The relationship between diffusion heterogeneity and microstructural changes in high-grade gliomas using Monte Carlo simulations

Abstract

Purpose: Diffusion-weighted imaging (DWI) may aid accurate tumor grading. Decreased diffusivity and increased diffusion heterogeneity measures have been observed in high-grade gliomas using the non-monoexponential models for DWI. However, DWI measures concerning tissue characteristics in terms of pathophysiological and structural changes are yet to be established. Thus, this study aims to investigate the relationship between the diffusion measurements and microstructural changes in the presence of high-grade gliomas using a three-dimensional Monte Carlo simulation with systematic changes of microstructural parameters.

Methods: Water diffusion was simulated in a microenvironment along with changes associated with the presence of high-grade gliomas, including increases in cell density, nuclear volume, extracellular volume (VF_ex), and extracellular tortuosity (λ_ex), and changes in membrane permeability (P_mem). DWI signals were simulated using a pulsed gradient spin-echo sequence. The sequence parameters, including the maximum gradient strength and diffusion time, were set to be comparable to those of clinical scanners and advanced human MRI systems. The DWI signals were fitted using the gamma distribution and diffusional kurtosis models with b-values up to 6000 and 2500 s/mm², respectively.

Results: The diffusivity measures (apparent diffusion coefficients (ADC), D_gamma of the gamma distribution model and D_app of the diffusional kurtosis model) decreased with increases in cell density and λ_ex, and a decrease in P_mem. These diffusivity measures increased with increases in nuclear volume and VF_ex. The diffusion heterogeneity measures (σ_gamma of the gamma distribution model and K_app of the diffusional kurtosis model) increased with increases in cell density or nuclear volume at the low P_mem, and a decrease in P_mem. Increased σ_gamma was also associated with an increase in VF_ex.

Conclusion: Among simulated microstructural changes, only increases in cell density at low P_mem or decreases in P_mem corresponded to both the decreased diffusivity and increased diffusion heterogeneity measures. The results suggest that increases in cell density at low P_mem or decreases in P_mem may be associated with the diffusion changes observed in high-grade gliomas.

Keywords: Diffusion; Diffusivity; Gamma; Gliomas; Heterogeneity; Kurtosis; MRI; Simulation.