Introduction

Restriction spectrum imaging (RSI) is a novel advanced diffusion-based technique, which has been used to image prostate cancer (PCa) in a few small studies (1-3). Some of the purported advantages over conventional diffusion-weighted imaging (DWI) include: less spatial distortion, superior tumor contrast-to-noise, and the ability to obtain a normalized in vivo measure of tumor cellularity (4), however, this technique has not yet been widely validated. The purpose of this study was to investigate the utility of RSI for prediction of PCa aggressiveness in men undergoing magnetic resonance (MR)-ultrasound (US) fusion biopsy (FB).

Methods

106 consecutive men enrolled in an institutional review board-approved National Cancer Institute-funded prospective clinical trial (PAIREDCaP) underwent pre-biopsy 3.0 T multiparametric (mp) MRI, which included multiplanar T2-weighted imaging (T2WI), conventional diffusion-weighted imaging (DWI), dynamic contrast enhancement (DCE) and RSI. RSI was performed using spin-echo echoplanar imaging with b values of 0, 250, 750, and 2000 s/mm2 with 6, 6 and 15 directions at each nonzero b value. RSI cellularity maps were derived using the signal fraction of the registered isotropic component of the diffusion spectrum and overlaid on axial T2WI, as has been described previously (5). Cellularity maps were constructed using data from all b values, which were standardized across all patients to obtain z score maps. RSI z score maps were calculated by measuring the mean and standard deviation of normal prostate signal from the raw RSI cellularity data (measured in the same zone, ipsilateral to the lesion in an area determined to be normal on MRI and on sextant biopsy) subtracting the measured mean value from each subject’s cellularity map, and dividing the result by the standard deviation of the measured normal prostate. The reference standard in all cases was MR-US FB, which included 12-core systematic biopsy and targeted biopsy (2-4 cores) through each lesion with a PI-RADSv2 assessment category > 3. Clinical and imaging features were compared among men with and without clinically significant (cs) PCa (Gleason > 3 + 4). Multivariate logistic regression was performed to determine significant predictors of csPCa.

Results

57/106 men (54%) had csPCa on FB. Mean age was significantly higher in men with csPCa compared to those without (65.9 + 6.2 years versus 64.2 + 7.0 years, P = 0.001). Median PSA density was significantly higher among men with csPCa (0.18 ng/mL2 versus 0.10 ng/mL2, P < 0.0001). PI-RADSv2 assessment category was significantly higher among men with csPCa, P < 0.0001. Median apparent diffusion coefficient was significantly lower among men with csPCa (798 versus 978, P < 0.0001), and median RSI z score was significantly higher among men with csPCa (3.3 versus 1.4, P = 0.0002). On multivariate logistic regression, controlling for PI-RADSv2 assessment category, an RSI z score > 3 had an odds ratio of 2.31 for Gleason > 3 + 4, with a trend toward statistical significance, P = 0.06.

Discussion

DWI has consistently been shown to be useful for PCa detection and characterization at mpMRI (6-8), but it is subject to significant distortion from B0 magnetic field inhomogeneities, such as occur in the presence of rectal gas or hemorrhage. Another limitation of DWI is that the ADC cannot be standardized across different imaging platforms. RSI z score, on the other hand, inherently normalizes across the population studied and thus could serve as a more useful imaging biomarker for comparison across different scanners and institutions. Our results show a statistically significant difference between RSI z scores among patients with and without csPCa. Additionally, on multivariate logistic regression there was a trend toward significance for prediction of csPCa, when controlling for PI-RADSv2 assessment category, with an odds ratio of 2.3 for an RSI z score >3.

Conclusion

RSI z score is significantly associated with csPCa and may hold promise as a more reproducible metric of diffusion restriction compared to ADC. Future studies are needed to validate these preliminary findings.

Acknowledgements

No acknowledgement found.

References

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