Spectral CT imaging of human osteoarthritic cartilage via quantitative assessment of glycosaminoglycan content using multiple contrast agents

Abstract

Detection of early osteoarthritis to stabilize or reverse the damage to articular cartilage would improve patient function, reduce disability, and limit the need for joint replacement. In this study, we investigated nondestructive photon-processing spectral computed tomography (CT) for the quantitative measurement of the glycosaminoglycan (GAG) content compared to destructive histological and biochemical assay techniques in normal and osteoarthritic tissues. Cartilage-bone cores from healthy bovine stifles were incubated in 50% ioxaglate (Hexabrix ® ) or 100% gadobenate dimeglumine (MultiHance ® ). A photon-processing spectral CT (MARS) scanner with a CdTe-Medipix3RX detector imaged samples. Calibration phantoms of ioxaglate and gadobenate dimeglumine were used to determine iodine and gadolinium concentrations from photon-processing spectral CT images to correlate with the GAG content measured using a dimethylmethylene blue assay. The zonal distribution of GAG was compared between photon-processing spectral CT images and histological sections. Furthermore, discrimination and quantification of GAG in osteoarthritic human tibial plateau tissue using the same contrast agents were demonstrated. Contrast agent concentrations were inversely related to the GAG content. The GAG concentration increased from 25 μ g/ml (85 mg/ml iodine or 43 mg/ml gadolinium) in the superficial layer to 75 μ g/ml (65 mg/ml iodine or 37 mg/ml gadolinium) in the deep layer of healthy bovine cartilage. Deep zone articular cartilage could be distinguished from subchondral bone by utilizing the material decomposition technique. Photon-processing spectral CT images correlated with histological sections in healthy and osteoarthritic tissues. Post-imaging material decomposition was able to quantify the GAG content and distribution throughout healthy and osteoarthritic cartilage using Hexabrix ® and MultiHance ® while differentiating the underlying subchondral bone.

Photon-counting detector CT – first experiences in the field of musculoskeletal radiology

“…4 shows a case with evidence of a small amount of urate crystals in the metatarsophalangeal joint and points out the value of PCD-CT for imaging in suspected gout. Spectral imaging can also be used for imaging of joint spaces and delineation of small cartilage defects after intraarticular contrast injection [9,59,60]. A recently published study by Garcelon et al showed the ability of spectral imaging to visualize cartilage and subchondral cysts on knee CT without using contrast agent in cases with osteoarthritis [61].…”

Latest advancements in imaging techniques in OA

“…Different contrast agents may be used simultaneously to assess the composition of cartilage by targeting different molecular components. 75 , 76 There is ongoing research to overcome the remaining technical challenges associated with PCCT before widespread clinical implantation.…”

Revealing the three-dimensional murine brain microstructure by contrast-enhanced computed tomography

“…To address the needs for non-destructive, yet effective CESAs with a more fundamental understanding of their affinity towards different brain constituents, we screened two sets of chemically related compounds for their staining potential in CECT of murine hemispheres: two inorganic polyoxometalate CESAs (1:2 Hafnium-substituted Wells-Dawson polyoxometalate (Hf-WD 1:2 POM) and the Preyssler anion) and two organic CESAs (Hexabrix ® and CA4+). These compounds, except Preyssler anion, have already been successfully explored as CESAs for CECT on various tissue types other than nervous tissue ( Kerckhofs et al, 2014 , 2018 ; Karhula et al, 2017 ; Stewart et al, 2017 ; de Bournonville et al, 2020 ; Baer et al, 2021 ). We studied their diffusional properties into the organ, their specificity towards certain tissue constituents and their potential for obtaining quantitative 3D structural information.…”