In vivo imaging of cartilage degeneration using μCT-arthrography

Objective. Evaluation of macrophage activation may provide essential information about the etiology and progression rate of osteoarthritis (OA). Activated macrophages abundantly express folate receptor ␤ (FR␤), which can be targeted using radioactive-labeled folic acid. This study was undertaken to investigate whether macrophage activation can be monitored in small animal models of OA using a folate radiotracer and to determine whether macrophage activation differs in different models of OA with different OA progression.Methods. Two rat models of OA were used: the mono-iodoacetate (MIA) model, which is a fastprogressing biochemically induced model, and the anterior cruciate ligament transection (ACLT) model, which induces OA at a slower pace. Images were obtained using high-resolution small animal singlephoton-emissioncomputedtomography/computedtomography. The specificity of the technique was tested by eradicating macrophages using clodronate-laden liposomes and blockade of FR␤ by cold folic acid.Results. The MIA model had high initial macrophage activation, with a peak after 2 weeks which disappeared after 8 weeks. The ACLT model showed less activation but was still active 12 weeks after induction. The technique allowed monitoring of the disease process over time, in which late stages of the disease showed less macrophage activation than early stages, especially in the fast-progressing MIA model of OA.Conclusion. Our findings indicate that macrophage activation in experimental OA can clearly be demonstrated and monitored by the folate radiotracer. The high resolution, high sensitivity, and high specificity of the technique allow clear localization of macrophage activity in a disease model that is not known for abundant macrophage involvement.

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“…The MIA model is known to progress quickly, even in the first weeks (27,28). The ACLT model is known to progress more slowly (23).…”

Section: Discussionmentioning

confidence: 99%

Imaging of activated macrophages in experimental osteoarthritis using folate-targeted animal single-photon-emission computed tomography/computed tomography

Piscaer

Müller

Mindt

et al. 2011

Arthritis & Rheumatism

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“…The GAG quantification by µMRI involves the use of the gadolinium (Gd) ions, which is a negatively charged paramagnetic contrast agent that reduces the T1 relaxation time in tissue. The reduction of T1 can be correlated with the Gd concentration in cartilage, which is inversely proportional to the GAG concentration in cartilage (26)(27)(28)(29)(30) with human CT scanners, can measure a number of changes in cartilage and bone, including the tissue volume, X-ray attenuation, and bone mineral density (31)(32)(33). The use of a negatively charged contrast agent ioxaglate enables µCT to measure the GAG concentration in cartilage (34)(35)(36).…”

Section: Imaging In Oa Detectionmentioning

confidence: 99%

Topographical and depth-dependent glycosaminoglycan concentration in canine medial tibial cartilage 3 weeks after anterior cruciate ligament transection surgery—a microscopic imaging study

Mittelstaedt¹,

Kahn²,

Xia³

2016

Quant. Imaging Med. Surg.

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Background: Medical imaging has become an invaluable tool to diagnose damage to cartilage. Depletion of glycosaminoglycans (GAG) has been shown to be one of the early signs of cartilage degradation. In order to investigate the topographical changes in GAG concentration caused by the anterior cruciate ligament transection (ACLT) surgery in a canine model, microscopic magnetic resonance imaging (µMRI) and microscopic computed tomography (µCT) were used to measure the GAG concentration with correlation from a biochemical assay, inductively coupled plasma optical emission spectroscopy (ICP-OES), to understand where the topographical and depth-dependent changes in the GAG concentration occur.Methods: This study used eight knee joints from four canines, which were examined 3 weeks after ACLT surgery. From right (n=3) and left (n=1) medial tibias of the ACLT and the contralateral side, two ex vivo specimens from each of four locations (interior, central, exterior and posterior) were imaged before and after equilibration in contrast agents. The cartilage blocks imaged using µMRI were approximately 3 mm × 5 mm and were imaged before and after eight hours submersion in a gadolinium (Gd) contrast agent with an in-plane pixel resolution of 17.6 µm 2 and an image slice thickness of 1 mm. The cartilage blocks imaged using µCT were approximately 2 mm × 1 mm and were imaged before and after 24 hours submersed in ioxaglate with an isotropic voxel resolution of 13.4 µm 3 . ICP-OES was used to quantify the bulk GAG at each topographical location.Results: The pre-contrast µMRI and µCT results did not demonstrate significant differences in GAG between the ACLT and contralateral cartilage at all topographical locations. The post-contrast µMRI and µCT results demonstrated topographically similar significant differences in GAG concentrations between the ACLT and contralateral tibia. Using µMRI, the GAG concentrations (mg/mL) were measured for the ACLT and contralateral respectively, the exterior (54.0±3.

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“…30 The former contains a negatively charged ioxaglate, which will be locally repulsed by the negative fixed charge density of the tissue; thus, all tissues that do not contain a negative charge will be stained. 31,32 Additionally, Hexabrix has been used for in vivo animal studies 33 and in a clinical setting 34 and, thus, is a potential candidate for noninvasive TE construct quality assessment. To evaluate the potential of CE-nano-CT for 3D visualization and quantification of in vitro engineered ECM by culture of human periosteum-derived cells (hPDCS, i.e., a cell type that has been seen to be mulitpotent and to contribute in bone regeneration 35,36 ) in 3D titanium alloy scaffolds, a comparison was made to routine physical measurement techniques, such as Live/Dead viability/ cytotoxicity for cell viability, Picrosirius Red staining for collagen content, and ECM weight measurements.…”

Section: Introductionmentioning

confidence: 99%

Three-Dimensional Characterization of Tissue-Engineered Constructs by Contrast-Enhanced Nanofocus Computed Tomography

Papantoniou

Sonnaert

Geris

et al. 2014

Tissue Engineering Part C: Methods

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To successfully implement tissue-engineered (TE) constructs as part of a clinical therapy, it is necessary to develop quality control tools that will ensure accurate and consistent TE construct release specifications. Hence, advanced methods to monitor TE construct properties need to be further developed. In this study, we showed proof of concept for contrast-enhanced nanofocus computed tomography (CE-nano-CT) as a whole-construct imaging technique with a noninvasive potential that enables three-dimensional (3D) visualization and quantification of in vitro engineered extracellular matrix (ECM) in TE constructs. In particular, we performed a 3D qualitative and quantitative structural and spatial assessment of the in vitro engineered ECM, formed during static and perfusion bioreactor cell culture in 3D TE scaffolds, using two contrast agents, namely, Hexabrix Ò and phosphotungstic acid (PTA). To evaluate the potential of CE-nano-CT, a comparison was made to standardly used techniques such as Live/Dead viability/cytotoxicity, Picrosirius Red staining, and to net dry weight measurements of the TE constructs. When using Hexabrix as the contrast agent, the ECM volume fitted linearly with the net dry ECM weight independent from the flow rate used, thus suggesting that it stains most of the ECM. When using PTA as the contrast agent, comparing to net weight measurements showed that PTA only stains a part of the ECM. This was attributed to the binding specificity of this contrast agent. In addition, the PTA-stained CE-nano-CT data showed pronounced distinction between flow conditions when compared to Hexabrix, indicating culture-specific structural ECM differences. This novel type of information can contribute to optimize bioreactor culture conditions and potentially critical quality characteristics of TE constructs such as ECM quantity and homogeneity, facilitating the gradual transformation of TE constructs in well-characterized TE products.

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In vivo imaging of cartilage degeneration using μCT-arthrography

Cited by 85 publications

References 31 publications

Imaging of activated macrophages in experimental osteoarthritis using folate-targeted animal single-photon-emission computed tomography/computed tomography

Imaging of activated macrophages in experimental osteoarthritis using folate-targeted animal single-photon-emission computed tomography/computed tomography

Topographical and depth-dependent glycosaminoglycan concentration in canine medial tibial cartilage 3 weeks after anterior cruciate ligament transection surgery—a microscopic imaging study

Three-Dimensional Characterization of Tissue-Engineered Constructs by Contrast-Enhanced Nanofocus Computed Tomography

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