OBJECTIVES: Intensity variation in multi-parametric magnetic resonance imaging (MP-MRI) is a confounding factor in MRI analyses. Previous studies have employed several normalization methods, but there is a lack of consensus on which method results in the most comparable images across vendors and acquisitions. This study used MP-MRI collected from patients with confirmed prostate, brain, or breast cancer to examine common intensity normalization methods to identify which best harmonizes intensity values across cofounds. MATERIALS AND METHODS: Multiple normalization methods were deployed for intensity comparison between three unique sites, MR vendors, and magnetic field strength. Additionally, we calculated radiomic features before and after intensity normalization to determine how downstream analyses may be affected. Specifically, in the prostate cancer cohort, we tested these methods on T2-weighted imaging (T2WI) and additionally looked at a subset of patients who were scanned with and without the use of an endorectal coil (ERC). In a cohort of glioblastoma (GBM) patients, we tested these methods in T1 pre- and post-contrast enhancement (T1, T1C), fluid attenuated inversion recovery (FLAIR), and apparent diffusion coefficient (ADC) maps. Finally, in the breast cancer cohort, we tested methods on T1-weighted nonfat-suppressed images. All methods were compared using a two one-sided test (TOST) to test for equivalence of mean and standard deviation of intensity distributions. RESULTS: While each organ had unique results, across every tested comparison, using the Z-score of intensity within a mask of the organ consistently provided an equivalent distribution (all p <
0.001). CONCLUSIONS: Our results suggest that intensity normalization using the Z-score of intensity within prostate, breast, and brain MR images produces the most comparable intensities between sites, MR vendors, magnetic field strength, and prostate endorectal coil usage. Likewise, Z-score normalization provided the highest percentage of radiomic features that were statistically equal across the three organs.