An improved method for correction of partial volume effects (PVE) in brain SPECT is proposed. It is fully three-dimensional, does not require particular patient positioning, and works with scans only partially covering the brain. The location of functionally inactive brain regions (primarily cerebrospinal fluid) is extracted from high-resolution MRI. An automatic 3D registration algorithm then determines the geometric transformation between MRI and SPECT. Correction consists of: 1) counting the volumetric active/inactive ratio in each volume element of the functional scan using the measured SPECT point spread function; 2) correcting the functional measures according to these ratios; 3) fusing functional and anatomical information at the resolution of MRI. Quantitative validation was performed using a phantom containing a test region in which multiple parallel acrylic plates thinner than SPECT resolution created high PVE, as well as a large reference region not suffering from PVE. Reference activity was recovered in the test region with an accuracy of 1-3%. The method was applied to clinical images demonstrating a combination of hypoperfusion and cortical atrophy. The composite anatomical-functional corrected images, in which the main sulci are visible, yield better differentiation between decreased function and focal atrophy. Hum.