Quantitative imaging of proteoglycan in cartilage using a gadolinium probe and microCT

Cockman, Michael D.; Blanton, Cindy; Chmielewski, Paula A.; Dong, Liang; Dufresne, Thomas E.; Hookfin, E.B.; Karb, Michael; Liu, S.; Wehmeyer, Kenneth R.

doi:10.1016/j.joca.2005.08.010

Cited by 61 publications

(49 citation statements)

References 12 publications

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“…Contrast-enhanced MRI techniques including dGEMRIC have shown success in monitoring PG concentration in cartilage in vitro and clinically (15,16), but the resolution of current clinical MRI systems (Ϸ300 m) and high-powered research MRI systems (Ϸ25 m in-plane) may limit their application in small-animal models. The use of gadolinium-based contrast agents with CT has also shown the potential to monitor PG content in cartilage explants (17). Optical coherence tomography (18) and Fourier transform infrared spectroscopy (19) may also be useful in the noninvasive monitoring of cartilage ECM changes, potentially providing information on collagen and PG contents.…”

Section: Discussionmentioning

confidence: 99%

Analysis of cartilage matrix fixed charge density and three-dimensional morphology via contrast-enhanced microcomputed tomography

Palmer

Guldberg

Levenston³

2006

Proc. Natl. Acad. Sci. U.S.A.

271

343

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Small animal models of osteoarthritis are often used for evaluating the efficacy of pharmacologic treatments and cartilage repair strategies, but noninvasive techniques capable of monitoring matrix-level changes are limited by the joint size and the low radiopacity of soft tissues. Here we present a technique for the noninvasive imaging of cartilage at micrometer-level resolution based on detecting the equilibrium partitioning of an ionic contrast agent via microcomputed tomography. The approach exploits electrochemical interactions between the molecular charges present in the cartilage matrix and an ionic contrast agent, resulting in a nonuniform equilibrium partitioning of the ionic contrast agent reflecting the proteoglycan distribution. In an in vitro model of cartilage degeneration we observed changes in x-ray attenuation magnitude and distribution consistent with biochemical and histological analyses of sulfated glycosaminoglycans, and x-ray attenuation was found to be a strong predictor of sulfated glycosaminoglycan density. Equilibration with the contrast agent also permits direct in situ visualization and quantification of cartilage surface morphology. Equilibrium partitioning of an ionic contrast agent via microcomputed tomography thus provides a powerful approach to quantitatively assess 3D cartilage composition and morphology for studies of cartilage degradation and repair.noninvasive imaging ͉ proteoglycans ͉ cartilage degeneration ͉ osteoarthritis A nalysis of small-animal models is limited by the availability of quantitative evaluation techniques for studying the extracellular matrix (ECM) changes associated with osteoarthritis (OA) and cartilage repair. Histology is traditionally used to monitor the spatial distribution of matrix macromolecules but is time-consuming and subject to distortion artifacts and tissue damage, and it produces only semiquantitative analysis of 2D sections that may provide inaccurate 3D representations. Biochemical assays are available to quantify the amount and type of matrix macromolecules in cartilage, but these assays fail to provide their spatial distributions, particularly in small animals where the limited thickness and volume of cartilage make it difficult or impossible to extract samples from multiple regions. Additionally, longitudinal monitoring of changes with time are impossible because of the destructive nature of these histological and biochemical techniques.Proteoglycans (PGs) are a particularly appropriate target for studying OA and for evaluating the efficacy of cartilage defect repair. PGs comprise 5-10% of articular cartilage by wet mass (1) and are key regulators of its equilibrium and dynamic mechanical properties. This regulation is the result of interactions between ionic interstitial fluid and negatively charged sulfated glycosaminoglycans (sGAGs) attached to the PG backbone (2). The amount and distribution of PGs changes substantially during development (3), during degeneration and repair (4, 5), and in response to blunt trauma (6). Of particular...

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Section: Discussionmentioning

confidence: 99%

Analysis of cartilage matrix fixed charge density and three-dimensional morphology via contrast-enhanced microcomputed tomography

Palmer

Guldberg

Levenston³

2006

Proc. Natl. Acad. Sci. U.S.A.

271

343

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“…Depending on the application and imaging modality, a contrast agent is used to enhance tissue differentiation, which is especially important for imaging soft tissues-like cartilage-with x-rays. Specifically, contrast materialenhanced CT is an emerging technique for imaging articular cartilage (1)(2)(3)(4)(5)(6)(7)(8)(9)(10) (12 mg I/mL) was injected into the same knee by using a similar approach. Time-course scans were obtained in the same way they were with ioxaglate.…”

Section: Preparation Of Contrast Agent Solutions and Osteochondral Plmentioning

confidence: 99%

Contrast-enhanced CT with a High-Affinity Cationic Contrast Agent for Imaging ex Vivo Bovine, Intact ex Vivo Rabbit, and in Vivo Rabbit Cartilage

Stewart

Bansal²,

Entezari³

et al. 2013

Radiology

104

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Purpose:To quantify the affinity of a cationic computed tomography (CT) contrast agent (CA 4+ ) and that of an anionic contrast agent (ioxaglate) to glycosaminoglycans (GAGs) in ex vivo cartilage tissue explants and to characterize the in vivo diffusion kinetics of CA 4+ and ioxaglate in a rabbit model. Materials and Methods:All in vivo procedures were approved by the institutional animal care and use committee. The affinities of ioxaglate and CA 4+ to GAGs in cartilage (six bovine osteochondral plugs) were quantified by means of a modified binding assay using micro-CT after plug equilibration in serial dilutions of each agent. The contrast agents were administered intraarticularly to the knee joints of five New Zealand white rabbits to determine the in vivo diffusion kinetics and cartilage tissue imaging capabilities. Kinetics of diffusion into the femoral groove cartilage and relative contrast agent uptake into bovine plugs were characterized by means of nonlinear mixed-effects models. Diffusion time constants (t) were compared by using a Student t test. Results:The uptake of CA 4+ in cartilage was consistently over 100% of the reservoir concentration, whereas it was only 59% for ioxaglate. In vivo, the contrast material-enhanced cartilage reached a steady CT attenuation for both CA 4+ and ioxaglate, with t values of 13.8 and 6.5 minutes, respectively (P = .04). The cartilage was easily distinguishable from the surrounding tissues for CA 4+ (12 mg of iodine per milliliter); comparatively, the anionic contrast agent provided less favorable imaging results, even when a higher concentration was used (80 mg of iodine per milliliter). Conclusion:The affinity of the cationic contrast agent CA 4+ to GAGs enables high-quality imaging and segmentation of ex vivo bovine and rabbit cartilage, as well as in vivo rabbit cartilage.q RSNA, 2012 Supplemental material: http://radiology.rsna.org/lookup /suppl

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“…The changes in collagen and PG content play an important factor in disease progression and need to be evaluated accurately for the development of successful intervention strategies. Several modalities are utilized to evaluate the composition of cartilage including optical arthroscopy, computed tomography (CT) based arthrography and magnetic resonance imaging (MRI) for in vivo studies (Hayes and Conway, 1992;Chung et al, 2001;Cockman et al, 2006;Domayer et al, 2008;Piscaer et al, 2008;Roemer et al, 2009;Siebelt et al, 2011b). MRI has been used extensively to evaluate the morphology and composition of osteoarthritic tissue non-invasively but has inadequate specificity and sensitivity at a molecular level, is expensive, and cannot be used intra-operatively (Gelb et al, 1996;Nishii et al, 2005;Lin et al, 2009a,b;Sutter et al, 2014).…”

Section: Introductionmentioning

confidence: 99%

Assessment of hyaline cartilage matrix composition using near infrared spectroscopy

2014

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Changes in the composition of the extracellular matrix (ECM) are characteristic of injury or disease in cartilage tissue. Various imaging modalities and biochemical techniques have been used to assess the changes in cartilage tissue but lack adequate sensitivity, or in the case of biochemical techniques, result in destruction of the sample. Fourier transform near infrared (FT-NIR) spectroscopy has shown promise for the study of cartilage composition. In the current study NIR spectroscopy was used to identify the contributions of individual components of cartilage in the NIR spectra by assessment of the major cartilage components, collagen and chondroitin sulfate, in pure component mixtures. The NIR spectra were obtained using homogenous pellets made by dilution with potassium bromide. A partial least squares (PLS) model was calculated to predict composition in bovine cartilage samples. Characteristic absorbance peaks between 4000 and 5000 cm(-1) could be attributed to components of cartilage, i.e. collagen and chondroitin sulfate. Prediction of the amount of collagen and chondroitin sulfate in tissues was possible within 8% (w/dw) of values obtained by gold standard biochemical assessment. These results support the use of NIR spectroscopy for in vitro and in vivo applications to assess matrix composition of cartilage tissues, especially when tissue destruction should be avoided.

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Quantitative imaging of proteoglycan in cartilage using a gadolinium probe and microCT

Abstract: Gadolinium and microCT allow an improved 3D visualization of cartilage and quantification of its proteoglycan content.

Cited by 61 publications

References 12 publications

Analysis of cartilage matrix fixed charge density and three-dimensional morphology via contrast-enhanced microcomputed tomography

Analysis of cartilage matrix fixed charge density and three-dimensional morphology via contrast-enhanced microcomputed tomography

Contrast-enhanced CT with a High-Affinity Cationic Contrast Agent for Imaging ex Vivo Bovine, Intact ex Vivo Rabbit, and in Vivo Rabbit Cartilage

Assessment of hyaline cartilage matrix composition using near infrared spectroscopy

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