A magnetic resonance proton spectroscopic imaging (SI) technique was developed to measure regional brain temperatures in human subjects. The technique was validated in a homogeneous phantom and in four healthy volunteers. Simulations and calculations determined the theoretical measurement precision as approximately +/-0.3 degrees C for individual 1-ml voxels. In healthy volunteers, repeated measurements oil individual voxels had all S.D.= 1.2 degrees C. In a clinical study. 40 patients with acute ischemic stroke were imaged within 26 h (mean. 10 h) of onset. Temperatures were highest in the region that appeared abnormal (i.e.. ischemic) on diffusion-weighted imaging (DWI) compared with a normal-appearing brain. The mean temperature difference between the DWI “lesion” area and the “normal brain” was 0.17 degrees C [P < 10(-3), range, 2.45 degrees C (hotter)-2.17 degrees C (cooler)]. Noninvasive temperature measurement by SI has sufficient precision to be used in Studies of pathophysiology in stroke and in other brain disorders and to monitor therapies. (C) 2006 Elsevier Inc. All rights reserved.