Direct 17O-MRI enables quantification of cerebral metabolic rate of oxygen consumption (CMRO2). The low MR sensitivity of the 17O nucleus prevents pixel-wise CMRO2 quantification and the fast T2*≈2ms decay leads to partial volume artifacts. In this work the DIESIS method is proposed, which performs a direct least squares estimation of the 17O‑MR signal in image regions (parcels) obtained from coregistered 1H data. CMRO2 values of 1.38-1.87µmol/gtissue/min and 0.51-0.77µmol/gtissue/min were found with DIESIS in gray and white matter consistent with rates from 15O-PET studies. With DIESIS, CMRO2 maps of high resolution can be reconstructed and partial volume artifacts can be reduced.