Novel Application of T1ρ Magnetic Resonance Imaging for Noninvasive Assessment of Bladder Hyperpermeability Biomarkers: A Focus on Glycosaminoglycan Content.

Abstract

Purpose: Bladder wall hyperpermeability due to glycosaminoglycan depletion is implicated in interstitial cystitis/bladder pain syndrome pathogenesis. This study sought to validate T1ρ MRI as a noninvasive imaging sequence for assessing bladder wall hyperpermeability biomarkers, with a focus on bladder glycosaminoglycan content, in protamine sulfate-induced models of interstitial cystitis/bladder pain syndrome.

Materials and methods: Rat bladders (n = 8) treated with saline (control), protamine sulfate, pentosan polysulfate, or protamine sulfate + pentosan polysulfate (rescue) were imaged in situ using T1ρ 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 (n = 12) were similarly imaged before and after protamine sulfate treatment, and post-imaging glycosaminoglycan analysis was performed. Data were compared between groups using one-way ANOVA or paired Student t-test. T1ρ relaxivity was correlated with chemically measured glycosaminoglycan content using linear regression.

Results: Protamine sulfate-treated rat bladders had decreased glycosaminoglycans and higher T1ρ relaxivity relative to controls. Pentosan polysulfate also decreased glycosaminoglycans versus controls and did not mitigate protamine-mediated glycosaminoglycan depletion. Importantly, T1ρ relaxivity correlated with chemical glycosaminoglycan quantification (chondroitin sulfate: r = 0.86, p < 0.01; heparan sulfate r = 0.80, p = 0.02). In human biopsies, T1ρ relaxivity increased after protamine sulfate treatment versus baseline (154.2 ± 5.9 vs. 131.0 ± 4.4 ms, p < 0.001), consistent with decreased glycosaminoglycans, while chemical analyses failed to capture statistically significant changes in bladder glycosaminoglycans.

Conclusions: T1ρ MRI accurately measured glycosaminoglycans in rat bladders and differentiated protamine sulfate-treated bladder biopsies from unperturbed specimens in humans. T1ρ MRI warrants further investigation as a novel biomarker of bladder glycosaminoglycan content in interstitial cystitis/bladder pain syndrome.