BackgroundDespite the widespread use of diffusion-weighted imaging (DWI) in metabolic dysfunction-associated fatty liver disease (MAFLD), MRI acquisition and quantification techniques vary in the literature suggesting the need for established and reproducible protocols. The goal of this study was to assess inter-visit and inter-reader reproducibility of DWI- and IVIM-derived parameters in patients with MAFLD and healthy volunteers using extensive sampling of the “fast” compartment, non-rigid registration, and exclusion voxels with poor fit quality. MethodsFrom June 2019 to April 2023, 31 subjects (20 patients with biopsy-proven MAFLD and 11 healthy volunteers) were included in this IRB-approved study. Subjects underwent MRI examinations twice within 40 days. 3.0 T DWI was acquired using a respiratory-triggered spin-echo diffusion-weighted echo-planar imaging sequence (b-values of 0, 10, 20, 30, 40, 50, 100, 200, 400, 800 s/mm2). DWI series were co-registered prior to voxel-wise non-linear regression of the IVIM model and voxels with poor fit quality were excluded (normalized root mean squared error ≥ 0.05). IVIM parameters (perfusion fraction, f; diffusion coefficient, D; and pseudo-diffusion coefficient, D*), and apparent diffusion coefficients (ADC) were computed from manual segmentation of the right liver lobe performed by two analysts on two MRI examinations. ResultsAll results are reported for f, D, D*, and ADC respectively. For inter-reader agreement on the first visit, ICC were of 0.985, 0.994, 0.986, and 0.993 respectively. For intra-reader agreement of analyst 1 assessed on both imaging examinations, ICC between visits were of 0.805, 0.759, 0.511, and 0.850 respectively. For inter-reader agreement on the first visit, mean bias and 95 % limits of agreement were (0.00 ± 0.03), (−0.01 ± 0.03) × 10−3 mm2/s, (0.70 ± 10.40) × 10−3 mm2/s, and (−0.02 ± 0.04) × 10−3 mm2/s respectively. For intra-reader agreement of analyst 1, mean bias and 95 % limits of agreement were (0.01 ± 0.09) × 10−3 mm2/s, (−0.01 ± 0.21) × 10−3 mm2/s, (−13.37 ± 56.19) × 10−3 mm2/s, and (−0.01 ± 0.16) × 10−3 mm2/s respectively. Except for parameter D* that was associated with between-subjects parameter variability (P = 0.009), there was no significant variability between subjects, examinations, or readers. ConclusionWith our approach, IVIM parameters f, D, D*, and ADC provided excellent inter-reader agreement and good to very good inter-visit or intra-reader agreement, thus showing the reproducibility of IVIM-DWI of the liver in MAFLD patients and volunteers.