Connecting macroscopic diffusion metrics of cardiac diffusion tensor imaging and microscopic myocardial structures based on simulation.

To investigate the relationship between microscopic myocardial structures and macroscopic measurements of diffusion tensor imaging (DTI), we proposed a cardiac DTI simulation method using the Bloch equation and the Monte Carlo random walk in a realistic myocardium model reconstructed from polarized light imaging (PLI) data of the entire human heart. To obtain a realistic simulation, with the constraints of prior knowledge pertaining to the maturational change of the myocardium structure, appropriate microstructure modeling parameters were iteratively determined by matching DTI simulations and real acquisitions of the same hearts in terms of helix angle, fractional anisotropy (FA) and mean diffusivity (MD) maps. Once a realistic simulation was obtained, we varied the extra-cellular volume (ECV) ratio, myocyte orientation heterogeneity and myocyte size, and explored the effects of microscopic changes in tissue structure on macroscopic diffusion metrics. The experimental results demonstrated the feasibility of simulating the DTI of the whole heart using PLI measurements. When varying ECV from 15% to 55%, mean FA decreased from 0.55 to 0.26, axial diffusivity increased by 0.6 μm/ms, and radial diffusivity increased by 0.7 μm/ms. When orientation heterogeneity was varied from 0 to 20, mean FA decreased from 0.4 to 0.3, axial diffusivity decreased by 0.08 μm/ms, and radial diffusivity increased by 0.03 μm/ms. When mean diameter of myocytes was varied from 6 μm to 10 μm, FA decreased from 0.67 to 0.46, axial and radial diffusivities increased by 0.05 and 0.2 μm/ms, respectively.