Contrast-enhanced CT with a high-affinity cationic contrast agent for imaging ex vivo bovine, intact ex vivo rabbit, and in vivo rabbit cartilage

Radiology. 2013 Jan;266(1):141-50. doi: 10.1148/radiol.12112246. Epub 2012 Nov 28.


Purpose: To quantify the affinity of a cationic computed tomography (CT) contrast agent (CA(4+)) and that of an anionic contrast agent (ioxaglate) to glycosaminoglycans (GAGs) in ex vivo cartilage tissue explants and to characterize the in vivo diffusion kinetics of CA(4+) and ioxaglate in a rabbit model.

Materials and methods: All in vivo procedures were approved by the institutional animal care and use committee. The affinities of ioxaglate and CA(4+) to GAGs in cartilage (six bovine osteochondral plugs) were quantified by means of a modified binding assay using micro-CT after plug equilibration in serial dilutions of each agent. The contrast agents were administered intraarticularly to the knee joints of five New Zealand white rabbits to determine the in vivo diffusion kinetics and cartilage tissue imaging capabilities. Kinetics of diffusion into the femoral groove cartilage and relative contrast agent uptake into bovine plugs were characterized by means of nonlinear mixed-effects models. Diffusion time constants (τ) were compared by using a Student t test.

Results: The uptake of CA(4+) in cartilage was consistently over 100% of the reservoir concentration, whereas it was only 59% for ioxaglate. In vivo, the contrast material-enhanced cartilage reached a steady CT attenuation for both CA(4+) and ioxaglate, with τ values of 13.8 and 6.5 minutes, respectively (P = .04). The cartilage was easily distinguishable from the surrounding tissues for CA(4+) (12 mg of iodine per milliliter); comparatively, the anionic contrast agent provided less favorable imaging results, even when a higher concentration was used (80 mg of iodine per milliliter).

Conclusion: The affinity of the cationic contrast agent CA(4+) to GAGs enables high-quality imaging and segmentation of ex vivo bovine and rabbit cartilage, as well as in vivo rabbit cartilage.

Supplemental material:

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cartilage, Articular / diagnostic imaging*
  • Cartilage, Articular / metabolism*
  • Cations
  • Cattle
  • Contrast Media
  • Glycosaminoglycans / metabolism*
  • Ioxaglic Acid / pharmacokinetics*
  • Metabolic Clearance Rate
  • Rabbits
  • Reproducibility of Results
  • Sensitivity and Specificity
  • Tissue Distribution
  • Tomography, X-Ray Computed / methods*


  • Cations
  • Contrast Media
  • Glycosaminoglycans
  • Ioxaglic Acid