Reproducibility of spatial penalty-based methodologies for intravoxel incoherent motion analysis with diffusion MRI

Objective was to assess the precision and reproducibility of spatial penalty-based intravoxel incoherent motion (IVIM) methods in comparison to the conventional bi-exponential (BE) model-based IVIM methods. IVIM-MRI (11 b-values; 0-800 s/mm²) of forty patients (N = 40; Age = 17.7 ± 5.9 years; Male:Female = 30:10) with biopsy-proven osteosarcoma were acquired on a 1.5 Tesla scanner at 3 time-points: (i) baseline, (ii) after 1-cycle and (iii) after 3-cycles of neoadjuvant chemotherapy. Diffusion coefficient (D), Perfusion coefficient (D*) and Perfusion fraction (f) were estimated at three time-points in whole tumor and healthy muscle tissue using five methodologies (1) BE with three-parameter-fitting (BE), (2) Segmented-BE with two-parameter-fitting (BESeg-2), (3) Segmented-BE with one-parameter-fitting (BESeg-1), (4) BE with adaptive Total-Variation-penalty (BE + TV) and (5) BE with adaptive Huber-penalty (BE + HPF). Within-subject coefficient-of-variation (wCV) and between-subject coefficient-of-variation (bCV) of IVIM parameters were measured in healthy and tumor tissue. For precision and reproducibility, intra-scan comparison of wCV and bCV among five IVIM methods were performed using Friedman test followed by Wilcoxon-signed-ranks (WSR) post-hoc test. Experimental results demonstrated that BE + TV and BE + HPF showed significantly (p < 10^-3) lower wCV and bCV for D (wCV: 24-32%; bCV: 22-31%) than BE method (wCV: 38-49%; bCV: 36-46%) across three time-points in healthy muscle and tumor. BE + TV and BE + HPF also demonstrated significantly (p < 10^-3) lower wCV and bCV for estimating D* (wCV: 89-108%; bCV: 83-102%) and f (wCV: 55-60%; bCV: 56-60%) than BE, BESeg-2 and BESeg-1 methods (D*-wCV: 102-122%; D*-bCV: 98-114% and f-wCV: 96-130%; f-bCV: 94-125%) in both tumor and healthy tissue across three time-points. Spatial penalty based IVIM analysis methods BE + TV and BE + HPF demonstrated lower variability and improved precision and reproducibility in the current clinical settings.