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Podium
Pradeep Tyagi, PhD
University of Pittsburgh
Introduction: 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