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, Rachel C.; Bansal, Prashant N.; Entezari, Vahid; Lusic, Hrvoje; Nazarian, Rosalynn M.; Snyder, Brian D.; Grinstaff, Mark W.

doi:10.1148/radiol.12112246

Cited by 85 publications

(111 citation statements)

References 43 publications

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“…The samples were rinsed in saline (overnight, room temperature) before repeat baseline scanning, CA4+ immersion, and CECT scanning (see SI). The cartilage was segmented from the subchondral bone using a region-growing algorithm (Analyze, see SI) [10, 18], and the mean CECT attenuation was obtained by averaging the x-ray attenuation over all transaxial μCT slices corresponding to cartilage tissue and is reported as grayscale intensities in Hounsfield Units (HU). To negate the effect of biologic variation or trace residual contrast agent, the cartilage CECT attenuation were normalized by their baseline (non-enhanced) CT attenuation.…”

Section: Methodsmentioning

confidence: 99%

“…Excised articular cartilage discs or osteochondral plugs are routinely used ex vivo to study cartilage functional properties (e.g., compressive stiffness) [7–12] and are commonly employed for ex vivo imaging studies, including delayed Gadolinium-Enhanced MRI of Cartilage (dGEMRIC) [13–15] and contrast-enhanced computed tomography (CECT) [9, 10, 16–18]. However, these ex vivo tissue models suffer from one or more of the following limitations.…”

Section: Introductionmentioning

confidence: 99%

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Contrast-enhanced CT facilitates rapid, non-destructive assessment of cartilage and bone properties of the human metacarpal

Lakin

Ellis

Shelofsky

et al. 2015

Osteoarthritis and Cartilage

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Objective The aim of this work is to establish the human metacarpal as a new whole joint surface early-stage osteoarthritis (OA) model that enables comparisons of articular cartilage and subchondral bone through high resolution contrast-enhanced CT (CECT) imaging, mechanical testing, and biochemical analysis. Design The 4th metacarpal was obtained from 12 human cadaveric donors and baseline μCT imaging was followed by indentation testing. The samples were then immersed in anionic (Ioxaglate) and cationic (CA4+) iodinated contrast agent solutions followed by CECT. Cartilage GAG content and distribution was measured using the 1,9 dimethylmethylene blue (DMMB) assay and Safranin-O histology staining. Linear regression was performed to compare cartilage and subchondral bone properties. Results Strong and significant positive correlations were observed between CA4+ CECT attenuation and both GAG content (R2=0.86) and equilibrium modulus (R2=0.84), while correlations using Ioxaglate were insignificant (R2≤0.24, p>0.05). Subchondral bone plate (SBP) thickness negatively and significantly correlated with SBP mineral density (R2=0.49). Cartilage GAG content significantly correlated with several trabecular bone properties, including positive correlations with bone volume fraction (%BV/TV, R2=0.67), trabecular number (Tb.N, R2=0.60), and trabecular thickness (R2=0.42), and negative relationships with structural model index (SMI, R2=0.78) and trabecular spacing (Tb.Sp, R2=0.56). Similarly, equilibrium modulus correlated positively with %BV/TV (R2=0.50), Tb.N (R2=0.59) and negatively with Tb.Sp (R2=0.55) and SMI (R2=0.60). Conclusion This study establishes the human metacarpal as a new early-stage OA model suitable for rapid, high resolution CECT imaging, mechanical testing, and biochemical analysis of the cartilage and subchondral bone, and for examining their inter-relationships.

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Contrast-enhanced CT facilitates rapid, non-destructive assessment of cartilage and bone properties of the human metacarpal

Lakin

Ellis

Shelofsky

et al. 2015

Osteoarthritis and Cartilage

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show abstract

“…From each patient, cores were exposed to a three different concentration of CA4+ (3,6, and 24 mgI/ml; n = 3 per concentration) and imaged with CEµCT in several time points (0, 1, 3, 5, 9, 18, 24, 32, 40, and 48 h). The CA4+ concentrations used in this study were selected based on the previous studies using CA4+ for animal AC (concentration ranged between 8 and 27 mgI/ml) [5,6,10] and our preliminary trials with the human AC.…”

Section: Sample Preparation and Contrast Agent Stainingmentioning

confidence: 99%

Micro-Scale Distribution of CA4+ in Ex vivo Human Articular Cartilage Detected with Contrast-Enhanced Micro-Computed Tomography Imaging

et al. 2017

Self Cite

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Contrast-enhanced micro-computed tomography (CEµCT) with cationic and anionic contrast agents reveals glycosaminoglycan (GAG) content and distribution in articular cartilage (AC). The advantage of using cationic stains (e.g., CA4+) compared to anionic stains (e.g., Hexabrix ® ), is that it distributes proportionally with GAGs, while anionic stain distribution in AC is inversely proportional to the GAG content. To date, studies using cationic stains have been conducted with sufficient resolution to study its distributions on the macro-scale, but with insufficient resolution to study its distributions on the micro-scale. Therefore, it is not known whether the cationic contrast agents accumulate in extra/pericellular matrix and if they interact with chondrocytes. The insufficient resolution has also prevented to answer the question whether CA4+ accumulation in chondrons could lead to an erroneous quantification of GAG distribution with low-resolution µCT setups. In this study, we use high-resolution µCT to investigate whether CA4+ accumulates in chondrocytes, and further, to determine whether it affects the low-resolution ex vivo µCT studies of CA4+ stained human AC with varying degree of osteoarthritis. Human osteochondral samples were immersed in three different concentrations of CA4+ (3 mgI/ml, 6 mgI/ml, and 24 mgI/ml) and imaged with high-resolution µCT at several timepoints. Different uptake diffusion profiles of CA4+ were observed between the segmented chondrons and the rest of the tissue. While the X-ray -detected CA4+ concentration in chondrons was greater than in the rest of the AC, its contribution to the uptake into the whole tissue was negligible and in line with macro-scale GAG Karhula et al. CA4+ Accumulation in Human Cartilagecontent detected from histology. The efficient uptake of CA4+ into chondrons and surrounding territorial matrix can be explained by the micro-scale distribution of GAG content. CA4+ uptake in chondrons occurred regardless of the progression stage of osteoarthritis in the samples and the relative difference between the interterritorial matrix and segmented chondron area was less than 4%. To conclude, our results suggest that GAG quantification with CEµCT is not affected by the chondron uptake of CA4+. This further confirms the use of CA4+ for macro-scale assessment of GAG throughout the AC, and highlight the capability of studying chondron properties in 3D at the micro scale.

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“…[1][2][3] The modalities of MI technologies are currently used in optical imaging, 4 ultrasound, 5 magnetic resonance imaging, 6 computed tomography (CT), 7 and positron-emission tomography. 8 As one of the most commonly used MI technologies, CT offers more spatial anatomic details with high resolution than other imaging modalities.…”

Section: Introductionmentioning

confidence: 99%

Engineering iodine-doped carbon dots as dual-modal probes for fluorescence and X-ray CT imaging

Zhang¹,

Ju²,

Zhang³

et al. 2015

IJN

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X-ray computed tomography (CT) is the most commonly used imaging technique for noninvasive diagnosis of disease. In order to improve tissue specificity and prevent adverse effects, we report the design and synthesis of iodine-doped carbon dots (I-doped CDs) as efficient CT contrast agents and fluorescence probe by a facile bottom-up hydrothermal carbonization process. The as-prepared I-doped CDs are monodispersed spherical nanoparticles (a diameter of ~2.7 nm) with favorable dispersibility and colloidal stability in water. The aqueous solution of I-doped CDs showed wavelength-dependent excitation and stable photoluminescence similar to traditional carbon quantum dots. Importantly, I-doped CDs displayed superior X-ray attenuation properties in vitro and excellent biocompatibility. After intravenous injection, I-doped CDs were distributed throughout the body and excreted by renal clearance. These findings validated that I-doped CDs with high X-ray attenuation potency and favorable photoluminescence show great promise for biomedical research and disease diagnosis.

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

Cited by 85 publications

References 43 publications

Contrast-enhanced CT facilitates rapid, non-destructive assessment of cartilage and bone properties of the human metacarpal

Contrast-enhanced CT facilitates rapid, non-destructive assessment of cartilage and bone properties of the human metacarpal

Micro-Scale Distribution of CA4+ in Ex vivo Human Articular Cartilage Detected with Contrast-Enhanced Micro-Computed Tomography Imaging

Engineering iodine-doped carbon dots as dual-modal probes for fluorescence and X-ray CT imaging

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