Redefining the biophysical basis of contrast in diffusion-weighted MRI of the prostate

Purpose: The study investigates the hypothesis that the clinically observed decrease in ADC with increasing prostate cancer Gleason grade can be attributed to an increasing volume of low diffusivity epithelial cells, and corresponding decreasing volumes of higher diffusivity stroma and lumen space, rather than increased cell density. Methods: Whole human prostates and tissue cores were imaged post radical prostatectomy on 9.4T and 16.4T Bruker MRI systems respectively. Digital histology images were analysed andDWI measurements were correlated with regions of interest in the prostate specimens. The morphometric measured volumes and diffusivities of these distinct tissue components were used to predict ADC. Results: There was a stronger correlationof Gleason pattern with gland component volumes (n=553) of epithelium (ρ=0.898), stroma (ρ=-0.651), and lumen (ρ=-0.912), than with cellularity metrics (n=288) nuclear area (ρ=0.422) or count (ρ=0.081). There was a stronger correlation between measured ADC and epithelium (r=0.688) and lumen volume (r=-0.647), than between measured ADC and nuclear count (r =-0.598) or area (r=-0.569) (n=57). The differences between cancer and normal tissue, and correlations with pathology are stronger, for the gland component volumes than for the cellularity metrics. ADC predicted (n=118) showed the strongest correlation (r=0.935) with measured ADC and follows the trends seen clinically. Conclusion: Differences in the gland compartment volumes of prostate tissue having distinct diffusivities, rather than changes in the conventionally cited ‘cellularity’ metrics, are the major contributor to clinically observed variations of ADC in prostate tissue. The findings affect the interpretation of prostate DWI in terms of tissue structure and indicate a closer relationship between diffusion contrast and the histopathologic features of cancer than previously assumed