title: Contrast-enhanced CT facilitates rapid, non-destructive assessment of cartilage and bone properties of the human metacarpal.
abstract: OBJECTIVE
  The aim of this work is to establish the human metacarpal as a new whole joint surface early-stage osteoarthritis (OA) model that enables comparisons of articular cartilage and subchondral bone through high resolution contrast-enhanced CT (CECT) imaging, mechanical testing, and biochemical analysis.
  
  
  METHODS
  The fourth metacarpal was obtained from 12 human cadaveric donors and baseline μCT imaging was followed by indentation testing. The samples were then immersed in anionic (Ioxaglate) and cationic (CA4+) iodinated contrast agent solutions followed by CECT. Cartilage GAG content and distribution was measured using the 1,9 dimethylmethylene blue (DMMB) assay and Safranin-O histology staining. Linear regression was performed to compare cartilage and subchondral bone properties.
  
  
  RESULTS
  Strong and significant positive correlations were observed between CA4+ CECT attenuation and both GAG content (R(2) = 0.86) and equilibrium modulus (R(2) = 0.84), while correlations using Ioxaglate were insignificant (R(2) ≤ 0.24, P > 0.05). Subchondral bone plate (SBP) thickness negatively and significantly correlated with SBP mineral density (R(2) = 0.49). Cartilage GAG content significantly correlated with several trabecular bone properties, including positive correlations with bone volume fraction (%BV/TV, R(2) = 0.67), trabecular number (Tb.N, R(2) = 0.60), and trabecular thickness (R(2) = 0.42), and negative relationships with structural model index (SMI, R(2) = 0.78) and trabecular spacing (Tb.Sp, R(2) = 0.56). Similarly, equilibrium modulus correlated positively with %BV/TV (R(2) = 0.50), Tb.N (R(2) = 0.59) and negatively with Tb.Sp (R(2) = 0.55) and SMI (R(2) = 0.60).
  
  
  CONCLUSIONS
  This study establishes the human metacarpal as a new early-stage OA model suitable for rapid, high resolution CECT imaging, mechanical testing, and biochemical analysis of the cartilage and subchondral bone, and for examining their inter-relationships.
authors.affiliation: Center for Advanced Orthopaedic Studies, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA; Department of Biomedical Engineering, Boston University, Boston, MA, USA.
authors.forename: B A
authors.initials: BA
authors.lastname: Lakin
authors.affiliation: Center for Advanced Orthopaedic Studies, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
authors.forename: D J
authors.initials: DJ
authors.lastname: Ellis
authors.affiliation: Center for Advanced Orthopaedic Studies, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA; Department of Biomedical Engineering, Boston University, Boston, MA, USA.
authors.forename: J S
authors.initials: JS
authors.lastname: Shelofsky
authors.affiliation: Center for Advanced Orthopaedic Studies, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA; Department of Pharmacology and Experimental Therapeutics, Boston University, Boston, MA, USA.
authors.forename: J D
authors.initials: JD
authors.lastname: Freedman
authors.affiliation: Department of Biomedical Engineering, Boston University, Boston, MA, USA; Department of Chemistry, Boston University, Boston, MA, USA. Electronic address: mgrin@bu.edu.
authors.forename: M W
authors.initials: MW
authors.lastname: Grinstaff
authors.affiliation: Center for Advanced Orthopaedic Studies, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA; Department of Orthopaedic Surgery, Boston Children's Hospital, Boston, MA, USA. Electronic address: bsnyder@bidmc.harvard.edu.
authors.forename: B D
authors.initials: BD
authors.lastname: Snyder
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D015519:Bone Density; D002102:Cadaver; D002358:Cartilage, Articular / Q000000981:diagnostic imaging* / Q000378:metabolism / Q000473:pathology; D019245:Compressive Strength; D003287:Contrast Media; D005260:Female; D006025:Glycosaminoglycans / Q000378:metabolism; D006801:Humans; D007485:Ioxaglic Acid; D016014:Linear Models; D008297:Male; D050279:Metacarpal Bones / Q000000981:diagnostic imaging* / Q000378:metabolism / Q000473:pathology; D008662:Metacarpophalangeal Joint / Q000000981:diagnostic imaging* / Q000378:metabolism / Q000473:pathology; D008875:Middle Aged; D014057:Tomography, X-Ray Computed; D055114:X-Ray Microtomography
chemical_list: D003287:Contrast Media; D006025:Glycosaminoglycans; D007485:Ioxaglic Acid
keywords: Cartilage; Compressive modulus; Computed tomography; Human; Osteoarthritis; Subchondral bone