There remains an unmet need for an imaging technique which will differentiate ulcerative Painful Bladder Syndrome/Interstitial Cystitis (PBS/IC) from non-ulcerative PBS/IC. MRI is a radiation-free imaging technique that demonstrates excellent contrast of pelvic tissues in 3D-anatomy. Past attempts at unenhanced [1] and contrast enhanced [2] T1 weighted MRI of human bladder wall were unable to improve the contrast-noise ratio (CNR) and the spatial resolution per image pixel. Intravesical novel contrast mixture (NCM) has been recently shown to improve the CNR of rat bladder wall injured with protamine sulfate [3]. In this clinical study, the safety and feasibility of MRI enhanced with intravesical NCM in evaluating patients with PBS/IC was tested.

After giving informed consent, 6 women (25-78y) submitted to 3T MRI before and after intravesical NCM.  The 6 women consisted of 2 controls, 2 with non-ulcerative PBS/IC, and 2 with ulcerative PBS/IC.  NCM 50 ml was freshly prepared by diluting Gadobutrol (Gadovist, Bayer) 1:250 and Ferumoxytol (Feraheme, AMAG Pharmaceuticals) 1:104 in sterile water for injection (Figure 1).  Respiratory monitoring belt was placed around patient and under receiver coil for checking breath-hold during fast image acquisition with repetition time/echo time of 5.5/2ms.  Single slice of 5mm thickness was acquired during single breath-hold of 17 seconds for each flip angle to minimize the motion and chemical shift artifacts.  Quantitative measurement of T1 made from the differences in signal intensity of 20 pixels representing bladder wall in pre-contrast and post-contrast images taken at different flip angles.

NCM instillation in subjects did not evoke pain or discomfort. Post-contrast bladder wall T1 relaxation times of ulcerative PBS/IC subjects were reduced from pre-contrast values by 44% compared to 18% for controls and non-ulcerative PBS/IC, *p<0.0001 using two-way ANOVA followed by Tukey’s test (Figure 2).  NCM enhanced-MRI increased the bladder wall CNR in all subjects by 4-fold in post-contrast images (57.84 ± 32.01 vs 12.34 ± 9.63, *p<0.02 using paired Student’s t test) compared to pre-contrast images acquired with same parameters.  Intravesical NCM allowed accurate determination of significant bladder wall thinning from 3.39±0.74 mm pre-contrast to 2.93±0.8 mm post-contrast,*p<0.05.

MRI enhanced with intravesical NCM allowed differentiation of the bladder wall into different tissue layers with an increased depth of gadolinium diffusion in the ulcerative-type PBS/IC patients.  This pilot study was limited by the small size and was not powered to demonstrate the group-wise differences in bladder wall thickness. The significantly reduced bladder wall T1 relaxation times in the ulcerative PBS/IC patients are promising and warrant further evaluation in an independent trial with a larger sample size.

NCM instillation achieves artifact-free differential contrast and spatial resolution of human bladder wall, which is not possible with instillation or injection of single contrast agents. These findings demonstrate the safety and feasibility of NCM enhanced MRI to characterize changes within the bladder wall for phenotyping PBS/IC.

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