{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T09:17:40Z","timestamp":1785489460531,"version":"3.56.0"},"reference-count":39,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2025,5,4]],"date-time":"2025-05-04T00:00:00Z","timestamp":1746316800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Neurourology and Urodynamics"],"published-print":{"date-parts":[[2025,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>Purpose<\/jats:title><jats:p>Bladder wall hyperpermeability due to glycosaminoglycan depletion is implicated in interstitial cystitis\/bladder pain syndrome pathogenesis. This study sought to validate T1\u03c1 MRI as a noninvasive imaging sequence for assessing bladder wall hyperpermeability biomarkers, with a focus on bladder glycosaminoglycan content, in protamine sulfate\u2010induced models of interstitial cystitis\/bladder pain syndrome.<\/jats:p><\/jats:sec><jats:sec><jats:title>Materials and Methods<\/jats:title><jats:p>Rat bladders (<jats:italic>n<\/jats:italic>\u2009=\u20098) treated with saline (<jats:italic>control<\/jats:italic>), protamine sulfate, pentosan polysulfate, or protamine sulfate + pentosan polysulfate (<jats:italic>rescue<\/jats:italic>) were imaged in situ using T1\u03c1 and standard MRI sequences. Predominant bladder glycosaminoglycans, chondroitin and heparan sulfate, were measured in subsequently harvested rat bladders via aniline tagging coupled with mass spectrometry. Human bladder biopsies (<jats:italic>n<\/jats:italic>\u2009=\u200912) were similarly imaged before and after protamine sulfate treatment, and post\u2010imaging glycosaminoglycan analysis was performed. Data were compared between groups using one\u2010way ANOVA or paired Student <jats:italic>t<\/jats:italic>\u2010test. T1\u03c1 relaxivity was correlated with chemically measured glycosaminoglycan content using linear regression.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Protamine sulfate\u2010treated rat bladders had decreased glycosaminoglycans and higher T1\u03c1 relaxivity relative to controls. Pentosan polysulfate also decreased glycosaminoglycans versus controls and did not mitigate protamine\u2010mediated glycosaminoglycan depletion. Importantly, T1\u03c1 relaxivity correlated with chemical glycosaminoglycan quantification (chondroitin sulfate: <jats:italic>r<\/jats:italic>\u2009=\u20090.86, <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.01; heparan sulfate <jats:italic>r<\/jats:italic>\u2009=\u20090.80, <jats:italic>p<\/jats:italic>\u2009=\u20090.02). In human biopsies, T1\u03c1 relaxivity increased after protamine sulfate treatment versus baseline (154.2\u2009\u00b1\u20095.9 vs. 131.0\u2009\u00b1\u20094.4\u2009ms, <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001), consistent with decreased glycosaminoglycans, while chemical analyses failed to capture statistically significant changes in bladder glycosaminoglycans.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>T1\u03c1 MRI accurately measured glycosaminoglycans in rat bladders and differentiated protamine sulfate\u2010treated bladder biopsies from unperturbed specimens in humans. T1\u03c1 MRI warrants further investigation as a novel biomarker of bladder glycosaminoglycan content in interstitial cystitis\/bladder pain syndrome.<\/jats:p><\/jats:sec>","DOI":"10.1002\/nau.70058","type":"journal-article","created":{"date-parts":[[2025,5,5]],"date-time":"2025-05-05T05:58:23Z","timestamp":1746424703000},"page":"1081-1089","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Novel Application of T1\u03c1 Magnetic Resonance Imaging for Noninvasive Assessment of Bladder Hyperpermeability Biomarkers: A Focus on Glycosaminoglycan Content"],"prefix":"10.1002","volume":"44","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-9017-2490","authenticated-orcid":false,"given":"Julie A.","family":"Suyama","sequence":"first","affiliation":[{"name":"Department of Obstetrics, Gynecology &amp; Reproductive Sciences, Division of Urogynecology &amp; Reconstructive Pelvic Surgery University of California San Diego La Jolla California USA"},{"name":"Department of Urology University of California San Diego La Jolla California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sheronda M.","family":"Statum","sequence":"additional","affiliation":[{"name":"Department of Radiology University of California San Diego La Jolla California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aurea V. R.","family":"Mohana\u2010Borges","sequence":"additional","affiliation":[{"name":"Department of Radiology University of California San Diego La Jolla California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Cheng","sequence":"additional","affiliation":[{"name":"Department of Radiology University of California San Diego La Jolla California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yajun","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Radiology University of California San Diego La Jolla California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey D.","family":"Esko","sequence":"additional","affiliation":[{"name":"Department of Cellular and Molecular Medicine, Glycobiology Research and Training Center University of California San Diego La Jolla California 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