Contrast – Enhanced Computed Tomography for Structural and Functional Evaluation of Ligament Microdamage

Abstract

Detecting microstructural damage in ligaments remains a challenging case when no visible tearing occurs. This study introduces a novel application of micro-CT for ligament evaluation in wet tissue state with potential for clinical translation. We utilize neutral iodixanol and cationic tantalum oxide nanoparticles (Ta₂O₅-cNPs) for quantitative and qualitative imaging of microdamaged bovine ligaments. We hypothesize that neutral iodixanol reflects the ligament's functional alterations, while Ta₂O₅-cNPs will depict ligament structure by highlighting biphasic differences between the interfascicular matrix and fascicular regions. To examine these hypotheses, bovine anterior (N = 6) and posterior (N = 5) cruciate ligaments were assigned to control and damaged groups. All samples underwent biomechanical tensile testing to quantify the functional properties. Ligaments in the damaged group were strained up to 16% to create microdamage. Young's modulus was significantly reduced by 68% in the damaged group relative to the healthy group (p < 0.001). Samples were then separately immersed in each contrast agent and imaged using micro-CT at several timepoints during diffusion. The neutral iodixanol diffused faster compared to Ta₂O₅-cNPs, while Ta₂O₅-cNPs achieved approximately three times higher maximum partition. Although statistically significant differences in contrast agent partition between control and damaged groups were not observed, the findings demonstrate that (1) Pmax of neutral iodixanol showed correlation with biomechanical properties specifically phase shift at frequencies of 0.1, 0.5, and 2 Hz indicating sensitivity to viscoelastic changes of the tissues, and (2) Ta₂O₅-cNPs enable visualization of the ligament's structures, supporting their potential for three-dimensional histological assessment.