Minimally invasive measurement of carotid artery and brain temperature in the mouse

Brain temperature is tightly regulated and reflects a balance between cerebral metabolic heat production and heat transfer between the brain, blood, and external environment. Blood temperature and flow are critical to the regulation of brain temperature. Current methods for measuring in vivo brain and blood temperature are invasive and impractical for use in small animals. This work presents a methodology to measure both brain and arterial blood temperature in anesthetized mice by MRI using a paramagnetic lanthanide complex: thulium tetramethyl-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (TmDOTMA^-).

A phase-based imaging approach using a multi-TE gradient echo sequence was used to measure the temperature-dependent chemical shift difference between thulium tetramethyl-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid methyl protons and water, and from this calculate absolute temperature using calibration data.

In a series of mice in which core body temperature was held stable but at different values within the range of 33° to 37°C, brain temperature away from the midline was independent of carotid artery blood temperature. In contrast, midline voxels correlated with carotid artery blood temperature, likely reflecting the preponderance of larger arteries and veins in this region.

These results are consistent with brain temperature being actively regulated. A limitation of the present implementation is that the spatial resolution in the brain is coarse relative to the size of the mouse brain, and further optimization is required for this method to be applied for finer spatial scale mapping or to characterize focal pathology.