Brain temperature regulation is a key parameter after injury and ischemia. Experimental magnetic resonance (MR)-based thermometry is promising but not always clinically feasible. To complement MR thermometry measures, an improved thermal model of the brain based on first principles has been developed that rigorously ensures energy conservation in thermally interacting brain domains. As initial validation, a temperature map was generated using our model with MR angiography (MRA) and structural MR imaging (MRI) data, and compared with experimental chemical shift thermometry (CST) in the same subject. Biophysical models provide further insight into brain thermoregulation by complementing experimental thermometry measurements.