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Restriction Spectrum Imaging (RSI) addresses these limitations with a multi-compartment biophysical model that separates the diffusion signal into four compartments, providing a more specific quantitative imaging biomarker, the Restriction Spectrum Imaging restriction score (RSIrs). Although RSIrs has demonstrated promising detection performance for csPCa, patient- and acquisition-related factors may influence its measured values and performance. Our retrospective analysis included 1,890 men (median age 70) from seven centers between 2018 and 2024. Our primary objective was to characterize the quantitative technical robustness of RSIrs using linear modeling. We assessed how age, race, ethnicity, prostate volume, medication use, and MRI acquisition parameters influenced prostate maximum RSIrs (RSIrs\n                    <jats:sub>max<\/jats:sub>\n                    ) values. Secondary, we conducted a functional validation of RSIrs\u2019 csPCa detection performance when accounting for any significant effects (if any). Non-csPCa patients in this analysis were (1) with confirmed benign or Grade Group 1 findings on biopsy or (2) with a non-suspicious mpMRI (PI-RADS 1 or 2) and a prostate-specific antigen density (PSAD)\u2009\u2264\u20090.15. Results revealed modest effects from age (1.8\/year increase), prostate volume (-0.83\/mL decrease), and acquisition methods (varying between \u2212\u200963.14 to +\u200956.23). While these acquisition- and patient-level variations partially overlapped with change in RSIrs\n                    <jats:sub>max<\/jats:sub>\n                    due to Grade Group 2 csPCa, these variations were secondary to the primary signal variation due to csPCa. Adjusting for them did not improve csPCa detection performance (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&gt;\u20090.05). AUC of RSIrs\n                    <jats:sub>max<\/jats:sub>\n                    for patient-level csPCa detection was 0.77 [95% CI: 0.75\u20130.79] compared to 0.74 [0.72\u20130.76] after. RSIrs demonstrates robust csPCa detection performance regardless of modest signal variations from patient and acquisition factors, supporting its potential as a generalizable quantitative imaging biomarker for csPCa.\n                  <\/jats:p>","DOI":"10.1186\/s40644-026-01032-w","type":"journal-article","created":{"date-parts":[[2026,4,16]],"date-time":"2026-04-16T09:39:34Z","timestamp":1776332374000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Systematic effects of patient factors and scanner\/protocol factors on a Restriction Spectrum Imaging (RSI) quantitative MRI biomarker for prostate cancer"],"prefix":"10.1186","volume":"26","author":[{"given":"Deondre D.","family":"Do","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariluz Rojo","family":"Domingo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher C.","family":"Conlin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ian","family":"Matthews","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karoline","family":"Kallis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Madison T.","family":"Baxter","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Courtney","family":"Ollison","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuze","family":"Song","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Allison Y.","family":"Zhong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aditya","family":"Bagrodia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tristan","family":"Barrett","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew","family":"Cooperberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Felix","family":"Feng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael E.","family":"Hahn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mukesh","family":"Harisinghani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gary M.","family":"Hollenberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan","family":"Javier-Desloges","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sophia C.","family":"Kamran","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher J.","family":"Kane","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dimitri","family":"Kessler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joshua","family":"Kuperman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kang-Lung","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan","family":"Levine","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael A.","family":"Liss","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel J. 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JAMA Netw Open. 2024;7(3):e244258.","DOI":"10.1001\/jamanetworkopen.2024.4258"}],"container-title":["Cancer Imaging"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s40644-026-01032-w","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s40644-026-01032-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s40644-026-01032-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T22:10:42Z","timestamp":1781647842000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1186\/s40644-026-01032-w"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,16]]},"references-count":39,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["1032"],"URL":"https:\/\/doi.org\/10.1186\/s40644-026-01032-w","relation":{"references":[{"id-type":"doi","id":"10.1016\/j.eururo.2019.02.033","asserted-by":"subject"}]},"ISSN":["1470-7330"],"issn-type":[{"value":"1470-7330","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,16]]},"assertion":[{"value":"31 December 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"30 March 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"16 April 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Participating institutions received approval from their respective institutional review boards (IRBs). Prospectively gathered data from UTHSCSA and Cambridge were collected with written informed consent from participants, while the remaining institutions obtained a consent waiver from their IRBs for retrospective use of clinical records.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Tyler M. Seibert. reports honoraria from CorTechs Labs, Varian Medical Systems, WebMD, GE Healthcare, and Janssen; has an equity interest in CorTechs Labs, Inc, and serves on its scientific advisory board; and 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. Michael E. Hahn reports honoraria from Multimodal Imaging Services Corporation and research funding from GE Healthcare. Anders M. Dale. is a founder of and holds equity in CorTechs Labs, Inc, and serves on its scientific advisory board; he also is a member of the scientific advisory board of Human Longevity, Inc, and receives funding through research agreements with GE Healthcare. Rebecca Rakow-Penner Human Longevity Inc: Consultant, Cortech Labs: Stock options, Curemetrix: Stock options, consultant Imagine Scientific, advisory board. SBIR GE Healthcare, research agreement Bayer consultant. Michael Liss Founder\/President of Oncobiomix with no relation to this manuscript. Research reported in this publication was supported by the National Cancer Institute of the National Institutes of Health under Award Number R01CA279667. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Sean Woolen Research grants paid to institution from Siemens Healthineers and General Electric. All other authors do not have any competing interests.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"70"}}