Understanding diffusion-weighted MRI analysis: Repeatability and performance of diffusion models in a benign breast...

Diffusion-weighted MRI (DWI) is an important tool for oncology research, with great clinical potential for the classification and monitoring of breast lesions. The utility of parameters derived from DWI, however, is influenced by specific analysis choices. The purpose of this study was to critically evaluate repeatability and curve-fitting performance of common DWI signal representations, for a prospective cohort of patients with benign breast lesions. Twenty informed, consented patients with confirmed benign breast lesions underwent repeated DWI (3 T) using: sagittal single-shot spin-echo echo planar imaging, bipolar encoding, TR/TE: 11,600/86 ms, FOV: 180 x 180 mm, matrix: 90 x 90, slices: 60 x 2.5 mm, iPAT: GRAPPA 2, fat suppression, and 13 b-values: 0-700 s/mm² . A phase-reversed scan (b = 0 s/mm² ) was acquired for distortion correction. Voxel-wise repeat-measures coefficients of variation (CoVs) were derived for monoexponential (apparent diffusion coefficient [ADC]), biexponential (intravoxel incoherent motion: f, D, D*) and stretched exponential (α, DDC) across the parameter histograms for lesion regions of interest (ROIs). Goodness-of-fit for each representation was assessed by Bayesian information criterion. The volume of interest (VOI) definition was repeatable (CoV 13.9%). Within lesions, and across both visits and the cohort, there was no dominant best-fit model, with all representations giving the best fit for a fraction of the voxels. Diffusivity measures from the signal representations (ADC, D, DDC) all showed good repeatability (CoV < 10%), whereas parameters associated with pseudodiffusion (f, D*) performed poorly (CoV > 50%). The stretching exponent α was repeatable (CoV < 12%). This pattern of repeatability was consistent over the central part of the parameter percentiles. Assumptions often made in diffusion studies about analysis choices will influence the detectability of changes, potentially obscuring useful information. No single signal representation prevails within or across lesions, or across repeated visits; parameter robustness is therefore a critical consideration. Our results suggest that stretched exponential representation is more repeatable than biexponential, with pseudodiffusion parameters unlikely to provide clinically useful biomarkers.