title: Manganese-based oral contrast agent for liver magnetic resonance imaging: evaluation of the time course and dose response of liver signal intensity enhancement.
abstract: OBJECTIVE
  Recently, an oral contrast agent (CMC-001, CMC Contrast, Lund, Sweden) containing manganese chloride tetrahydrate (MnCl2) as active substance has been introduced for liver magnetic resonance imaging (MRI). The aim of this study was to evaluate the time course and dose response of liver signal intensity (SI) enhancement and liver-lesion contrast (LLC) after administration of 2 doses of CMC-001 corresponding to 0.8 g MnCl2 and 1.6 g MnCl2.
  
  
  METHODS
  A total of 20 patients with liver metastases diagnosed by computed tomography were included in this prospective study. Patients were randomly assigned to receive either 0.8 g MnCl2 (n = 11) or 1.6 g MnCl2 (n = 9). MRI was performed precontrast (0 hour) and at 1, 2, 3, and 6 hours after contrast agent administration using a breath-hold T1-weighted gradient echo sequence (GRE). For quantitative analysis, SI was measured in regions of interest in the liver and in representative liver metastases. Liver SI enhancement and LLC were calculated. Area under the curve analysis was performed for liver SI enhancement and LLC in both dose groups. The dose groups were compared with a Wilcoxon rank-sum test for independent samples. Tests for pairwise differences between the time points were performed with paired Wilcoxon signed-rank tests.
  
  
  RESULTS
  Area under the curve analysis revealed no statistical significant differences for liver SI enhancement and LLC between the 0.8 and 1.6 g MnCl2 dose group (P = 1.00 and P = 0.94, respectively). Liver parenchyma showed significant SI enhancement until 3 hours after contrast agent administration (median of pooled data from both dose groups: 1 hour, 24.7%; 2 hours, 37.2%; 3 hours, 54.9%; 6 hours, 47.3%). LLC significantly increased until 2 hours after contrast agent administration (median of pooled data from both dose groups: 0 hour, 0.19; 1 hour, 0.29; 2 hours, 0.36; 3 hours, 0.37; 6 hours, 0.36). Liver SI enhancement and LLC showed no significant differences between 3 hours and 6 hours after contrast agent administration (P = 0.75 and P = 0.25, respectively). Mild adverse events occurred in 6 patients (30%) after contrast agent administration.
  
  
  CONCLUSIONS
  CMC-001 at doses corresponding to 0.8 and 1.6 g MnCl2 offers robust liver SI enhancement with a diagnostic time window for liver MRI between 2 and 6 hours after oral administration.
authors.affiliation: Department of Radiology, Charité-Universitätsmedizin Berlin, Berlin, Germany. matthias.rief@charite.de
authors.forename: Matthias
authors.initials: M
authors.lastname: Rief
authors.forename: Alexander
authors.initials: A
authors.lastname: Huppertz
authors.forename: Patrick
authors.initials: P
authors.lastname: Asbach
authors.forename: Tobias
authors.initials: T
authors.lastname: Franiel
authors.forename: Carsten
authors.initials: C
authors.lastname: Schwenke
authors.forename: Bernd
authors.initials: B
authors.lastname: Hamm
authors.forename: Matthias
authors.initials: M
authors.lastname: Taupitz
authors.forename: Moritz
authors.initials: M
authors.lastname: Wagner
mesh_terms: D000368:Aged; D019540:Area Under Curve; D002712:Chlorides; D003287:Contrast Media; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008099:Liver / Q000000981:diagnostic imaging* / Q000187:drug effects; D008113:Liver Neoplasms / Q000175:diagnosis / Q000000981:diagnostic imaging* / Q000473:pathology; D008279:Magnetic Resonance Imaging / Q000295:instrumentation / Q000379:methods*; D008297:Male; D008345:Manganese; D017895:Manganese Compounds; D008875:Middle Aged; D009362:Neoplasm Metastasis / Q000175:diagnosis / Q000000981:diagnostic imaging / Q000473:pathology; D011446:Prospective Studies; D011856:Radiographic Image Enhancement; D011877:Radionuclide Imaging; D013223:Statistics as Topic; D018709:Statistics, Nonparametric; D013997:Time Factors; D014131:Trace Elements
chemical_list: D002712:Chlorides; D003287:Contrast Media; D017895:Manganese Compounds; D014131:Trace Elements; D008345:Manganese; C025340:manganese chloride