Multiple factors (attenuation, scattering, scanner response, etc) significantly degrade SPECT images. and multiple techniques have been proposed to correct for those and therefore yield more quantitatively exact SPECT studies, with the aim of improving clinical classification of patients as well as results from research using this technique. Application of a Wiener filter during reconstruction, which minimizes the mean square error between the original object and its estimate (the image), is a well-validated and relatively simple approach to this problem. Optimal use of this technique requires a priori information such as the point spread function (PSF) of the imaging system and the power spectrum ratio of the original object to image noise, but this information is not generally available. We have applied a new adaptation of this approach to cerebral blood flow studies obtained in SPECT with 99mTc labeled agents. Here, we start with a Gaussian function to model the PSF of the SPECT system, and a constant to replace the noise-to-signal power spectrum ratio 1. The PSF width and power-spectrum ratio are then iteratively optimized to improve image contrast between white and gray matter while keeping image mottle (or variance) within each region at a tolerable level (as defined in 2, 3). To track precisely the contrast and mottle, the white and gray matter regions are identified from an anatomical MRI of the same patient previously co-registered to the SPECT study 4. Simulation results with a realistic brain model (digital Hoffman phantom 5, with 3D Gaussian noise (at such count levels, Poisson noise would yield comparable results) and then blurred with a 3D Gaussian function to simulate an actual SPECT study) show marked contrast improvement while maintaining the mottle at an acceptable level: with object contrast between white and gray matter (as defined in 2) set at 0.427 and degraded to 0.074 post blurring, filtering increased contrast to 0.378, with the mottle (proportionally averaged for gray and white matter) actually decreasing (0.224 to 0.182). Tests conducted with actual clinical SPECT cases exhibit similar contrast improvement (0.045 to 0.104) with a limited (and still acceptable 2) mottle increase (0.198 to 0.276). We believe that this technique for defining the parameters of a 3D adaptive Wiener filter will be useful in clinical practice, where significant data degradation limits detection of anomalies with SPECT, because it automatically generates the best combination of those parameters, leading to significantly improved contrast quantification with little noise amplification.