The effect of noise and lipid signals on determination of Gaussian and non-Gaussian diffusion parameters in skeletal muscle

This work characterizes the effect of lipid and noise signals on muscle diffusion parameter estimation in several conventional and non-Gaussian models, the ultimate objectives being to characterize popular fat suppression approaches for human muscle diffusion studies, to provide simulations to inform experimental work and to report normative non-Gaussian parameter values. The models investigated in this work were the Gaussian monoexponential and intravoxel incoherent motion (IVIM) models, and the non-Gaussian kurtosis and stretched exponential models. These were evaluated via simulations, and in vitro and in vivo experiments. Simulations were performed using literature input values, modeling fat contamination as an additive baseline to data, whereas phantom studies used a phantom containing aliphatic and olefinic fats and muscle-like gel. Human imaging was performed in the hamstring muscles of 10 volunteers. Diffusion-weighted imaging was applied with spectral attenuated inversion recovery (SPAIR), slice-select gradient reversal and water-specific excitation fat suppression, alone and in combination. Measurement bias (accuracy) and dispersion (precision) were evaluated, together with intra- and inter-scan repeatability. Simulations indicated that noise in magnitude images resulted in <6% bias in diffusion coefficients and non-Gaussian parameters (α, K), whereas baseline fitting minimized fat bias for all models, except IVIM. In vivo, popular SPAIR fat suppression proved inadequate for accurate parameter estimation, producing non-physiological parameter estimates without baseline fitting and large biases when it was used. Combining all three fat suppression techniques and fitting data with a baseline offset gave the best results of all the methods studied for both Gaussian diffusion and, overall, for non-Gaussian diffusion. It produced consistent parameter estimates for all models, except IVIM, and highlighted non-Gaussian behavior perpendicular to muscle fibers (α ~ 0.95, K ~ 3.1). These results show that effective fat suppression is crucial for accurate measurement of non-Gaussian diffusion parameters, and will be an essential component of quantitative studies of human muscle quality.