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.

Keywords: computed tomography arthrography (CTa); equilibrium partitioning of an iodinated contrast agent (EPIC); glycosaminoglycan; magnetic resonance imaging; osteoarthritis.

Figure 1:

Chemical structures of the cationic (Gd(DTPA)Lys2 (Gd4+) & CA4+) and anionic (Gadopentetic acid (Gd2−) & Ioxaglate (Iox1−)) MRI and CT contrasts agents, respectively, overlaid a drawing of a human hand noting the metacarpal phalangeal joint (MCPJ) under study.

Figure 2:

Diffusion uptake MRI and CT plots for cationic Gd(DTPA)Lys₂ (Gd4+) and CA4+, as well as anionic Gadopentetic Acid (Gd2−) and Ioxaglate, Iox1− contrast agents into ex vivo human metacarpal samples..

Figure 3.

a) Contrast agent uptake versus GAG content for MRI and CT imaging using cationic (Gd4+ & CA4+) and anionic (Gd2− & Iox1−) contrast agents (n=12). b) Contrast agent uptake versus indentation equilibrium modulus (E, MPa) for MRI and CT imaging using cationic (Gd4+ & CA4+) and anionic (Gd2− & Iox1−) contrast agents.

Figure 4:

Images of ex vivo human metacarpal cartilage obtained with anionic and cationic contrast enhanced CT and MRI. Color maps qualitatively agreed with the Safranin-O histology results. Color scale bars reflect the range of T1 values or Hounsfield units associated with high or low contrast agent uptake in tissue. The red stain or lack thereof from histological section of tissue stained with Safranin-O corresponds to high or low concentrations of GAG.