Abstract: PD01-08
Sources of Funding: 1R41DK108397;P30CA047904

Introduction

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.

Funding

1R41DK108397;P30CA047904