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

Area of Science:

• Medical Imaging
• Biophysics
• Oncology

Background:

• Diffusion-weighted imaging (DWI) shows promise for accurate tumor grading.
• High-grade gliomas exhibit decreased diffusivity and increased diffusion heterogeneity on DWI using non-monoexponential models.
• The precise tissue characteristics underlying these DWI changes in gliomas remain to be fully established.

Purpose of the Study:

• To investigate the relationship between diffusion measurements and microstructural changes in high-grade gliomas.
• To utilize a three-dimensional Monte Carlo simulation to model these relationships.
• To systematically alter microstructural parameters to understand their impact on DWI signals.

Main Methods:

• Simulated water diffusion in a microenvironment mimicking high-grade glioma conditions.
• Varied parameters including cell density, nuclear volume, extracellular volume (VF_ex), extracellular tortuosity (λ_ex), and membrane permeability (P_mem).
• Analyzed DWI signals using gamma distribution and diffusional kurtosis models with parameters comparable to clinical MRI scanners.

Main Results:

• Diffusivity measures decreased with increased cell density and λ_ex, and decreased P_mem.
• Diffusivity measures increased with increased nuclear volume and VF_ex.
• Diffusion heterogeneity increased with cell density or nuclear volume at low P_mem, and with decreased P_mem; increased heterogeneity also correlated with increased VF_ex.

Conclusions:

• Increased cell density at low membrane permeability or decreased membrane permeability were the only simulated microstructural changes correlating with both decreased diffusivity and increased diffusion heterogeneity.
• These findings suggest that elevated cell density and/or reduced membrane permeability may underlie the diffusion changes observed in high-grade gliomas.