The impeded diffusion fraction quantitative imaging assay demonstrated in multi-exponential diffusion phantom and prostate cancer

Abstract

Purpose: To demonstrate a method for quantification of impeded diffusion fraction (IDF) using conventional clinical DWI protocols.

Methods: The IDF formalism is introduced to quantify contribution from water coordinated by macromolecules to DWI voxel signal based on fundamentally different diffusion constants in vascular capillary, bulk free, and coordinated water compartments. IDF accuracy was studied as a function of b-value set. The IDF scaling with restricted compartment size and polyvinylpirrolidone (PVP) macromolecule concentration was compared to conventional apparent diffusion coefficient (ADC) and isotropic kurtosis model parameters for a diffusion phantom. An in vivo application was demonstrated for six prostate cancer (PCa) cases with low and high grade lesions annotated from whole mount histopathology.

Results: IDF linearly scaled with known restricted (vesicular) compartment size and PVP concentration in phantoms and increased with histopathologic score in PCa (from median 9% for atrophy up to 60% for Gleason 7). IDF via non-linear fit was independent of b-value subset selected between b = 0.1 and 2 ms/µm² , including standard-of-care (SOC) PCa protocol. With maximum sensitivity for high grade PCa, the IDF threshold below 51% reduced false positive rate (FPR = 0/6) for low-grade PCa compared to apparent diffusion coefficient (ADC > 0.81 µm² /ms) of PIRADS PCa scoring (FPR = 3/6).

Conclusion: The proposed method may provide quantitative imaging assays of cancer grading using common SOC DWI protocols.

Keywords: clinical oncology DWI; collective coordinated diffusion; impeded diffusion fraction (IDF); macromolecular density; sub-cellular compartment.