Denoising Improves Cross‐Scanner and Cross‐Protocol Test–Retest Reproducibility of Diffusion Tensor and Kurtosis Imaging

ABSTRACT The clinical translation of diffusion magnetic resonance imaging (dMRI)‐derived quantitative contrasts hinges on robust reproducibility, minimizing both same‐scanner and cross‐scanner variability. As multi‐site data sets, including multi‐shell dMRI, expand in scope, enhancing reproducibility across variable MRI systems and MRI protocols becomes crucial. This study evaluates the reproducibility of diffusion kurtosis imaging (DKI) metrics (beyond conventional diffusion tensor imaging (DTI)), at the voxel and region‐of‐interest (ROI) levels on magnitude and complex‐valued dMRI data, using denoising with and without harmonization. We compared same‐scanner, cross‐scanner, and cross‐protocol variability for a multi‐shell dMRI protocol (2‐mm isotropic resolution, b = 0, 1000, 2000 s/mm 2 ) in 20 subjects. We first evaluated the effectiveness of Marchenko‐Pastur Principal Component Analysis (MPPCA) based denoising strategies for both magnitude and complex data to mitigate noise‐induced bias and variance, to improve dMRI parametric maps and reproducibility. Next, we examined the impact of denoising under different population analysis approaches, specifically comparing voxel‐wise versus region of interest (ROI)‐based methods. We also evaluated the role of denoising when harmonizing dMRI across scanners and protocols. The results indicate that DTI and DKI maps visually improve after MPPCA denoising, with noticeably fewer outliers in kurtosis maps. Denoising, either using magnitude or complex dMRI, enhances voxel‐wise reproducibility, with test–retest variability of kurtosis indices reduced from 15%–20% without denoising to 5%–10% after denoising. Complex dMRI denoising reduces the noise floor by up to 60%. Denoising not only reduced variability across scans and protocols, but also increased statistical power for low SNR voxel‐wise comparisons when comparing cross sectional groups. In conclusion, MPPCA denoising, either over magnitude or complex dMRI data, enhances the reproducibility and precision of higher‐order diffusion metrics across same‐scanner, cross‐scanner, and cross‐protocol assessments. The enhancement in data quality and precision facilitates the broader application and acceptance of these advanced imaging techniques in both clinical practice and large‐scale neuroimaging studies.