PD01-05 PROBING THE BLADDER WALL DIFFUSION OF INSTILLED GADOBUTROL BY MRI

Abstract

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 ...