Patient outcomes after cardiac arrest and stroke are strongly associated with temperature, where modest increases in body and brain temperatures correlate positively with severity of brain injury and mortality. Conversely, induced hypothermia or cooling is recognized as a therapeutic measure to mitigate further injury of the brain and maximally preserve tissue for recovery after cardiac arrest, stroke, and brain trauma. Therapeutic hypothermia is implemented using core body temperature monitoring and biofeedback, but it is well- established that these measurements are inaccurate and inconsistent proxies of brain temperature. Implanted temperature probes have demonstrated that brain temperature is higher than body temperature and these differences are further exaggerated after injury. As cooling has not been optimized in terms of dosage or patient selection, and patient outcomes after treatment are variable, brain temperature measurements may be a critical yet unexplored aspect of improving and optimizing this promising intervention. Clinical brain thermometry is limited to invasive temperature probes surgically implanted at a single location and is impractical in most patient cohorts. While several magnetic resonance (MR)-based thermometry methods have been proposed and demonstrated in research environments, most are still limited to relative estimations of temperature and are highly vulnerable to tissue heterogeneity-related errors. The overall goal of this R21 Trailblazer proposal is to develop a new approach for MR chemical shift thermometry and, in parallel, characterize brain-body temperature differences in patients during hypothermia treatment. We will develop a tissue-specific approach for MR thermometry, correcting for temperature-independent chemical shifts that introduce errors in absolute measurements (Aim 1). As brain-body temperature decoupling may be an important marker for injury and treatment monitoring, brain thermometry will be implemented in cardiac arrest patients undergoing therapeutic hypothermia to non-invasively measure brain-body temperature differences (Aim 2). We anticipate that these studies will expand our understanding of brain thermoregulation and neuroprotection during therapeutic hypothermia and provide a crucial first step towards a personalized approach to temperature management.

Project Narrative Brain temperature regulation is crucial for recovery after injury, and induced hypothermia or cooling has been recognized as a therapeutic measure to mitigate brain damage after cardiac arrest. Currently, therapeutic hypothermia is monitored using core body temperature due to a lack of non-invasive brain thermometry tools, but as brain and body temperatures are decoupled after injury, body temperature may be an inaccurate surrogate for brain temperature. Our goal is to develop a new method for non-invasive brain temperature monitoring and to demonstrate the ability to measure brain-body temperature differences in cardiac arrest patients during cooling.