University of Oulu

Stewart, R., Honkanen, J., Kokkonen, H., Tiitu, V., Saarakkala, S., Joukainen, A., Snyder, B., Jurvelin, J., Grinstaff, M., Töyräs, J. (2016) Contrast-Enhanced Computed Tomography Enables Quantitative Evaluation of Tissue Properties at Intrajoint Regions in Cadaveric Knee Cartilage. Cartilage, 8 (4), 391-399. doi:10.1177/1947603516665443

Contrast-enhanced computed tomography enables quantitative evaluation of tissue properties at intrajoint regions in cadaveric knee cartilage

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Author: Stewart, Rachel C.1,2; Honkanen, Juuso T. J.3,4; Kokkonen, Harri T.4;
Organizations: 1Department of Biomedical Engineering, Boston University
2Center for Advanced Orthopaedic Studies, Beth Israel Deaconess Medical Center and Harvard Medical School
3Department of Applied Physics, University of Eastern Finland, Kuopio
4Diagnostic Imaging Center, Kuopio University Hospital
5Institute of Biomedicine, Anatomy, University of Eastern Finland, Kuopio
6Research Unit of Medical Imaging, Physics and Technology, Faculty of Medicine, University of Oulu
7Department of Diagnostic Radiology, Oulu University Hospital
8Medical Research Center Oulu, Oulu University Hospital and University of Oulu
9Department of Orthopaedics, Traumatology and Hand Surgery, Kuopio University Hospital
10Department of Chemistry, Boston University
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 0.6 MB)
Persistent link:
Language: English
Published: SAGE Publications, 2017
Publish Date: 2017-12-20


Objective: The aim of this study was to investigate whether the concentration of the anionic contrast agent ioxaglate, as quantitated by contrast-enhanced computed tomography (CECT) using a clinical cone-beam CT (CBCT) instrument, reflects biochemical, histological, and biomechanical characteristics of articular cartilage imaged in an ex vivo, intact human knee joint.

Design: An osteoarthritic human cadaveric knee joint (91 years old) was injected with ioxaglate (36 mg I/mL) and imaged using CBCT over 61 hours of ioxaglate diffusion into cartilage. Following imaging, the joint surfaces were excised, rinsed to remove contrast agent, and compressive stiffness (equilibrium and instantaneous compressive moduli) was measured via indentation testing (n = 17 sites). Each site was sectioned for histology and assessed for glycosaminoglycan content using digital densitometry of Safranin-O stained sections, Fourier transform infrared spectroscopy for collagen content, and morphology using both the Mankin and OARSI semiquantitative scoring systems. Water content was determined using mass change after lyophilization.

Results: CECT attenuation at all imaging time points, including those <1 hour of ioxaglate exposure, correlated significantly (P < 0.05) with cartilage water and glycosaminoglycan contents, Mankin score, and both equilibrium and instantaneous compressive moduli. Early time points (<30 minutes) also correlated (P < 0.05) with collagen content and OARSI score. Differences in cartilage quality between intrajoint regions were distinguishable at diffusion equilibrium and after brief ioxaglate exposure.

Conclusions: CECT with ioxaglate affords biochemical and biomechanical measurements of cartilage health and performance even after short, clinically relevant exposure times, and may be useful in the clinic as a means for detecting early signs of cartilage pathology.

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Series: Cartilage
ISSN: 1947-6035
ISSN-E: 1947-6043
ISSN-L: 1947-6035
Volume: 8
Issue: 4
Pages: 391 - 399
DOI: 10.1177/1947603516665443
Type of Publication: A1 Journal article – refereed
Field of Science: 3126 Surgery, anesthesiology, intensive care, radiology
Funding: This research was supported by the United States National Institutes of Health (grant R01GM098361), The Osteoarthritis Research Society International (Collaborative Scholarship) and the American-Scandinavian Foundation (The Jane and Aatos Erkko Fund). Kuopio University Hospital (EVO 5041746, PY 210 and EVO 5063535, PY 210), strategic funding from the University of Eastern Finland, The Academy of Finland (projects 269315 and 268378), Magnus Ehrnrooth Foundation, European Research Council under the European Union’s Seventh Framework Programme (FP/2007-2013)/ERC Grant Agreement no. 336267, TBDP graduate school and the Saastamoinen Foundation are also acknowledged for financial support.
EU Grant Number: (336267) 3D-OA-HISTO - Development of 3D Histopathological Grading of Osteoarthritis
Academy of Finland Grant Number: 269315
Detailed Information: 269315 (Academy of Finland Funding decision)
268378 (Academy of Finland Funding decision)
Copyright information: © The Author(s) 2016. This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License ( which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access page (