Abstract
ABSTRACTDual contrast micro computed tomography (CT) shows potential for detecting articular cartilage degeneration. However, the performance of conventional CT systems is limited by beam hardening, low image resolution (full‐body CT), and long acquisition times (conventional microCT). Therefore, to reveal the full potential of the dual contrast technique for imaging cartilage composition we employ the technique using synchrotron microCT. We hypothesize that the above‐mentioned limitations are overcome with synchrotron microCT utilizing monochromatic X‐ray beam and fast image acquisition. Human osteochondral samples (n = 41, four cadavers) were immersed in a contrast agent solution containing two agents (cationic CA4+ and non‐ionic gadoteridol) and imaged with synchrotron microCT at an early diffusion time point (2 h) and at diffusion equilibrium (72 h) using two monochromatic X‐ray energies (32 and 34 keV). The dual contrast technique enabled simultaneous determination of CA4+ (i.e., proteoglycan content) and gadoteridol (i.e., water content) partitions within cartilage. Cartilage proteoglycan content and biomechanical properties correlated significantly (0.327 < r < 0.736, p < 0.05) with CA4+ partition in superficial and middle zones at both diffusion time points. Normalization of the CA4+ partition with gadoteridol partition within the cartilage significantly (p < 0.05) improved the detection sensitivity for human osteoarthritic cartilage proteoglycan content, biomechanical properties, and overall condition (Mankin, Osteoarthritis Research Society International, and International Cartilage Repair Society grading systems). The dual energy technique combined with the dual contrast agent enables assessment of human articular cartilage proteoglycan content and biomechanical properties based on CA4+ partition determined using synchrotron microCT. Additionally, the dual contrast technique is not limited by the beam hardening artifact of conventional CT systems. © 2019 The Authors. Journal of Orthopaedic Research® published by Wiley Periodicals, Inc. on behalf of Orthopaedic Research Society. J Orthop Res 38:563–573, 2020
Highlights
Cationic contrast agents are more sensitive to cartilage PG content at diffusion equilibrium than anionic agents due to electrostatic attraction between cationic molecules and negatively charged PGs
The microCT measured composition of the contrast agent mixture phantoms agreed with the true composition (Pearson’s correlation, R2 = 1.000, p < 0.0001)
At early diffusion time points, degeneration‐induced PG loss decreases the diffusion while the increase in water content and permeability increase the diffusion
Summary
As monochromatized synchrotron microCT X‐ray beams exhibit a narrow energy spectra, the contrast difference between the two images and between the contrast agents is maximized. For the first time, we employ two different monochromatic X‐ray energies in high‐resolution synchrotron‐based microCT to image the diffusion of dual contrast agent in human articular cartilage. The aim of this study is to assess the full potential of the dual contrast technique to detect human articular cartilage degeneration at a clinically relevant diffusion time point (2 h) and at diffusion equilibrium (72 h). We hypothesize that synchrotron‐based microCT will provide sensitive dual contrast diagnosis of spontaneous arthritic human articular cartilage and that limitations of conventional CT systems are overcome with synchrotron microCT employing monochromatic X‐ray beam and fast image acquisition
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