MRI imaging of human bladder wall using intravesical novel contrast mixture: applications in painful bladder syndrome/interstitial cystitis (PBS/IC)

Chermansky C1, Janicki J2, Moon C3, Kaufman J2, Tyagi P1

Research Type

Clinical

Abstract Category

Pelvic Pain Syndromes / Sexual Dysfunction

PRIZE AWARD: Best in Category Prize - Pelvic Pain Syndromes / Sexual Dysfunction
Abstract 56
Interstitial Cystitis / Bladder Pain Syndrome 1
Scientific Podium Short Oral Session 6
Wednesday 29th August 2018
10:37 - 10:45
Hall C
Painful Bladder Syndrome/Interstitial Cystitis (IC) Imaging Female
1. University of Pittsburgh Dept of Urology, 2. Lipella Pharmaceuticals Inc, 3. University of Pittsburgh Dept of Radiology
Presenter
C

Christopher Chermansky

Links

Abstract

Hypothesis / aims of study
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.
Study design, materials and methods
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.
Results
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.
Interpretation of results
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.
Concluding message
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.
Figure 1
Figure 2
References
  1. Verma S, Rajesh A, Prasad SR, Gaitonde K, Lall CG, Mouraviev V, Aeron G, Bracken RB, Sandrasegaran K (2012) Urinary bladder cancer: role of MR imaging. Radiographics 32:371–387.
  2. Towner RA, Wisniewski AB, Wu DH, Van Gordon SB, Smith N, North JC, McElhaney R, Aston CE, Shobeiri SA, Kropp BP, Greenwood-Van Meerveld B, Hurst RE (2016) A feasibility study to determine whether clinical contrast enhanced magnetic resonance imaging can detect increased bladder permeability in patients with interstitial cystitis. J Urol 195:631–638.
  3. Tyagi P, Janicki JJ, Hitchens TK, Foley LM, Kashyap M, Yoshhimura N, Kaufman J (2017) Novel contrast mixture improves bladder wall contrast for visualizing bladder injury. Am J Physiol Renal Physiol 313:F155–F162.
Disclosures
Funding NIH NIDDK 1 R41 DK108397-01 Clinical Trial No Subjects Human Ethics Committee Institutional Review Board of University of Pittsburgh Helsinki Yes Informed Consent Yes