Unraveling the complexity of bladder-centric chronic pain by intravesical contrast enhanced MRI

Bladder pain, a common symptom associated with various urological conditions, poses a diagnostic challenge as existing imaging modalities fail to pinpoint the bladder as the definitive source of pain. While bladder pain is often linked to localized inflammation resulting from urinary tract infections (UTIs) or Interstitial Cystitis/Bladder Pain Syndrome (IC/BPS), which can be exacerbated by emotional stress, current urine-based markers cannot precisely identify the specific site of inflammation within the urinary tract, spanning from the kidneys to the urethral meatus. Cystoscopy, currently considered the gold standard, is recommended by the American Urological Association (AUA) prior to aggressive treatment for IC/BPS patients, as it confirms the presence of bladder inflammation, particularly in Hunner lesions, and predicts a higher response rate to anti-inflammatory medication like cyclosporine. Nonetheless, the invasiveness of cystoscopy, which relies on investigator expertise, coupled with the significant variability in detecting Hunner lesions, underscores its limitations for inflammatory phenotyping. These factors contribute to the reluctance in choosing cystoscopy as a preferred diagnostic method and may also contribute to the lack of success observed in clinical trials assessing the efficacy of novel anti-inflammatory drugs. Given that immune cell infiltration into inflammatory sites relies on tight junction dilatation, the paracellular entry of injected or instilled paramagnetic dyes, mimicking the extravasation of colored dyes such as Evans blue dye could be a robust index of vascular or urothelial hyperpermeability—a characteristic sign of inflammation. This article aims to delve into the pathophysiology of bladder-centric chronic pain within the context of the challenging diagnosis of IC/BPS and explore the pivotal role of Stokesian and Fickian diffusion in the evolution of intravesical contrast-enhanced MRI (ICE-MRI) as a phenotyping tool for bladder pain, transitioning from laboratory research to practical clinical application. [Display omitted] •Bladder pain relieved by voiding is likely to be triggered by urothelial permeability or neuropathic pain.•Stokesian a diffusion governs urothelial permeability and urinary albumin-creatinine ratio (ACR) for kidney function.•ICE-MRI capitalizes on Stokesian diffusion and magnetic moment of Gadolinium-Based Contrast Agent, Gadobutrol and Ferumoxytol for a virtual measurement of urothelial permeability