title: Novel contrast mixture improves bladder wall contrast for visualizing bladder injury.
abstract: Here, we tested whether combined contrast-enhanced magnetic resonance imaging (CCE-MRI), using a mixture of gadolinium- and iron oxide-based contrast agents, can segment the bladder wall from the bladder lumen. CCE-MRI relies on the differences in particle size and contrast mechanisms of two agents for improved image contrast. Under isoflurane anesthesia, T1-weighted imaging of adult female Sprague-Dawley rat bladder was performed using standard turbospin echo sequences at 7 Tesla, before and after transurethral instillation of 0.3 ml of single-contrast MRI or CCE-MRI composed of 0.4-64 mM of gadolinium chelate (Gd-DTPA/Gadavist) and 5 mM ferumoxytol. Bladder wall contrast was assessed in the control group exposed to saline and in the bladder injury group exposed to 0.5 ml of protamine sulfate (10 mg/ml) for 30 min. CCE-MRI following instillation of 0.4-4 mM Gd-DTPA and 5 mM ferumoxytol mixture achieved segmentation between the bladder lumen and bladder wall. Hyperintensity in the bladder wall combined with hypointensity in the lumen is consistent with the increased diffusion of the dissolved Gd-DTPA and simultaneous localization of the larger nanoparticles of ferumoxytol in the lumen. The normalized hyperintense signal in the bladder wall increased from 0.46 ± 0.07 in control group to 0.73 ± 0.14 in the protamine sulfate-exposed group (P< 0.0001). CCE-MRI following instillation of contrast mixture identifies bladder wall changes likely associated with bladder injury with improved image contrast.
authors.affiliation: Department of Urology, University of Pittsburgh, Pittsburgh, Pennsylvania; tyagip@upmc.edu.
authors.forename: Pradeep
authors.initials: P
authors.lastname: Tyagi
authors.affiliation: Lipella Pharmaceuticals, Pittsburgh, Pennsylvania.
authors.forename: Joseph J
authors.initials: JJ
authors.lastname: Janicki
authors.affiliation: Animal Imaging Center, University of Pittsburgh, Pittsburgh, Pennsylvania.|Department of Neurobiology, University of Pittsburgh, Pittsburgh, Pennsylvania; and.
authors.forename: T Kevin
authors.initials: TK
authors.lastname: Hitchens
authors.affiliation: Animal Imaging Center, University of Pittsburgh, Pittsburgh, Pennsylvania.
authors.forename: Lesley M
authors.initials: LM
authors.lastname: Foley
authors.affiliation: Department of Urology, University of Pittsburgh, Pittsburgh, Pennsylvania.
authors.forename: Mahendra
authors.initials: M
authors.lastname: Kashyap
authors.affiliation: Department of Urology, University of Pittsburgh, Pittsburgh, Pennsylvania.
authors.forename: Naoki
authors.initials: N
authors.lastname: Yoshimura
authors.affiliation: Lipella Pharmaceuticals, Pittsburgh, Pennsylvania.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Kaufman
mesh_terms: D000283:Administration, Intravesical; D000818:Animals; D003287:Contrast Media / Q000008:administration & dosage*; D004195:Disease Models, Animal; D005260:Female; D052203:Ferrosoferric Oxide / Q000008:administration & dosage*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D053758:Nanoparticles; D009942:Organometallic Compounds / Q000008:administration & dosage*; D010316:Particle Size; D011237:Predictive Value of Tests; D011479:Protamines; D017207:Rats, Sprague-Dawley; D015203:Reproducibility of Results; D013997:Time Factors; D001743:Urinary Bladder / Q000000981:diagnostic imaging* / Q000473:pathology; D001745:Urinary Bladder Diseases / Q000139:chemically induced / Q000000981:diagnostic imaging* / Q000473:pathology
chemical_list: D003287:Contrast Media; D009942:Organometallic Compounds; D011479:Protamines; C090600:gadobutrol; D052203:Ferrosoferric Oxide
keywords: T1; combined contrast-enhanced magnetic resonance imaging; ferumoxytol; gadolinium; protamine