Multicenter Study

. 2025 Sep;214(3):259-271.

doi: 10.1097/JU.0000000000004611. Epub 2025 May 16.

Restriction Spectrum Imaging as a Quantitative Biomarker for Prostate Cancer With Reliable Positive Predictive Value

Mariluz Rojo Domingo^{1

2}, Deondre D Do^{1

2}, Christopher C Conlin³, Aditya Bagrodia⁴, Tristan Barrett⁵, Madison T Baxter², Matthew Cooperberg⁶, Felix Feng⁷, Michael E Hahn³, Mukesh Harisinghani⁸, Gary Hollenberg⁹, Juan Javier-Desloges⁴, Karoline Kallis², Sophia Kamran¹⁰, Christopher J Kane⁴, Dimitri Kessler⁵, Joshua Kuperman², Kang-Lung Lee⁵, Jonathan Levine⁶, Michael A Liss¹¹, Daniel J A Margolis¹², Ian Matthews², Paul M Murphy³, Nabih Nakrour⁸, Michael Ohliger¹³, Courtney Ollison², Thomas Osinski¹⁴, Anthony James Pamatmat¹⁴, Isabella R Pompa⁸, Rebecca Rakow-Penner³, Jacob L Roberts⁴, Ahmed S Shabaik¹⁵, Yuze Song^{2

16}, David Song¹⁴, Clare M Tempany⁸, Shaun Trecarten¹¹, Natasha Wehrli¹², Eric P Weinberg⁹, Sean Woolen¹³, George Xu², Allison Y Zhong², Anders M Dale^{3

17

18}, Tyler M Seibert^{1

2

3

4}

Affiliations

¹ Department of Bioengineering, University of California San Diego, La Jolla, California.
² Department of Radiation Medicine, University of California San Diego, La Jolla, California.
³ Department of Radiology, University of California San Diego, La Jolla, California.
⁴ Department of Urology, University of California San Diego, La Jolla, California.
⁵ Department of Radiology, University of Cambridge, Cambridge, United Kingdom.
⁶ Department of Urology, University of California San Francisco, San Francisco, California.
⁷ Department of Radiation Oncology, University of California San Francisco, San Francisco, California.
⁸ Department of Radiology, Massachusetts General Hospital, Boston, Massachusetts.
⁹ Department of Clinical Imaging Sciences, University of Rochester Medical Center, Rochester, New York.
¹⁰ Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts.
¹¹ Department of Urology, University of Texas Health Sciences Center San Antonio, San Antonio, Texas.
¹² Department of Radiology, Weill Cornell Medicine, New York, New York.
¹³ Department of Radiology and Biomedical Imaging, University of California San Francisco, San Francisco, California.
¹⁴ Department of Urology, University of Rochester Medical Center, Rochester, New York.
¹⁵ Department of Pathology, University of California San Diego, La Jolla, California.
¹⁶ Department of Electrical and Computer Engineering, University of California San Diego, La Jolla, California.
¹⁷ Department of Neurosciences, University of California San Diego, La Jolla, California.
¹⁸ Halıcıoğlu Data Science Institute, University of California San Diego, La Jolla, California.

PMID: 40377262
PMCID: PMC12334330 (available on 2026-05-16)
DOI: 10.1097/JU.0000000000004611

Multicenter Study

Restriction Spectrum Imaging as a Quantitative Biomarker for Prostate Cancer With Reliable Positive Predictive Value

Mariluz Rojo Domingo et al. J Urol. 2025 Sep.

. 2025 Sep;214(3):259-271.

doi: 10.1097/JU.0000000000004611. Epub 2025 May 16.

Authors

Affiliations

¹ Department of Bioengineering, University of California San Diego, La Jolla, California.
² Department of Radiation Medicine, University of California San Diego, La Jolla, California.
³ Department of Radiology, University of California San Diego, La Jolla, California.
⁴ Department of Urology, University of California San Diego, La Jolla, California.
⁵ Department of Radiology, University of Cambridge, Cambridge, United Kingdom.
⁶ Department of Urology, University of California San Francisco, San Francisco, California.
⁷ Department of Radiation Oncology, University of California San Francisco, San Francisco, California.
⁸ Department of Radiology, Massachusetts General Hospital, Boston, Massachusetts.
⁹ Department of Clinical Imaging Sciences, University of Rochester Medical Center, Rochester, New York.
¹⁰ Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts.
¹¹ Department of Urology, University of Texas Health Sciences Center San Antonio, San Antonio, Texas.
¹² Department of Radiology, Weill Cornell Medicine, New York, New York.
¹³ Department of Radiology and Biomedical Imaging, University of California San Francisco, San Francisco, California.
¹⁴ Department of Urology, University of Rochester Medical Center, Rochester, New York.
¹⁵ Department of Pathology, University of California San Diego, La Jolla, California.
¹⁶ Department of Electrical and Computer Engineering, University of California San Diego, La Jolla, California.
¹⁷ Department of Neurosciences, University of California San Diego, La Jolla, California.
¹⁸ Halıcıoğlu Data Science Institute, University of California San Diego, La Jolla, California.

PMID: 40377262
PMCID: PMC12334330 (available on 2026-05-16)
DOI: 10.1097/JU.0000000000004611

Abstract

Purpose: The positive predictive value of the Prostate Imaging Reporting and Data System (PI-RADS) for clinically significant prostate cancer (csPCa, grade group [GG] ≥2) varies widely between radiologists. The restriction spectrum imaging restriction score (RSIrs) is a biophysics-based metric derived from diffusion MRI that could be an objectively interpretable biomarker for csPCa. We aimed to evaluate performance of RSIrs for patient-level detection of csPCa in a large and heterogenous dataset, and to combine RSIrs with clinical and imaging parameters for csPCa detection.

Materials and methods: At 7 centers, participants underwent prostate MRI between January 2016 and March 2024. We calculated patient-level csPCa probability based on maximum RSIrs in the prostate and compared patient-level csPCa detection to apparent diffusion coefficient (ADC) and PI-RADS using AUC. We also evaluated csPCa discrimination by GG and combining RSIrs with clinical risk factors through multivariable regression.

Results: Among patients who met the inclusion criteria (n = 1892), probability of csPCa increased with higher RSIrs. Among biopsy-naïve patients (n = 877), AUCs for GG ≥ 2 vs non-csPCa were RSIrs = 0.73 (0.69-0.76), ADC = 0.54 (0.50-0.57), and PI-RADS = 0.75 (0.71-0.78). RSIrs significantly outperformed ADC (P < .01) and was comparable with PI-RADS (P = .31). RSIrs and PI-RADS combined outperformed either alone. The model with RSIrs, PI-RADS, age, and PSA density achieved the best discrimination of csPCa.

Conclusions: RSIrs is an accurate and reliable quantitative biomarker that performs better than conventional ADC and comparably with expert-defined PI-RADS for patient-level detection of csPCa. RSIrs provides objective estimates of probability of csPCa that do not require radiology expertise.

Keywords: diffusion-weighted imaging; prostate MRI; prostate cancer detection; quantitative biomarker; restriction spectrum imaging.

PubMed Disclaimer

Conflict of interest statement

Tyler M. Seibert reports honoraria from CorTechs Labs, Varian Medical Systems, WebMD, GE Healthcare, and Janssen. TMS has an equity interest in CorTechs Labs, Inc, and serves on its scientific advisory board. TMS has received in-kind research support from GE Healthcare via a research agreement with the University of California, San Diego. These companies might potentially benefit from the research results. The terms of these arrangements have been reviewed and approved by the University of California, San Diego in accordance with its conflict-of-interest policies. Anders M. Dale is a founder of and holds equity in CorTechs Labs, Inc, and serves on its scientific advisory board. AMD is a member of the scientific advisory board of Human Longevity, Inc, and receives funding through research agreements with GE Healthcare. Rebecca Rakow-Penner is a consultant of Human Longevity Inc. RRP has stock options at Cortech Labs and Curemetrix. RRP is a consultant of Curemetrix and is in the advisory board of Imagine Scientific. RRP has a research agreement with SBIR GE Healthcare and is a Bayer consultant. Michael E. Hahn reports honoraria from Multimodal Imaging Services Corporation and research funding from GE Healthcare. Michael A. Liss is the Founder/President of Oncobiomix, with no relation to this manuscript. MAL discloses that research reported in this publication was supported by the National Cancer Institute of the National Institutes of Health under Award Number R01CA279667 and that the manuscript’s content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. The spouse of Sophia C Kamran is employed by Sanof. Sean A Woolen was supported by funding from the ARRS Scholarship for professional development and has received investigator-initiated research grants from Siemens Healthineers and General Electric. Daniel JA Margolis reports a clinical advisor role for Stratagen Bio and an ad hoc consultant role for Guerbet and Promaxo.

Comment in

Editorial Comment.
Waggener K, Snipes M, Rais-Bahrami S. Waggener K, et al. J Urol. 2025 Sep;214(3):268-269. doi: 10.1097/JU.0000000000004620. Epub 2025 Jun 4. J Urol. 2025. PMID: 40464320 No abstract available.
Editorial Comment.
Lewicki P, Borza T. Lewicki P, et al. J Urol. 2025 Sep;214(3):269-270. doi: 10.1097/JU.0000000000004621. Epub 2025 Jun 4. J Urol. 2025. PMID: 40464329 No abstract available.

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Restriction Spectrum Imaging as a Quantitative Biomarker for Prostate Cancer With Reliable Positive Predictive Value

Affiliations

Restriction Spectrum Imaging as a Quantitative Biomarker for Prostate Cancer With Reliable Positive Predictive Value

Authors

Affiliations

Abstract

Conflict of interest statement

Comment in

References

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