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

Caroline Löbker,Timen Ten Harkel,Kishore Rajendran,Christopher Bateman,Nigel Anderson,Aamir Raja,Mohsen Ramyar,Sandra Kieser,Gary Hooper,Anthony Butler,Kenzie Baer,Ben Schon,Tim Woodfield

doi:10.1063/5.0035312

Caroline Löbker, Timen Ten Harkel + Show 11 more

Open Access

https://doi.org/10.1063/5.0035312

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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 μg/ml (85 mg/ml iodine or 43 mg/ml gadolinium) in the superficial layer to 75 μg/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.

Highlights

Osteoarthritis (OA) is a common cause of disability and the most common indication for both knee and hip joint replacements.[1]
We aimed to demonstrate that photon-processing spectral computed tomography (CT) imaging could spatially locate and quantify the GAG content using multiple commonly used contrast agents, yet clearly differentiates cartilage from bone
Ioxaglate and gadobenate dimeglumine reached diffusion equilibrium within 24 h as no statistical difference was found between the 24 h and 48 h measurements of both iodine and gadolinium concentrations, with respective p-values of 0.710 and 0.957

Summary

Introduction

Osteoarthritis (OA) is a common cause of disability and the most common indication for both knee and hip joint replacements.[1] Theoretically, treating OA by stabilizing or reversing the articular cartilage damage would reduce pain and improve patient function, potentially negating the need for joint replacements and, reducing the burgeoning social and economic cost of joint replacements in an everaging population that increasingly expects greater levels of physical activity and mobility.[2,3,4,5]. Cost-effective noninvasive methods for evaluating tissue quality and regeneration following articular cartilage treatments are not yet available. The existing clinical diagnostic methods have difficulty in detecting early osteoarthritic changes and cartilage lesions.[6] Clinical assessment of OA is indirect, relying on symptoms and signs of stiffness, pain, swelling, and muscle weakness. Imaging of joints with plain x-ray to assess joint space narrowing, the appearance of subchondral bone sclerosis, and the presence of osteophytes is cheap and simple but unsuitable for early diagnosis as the cartilage is not imaged directly.[7,8,9] Magnetic resonance imaging (MRI) and computed tomography (CT) imaging showed early promise for detection of OA and assessment of cartilage treatments but have proven to be limited in resolution or quantitative capability for detecting early OA.[10,11] quantitative imaging of an in situ biomarker of cartilage health remains the most desirable strategy.[12]

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