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DGEMRIC and CECT Comparison of Cationic and Anionic Contrast Agents in Cadaveric Human Metacarpal Cartilage.

ABSTRACT: Magnetic resonance imaging (MRI) and computed tomography (CT) are widely used to image cartilage and their diagnostic capability is enhanced in the presence of contrast agents. The aim of the study is to directly compare the performance between commercial anionic MRI (Gd(DTPA), Gd2-) and CT (Ioxaglate, Iox1-) contrast agents with novel cationic MRI (Gd(DTPA)Lys₂ , Gd4+) and CT (CA4+) contrast agents for assessment of cartilage mechanical and biochemical properties using the ex vivo human osteoarthritis metacarpal cartilage model. First, indentation testing was conducted to obtain the compressive modulus of the human fifth metacarpals. The samples were then immersed in the anionic and cationic contrast agents prior to delayed gadolinium-enhanced MRI of cartilage and CT scanning, respectively. The cartilage glycosaminoglycan (GAG) content and distribution were determined using the 1,9-dimethylmethylene blue assay and Safranin-O histology. Cationic agents significantly accumulate in cartilage compared with anionic agents. Significant positive correlations (p < 0.05) exist between imaging results of cationic agents and GAG content (Gd4+: R² = 0.43; CA4+: R² = 0.67) and indentation equilibrium modulus (Gd4+: R² = 0.48; CA4+: R² = 0.77). Significant negative correlations are observed between anionic MRI relaxation times, but not contrast-enhanced computed tomography attenuation and cartilage GAG content (Gd2-: R² = 0.56, p < 0.05; Iox1-: R² = 0.31, p > 0.05) and indentation equilibrium modulus (Gd2-: R² = 0.38, p < 0.05; Iox1-: R² = 0.17, p > 0.05). MRI or CT with cationic contrast agents provides greater sensitivity than their anionic analogs at assessing the biochemical and biomechanical properties of ex vivo human metacarpal cartilage. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 38:719-725, 2020.

SUBMITTER: Freedman JD

PROVIDER: S-EPMC7071952 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Articular cartilage lines the load-bearing surfaces of long bones and undergoes compositional and structural degeneration during osteoarthritis progression. Contrast enhanced microcomputed tomography (?CT) is being applied to a variety of preclinical models, including the mouse, to map structural and compositional properties in 3-D. The thinness (?30-50??m) and high cellularity of mouse articular cartilage presents a significant imaging challenge. Our group previously showed that mouse articular cartilage and proteoglycan (PG) content can be assessed by ?CT with the ioxagalate-based contrast agent Hexabrix, but the voxel size used (6??m) was deemed to be barely adequate. The objective of the present study is to assess the utility of a novel contrast agent, CA4+, to quantify mouse articular cartilage morphology and composition with high resolution ?CT imaging (3??m voxels) and to compare the sensitivity of CA4+ and Hexabrix to detect between-group differences. While both contrast agents are iodine-based, Hexabrix is anionic and CA4+ is cationic so they interact differently with negatively charged PGs. With CA4+, a strong correlation was found between non-calcified articular cartilage thickness measurements made with histology and ?CT (R2 ?=?0.72, p?<?0.001). Cartilage degeneration-as assessed by loss in volume, thickness, and PG content-was observed in 34-week-old mice when compared to both 7- and 12-week-old mice. High measurement precision was observed with CA4+, with the coefficient of variation after repositioning and re-imaging samples equaling 2.8%, 4.5%, 7.4% and 5.9% for attenuation, thickness, volume, and PG content, respectively. Use of CA4+ allowed increased sensitivity for assessing PG content compared to Hexabrix, but had no advantage for measurement of cartilage thickness or volume. This improvement in imaging should prove useful in preclinical studies of cartilage degeneration and regeneration. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:2740-2748, 2017.

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DGEMRIC and CECT Comparison of Cationic and Anionic Contrast Agents in Cadaveric Human Metacarpal Cartilage.

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