Stefanie Hectors^{1}, Sahar Semaan^{1}, Christopher Song^{1}, Ashutosh Tewari^{2}, George K Haines^{3}, and Bachir Taouli^{1}

In this study, we correlated advanced DWI
[diffusion kurtosis imaging (DKI), stretched-exponential (SE) DWI and diffusion
tensor imaging DTI)] parameters with fractional tissue fractions of nuclei,
cytoplasm, cells, stroma and lumen and the nuclear-cytoplasmic ratio in
prostate cancer (PCa) lesions. We found that all assessed diffusion methods
showed significant correlations with cytoplasmic, cellular and/or stromal
tissue fractions. Specifically, DKI seems promising for characterization of PCa
tissue composition, since multiple significant correlations between histology
parameters and both ADC_{DKI} and kurtosis parameter K were observed.

*MRI acquisition and analysis*

24 patients (mean age 63 y, range 53 – 76 y) with PCa who underwent prostate MRI including high b-value DWI and DTI at 3.0T (Siemens Skyra) before undergoing prostatectomy (within 2 – 102 days) were included in this prospective IRB-approved study. Trace-weighted DWI was performed using axial SS-EPI DWI with b-values 50, 1000, 1600 and 2000 s/mm^{2} (TR/TE 8700/72 ms, matrix 114x114, FOV 250x250 mm^{2}, slice thickness 3 mm, 39 slices). DTI was performed using SS-EPI with 6 different diffusion directions and b 100 and 600 s/mm^{2} (TR/TE 4500/60 ms, matrix 114x114, FOV 250x250 mm^{2}, slice thickness 4 mm, 30 slices). DKI [ADC_{DKI} and kurtosis parameter K] and SE [ADC_{SE} and anomalous exponent α] parameter maps were constructed from the high b-value DWI data. A monoexponential fit was performed to determine ADC_{ME} (conventional ADC). DTI (ADC_{DTI} and FA) parameter maps were generated by the scanner. Regions of interest were drawn in healthy peripheral zone (PZ) tissue and in the index PCa lesion.

*Histopathology*

For each index PCa lesion, an H&E-stained section was available. Using semi-automated segmentation (Positive Pixel Count in ImageScope; Aperio Technologies)^{4}, nuclear, cytoplasmic, cellular (nucleus + cytoplasm), stromal and luminal tumor tissue fractions and nuclear-cytoplasmic ratios (N/C=nuclear/cytoplasmic fraction) were derived (**Figure 1**). Gleason score (GS) and pathology stage were retrieved from the pathology report.

*Statistics*

Differences in diffusion parameters between PZ and PCa lesions were tested using Wilcoxon signed-rank tests. Differences in DWI parameters between GS≤7 and GS>7 and between pathology stage pT2 and pT3 were tested using Mann-Whitney U tests. Spearman correlation analysis was performed to assess the correlation between PCa diffusion parameter values and histological measurements. In addition, correlation between histology and combinations of parameters was assessed using multiple linear regression.

**Discussion and Conclusions**

^{1} Li L, Margolis DJ, Deng M et al. Correlation of Gleason Scores with Magnetic Resonance Diffusion Tensor Imaging in Peripheral Zone Prostate Cancer. J Magn Reson Imaging 2015;42:460–467.

^{2} Rosenkrantz AB, Padhani AR, Chenevert TL et al. Body Diffusion Kurtosis Imaging: Basic Principles, Applications, and Considerations for Clinical Practice. J Magn Reson Imaging 2015;42(5):1190-202

^{3} Toivonen J, Merisaari H, Pesola M et al. Mathematical models for diffusion-weighted imaging of prostate cancer using b values up to 2000 s/mm(2) : correlation with Gleason score and repeatability of region of interest analysis. Magn Reson Med. 2015;74(4):1116-24.

^{4} Langer DL, van der Kwast TH, Evans AJ et al. Prostate tissue composition and MR measurements: investigating the relationships between ADC, T2, Ktrans, ve, and corresponding histologic features. Radiology. 2010;255(2):485-94.

^{5} Lawrence EM, Warren AY, Priest AN, Barrett T, Goldman DA, Gill AB, Gnanapragasam VJ, Sala E, Gallagher FA. Evaluating Prostate Cancer Using Fractional Tissue Composition of Radical Prostatectomy Specimens and Pre-Operative Diffusional Kurtosis Magnetic Resonance Imaging. PLoS One. 2016;28:11(7):e0159652.