Interstitial Cystitis/Bladder Pain Syndrome (IC/BPS) is a chronic, debilitating condition that affects more than 2 million individuals within the US. Recently, the chronic pelvic pain working group of the ICS has classified IC/BPS into either hypersensitive bladder with no identifiable pathology explaining the symptoms of IC/BPS, IC/BPS with Hunner lesion (HIC) or IC/BPS with no lesions on cystoscopy (NHIC). Though the etiology of IC/BPS is multifactorial, a large body of evidence supports the impairment of bladder mucosal permeability as a major pathophysiological cause in HIC. Yet, there remains variability (5-57%) in the true identification of IC/BPS that is bladder-centric on the basis on cystoscopy. Therefore, a minimally invasive, assay that reliably measures bladder permeability without evoking pain or exposing ionizing radiation to subjects may be able to meet the FDA regulatory criteria for a diagnostic test. With the past funding support, we developed a radiation free, minimally invasive assay of bladder mucosal permeability, and we demonstrated the validity of intravesical contrast enhanced magnetic resonance imaging (ICE-MRI) to measure permeability of thin mouse and rat bladder at high field scanners of 7T and 9.4T (PMC7509285; PMC6028942; PMC8484474). A key feature of our ICE-MRI assay of bladder permeability is the transurethral catheter instillation of Gadobutrol and Ferumoxytol mixture and then MRI capitalizes on the linear relationship between the concentration of instilled Gadobutrol diffusing passively into the mucosa to cause concentration dependent changes in T1 relaxation rate (1/T1 relaxation time) of the mucosa. While Gadobutrol instilled into bladder lumen diffuses into mucosa down the concentration gradient, our preliminary data demonstrates that mucosa lesion accelerates the Gadobutrol diffusion relative to normal areas. We now seek funding support to generate clinical evidence for demonstrating that ICE-MRI can be a diagnostic test for bladder-centric phenotype in IC/BPS patients to complement conventional cystoscopy-based diagnosis. Following Specific Aims will test the hypothesis that bladder mucosal permeability of instilled Gadobutrol mixture descends quantitatively from HIC >NHIC >asymptomatic control subjects.: Aim 1: To calibrate the ICE-MRI based bladder mucosal permeability assay on HIC, NHIC patients and asymptomatic subjects who have normal cystoscopic findings. In a cross-sectional prospective study on previously cystoscoped 10 HIC patients, 10 NHIC patients, and 10 asymptomatic controls, we will calibrate the ICE-MRI based bladder mucosal permeability assay. Aim 2: To manufacture sterile clinical trial materials and complete the IND/IDE submission for the ICE-MRI based bladder permeability assay kit. A radiation-free, objective diagnostic test of bladder permeability can objectively phenotype IC/BPS IC/BPS that is bladder-centric, thereby identifying patients who would be most likely to benefit from anti-...