Cerebral Temperature Dysregulation: MR Thermographic Monitoring in a Nonhuman Primate Study of Acute Ischemic Stroke

Cerebral thermoregulation remains poorly understood. Temperature dysregulation is deeply implicated in the potentiation of cerebrovascular ischemia. We present a multiphasic, MR thermographic study in a nonhuman primate model of MCA infarction, hypothesizing detectable brain temperature disturbances and brain-systemic temperature decoupling.

Three Rhesus Macaque nonhuman primates were sourced for 3-phase MR imaging: 1) baseline MR imaging, 2) 7-hour continuous MR imaging following minimally invasive, endovascular MCA stroke induction, and 3) poststroke day 1 MR imaging follow-up. MR thermometry was achieved by multivoxel spectroscopy (semi-localization by adiabatic selective refocusing) by using the proton resonance frequency chemical shift. The relationship of brain and systemic temperatures with time and infarction volumes was characterized by using a mixed-effects model.

Following MCA infarction, progressive cerebral hyperthermia was observed in all 3 subjects, significantly outpacing systemic temperature fluctuations. Highly significant associations were observed for systemic, hemispheric, and global brain temperatures (F-statistic, P = .0005 for all regressions) relative to the time from stroke induction. Significant differences in the relationship between temperature and time following stroke onset were detected when comparing systemic temperatures with ipsilateral (P = .007), contralateral (P = .004), and infarction core (P = .003) temperatures following multiple-comparisons correction. Significant associations were observed between infarction volumes and both systemic (P ≤ .01) and ipsilateral (P = .04) brain temperatures, but not contralateral brain temperature (P = .08).

Successful physiologic and continuous postischemic cerebral MR thermography was conducted and prescribed in a nonhuman primate infarction model to facilitate translatability. The results confirm hypothesized temperature disturbance and decoupling of physiologic brain-systemic temperature gradients. These findings inform a developing paradigm of brain thermoregulation and the applicability of brain temperature as a neuroimaging biomarker in CNS injury.