Assessment of fitting methods and variability of IVIM parameters in muscles of the lumbar spine at rest

Intravoxel incoherent motion (IVIM) MRI provides insight into tissue diffusion and perfusion. Here, estimates of perfusion fraction (f), pseudo-diffusion coefficient (D*), and diffusion coefficient (D) obtained via different fitting methods are compared to ascertain (1) the optimal analysis strategy for muscles of the lumbar spine and (2) repeatability of IVIM parameters in skeletal muscle at rest. Diffusion-weighted images were acquired in the lumbar spine at rest in 15 healthy participants. Data were fit to the bi-exponential IVIM model to estimate f, D* and D using three variably segmented approaches based on non-linear least squares fitting, and a Bayesian fitting method. Assuming that perfusion and diffusion are temporally stable in skeletal muscle at rest, and spatially uniform within a spinal segment, the optimal analysis strategy was determined as the approach with the lowest temporal or spatial variation and smallest residual between measured and fit data. Inter-session repeatability of IVIM parameters was evaluated in a subset of 11 people. Finally, simulated IVIM signal at varying signal to noise ratio were evaluated to understand precision and bias. Experimental results showed that IVIM parameter values differed depending on the fitting method. A three-step non-linear least squares fitting approach, where D, f, and D* were estimated sequentially, generally yielded the lowest spatial and temporal variation. Solving all parameters simultaneously yielded the lowest residual between measured and fit data, however there was substantial spatial and temporal variability. Results obtained by Bayesian fitting had high spatial and temporal variability in addition to a large residual between measured and fit data. Simulations showed that all fitting methods can fit the IVIM data at signal to noise ratios >35, and that D* was the most challenging to accurately obtain. Overall, this study motivates use of a three-step non-linear least squares fitting strategy to quantify IVIM parameters in skeletal muscle.