Interstitial cystitis/ bladder pain syndrome (IC/BPS) with Hunner lesion (HIC) patients tend to exhibit higher bladder permeability than controls based on pain at 5 minutes post-instillation of 400mM potassium (K+) chloride in potassium sensitivity test (PST) and 10fold higher xenon (133 Daltons) levels in exhaled air at 5min (ref.1) and lower excretion of instilled urea at 45 minutes post- instillation. However, these findings of bladder hyperpermeability in IC/BPS were disputed by the variable serum levels of radionuclide, technetium-99m diethylene triamine penta-acetic acid (99mTc DTPA) at 30minutes post-instillation (ref.2). We enquired whether 99mTc DTPA permeability assay was imperiled by delayed assay timing?   We hypothesize that analogous to K+ and xenon, rapid intravesical absorption 99mTc DTPA is indexed by the upslope of serum 99mTc DTPA levels ≤5min post-instillation (ref.2), whereas plateaued serum levels at 30min display the steady state of absorption and renal excretion because 99mTc DTPA is excluded from intracellular space. Because renal excretion of creatinine is matched by 99mTc DTPA (487.21 Daltons) and paramagnetic dye, Gadobutrol (604.71 Daltons), we instilled Gadobutrol to track its renal excretion by dynamic contrast enhancement of ureteral jets at 5min-post-instillation in HIC and IC/BPS without Hunner lesion (NHIC) patients.

We prospectively consented six female subjects (age 18-80years) having a history of IC/BPS and cystoscopy within 6 months recorded Hunner lesions in 2 subjects, with ICSI >9 and an ICPI > 8 for intravesical contrast enhanced(ICE)-MRI at 3T. A logistical delay of 5min occurred between 50mL instillation of Gadobutrol [20mM]and Ferumoxytol [0.1mM] mixture in sterile water by 14Fr catheter and abdominal placement of 4-channel flexible receiver coil for multi-slice T1 weighted Time-resolved Interleaved Stochastic Trajectories (TWIST; ref.3) in axial plane with temporal resolution of 22.2s. The dynamic signal intensity (artificial units; a.u.) of urine jets was measured in 20 frames of the same slice acquired over 446.3s and ureteral jets were also visualized in axial and sagittal T2 weighted turbo spin echo (TSE) scans.

Dynamic TWIST scan (ref.3) displayed a significant decline in color coded luminal signal intensity (SI) of HIC subjects to 120-163 a.u. (n=2) vs 182.5±5 a.u. of NHIC subjects (n=4). The decline in luminal SI was converse of fresh urine jets SI for HIC>NHIC at 5min post-instillation. While rapid intravesical absorption of Gadobutrol from Hunner lesion resulted in higher urine signal at 5min in HIC, slower Gadobutrol absorption from NHIC is signified by delayed peak for urine SI at 10min post- instillation. Dynamic signal of ureter jets in T1 weighted ICE-MRI (TWIST scan) was confirmed by T2 weighted ICE-MRI.

While previously used for imaging ureteral peristalsis following injection (ref.3),  we used TWIST with Gadobutrol instillation to determine bladder permeability, HIC>NHIC at 5min. The timing for two-fold higher SI of urine jets in HIC>NHIC at 5min coincides with peak levels of instilled xenon gas in exhaled air (ref.1),  PST pain and four fold higher serum levels of 99mTc DTPA at 5min post-instillation in IC/BPS compared to controls  (ref.2). Delayed peak of ureteral jet SI at 10min post-instillation in NHIC implicates variable renal excretion as the cause for variable 99mTc DTPA  serum levels at 30min imperiling the bladder permeability assay (ref.2). Meanwhile, bright urine signal at 5min in HIC affirms the integral role of mucosal perfusion in bladder permeability.

Thus, Gadobutrol traces rapid renal excretion of 99mTc DTPA at 5min to highlight the importance of uniform assay timings in reaching consensus on bladder permeability in IC/BPS.  ICE-MRI assays bladder permeability in a radiation-free manner, without biofluid analysis and can aid in phenotyping violent urges and pain from naturalistic urine filling (joint 2025 statement of AUGS and IUGA) via ureteral peristalsis without water loading or cystoscopy.

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