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), and extracellular tortuosity (λ), and changes in membrane permeability (P). 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/mm, respectively.

RESULTS

The diffusivity measures (apparent diffusion coefficients (ADC), D of the gamma distribution model and D of the diffusional kurtosis model) decreased with increases in cell density and λ, and a decrease in P. These diffusivity measures increased with increases in nuclear volume and VF. The diffusion heterogeneity measures (σ of the gamma distribution model and K of the diffusional kurtosis model) increased with increases in cell density or nuclear volume at the low P, and a decrease in P. Increased σ was also associated with an increase in VF.

CONCLUSION

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