Abstract
Purpose
Instillation of novel contrast mixture (NCM) was recently shown to improve the contrast resolution of rat bladder wall with high contrast-to-noise ratio (CNR). Here, the clinical safety and the feasibility of NCM-enhanced MRI to achieve artifact-free visualization of human bladder wall suitable for quantitative measurement of the magnetic resonance (MR) longitudinal relaxation time (T1) was assessed.
Methods
Six female subjects [two controls and two with Hunner-type interstitial cystitis IC and two with non-Hunner-type IC] consented for MRI at 3 T before and after instillation of NCM [4 mM gadobutrol and 5 mM ferumoxytol in 50 mL of sterile water for injection]. Single breath-hold fast MR acquisition in large readout bandwidth for 5-mm-thick single slice with variable flip angle was applied to minimize the motion and chemical shift artifacts in measurements of bladder wall thickness (BWT), CNR and T1 from 20 pixels.
Results
NCM instillation in subjects did not evoke pain or discomfort. Fourfold increase in bladder wall CNR (*p < 0.02) and pixel size of 0.35 mm with minimal influence of artifacts allowed accurate determination of bladder wall thinning ~ 0.46 mm from 50 mL NCM (*p < 0.05). Pre-contrast bladder wall T1 of 1544 ± 34.2 ms was shortened to 860.09 ± 13.95 ms in Hunner-type IC (*p < 0.0001) relative to only 1257.42 ± 20.59 and 1258.16 ± 6.16 ms in non-Hunner-type IC and controls, respectively.
Conclusion
Findings demonstrate the safety and feasibility of NCM-enhanced MRI to achieve artifact-free differential contrast and spatial resolution of human bladder wall, which is suitable for measuring BWT and pixel-wise measurement of T1 in post-contrast setting.
Similar content being viewed by others
References
Ackerman AL, Lee UJ, Jellison FC, Tan N, Patel M, Raman SS, Rodriguez LV (2016) MRI suggests increased tonicity of the levator ani in women with interstitial cystitis/bladder pain syndrome. Int Urogynecol J 27(1):77–83. https://doi.org/10.1007/s00192-015-2794-6
Rabie E, Faeghi F, Izadpanahi MH, Dayani MA (2016) Role of dynamic contrast-enhanced magnetic resonance imaging in staging of bladder cancer. J Clin Diagn Res JCDR 10(4):01–05. https://doi.org/10.7860/jcdr/2016/17596.7690
Magnotta VA, Friedman L, First B (2006) Measurement of signal-to-noise and contrast-to-noise in the fBIRN multicenter imaging study. J Digit Imaging 19(2):140–147. https://doi.org/10.1007/s10278-006-0264-x
Fisher MR, Hricak H, Crooks LE (1985) Urinary bladder MR imaging. Part I. Normal and benign conditions. Radiology 157(2):467–470. https://doi.org/10.1148/radiology.157.2.4048457
Ma Z, Jorge RN, Mascarenhas T, Tavares JM (2011) Novel approach to segment the inner and outer boundaries of the bladder wall in T2-weighted magnetic resonance images. Ann Biomed Eng 39(8):2287–2297. https://doi.org/10.1007/s10439-011-0324-3
Takeda K, Kawaguchi T, Shiraishi T, Kobayashi S, Hayashi N, Yanagawa M, Tochigi H, Sakuma H, Kawamura J, Nakagawa T (1998) Normal bladder wall morphology in Gd-DTPA-enhanced clinical MR imaging using an endorectal surface coil and histological assessment of submucosal linear enhancement using [14C]Gd-DOTA autoradiography in an animal model. Eur J Radiol 26(3):290–296
Alsinnawi M, Torreggiani W, Sheikh M, Thomas A, Donnellan J, Flynn R, McDermott TE, Thornhill J (2015) Delayed contrast-enhanced MRI to localize Botox after cystoscopic intravesical injection. Int Urol Nephrol 47(6):893–898. https://doi.org/10.1007/s11255-015-0976-2
Oelke M, Khullar V, Wijkstra H (2013) Review on ultrasound measurement of bladder or detrusor wall thickness in women: techniques, diagnostic utility, and use in clinical trials. World J Urol 31(5):1093–1104. https://doi.org/10.1007/s00345-013-1030-6
Bloch F (1953) The principle of nuclear induction. Science 118(3068):425–430. https://doi.org/10.1126/science.118.3068.425
Arheden H, Saeed M, Higgins CB, Gao DW, Bremerich J, Wyttenbach R, Dae MW, Wendland MF (1999) Measurement of the distribution volume of gadopentetate dimeglumine at echo-planar MR imaging to quantify myocardial infarction: comparison with 99mTc-DTPA autoradiography in rats. Radiology 211(3):698–708. https://doi.org/10.1148/radiology.211.3.r99jn41698
Stadler A, Jakob PM, Griswold M, Stiebellehner L, Barth M, Bankier AA (2008) T1 mapping of the entire lung parenchyma: influence of respiratory phase and correlation to lung function test results in patients with diffuse lung disease. Magn Reson Med 59(1):96–101. https://doi.org/10.1002/mrm.21446
Maeda H, Kinukawa T, Hattori R, Toyooka N, Furukawa T, Kuhara H (1995) Detection of muscle layer invasion with submillimeter pixel MR images: staging of bladder carcinoma. Magn Reson Imaging 13(1):9–19
Lammle M, Beer A, Settles M, Hannig C, Schwaibold H, Drews C (2002) Reliability of MR imaging-based virtual cystoscopy in the diagnosis of cancer of the urinary bladder. AJR Am J Roentgenol 178(6):1483–1488. https://doi.org/10.2214/ajr.178.6.1781483
Hood MN, Ho VB, Smirniotopoulos JG, Szumowski J (1999) Chemical shift: the artifact and clinical tool revisited. Radiographics 19(2):357–371. https://doi.org/10.1148/radiographics.19.2.g99mr07357
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(2):371–387. https://doi.org/10.1148/rg.322115125
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(3):631–638. https://doi.org/10.1016/j.juro.2015.08.077
Lee SK, Chang Y, Park NH, Kim YH, Woo S (2005) Magnetic resonance voiding cystography in the diagnosis of vesicoureteral reflux: comparative study with voiding cystourethrography. J Magn Reson Imaging JMRI 21(4):406–414. https://doi.org/10.1002/jmri.20273
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(2):F155–F162. https://doi.org/10.1152/ajprenal.00609.2016
Johnson GA, Cofer GP, Gewalt SL, Hedlund LW (2002) Morphologic phenotyping with MR microscopy: the visible mouse. Radiology 222(3):789–793. https://doi.org/10.1148/radiol.2223010531
Xie L, Layton AT, Wang N, Larson PE, Zhang JL, Lee VS, Liu C, Johnson GA (2016) Dynamic contrast-enhanced quantitative susceptibility mapping with ultrashort echo time MRI for evaluating renal function. Am J Physiol Renal Physiol 310(2):F174–F182. https://doi.org/10.1152/ajprenal.00351.2015
Elster AD, Sobol WT, Hinson WH (1990) Pseudolayering of Gd-DTPA in the urinary bladder. Radiology 174(2):379–381. https://doi.org/10.1148/radiology.174.2.2296649
Beyersdorff D, Taupitz M, Giessing M, Turk I, Schnorr D, Loening S, Hamm B (2000) The staging of bladder tumors in MRT: the value of the intravesical application of an iron oxide-containing contrast medium in combination with high-resolution T2-weighted imaging. RoFo Fortschritte auf dem Gebiete der Rontgenstrahlen und der Nuklearmedizin 172(6):504–508. https://doi.org/10.1055/s-2000-3751
Coolen BF, Geelen T, Paulis LE, Nauerth A, Nicolay K, Strijkers GJ (2011) Three-dimensional T1 mapping of the mouse heart using variable flip angle steady-state MR imaging. NMR Biomed 24(2):154–162. https://doi.org/10.1002/nbm.1566
Gowland P, Mansfield P, Bullock P, Stehling M, Worthington B, Firth J (1992) Dynamic studies of gadolinium uptake in brain tumors using inversion-recovery echo-planar imaging. Magn Reson Med 26(2):241–258
Sparenberg A, Hamm B, Hammerer P, Samberger V, Wolf KJ (1991) The diagnosis of bladder carcinomas by NMR tomography: an improvement with Gd-DTPA? RoFo Fortschritte auf dem Gebiete der Rontgenstrahlen und der Nuklearmedizin 155(2):117–122. https://doi.org/10.1055/s-2008-1033231
Rawls WF, Cox L, Rovner ES (2017) Dimethyl sulfoxide (DMSO) as intravesical therapy for interstitial cystitis/bladder pain syndrome: a review. Neurourol Urodyn 36(7):1677–1684. https://doi.org/10.1002/nau.23204
Walker SJ, Zambon J, Andersson KE, Langefeld C, Matthews CA, Badlani G, Bowman H, Evans RJ (2017) Bladder capacity is a biomarker for a bladder-centric versus systemic manifestation in interstitial cystitis/bladder pain syndrome. J Urol. https://doi.org/10.1016/j.juro.2017.02.022
Tiderius C, Hori M, Williams A, Sharma L, Prasad PV, Finnell M, McKenzie C, Burstein D (2006) dGEMRIC as a function of BMI. Osteoarthr Cartil 14(11):1091–1097. https://doi.org/10.1016/j.joca.2006.05.007
Mehnert U, Boy S, Schmid M, Reitz A, von Hessling A, Hodler J, Schurch B (2009) A morphological evaluation of botulinum neurotoxin A injections into the detrusor muscle using magnetic resonance imaging. World J Urol 27(3):397–403. https://doi.org/10.1007/s00345-008-0362-0
Deoni SC, Rutt BK, Peters TM (2003) Rapid combined T1 and T2 mapping using gradient recalled acquisition in the steady state. Magn Reson Med 49(3):515–526. https://doi.org/10.1002/mrm.10407
Kanazawa Y, Miyati T, Sato O (2012) Hemodynamic analysis of bladder tumors using T1-dynamic contrast-enhanced fast spin-echo MRI. Eur J Radiol 81(8):1682–1687. https://doi.org/10.1016/j.ejrad.2011.04.013
Funding
This project was funded by NIDDK Grant 1R41DK108397. Authors would also like to acknowledge the contribution of Janet Erickson and Anna Wecht in patient recruitment and for assistance during scanning.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
Pradeep Tyagi, Chan-Hong Moon and Christopher Chermansky declare that they have no conflict of interest. Joseph Janicki and Jonathan Kaufman are the employees of Lipella Pharmaceuticals, and Jonathan Kaufman is the inventor of the novel contrast mixture.
Ethical approval
All procedures performed in studies involving human participants were in accordance with the Ethical Standards of the University of Pittsburgh Institutional Review Board and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.
Informed consent
Informed consent was obtained from all individual participants included in the study.
Rights and permissions
About this article
Cite this article
Tyagi, P., Janicki, J., Moon, CH. et al. Novel contrast mixture achieves contrast resolution of human bladder wall suitable for T1 mapping: applications in interstitial cystitis and beyond. Int Urol Nephrol 50, 401–409 (2018). https://doi.org/10.1007/s11255-018-1794-0
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11255-018-1794-0