title: Micro-computed tomography and nuclear magnetic resonance imaging for noninvasive, live-mouse cholangiography.
abstract: The cholangiopathies are a diverse group of biliary tract disorders, many of which lack effective treatment. Murine models are an important tool for studying their pathogenesis, but existing noninvasive methods for assessing biliary disease in vivo are not optimal. Here we report our experience with using micro-computed tomography (microCT) and nuclear magnetic resonance (MR) imaging to develop a technique for live-mouse cholangiography. Using mdr2 knockout (mdr2KO, a model for primary sclerosing cholangitis (PSC)), bile duct-ligated (BDL), and normal mice, we performed in vivo: (1) microCT on a Siemens Inveon PET/CT scanner and (2) MR on a Bruker Avance 16.4 T spectrometer, using Turbo Rapid Acquisition with Relaxation Enhancement, IntraGate Fast Low Angle Shot, and Half-Fourier Acquisition Single-shot Turbo Spin Echo methods. Anesthesia was with 1.5-2.5% isoflurane. Scans were performed with and without contrast agents (iodipamide meglumine (microCT), gadoxetate disodium (MR)). Dissection and liver histology were performed for validation. With microCT, only the gallbladder and extrahepatic bile ducts were visualized despite attempts to optimize timing, route, and dose of contrast. With MR, the gallbladder, extra-, and intrahepatic bile ducts were well-visualized in mdr2KO mice; the cholangiographic appearance was similar to that of PSC (eg, multifocal strictures) and could be improved with contrast administration. In BDL mice, MR revealed cholangiographically distinct progressive dilation of the biliary tree without ductal irregularity. In normal mice, MR allowed visualization of the gallbladder and extrahepatic ducts, but only marginal visualization of the diminutive intrahepatic ducts. One mouse died during microCT and MR imaging, respectively. Both microCT and MR scans could be obtained in ≤20 min. We, therefore, demonstrate that MR cholangiography can be a useful tool for longitudinal studies of the biliary tree in live mice, whereas microCT yields suboptimal duct visualization despite requiring contrast administration. These findings support further development and application of MR cholangiography to the study of mouse models of PSC and other cholangiopathies.
authors.affiliation: Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN 55905, USA.
authors.forename: James H
authors.initials: JH
authors.lastname: Tabibian
authors.forename: Slobodan I
authors.initials: SI
authors.lastname: Macura
authors.forename: Steven P
authors.initials: SP
authors.lastname: O'Hara
authors.forename: Jeff L
authors.initials: JL
authors.lastname: Fidler
authors.forename: James F
authors.initials: JF
authors.lastname: Glockner
authors.forename: Naoki
authors.initials: N
authors.lastname: Takahashi
authors.forename: Val J
authors.initials: VJ
authors.lastname: Lowe
authors.forename: Bradley J
authors.initials: BJ
authors.lastname: Kemp
authors.forename: Prasanna K
authors.initials: PK
authors.lastname: Mishra
authors.forename: Pamela S
authors.initials: PS
authors.lastname: Tietz
authors.forename: Patrick L
authors.initials: PL
authors.lastname: Splinter
authors.forename: Christy E
authors.initials: CE
authors.lastname: Trussoni
authors.forename: Nicholas F
authors.initials: NF
authors.lastname: LaRusso
mesh_terms: D000818:Animals; D001649:Bile Duct Diseases / Q000000981:diagnostic imaging*; D002758:Cholangiography; D003287:Contrast Media; D004195:Disease Models, Animal; D005260:Female; D019786:Gadolinium DTPA; D008279:Magnetic Resonance Imaging; D008297:Male; D051379:Mice; D055114:X-Ray Microtomography
chemical_list: D003287:Contrast Media; C073590:gadolinium ethoxybenzyl DTPA; D019786:Gadolinium DTPA