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.