title: A comparative analysis of water-soluble and blood-pool contrast agents for in vivo vascular imaging with micro-CT.
abstract: OBJECTIVE
  In recent years, micro-computed tomography (micro-CT) has emerged as a high-resolution modality for vascular exploration in vivo. Several x-ray contrast agents for in vivo imaging are on the market and are based on different formulations. The objective of this study was to compare contrast-related and pharmacokinetic properties of a water-soluble compound containing iomeprol (Iomeron 400) and blood-pool agents (eXIA160XL, AuroVist 15 nm, and ExiTron nano 12000) for the identification of suitable in vivo vascular imaging applications.
  
  
  METHODS
  Forty-four healthy C57BL/6J mice were used in this study. Iomeprol was administered with a continuous infusion protocol; the other agents as a bolus. Anatomical micro-CT was applied at the head, neck, and lower hind limb before (baseline) and immediately after contrast injection, and used to quantify contrast-related properties of the agents. Dynamic micro-CT was applied at the same regions to characterize the agents pharmacokinetics.
  
  
  RESULTS
  All contrast media revealed safe, except for eXIA160XL, which caused death in four of eight tested animals and was therefore excluded early from the study. AuroVist 15 nm provided the highest attenuation (2.33/mm) as compared to iomeprol (1.97/mm) and ExiTron nano 12000 (1.58/mm) and a maximum temporal variation of contrast of 20% after 30 minutes, but the appearance of a dark skin staining did not allow multiple injections of the agent. Iomeprol passively diffused across capillary membranes, and after 30 minutes doubled the tissue contrast with respect to its initial levels. ExiTron nano 12000 revealed temporal variations of contrast below 10% and significantly reduced clearance rates after the third consecutive injection.
  
  
  CONCLUSIONS
  AuroVist 15 nm is best suited for anatomical investigation of the vascular network, while the high extravasation levels of iomeprol can be exploited for perfusion analysis. ExiTron nano 12000 is indicated for use in longitudinal monitoring with repeated injections.
authors.affiliation: Institute for Biomechanics, ETH Zurich, Wolfgang-Pauli-Strasse 10, 8093 Zurich, Switzerland.
authors.forename: Laura
authors.initials: L
authors.lastname: Nebuloni
authors.forename: Gisela A
authors.initials: GA
authors.lastname: Kuhn
authors.forename: Ralph
authors.initials: R
authors.lastname: Müller
mesh_terms: D000792:Angiography / Q000379:methods / Q000662:veterinary*; D000818:Animals; D003287:Contrast Media / Q000737:chemistry / Q000493:pharmacokinetics; D005260:Female; D007479:Iopamidol / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D053768:Metal Nanoparticles; D051379:Mice; D008810:Mice, Inbred C57BL; D055806:Microvessels / Q000000981:diagnostic imaging*; D011856:Radiographic Image Enhancement / Q000379:methods; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D012995:Solubility; D014057:Tomography, X-Ray Computed / Q000379:methods / Q000662:veterinary*; D014867:Water / Q000737:chemistry
chemical_list: D003287:Contrast Media; D014867:Water; C057937:iomeprol; D007479:Iopamidol
keywords: C57BL/6J mice; In vivo micro-CT; contrast agent; vascular network