Alexander Koven, Xiaolin He, Tianzhou Zhang, Shukai Huang, Monica Farcas, Eno Hysi, Darren A Yuen
Bladder remodelling in pBOO is spatially heterogeneous, involving coordinated alterations in collagen deposition and detrusor muscle architecture that are most pronounced in the midsection. Collagen-specific PA imaging enables quantitative assessment of these structural changes and represents a promising noninvasive tool for early detection and longitudinal monitoring of obstruction-associated bladder wall remodelling.
OBJECTIVES: Our objective was to characterize regional bladder remodelling in a rat model of partial bladder outlet obstruction (pBOO) and to evaluate collagen-specific photoacoustic (PA) imaging as a noninvasive tool for detecting early structural and collagen remodelling of the bladder wall.
MATERIALS AND METHODS: Female Sprague-Dawley rats underwent nerve-sparing midurethral obstruction or sham surgery and were evaluated at 4 and 8 weeks. Two independent cohorts of 30 rats each were studied. Cohort 1 bladders underwent ex vivo multispectral PA imaging (680-970 nm, 40 MHz) and histologic analysis. A custom spectral unmixing algorithm quantified collagen density across bladder regions (dome, midsection, and neck) and compared it with histologic collagen-to-muscle area ratios. Cohort 2 underwent molecular and biochemical analyses, including hydroxyproline quantification and assessment of collagen- and matrix-associated gene expression.
RESULTS: pBOO resulted in significant bladder enlargement, with increased absolute bladder mass and bladder-to-body mass ratios at 4 and 8 weeks (P < 0.05). Metabolic cage analysis demonstrated an increased frequency of small-volume voids at 8 weeks, despite preserved mean, maximum, and total voided volumes. Region-specific analysis identified the midsection as the site of greatest collagen accumulation with even greater detrusor muscle expansion, leading to a reduction in the collagen-to-muscle ratio. Molecular markers of collagen and matrix remodelling, along with hydroxyproline content, were significantly elevated, particularly in the midsection. Ex vivo PA imaging quantitatively mapped collagen distribution and demonstrated a strong correlation with histologic collagen-to-muscle ratios (r = 0.75), supporting its validity as a quantitative marker of regional remodelling.
CONCLUSION: Bladder remodelling in pBOO is spatially heterogeneous, involving coordinated alterations in collagen deposition and detrusor muscle architecture that are most pronounced in the midsection. Collagen-specific PA imaging enables quantitative assessment of these structural changes and represents a promising noninvasive tool for early detection and longitudinal monitoring of obstruction-associated bladder wall remodelling.