Abstract
Early diagnosis of acute cartilage injuries enables monitoring of disease progression and improved treatment option planning to prevent post-traumatic osteoarthritis. In contrast-enhanced computed tomography (CECT), the changes in cationic agent diffusion within the tissue reflect cartilage degeneration. The diffusion in degenerated cartilage depends on proteoglycan (PG) content and water content, but each having an opposite effect on diffusion, thus compromising the diagnostic sensitivity. To overcome this limitation, we propose the simultaneous imaging of cationic (sensitive to PG and water contents) and non-ionic (sensitive to water content) agents. In this study, quantitative dual-energy CT (QDECT) imaging of two agents is reported for the first time at clinically feasible imaging time points. Furthermore, this is the first time synchrotron microCT with monochromatic X-rays is employed in cartilage CECT. Imaging was conducted at 1 and 2 h post contrast agent immersion. Intact, PG-depleted, and mechanically injured + PG-depleted cartilage samples (n = 33) were imaged in a mixture of cationic (iodine-based CA4+) and non-ionic (gadolinium-based gadoteridol) agents. Concurrent evaluation of CA4+ and gadoteridol partitions in cartilage is accomplished using QDECT. Subsequent normalization of the CA4+ partition with that of the gadoteridol affords CA4+ attenuations that significantly correlate with PG content – a key marker of OA.
Highlights
Www.nature.com/scientificreports tissue changes after an acute injury
The quantitative dualenergy CT (QDECT) technique allows the simultaneous quantification of interstitial water and PG contents in articular cartilage based on CA4+ and gadoteridol distributions within tissue, enabling better diagnostic sensitivity for tissue degradation and osteoarthritic stage
For normalized CA4+ partitions the spearman’s rhos after 1 and 2 h were ρ = 0.734 and ρ = 0.662. In this synchrotron-based microCT study, the QDECT technique is evaluated along with a dual contrast agent solution consisting of a mixture of the cationic, iodinated contrast agent (CA4+) and the non-ionic, gadolinium-based contrast agent
Summary
Www.nature.com/scientificreports tissue changes after an acute injury. CECT has been recently introduced in clinics, it is not yet widely used[6,7,8,9,10]. The loss of PGs decreases the uptake (less attraction) while increased water content and reduced steric hindrance enhance the diffusion of cationic agents into cartilage, impairing diagnostic sensitivity of CECT especially at early imaging time points. Gadoteridol, on the other hand, distributes into cartilage in relation to water content and steric hindrance of the tissue (i.e., physical diffusion barrier caused by collagen network architecture and PGs in the matrix), and is unaffected by the negative charge of PGs. the diagnostic value of CA4+ in clinical applications with a typical diffusion time frame of 30–60 minutes may be improved by normalizing the uptake of CA4+ with that of gadoteridol. QDECT relies on element specific absorption k-edge energies of 33.2 and 50.3 keV for iodine and gadolinium, respectively In this context, the QDECT technique allows the simultaneous quantification of interstitial water and PG contents in articular cartilage based on CA4+ and gadoteridol distributions within tissue, enabling better diagnostic sensitivity for tissue degradation and osteoarthritic stage. QDECT provides an important alternative for MRI and CT imaging in cases where more specific information is needed in order to select the best treatment option after acute cartilage injury
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