PURPOSE: To study the spontaneous low-frequency blood oxygenation level-dependent (BOLD) functional MRI (fMRI) signal fluctuations during hyperacute focal cerebral ischemia. MATERIALS AND METHODS: A stroke model in nonhuman primates (macaques) was used in this study. Spontaneous fluctuations were recorded using a series of gradient-recalled echo (GRE) echo-planar imaging (EPI) images. Fast Fourier transformation (FFT) was performed on the serial EPI data to calculate the frequency and magnitude of the spontaneous fluctuations. Diffusion tensor imaging (DTI) and perfusion-weighted imaging (PWI) were preformed to detect the ischemic lesion. RESULTS: The frequency of these fluctuations decreased in the periinfarct tissue in the ipsilateral hemisphere, while their magnitude increased. This area of abnormal signal fluctuations often extended beyond the hyperacute diffusion/perfusion abnormality. CONCLUSION: This study suggests that measurement of the spontaneous fMRI signal fluctuations provides different information than is available from diffusion/perfusion or T2-weighted MRI. (c) 2007 Wiley-Liss, Inc.