Varying diffusion time to discriminate between simulated skeletal muscle injury models using stimulated echo diffusion tensor imaging

Purpose: Evaluate the relationship between muscle microstructure, diffusion time (Delta), and the diffusion tensor (DT) to identify the optimal Delta where changes in muscle fiber size may be detected. Methods: The DT was simulated in models with histology informed geometry over a range of Delta with a stimulated echo DT imaging (DTI) sequence using the numerical simulation application DifSim. The difference in the DT at each Delta between healthy and injured skeletal muscle models was calculated, to identify the optimal Delta at which changes in muscle fiber size may be detected. The random permeable barrier model (RPBM) was used to estimate muscle microstructure from the simulated DT measurements, which were compared to the ground truth. Results: Across all models, fractional anisotropy provided greater contrast between injured and control models than diffusivity measurements. Compared to control models, in atrophic injury models, the greatest difference in the DT was found between 90 ms and 250 ms. In models with acute edema, the contrast between injured and control muscle increased with increasing diffusion time, although these models had smaller mean fiber areas. RPBM systematically underestimated fiber size but accurately estimated surface area-to-volume ratio of simulated models. Conclusion: These findings may better inform pulse sequence parameter selection when performing DTI experiments in vivo. If only a single diffusion experiment can be performed, the selected Delta should be similar to 170 ms to maximize the ability to discriminate between different injury models. Ideally several diffusion times between 90 ms and 500 ms should he sampled in order to maximize diffusion contrast, particularly when the disease process is unknown.