Purpose <p>Heat stroke is the most serious heat-related illness and is recognized as a worldwide public concern as global temperatures continue to rise. Although the clinical neurological complications of heat stroke are relatively well described, a limited number of studies exist that document imaging findings. Therefore, in this preclinical study, we aimed to identify the imaging findings of ¹⁸F-FDG brain PET following heat stroke and elucidate the utility of FDG PET in the evaluation of heat stroke-induced brain injury.</p> Methods <p>Heat stroke was induced in Sprague Dawley rats by placing them in a hot and humid chamber maintained without food and water until they exhibited the heat stroke onset diagnostic criterion. Three hours after the induction ended, ¹⁸F-FDG brain PET images were acquired in 7 controls and 14 rats with heat stroke. Between groups, region-based (standardized uptake values were normalized to the whole brain and SUV of the whole brain (SUV_WB), and voxel-based analyses were performed.</p> Results <p>Of the 14 rats with heat stroke, 8 survived, whereas 6 did not. In the region-based and voxel-base analyses, the rats that did not survive showed significantly higher SUVR_HB in the hypothalamus and significantly lower SUVR_HB in several cortical regions than the controls as well as the survived rats. In the region-based analysis, the survived rats showed a significant increase or decrease in SUVR_HB compared to the controls in a few cortical regions. However, no difference was observed in the voxel-based analysis.</p> Conclusions <p>The 3-h post-injury PET scan showed a distinctly different regional distribution of ¹⁸F-FDG in the brains of lethally injured heat stroke rats compared to the controls as well as the survived rats. The ¹⁸F-FDG brain PET may have the potential to provide early indicators of catastrophic injury and reflect the early neurological pathophysiology of heat stroke.</p>