e14687 Background: A major hallmark of bladder cancer (BCa) is a higher treatment success rate than prostate cancer following stimulation of innate anti-tumor immune response either by intravesical BCG or to FDA approved intravenous anti-PD1 checkpoint antibody (pembrolizumab) approved for BCG resistant BCa since 2021. However, injected pembrolizumab is characterized by a markedly higher incidence (66%) of serious adverse events than the median duration of complete response of ~40% for non-muscle invasive BCa (NMIBC) and 15-20% for invasive BCa. Since the toxicity (fatigue, Pneumonitis and diarrhea) of injected pembrolizumab is linked to systemic breakdown of T-cell mediated immune surveillance we enquired whether analogous to BCG, pembrolizumab can be administered intravesically to safely induce a localized anti-tumor response in mouse model of BCa. Methods: Six weeks old female mice of B6D2F1 strain (n=10) were ad libitum fed carcinogen, N-butyl-N-4-hydroxybutyl nitrosamine (BBN) in drinking water (0.05% w/v) for 12 weeks. The presence of BBN evoked tumor was ascertained by unenhanced T2 weighted MRI at week 11 prior to single intravesical dosing by 24G transurethral catheter under isoflurane anesthesia of 0.1mL vehicle (sterile water) with or without 0.3mg of Pembrolizumab (Lipella Pharmaceuticals). 6 weeks later, T2 weighted MRI was repeated together with T1 mapping by ICE-MRI prior to organ harvest. Results: BBN feeding evoked multiclonal tumors (red*) of comparable size on T2 weighted MRI at week 11 but repeat MRI 7 weeks after treatment revealed that tumor progression and perivesical invasion noted in vehicle group was arrested in pembrolizumab group. Longest dimension of BBN tumor in vehicle treated mice was ≥ 1mm longer (p<0.05) than in pembrolizumab treated mice. T1 mapping revealed thickened bladder wall missed by T2 MRI. Conclusions: These findings on single intravesical dose of pembrolizumab (10mg/kg) in mice are consistent with human study on multiple intravesical dosing of BCG plus pembrolizumab (1-2mg/kg) in BCG resistant NMIBC patients. Intravesical pembrolizumab mirrors the limited systemic uptake of radiolabelled antibodies together with substantially higher ingress into tumor foci. The tumor selective ingress for BCa immunotherapy without any toxicity will be enhanced with Lipella Pharmaceutical’s liposomal delivery of Pembrolizumab.

Bladder cancer (BC) presents a significant global health burden, characterized by high recurrence rates post-initial treatment. Gender differences in BC prevalence and response to therapy emphasize the importance of personalized treatment strategies. While Bacillus Calmette–Guérin (BCG) remains a cornerstone of BC therapy, resistance poses a challenge, necessitating alternative strategies. Immune checkpoint inhibitors (ICIs) have shown promise, yet systemic toxicity raises concern. Intravesical administration of ICIs offers a potential solution, with recent studies demonstrating the feasibility and efficacy of intravesical pembrolizumab. Although systemic toxicity remains a concern, its localized administration may mitigate adverse events. Additionally, liposomal delivery of ICIs exhibits promises in enhancing drug penetration and reducing toxicity. Novel imaging modalities compatible with Vesical Imaging-Reporting and Data System (VI-RADS) and capable of predicting high-grade bladder cancer can aid the pre-operative shared decision making of patient and surgeon. Future research should focus on refining treatment approaches, optimizing dosing regimens, and leveraging advanced imaging techniques to improve patient outcomes. In conclusion, intravesical immunotherapy presents a promising avenue for BC treatment, offering enhanced therapeutic effectiveness while minimizing systemic toxicity. Continued research efforts are essential to validate these findings and optimize intravesical immunotherapy’s role in BC management, ultimately improving patient outcomes.

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.

This article provides an overview of the diagnosis and the treatment of lower urinary tract symptoms in older adults complicated by the neurodegenerative changes in the micturition reflex and further confounded by age-related decline in hepatic and renal clearance raising the propensity of adverse drug reactions. The first-line drug treatment for lower urinary tract symptoms, orally administered antimuscarinics, fails to reach the equilibrium dissociation constant of muscarinic receptors even at their maximum plasma concentration and tends to evoke a half-maximal response at a muscarinic receptor occupancy of just 0.206

You have accessJournal of UrologyCME1 May 2022PD08-03 CAPTURING REAL TIME EVIDENCE OF UROTHELIAL PERMEABILITY IN LIVE RODENT BY MRI Pradeep Tyagi, Nishant Singh, Lesley Foley, T. Kevin Hitchens, Jodi Maranchie, Christopher Chermansky, Naoki Yoshimura, and Jonathan Kaufman Pradeep TyagiPradeep Tyagi More articles by this author , Nishant SinghNishant Singh More articles by this author , Lesley FoleyLesley Foley More articles by this author , T. Kevin HitchensT. Kevin Hitchens More articles by this author , Jodi MaranchieJodi Maranchie More articles by this author , Christopher ChermanskyChristopher Chermansky More articles by this author , Naoki YoshimuraNaoki Yoshimura More articles by this author , and Jonathan KaufmanJonathan Kaufman More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002527.03AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: The epithelial lining of urinary bladder- urothelium erects a blood-urine barrier for restricting the ingress of water, cations, and organic substances (urea) from urine back into the capillary perfused mammalian bladder wall. Multiple lines of evidence now support that the restricted ingress of urine constituents is not static but dynamically sustained at the cost of metabolic activity and mucosal perfusion during the storage phase of micturition. Therefore, the pleiotropic impact of perfusion on urothelial permeability cannot be dissected by in vitro systems like Ussing chamber but require non-invasive approaches capable of real-time measurement in live animal. METHODS: Adult Female Sprague-Dawley rats (250-300g) were anesthetized with isoflurane for Turbo-spin echo MRI at 7-Tesla 30-cm-bore Bruker ClinScan system equipped with an 86-mm volume transmit coil and a four-channel array receive coil. Before and after trans-urethral 0.3mL instillation using a 24-gauge Angiocath catheter of Gadobutrol and Ferumoxytol mixture, coronal and sagittal images were acquired at repetition time of 650ms, echo time (TE) of 10–36 ms, slice thickness 1.5mm, 256 × 256 matrix and a 6 × 6 cm2 field of view with 2-8 signal averages. RESULTS: Compared to images taken before the instillation of Gadobutrol and Ferumoxytol mixture, we were able to achieve susceptibility-induced signal loss within the bladder lumen leading to a dark lumen to generate the necessary image contrast for visualizing the signal enhancement in superior vesicle vein (SVV) by diffused Gadobutrol while arteries remain dark. Increasing the TE from 10 to 36 ms emphasizes the susceptibility-induced signal loss within lumen and the enhancement of vascular signal. CONCLUSIONS: The time dependent detection enhancement in bladder veins after instillation is a real-time evidence for the urothelial permeability for instilled probe before its gets diluted into systemic circulation and experiences a first- pass effect. Instilled Gadobutrol traces the path taken by instilled inulin and oxybutynin into systemic circulation and the loss of diffused Gadobutrol into blood visualizes the exponential drop in the concentration of drugs and dyes from urothelium to detrusor muscle. Thus, MRI can visualize the differential impact of stress and neural inputs on mucosal perfusion and the impact on urothelial permeability. Source of Funding: NIDDK 108397; CA252590 © 2022 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 207Issue Supplement 5May 2022Page: e106 Advertisement Copyright & Permissions© 2022 by American Urological Association Education and Research, Inc.MetricsAuthor Information Pradeep Tyagi More articles by this author Nishant Singh More articles by this author Lesley Foley More articles by this author T. Kevin Hitchens More articles by this author Jodi Maranchie More articles by this author Christopher Chermansky More articles by this author Naoki Yoshimura More articles by this author Jonathan Kaufman More articles by this author Expand All Advertisement PDF downloadLoading ...

To quantify the urinary bladder wall T 1 relaxation time (T 1 ) before and after the instillation contrast mixture in rats previously subjected to water avoidance stress (WAS) and/or acute exposure to protamine sulfate (PS). Female Wistar rats were randomized to receive either sham (control) or 1 h of WAS for ten consecutive days before the evaluation of nocturnal urination pattern in metabolic cages. T 1 mapping of urinary bladder wall at 9.4 T was performed pre- and post- instillation of 4 mM Gadobutrol in a mixture with 5 mM Ferumoxytol. Subsequently, either T 1 mapping was repeated after brief intravesical PS exposure or the animals were sacrificed for histology and analyzing the mucosal levels of mRNA. Compared to the control group, WAS exposure decreased the single void urine volume and shortened the post-contrast T 1 relaxation time of mucosa- used to compute relatively higher ingress of instilled Gadobutrol. Compromised permeability in WAS group was corroborated by the urothelial denudation, edema and ZO-1 downregulation. PS exposure doubled the baseline ingress of Gadobutrol in both groups. These findings confirm that psychological stress compromises the paracellular permeability of bladder mucosa and its non-invasive assay with MRI was validated by PS exposure.

You have accessJournal of UrologyInfections/Inflammation/Cystic Disease of the Genitourinary Tract: Interstitial Cystitis (PD01)1 Sep 2021PD01-05 PROBING THE BLADDER WALL DIFFUSION OF INSTILLED GADOBUTROL BY MRI Pradeep Tyagi, Chan-Hong Moon, Nishant Singh, Marc Connell, Jodi Maranchie, Christopher Chermansky, Naoki Yoshimura, and Jonathan Kaufman Pradeep TyagiPradeep Tyagi More articles by this author , Chan-Hong MoonChan-Hong Moon More articles by this author , Nishant SinghNishant Singh More articles by this author , Marc ConnellMarc Connell More articles by this author , Jodi MaranchieJodi Maranchie More articles by this author , Christopher ChermanskyChristopher Chermansky More articles by this author , Naoki YoshimuraNaoki Yoshimura More articles by this author , and Jonathan KaufmanJonathan Kaufman More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000001965.05AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Intravesical therapy is critical for bladder cancer and a secondary option for interstitial cystitis and overactive bladder patient's refractory to oral treatment. Although paracellular diffusion of instilled drugs and radioactive agents from urine is suggested by ultrastructural studies and studies on diffusion across the excised whole bladder wall in Ussing chamber, the kinetics of diffusion across just the thickness of bladder mucosa is yet to be probed directly in a radiation-free manner with a non-invasive, non-tissue destructive method. Since MRI is capable of imaging the microscopic dimensions of bladder mucosa (Am J Physiol Renal Physiol 2020;319(3): F506-F514.), we investigated the diffusion kinetics of instilled Gadobutrol in a phantom constructed with 12% polyacrylamide (PLGA) gel, whose nanometer sized pores can partly mimic the nanometer gap of the apico-lateral tight junctions in mammalian urothelium. METHODS: PLGA gel was poured into a plastic jar while embedding 9 glass tubes which were removed upon setting of gel to create 9 cylindrical cavities for instilling ascending concentrations [0.5-20 mM] of Gadobutrol together with a fixed concentration of Ferumoxytol 0.1 mM. Phantom was wrapped by a 4 channel-flexible receiver coil for imaging in 3T scanner (Siemens, BioGraph) using T2 weighted Half-Fourier Acquisition Single-shot Turbo spin Echo imaging (HASTE) (repetition time 1000-1300 ms/echo time 80-90 ms). Gel diffusion of Gadobutrol was assessed by imaging at 30 min and at 5 h. RESULTS: The bright ring around the cavities demonstrates that molecular size of 0.8 nm permits easy diffusion of Gadobutrol into the >40 times bigger pores of 12% PLGA gel. The concentration gradient is the driving force for Gadobutrol diffusion is supported by the dependence of ring brightness on Gadobutrol concentration [0.5-20 mM] at room temperature and on the expansion of dark blob at 5 h in cavities filled with Gadobutrol 5-20 mM to recapitulate the classical pseudolayering effect of Gadobutrol accumulating into stored urine of bladder. CONCLUSIONS: MR imaging validated the linear relationship between Gadobutrol concentration in cavity and the signal gain in the surrounding gel, a surrogate for bladder mucosa. Findings support that MRI at clinical scanner can reliably assess the mucosal diffusion of instilled drugs and probes in bladder permeability assay. Source of Funding: DK 108397;CA252590 © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e32-e32 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information Pradeep Tyagi More articles by this author Chan-Hong Moon More articles by this author Nishant Singh More articles by this author Marc Connell More articles by this author Jodi Maranchie More articles by this author Christopher Chermansky More articles by this author Naoki Yoshimura More articles by this author Jonathan Kaufman More articles by this author Expand All Advertisement Loading ...

You have accessJournal of UrologyImaging/Radiology: Uroradiology II (MP22)1 Sep 2021MP22-01 HIGH RESOLUTION 3D T1-MAPPING OF PIG BLADDER WALL BY INTRAVESICAL CONTRAST ENHANCED MRI AT 3T Pradeep Tyagi, Chan-Hong Moon, Nishant Singh, Marc Connell, Jodi Maranchie, Christopher Chermansky, Naoki Yoshimura, and Jonathan Kaufman Pradeep TyagiPradeep Tyagi More articles by this author , Chan-Hong MoonChan-Hong Moon More articles by this author , Nishant SinghNishant Singh More articles by this author , Marc ConnellMarc Connell More articles by this author , Jodi MaranchieJodi Maranchie More articles by this author , Christopher ChermanskyChristopher Chermansky More articles by this author , Naoki YoshimuraNaoki Yoshimura More articles by this author , and Jonathan KaufmanJonathan Kaufman More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002013.01AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: We previously reported on the single slice T1 mapping of human bladder using a pair of spoiled gradient recalled echo (SPGR) images acquired at different flip angles. Here, we used pig bladder to develop a three-dimensional, multi-slice imaging protocol for voxel-wise T1 mapping of mucosal enhancement after instilling Gadobutrol and Ferumoxytol mixture. METHODS: Freshly harvested pig bladders (n=10) were preserved in ice-cold Krebs Buffer and then instilled with either 40mL of same buffer (pre-contrast) or Millipore water containing ascending concentrations of Gadobutrol [4-80 mM] and Ferumoxytol [0.1-30 mM] (post-contrast imaging). Bladder placed in jar was wrapped around with four channel flexible receiver coil for volumetric coverage with 2mm slice thickness in voxel size 0.7×0.7×2.0 mm using Qfat suppressed 3D SPGR acquisition in cartesian trajectory. Repetition time/ echo time (TR/TE) 5.5/2.4 ms, variable flip angle 3°-25° and total acquisition time of 1:15 min. RESULTS: Instillation of Gadobutrol as a mixture with Ferumoxytol precludes Gadobutrol mediated signal enhancement in rat bladder lumen via rapid signal dephasing in spin echo images. However, clinically used gradient echo pulse sequences accentuates the phase aliasing from the luminal presence of Ferumoxytol [>0.1mM] and Gadobutrol [>20mM] mixture due to a dramatic increase in the inhomogeneities of static magnetic field around bladder wall and the susceptibility-related distortion in the phase-encoding direction limits the geometric accuracy of bladder wall anatomy. Acquisition of high-resolution images devoid of susceptibility artifacts, that is, signal drop and distortion can be accomplished after instillation of Gadobutrol 20mM mixed with Ferumoxytol 0.1mM (Fig.1), where pig bladder wall is visually segmented into an inner thin layer of high intensity, a middle layer of lower signal and a darker outer layer and color coded voxel wise T1 maps. CONCLUSIONS: Findings display a real-time acquisition and display of the whole bladder, color -coded T1 maps at 3T for first time. A freshly mixed instillation of Gadobutrol together Ferumoxytol visually segments the bladder wall into three layers for potential applications in staging of bladder tumors and the phenotyping bladder-centric manifestation of IC/BPS. Source of Funding: DK 108397;CA252590 © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e390-e390 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information Pradeep Tyagi More articles by this author Chan-Hong Moon More articles by this author Nishant Singh More articles by this author Marc Connell More articles by this author Jodi Maranchie More articles by this author Christopher Chermansky More articles by this author Naoki Yoshimura More articles by this author Jonathan Kaufman More articles by this author Expand All Advertisement PDF downloadLoading ...

To assess whether quantitative T-1 relaxometry can measure permeability, chronic inflammation and mural thickening of mouse bladder wall. Adult female C57BL6 mice unexposed to radiation (controls) or 40 wk postirradiation of 10 Gy were scanned at 9.4 T before and after instillation (0.1 mL) of aqueous, novel contrast mixture (NCM) containing 4 mM gadobutrol and 5 mM ferumoxytol. Rapid acquisition with refocused echo (RARE) sequence was used with variable repetition times (TR). Pixel-wise maps of T-1 relaxation times for the segmented bladder wall layers were generated from voxel-wise, nonlinear least square data fitting of TR-dependent signal intensity acquired with TR array of 0.4-10 s followed by the histology of harvested bladder. Significant differences between precontrast and postcontrast T-1 (Delta T-1) were noted in urothelium and lamina propria of both groups but only in detrusor of irradiated group (P < 0.001; 2-way ANOVA). Nearly twofold higher gadobutrol permeability (550 +/- 73 vs. 294 +/- 160 mu M; P < 0.01) derived as per 1/Delta T-1 = r1. [C] in urothelium of irradiated group. Inflammation and bladder wall thickening (0.75 +/- 0. vs. 0.44 +/- 0.08 mm; P < 0.001) predicted by MRI was subsequently confirmed by histology and altered expression of CD45 and zonula occludens-1 (ZO-1) relative to controls. NCM enhanced MRI relies on the retention of large molecular weight ferumoxytol in lumen for negative contrast, while permeation of the non-ionic, small molecular weight gadobutrol through ZO-1 generates positive contrast in bladder wall for virtual measurement of paracellular permeability and assessment of chronic inflammation in thin and distensible bladder wall, which is also defined by its variable shape and location within pelvis.

You have accessJournal of UrologyInfections/Inflammation/Cystic Disease of the Genitourinary Tract: Interstitial Cystitis1 Apr 2018MP39-10 NOVEL CONTRAST MIXTURE ACHIEVES CONTRAST RESOLUTION OF HUMAN BLADDER WALL SUITABLE FOR T1 MAPPING: APPLICATIONS IN INTERSTITIAL CYSTITIS (IC) AND BEYOND Pradeep Tyagi, Joe Janicki, Chan-Hong Moon, Jonathan Kaufman, and Christopher Chermansky Pradeep TyagiPradeep Tyagi More articles by this author , Joe JanickiJoe Janicki More articles by this author , Chan-Hong MoonChan-Hong Moon More articles by this author , Jonathan KaufmanJonathan Kaufman More articles by this author , and Christopher ChermanskyChristopher Chermansky More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2018.02.1257AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Instillation of novel contrast mixture (NCM) was recently shown to improve the contrast resolution of rat bladder wall with high contrast-to-noise ratio (CNR). Here, the clinical safety and the feasibility of NCM enhanced MRI to achieve artifact-free visualization of human bladder wall suitable for quantitative measurement of the magnetic resonance (MR) longitudinal relaxation time (T1) was accessed. METHODS Six female subjects [2 controls and 4 IC] consented for MRI at 3T before and after instillation of NCM [4mM Gadobutrol and 5mM Ferumoxytol in 50mL of sterile water for injection]. Respiratory monitoring belt was placed under the receiver coil for monitoring the breath-hold. Single breath hold fast MR acquisition from 5mm thick single slice in large readout bandwidth at variable flip angles was applied to minimize the motion and chemical shift artifacts in the measurements of bladder wall thickness (BWT), CNR and T1 from 20 pixels. RESULTS Subjects did not complain of any pain or discomfort from 50mL NCM instillation, beyond that caused by the catheterization process. Four-fold increase in bladder wall CNR (*p<0.02) and spatial resolution of 0.35mm with minimal influence of artifacts made it feasible to determine the significant bladder wall thinning of ~0.46mm (*p<0.05) from 50mL NCM. Pre-contrast bladder wall T1 of 1544± 34.2ms was shortened by Gadobutrol diffusion into the bladder wall to 860.09 ±13.95 ms in Hunner type IC (*p<0.0001, two way ANOVA) relative to only 1257.42± 20.59 ms and 1258.16 ± 6.16ms in non-Hunner type IC and controls, respectively. Post-contrast pixel-wise T1 mapping differentiated the bladder wall into layers with greater Gadobutrol mediated T1 shortening in pixels representing the urothelium and lamina propria (blue and green) compared to the detrusor region (yellow in attached picture). CONCLUSIONS Recapitulation of the published pre-clinical findings in the clinical setting demonstrates the safety and feasibility of NCM enhanced MRI to achieve artifact-free differential contrast and spatial resolution of human bladder wall, which is suitable for first pixel-wise measurement of T1 in both pre-and post-contrast settings. Quantitative T1 measurement holds promise in the non-invasive characterization of diffuse pathophysiological changes in bladder wall of IC patients. © 2018FiguresReferencesRelatedDetails Volume 199Issue 4SApril 2018Page: e513-e514 Advertisement Copyright & Permissions© 2018MetricsAuthor Information Pradeep Tyagi More articles by this author Joe Janicki More articles by this author Chan-Hong Moon More articles by this author Jonathan Kaufman More articles by this author Christopher Chermansky More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Interstitial cystitis/bladder pain syndrome (IC/BPS) is a debilitating condition associated with intense pelvic pain and bladder storage symptoms. Since diagnosis is difficult, prevalence estimates vary with the methodology used. There is also a lack of proven imaging tools and biomarkers to assist in differentiation of IC/BPS from other urinary disorders (overactive bladder, vulvodynia, endometriosis, and prostatitis). Current uncertainty regarding the etiology and pathology of IC/BPS ultimately impacts its timely and successful treatment, as well as hampers future drug development. This review will cover recent developments in imaging methods, such as magnetic resonance imaging, that advance the understanding of IC/BPS and guide drug development.

Instillation of novel contrast mixture (NCM) was recently shown to improve the contrast resolution of rat bladder wall with high contrast-to-noise ratio (CNR). Here, the clinical safety and the feasibility of NCM-enhanced MRI to achieve artifact-free visualization of human bladder wall suitable for quantitative measurement of the magnetic resonance (MR) longitudinal relaxation time (T1) was assessed.

You have accessJournal of UrologyInfections/Inflammation/Cystic Disease of the Genitourinary Tract: Interstitial Cystitis I1 Apr 2017PD01-08 NOVEL CONTRAST MIXTURE IMPROVES BLADDER WALL CONTRAST FOR VISUALIZING INTERSTITIAL CYSTITIS Pradeep Tyagi, Joseph Janicki, T. Kevin Hitchens, Lesley Foley, Mahendra Kashyap, Naoki Yoshimura, and Jonathan Kaufman Pradeep TyagiPradeep Tyagi More articles by this author , Joseph JanickiJoseph Janicki More articles by this author , T. Kevin HitchensT. Kevin Hitchens More articles by this author , Lesley FoleyLesley Foley More articles by this author , Mahendra KashyapMahendra Kashyap More articles by this author , Naoki YoshimuraNaoki Yoshimura More articles by this author , and Jonathan KaufmanJonathan Kaufman More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2017.02.188AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Past attempts at contrast enhanced MRI (CE-MRI) of the bladder have been unable to enhance the image contrast between bladder wall and lumen in order to effectively resolve the bladder wall changes associated with cystitis or malignancy. Here we tested whether combined contrast-enhanced magnetic resonance imaging (CCE-MRI), using a mixture of Gadolinium and iron-oxide based contrast agent (ferumoxytol) is superior to CE-MRI in enhancing the image contrast of bladder wall. Each FDA approved agent in the contrast mixture is constituted of different particle size and have different contrast effects on the spin-echo imaging protocol. METHODS Under isoflurane anesthesia, T1-weighted imaging of adult female Sprague-Dawley rat bladder was performed using standard turbo spin echo sequences at 7 Tesla, before and after transurethral instillation of 0.3 mL of single contrast (CE-MRI) or combined contrast mixture (CCE-MRI) composed of 0.4-64 mM of gadolinium chelate (Gadavist/Gd-DTPA) and 5 mM ferumoxytol. Bladder wall contrast was assessed in control group exposed to saline and in cystitis group exposed to 0.5 mL of protamine sulfate (10 mg/mL) for 30min RESULTS CCE-MRI following instillation of 0.4-4 mM gadavist (gadolinium ) and 5 mM ferumoxytol mixture was superior to CE-MRI (instillation of either Gadavist or ferumoxytol) in achieving the maximum contrast between the lumen and bladder wall. T1-relaxation enhancement in bladder lumen by gadavist is masked by the T2 effect from localization of the larger ferumoxytol nanoparticles in the lumen, but the diffusion of gadavist into the lesions caused by protamine is marked by the hyperintense signal in bladder wall. The normalized hyperintensity in the bladder wall increased from 0.46 ±0.07 in control group to 0.73± 0.14 in the protamine group (p < 0.0001). CONCLUSIONS CCE-MRI following instillation of the contrast mixture is superior to CE-MRI using individual contrast agents in the visualization of bladder wall changes likely associated with cystitis or malignancy. CCE-MRI relies on differences in particle size and contrast mechanisms of gadolinium chelates and ferumoxytol. This novel approach has the potential to distinguish diffuse versus a focal disruption in the bladder wall integrity of interstitial cystitis patients, facilitating accurate diagnosis and improved patient care. © 2017FiguresReferencesRelatedDetails Volume 197Issue 4SApril 2017Page: e49 Advertisement Copyright & Permissions© 2017MetricsAuthor Information Pradeep Tyagi More articles by this author Joseph Janicki More articles by this author T. Kevin Hitchens More articles by this author Lesley Foley More articles by this author Mahendra Kashyap More articles by this author Naoki Yoshimura More articles by this author Jonathan Kaufman More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...