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

Lakin, Benjamin A.; Ellis, D; Shelofsky, Joshua S.; Freedman, Jonathan D.; Grinstaff, Mark W.; Snyder, Brian D.

doi:10.1016/j.joca.2015.05.033

Cited by 32 publications

(66 citation statements)

References 44 publications

(72 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Successful application of these cationic contrast agents in ex vivo and in vivo studies [7,8] indicate significant research potential. The distribution of CA4+ in AC is based on the attraction between the positive CA4+ and the negatively charged GAG macromolecules [5].…”

Section: Introductionmentioning

confidence: 99%

“…Thus, we hypothesize that cationic CA4+ will accumulate in the chondrons or in the close proximity of the chondrons. However, the previous studies using CA4+ enhanced micro-computed tomography (µCT) [5][6][7][8][9] have been conducted with insufficient resolution to answer this hypothesis. 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.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

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

et al. 2017

View full text Add to dashboard Cite

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.

show abstract

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

et al. 2017

View full text Add to dashboard Cite

show abstract

“…Contrast‐enhanced computed tomography (CECT) enables detection of changes in cartilage composition along with quantitative evaluation of subchondral bone density and structure . Advantages of CECT compared with MRI are shorter acquisition times, higher resolution, and lower costs.…”

mentioning

confidence: 99%

Synchrotron MicroCT Reveals the Potential of the Dual Contrast Technique for Quantitative Assessment of Human Articular Cartilage Composition

Honkanen

Saukko

Turunen

et al. 2019

Journal Orthopaedic Research

View full text Add to dashboard Cite

Dual contrast micro computed tomography (CT) shows potential for detecting articular cartilage degeneration. However, the performance of conventional CT systems is limited by beam hardening, low image resolution (full‐body CT), and long acquisition times (conventional microCT). Therefore, to reveal the full potential of the dual contrast technique for imaging cartilage composition we employ the technique using synchrotron microCT. We hypothesize that the above‐mentioned limitations are overcome with synchrotron microCT utilizing monochromatic X‐ray beam and fast image acquisition. Human osteochondral samples (n = 41, four cadavers) were immersed in a contrast agent solution containing two agents (cationic CA4+ and non‐ionic gadoteridol) and imaged with synchrotron microCT at an early diffusion time point (2 h) and at diffusion equilibrium (72 h) using two monochromatic X‐ray energies (32 and 34 keV). The dual contrast technique enabled simultaneous determination of CA4+ (i.e., proteoglycan content) and gadoteridol (i.e., water content) partitions within cartilage. Cartilage proteoglycan content and biomechanical properties correlated significantly (0.327 < r < 0.736, p < 0.05) with CA4+ partition in superficial and middle zones at both diffusion time points. Normalization of the CA4+ partition with gadoteridol partition within the cartilage significantly (p < 0.05) improved the detection sensitivity for human osteoarthritic cartilage proteoglycan content, biomechanical properties, and overall condition (Mankin, Osteoarthritis Research Society International, and International Cartilage Repair Society grading systems). The dual energy technique combined with the dual contrast agent enables assessment of human articular cartilage proteoglycan content and biomechanical properties based on CA4+ partition determined using synchrotron microCT. Additionally, the dual contrast technique is not limited by the beam hardening artifact of conventional CT systems. © 2019 The Authors. Journal of Orthopaedic Research® published by Wiley Periodicals, Inc. on behalf of Orthopaedic Research Society. J Orthop Res 38:563–573, 2020

show abstract

“…Mean cartilage thickness was measured (analyze) from the baseline scan at the central apex of the hemispherical cartilage surface prior to indentation testing. The indentation equilibrium modulus ( E ) of each sample was evaluated using a standard, four‐step indentation testing procedure (see Supplementary Information, SI) …”

Section: Methodsmentioning

confidence: 99%

“…For the equilibrium study, samples were imaged in the air after a 24‐h immersion, as this was found to be sufficiently beyond the equilibrium immersion time from the diffusion‐in data. The data were converted to DICOM format (Scanco Medical) before post‐processing analysis (Analyze™; AnalyzeDirect, Overland Park, KS) …”

Section: Methodsmentioning

confidence: 99%

dGEMRIC and CECT Comparison of Cationic and Anionic Contrast Agents in Cadaveric Human Metacarpal Cartilage

Freedman

Ellis

Lusic

et al. 2019

Journal Orthopaedic Research

View full text Add to dashboard Cite

Magnetic resonance imaging (MRI) and computed tomography (CT) are widely used to image cartilage and their diagnostic capability is enhanced in the presence of contrast agents. The aim of the study is to directly compare the performance between commercial anionic MRI (Gd(DTPA), Gd2−) and CT (Ioxaglate, Iox1−) contrast agents with novel cationic MRI (Gd(DTPA)Lys2, Gd4+) and CT (CA4+) contrast agents for assessment of cartilage mechanical and biochemical properties using the ex vivo human osteoarthritis metacarpal cartilage model. First, indentation testing was conducted to obtain the compressive modulus of the human fifth metacarpals. The samples were then immersed in the anionic and cationic contrast agents prior to delayed gadolinium‐enhanced MRI of cartilage and CT scanning, respectively. The cartilage glycosaminoglycan (GAG) content and distribution were determined using the 1,9‐dimethylmethylene blue assay and Safranin‐O histology. Cationic agents significantly accumulate in cartilage compared with anionic agents. Significant positive correlations (p < 0.05) exist between imaging results of cationic agents and GAG content (Gd4+: R2 = 0.43; CA4+: R2 = 0.67) and indentation equilibrium modulus (Gd4+: R2 = 0.48; CA4+: R2 = 0.77). Significant negative correlations are observed between anionic MRI relaxation times, but not contrast‐enhanced computed tomography attenuation and cartilage GAG content (Gd2−: R2 = 0.56, p < 0.05; Iox1−: R2 = 0.31, p > 0.05) and indentation equilibrium modulus (Gd2−: R2 = 0.38, p < 0.05; Iox1−: R2 = 0.17, p > 0.05). MRI or CT with cationic contrast agents provides greater sensitivity than their anionic analogs at assessing the biochemical and biomechanical properties of ex vivo human metacarpal cartilage. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 38:719‐725, 2020

show abstract

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

Cited by 32 publications

References 44 publications

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

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

Synchrotron MicroCT Reveals the Potential of the Dual Contrast Technique for Quantitative Assessment of Human Articular Cartilage Composition

dGEMRIC and CECT Comparison of Cationic and Anionic Contrast Agents in Cadaveric Human Metacarpal Cartilage

Contact Info

Product

Resources

About