title: Contrast-enhanced CT using a cationic contrast agent enables non-destructive assessment of the biochemical and biomechanical properties of mouse tibial plateau cartilage.
abstract: Mouse models of osteoarthritis (OA) are commonly used to study the disease's pathogenesis and efficacy of potential treatments. However, measuring the biochemical and mechanical properties of articular cartilage in these models currently requires destructive and time-consuming histology and mechanical testing. Therefore, we examined the feasibility of using contrast-enhanced CT (CECT) to rapidly and non-destructively image and assess the glycosaminoglycan (GAG) content. Using three ex vivo C57BL/6 mouse tibial plateaus, we determined the time required for the cationic contrast agent CA4+ to equilibrate in the cartilage. The whole-joint coefficient of friction (μ) of 10 mouse knees (some digested with Chondroitenase ABC to introduce variation in GAG) was evaluated using a modified Stanton pendulum. For both the medial and lateral tibial plateau cartilage of these knees, linear regression was used to compare the equilibrium CECT attenuations to μ, as well as each side's indentation equilibrium modulus (E) and Safranin-O determined GAG content. CA4+ equilibrated in the cartilage in 30.9 ± 0.95 min (mean ± SD, tau value of 6.17 ± 0.19 min). The mean medial and lateral CECT attenuation was correlated with μ (R(2)  = 0.69, p < 0.05), and the individual medial and lateral CECT attenuations correlated with their respective GAG contents (R(2)  ≥ 0.63, p < 0.05) and E (R(2)  ≥ 0.63, p < 0.05). In conclusion, CECT using CA4+ is a simple, non-destructive technique for three-dimensional imaging of ex vivo mouse cartilage, and significant correlations between CECT attenuation and GAG, E, and μ are observed. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:1130-1138, 2016.
authors.affiliation: Center for Advanced Orthopaedic Studies, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts.|Department of Biomedical Engineering, Boston University, Boston, Massachusetts.
authors.forename: Benjamin A
authors.initials: BA
authors.lastname: Lakin
authors.affiliation: Center for Advanced Orthopaedic Studies, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts.|Department of Biomedical Engineering, Boston University, Boston, Massachusetts.
authors.forename: Harsh
authors.initials: H
authors.lastname: Patel
authors.affiliation: Department of Biomedical Engineering, Boston University, Boston, Massachusetts.
authors.forename: Conor
authors.initials: C
authors.lastname: Holland
authors.affiliation: Center for Advanced Orthopaedic Studies, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts.|Department of Pharmacology and Experimental Therapeutics, Boston University, Boston, Massachusetts.
authors.forename: Jonathan D
authors.initials: JD
authors.lastname: Freedman
authors.affiliation: Center for Advanced Orthopaedic Studies, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts.|Department of Biomedical Engineering, Boston University, Boston, Massachusetts.
authors.forename: Joshua S
authors.initials: JS
authors.lastname: Shelofsky
authors.affiliation: Center for Advanced Orthopaedic Studies, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts.|Department of Orthopaedic Surgery, Children's Hospital, Boston, Massachusetts.
authors.forename: Brian D
authors.initials: BD
authors.lastname: Snyder
authors.affiliation: Institute for Biomechanics, ETH Zürich, Zürich, Switzerland.|Scanco Medical AG, Brüttisellen, Switzerland.
authors.forename: Kathryn S
authors.initials: KS
authors.lastname: Stok
authors.affiliation: Department of Biomedical Engineering, Boston University, Boston, Massachusetts.|Department of Chemistry, Boston University, Boston, Massachusetts.
authors.forename: Mark W
authors.initials: MW
authors.lastname: Grinstaff
mesh_terms: D000818:Animals; D002358:Cartilage, Articular / Q000737:chemistry / Q000000981:diagnostic imaging*; D003287:Contrast Media; D005029:Ethylenediamines; D005260:Female; D006025:Glycosaminoglycans / Q000032:analysis; D007462:Iodobenzenes; D008810:Mice, Inbred C57BL; D010619:Phenazines; D011897:Random Allocation; D013977:Tibia; D014057:Tomography, X-Ray Computed
chemical_list: D003287:Contrast Media; D005029:Ethylenediamines; D006025:Glycosaminoglycans; D007462:Iodobenzenes; D010619:Phenazines; C009195:safranine T
keywords: coefficient of friction; compressive modulus; glycosaminoglycan; micro-computed tomography; osteoarthritis