Triple Contrast CT Method Enables Simultaneous Evaluation of Articular Cartilage Composition and Segmentation

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Osteoarthritis (OA) is a disease of the entire joint, often triggered by cartilage injury, mediated by a cascade of inflammatory pathways involving a complex interplay among metabolic, genetic, and enzymatic factors that alter the biochemical composition, microstructure, and biomechanical performance. Clinically, OA is characterized by degradation of the articular cartilage, thickening of the subchondral bone, inflammation of the synovium, and degeneration of ligaments that in aggregate reduce joint function and diminish quality of life. OA is the most prevalent joint disease, affecting 140 million people worldwide; these numbers are only expected to increase, concomitant with societal and financial burden of care. We present a two‐part review encompassing the applications of nanotechnology to the diagnosis and treatment of OA. Herein, part 1 focuses on OA treatment options and advancements in nanotechnology for the diagnosis of OA and imaging of articular cartilage, while part 2 (10.1002/jor.24842) summarizes recent advances in drug delivery, tissue scaffolds, and gene therapy for the treatment of OA. Specifically, part 1 begins with a concise review of the clinical landscape of OA, along with current diagnosis and treatments. We next review nanoparticle contrast agents for minimally invasive detection, diagnosis, and monitoring of OA via magnetic resonace imaging, computed tomography, and photoacoustic imaging techniques as well as for probes for cell tracking. We conclude by identifying opportunities for nanomedicine advances, and future prospects for imaging and diagnostics.

Section: Oa Diagnosismentioning

confidence: 99%

Section: Oa Diagnosismentioning

confidence: 99%

Section: Oa Diagnosismentioning

confidence: 99%

Section: Magnetic Resonance Imagingmentioning

confidence: 99%

Section: Magnetic Resonance Imagingmentioning

confidence: 99%

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Nanotechnology and Osteoarthritis. Part 1: Clinical landscape and opportunities for advanced diagnostics

Lawson

Mäkelä

Snyder

et al. 2020

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Dual‐contrast computed tomography enables detection of equine posttraumatic osteoarthritis in vitro

Saukko

Nykänen

Sarin

et al. 2021

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To prevent the progression of posttraumatic osteoarthritis, assessment of cartilage composition is critical for effective treatment planning. Posttraumatic changes include proteoglycan (PG) loss and elevated water content. Quantitative dual‐energy computed tomography (QDECT) provides a means to diagnose these changes. Here, we determine the potential of QDECT to evaluate tissue quality surrounding cartilage lesions in an equine model, hypothesizing that QDECT allows detection of posttraumatic degeneration by providing quantitative information on PG and water contents based on the partitions of cationic and nonionic agents in a contrast mixture. Posttraumatic osteoarthritic samples were obtained from a cartilage repair study in which full‐thickness chondral defects were created surgically in both stifles of seven Shetland ponies. Control samples were collected from three nonoperated ponies. The experimental (n = 14) and control samples (n = 6) were immersed in the contrast agent mixture and the distributions of the agents were determined at various diffusion time points. As a reference, equilibrium moduli, dynamic moduli, and PG content were measured. Significant differences (p < 0.05) in partitions between the experimental and control samples were demonstrated with cationic contrast agent at 30 min, 60 min, and 20 h, and with non‐ionic agent at 60 and 120 min. Significant Spearman's rank correlations were obtained at 20 and 24 h (ρ = 0.482–0.693) between the partition of cationic contrast agent, cartilage biomechanical properties, and PG content. QDECT enables evaluation of posttraumatic changes surrounding a lesion and quantification of PG content, thus advancing the diagnostics of the extent and severity of cartilage injuries.

Triple contrast computed tomography reveals site‐specific biomechanical differences in the human knee joint—A proof of concept study

Orava,

Paakkari,

Jäntti

et al. 2023

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Cartilage and synovial fluid are challenging to observe separately in native computed tomography (CT). We report the use of triple contrast agent (bismuth nanoparticles, CA4+, and gadoteridol) to image and segment cartilage in cadaveric knee joints with a clinical CT scanner. We hypothesize that bismuth nanoparticles will remain in synovial fluid while the CA4+ and gadoteridol will diffuse into cartilage, allowing 1) segmentation of cartilage, and 2) evaluation of cartilage biomechanical properties based on contrast agent concentrations. To investigate these hypotheses, triple contrast agent was injected into both knee joints of a cadaver (N = 1), imaged with a clinical CT at multiple timepoints during the contrast agent diffusion. Knee joints were extracted, imaged with µCT, and biomechanical properties of the cartilage surface were determined by stress‐relaxation mapping. Cartilage was segmented and contrast agent concentrations (CA4+ and gadoteridol) were compared with the biomechanical properties at multiple locations (n = 185). Spearman's correlation between cartilage thickness from clinical CT and reference µCT images verifies successful and reliable segmentation. CA4+ concentration is significantly higher in femoral than in tibial cartilage at 60‐min and further timepoints, which corresponds to the higher Young's modulus observed in femoral cartilage. In this pilot study, we show that 1) large bismuth nanoparticles do not diffuse into cartilage, facilitating straightforward segmentation of human knee joint cartilage in a clinical setting, and 2) CA4+ concentration in cartilage reflects the biomechanical differences between femoral and tibial cartilage. Thus, the triple contrast agent CT shows potential in cartilage morphology and condition estimation in clinical CT.This article is protected by copyright. All rights reserved.