Effect of collagen cross-linking on quantitative MRI parameters of articular cartilage

Rautiainen, Jari; Nieminen, Miika T.; Salo, Elli Noora; Kokkonen, Harri; Mangia, Silvia; Michaeli, Shalom; Gröhn, Olli; Jurvelin, Jukka S.; Töyräs, Juha; Nissi, Mikko J.

doi:10.1016/j.joca.2016.04.017

Cited by 6 publications

(4 citation statements)

References 50 publications

(83 reference statements)

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“…Importantly, this study found significant, inverse correlations between pyridinoline cross-links and both T1 time and T2 time of self-assembling fibrocartilage. These findings corroborate recent work demonstrating a relationship between qMRI metrics and cross-link content in native articular cartilage [42]. It is known that molecular size and rate of molecular motion in a tissue influences the tissue’s T1 and T2 times [43].…”

Section: Discussionsupporting

confidence: 89%

Temporal development of near-native functional properties and correlations with qMRI in self-assembling fibrocartilage treated with exogenous lysyl oxidase homolog 2

Hadidi

Cissell

et al. 2017

Acta Biomaterialia

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Advances in cartilage tissue engineering have led to constructs with mechanical integrity and biochemical composition increasingly resembling that of native tissues. In particular, collagen cross-linking with lysyl oxidase has been used to significantly enhance the mechanical properties of engineered neotissues. In this study, development of collagen cross-links over time, and correlations with tensile properties, were examined in self-assembling neotissues. Additionally, quantitative MRI metrics were examined in relation to construct mechanical properties as well as pyridinoline cross-link content and other engineered tissue components. Scaffold-free meniscus fibrocartilage was cultured in the presence of exogenous lysyl oxidase, and assessed at multiple time points over 8 weeks starting from the first week of culture. Engineered constructs demonstrated a 9.9-fold increase in pyridinoline content, reaching 77% of native tissue values, after 8 weeks of culture. Additionally, engineered tissues reached 66% of the Young’s modulus in the radial direction of native tissues. Further, collagen cross-links were found to correlate with tensile properties, contributing 67% of the tensile strength of engineered neocartilages. Finally, examination of quantitative MRI metrics revealed several correlations with mechanical and biochemical properties of engineered constructs. This study displays the importance of culture duration for collagen cross-link formation, and demonstrates the potential of quantitative MRI in investigating properties of engineered cartilages.

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Section: Discussionsupporting

confidence: 89%

Temporal development of near-native functional properties and correlations with qMRI in self-assembling fibrocartilage treated with exogenous lysyl oxidase homolog 2

Hadidi

Cissell

et al. 2017

Acta Biomaterialia

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“…Human osteochondral plugs (N = 33, d = 8 mm) were extracted from the lateral and medial tibial plateaus and femoral condyles in left and right knee joints of human cadavers (n = 4, mean age = 71.25 ± 5.18 years). [27][28][29] The Research Committee of the Northern Savo Hospital District granted a favorable opinion on collecting the human tissue (Kuopio University Hospital, Kuopio, Finland, Decision numbers: 134/2015 and58/2013).…”

Section: Sample Extraction and Preparationmentioning

confidence: 99%

Dual contrast in computed tomography allows earlier characterization of articular cartilage over single contrast

Bhattarai

Pouran

Mäkelä

et al. 2020

Journal Orthopaedic Research

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Cationic computed tomography contrast agents are more sensitive for detecting cartilage degeneration than anionic or non‐ionic agents. However, osteoarthritis‐related loss of proteoglycans and increase in water content contrarily affect the diffusion of cationic contrast agents, limiting their sensitivity. The quantitative dual‐energy computed tomography technique allows the simultaneous determination of the partitions of iodine‐based cationic (CA4+) and gadolinium‐based non‐ionic (gadoteridol) agents in cartilage at diffusion equilibrium. Normalizing the cationic agent partition at diffusion equilibrium with that of the non‐ionic agent improves diagnostic sensitivity. We hypothesize that this sensitivity improvement is also prominent during early diffusion time points and that the technique is applicable during contrast agent diffusion. To investigate the validity of this hypothesis, osteochondral plugs (d = 8 mm, N = 33), extracted from human cadaver (n = 4) knee joints, were immersed in a contrast agent bath (a mixture of CA4+ and gadoteridol) and imaged using the technique at multiple time points until diffusion equilibrium. Biomechanical testing and histological analysis were conducted for reference. Quantitative dual‐energy computed tomography technique enabled earlier determination of cartilage proteoglycan content over single contrast. The correlation coefficient between human articular cartilage proteoglycan content and CA4+ partition increased with the contrast agent diffusion time. Gadoteridol normalized CA4+ partition correlated significantly (P < .05) with Mankin score at all time points and with proteoglycan content after 4 hours. The technique is applicable during diffusion, and normalization with gadoteridol partition improves the sensitivity of the CA4+ contrast agent.

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“…Thickness can be an important factor when choosing the imaging facility particularly when investigating zone-dependent transport properties. For example, even 9.4 T MRI provides relatively low resolutions in out -of-plane orientation (Figure 1) (Rautiainen et al, 2016), which hampers the 3D characterizations, particularly in very thin cartilage of small animals. Therefore, for mice and rat cartilage, the preferred modalities would be either micro-CT (voxel size ~ a few microns) or fluorescent microscopy techniques (planar resolution <1 µm).…”

Section: Tissue Thicknessmentioning

confidence: 99%

Multi-scale imaging techniques to investigate solute transport across articular cartilage

Pouran

Arbabi

Bajpayee

et al. 2018

Journal of Biomechanics

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As articular cartilage is an avascular tissue, the transport of nutrients and cytokines through the tissue is essential for the health of cells, i.e. chondrocytes. Transport of specific contrast agents through cartilage has been investigated to elucidate cartilage quality. In laboratory, pre-clinical and clinical studies, imaging techniques such as magnetic imaging resonance (MRI), computed tomography (CT) and fluorescent microscopy have been widely employed to visualize and quantify solute transport in cartilage. Many parameters related to the physico-chemical properties of the solute, such as molecular weight, net charge and chemical structure, have a profound effect on the transport characteristics. Information on the interplay of the solute parameters with the imaging-dependent parameters (e.g. resolution, scan and acquisition time) could assist in selecting the most optimal imaging systems and data analysis tools in a specific experimental set up. Here, we provide a comprehensive review of various imaging systems to investigate solute transport properties in articular cartilage, by discussing their potentials and limitations. The presented information can serve as a guideline for applications in cartilage imaging and therapeutics delivery and to improve understanding of the set-up of solute transport experiments in articular cartilage.

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Effect of collagen cross-linking on quantitative MRI parameters of articular cartilage

Cited by 6 publications

References 50 publications

Temporal development of near-native functional properties and correlations with qMRI in self-assembling fibrocartilage treated with exogenous lysyl oxidase homolog 2

Temporal development of near-native functional properties and correlations with qMRI in self-assembling fibrocartilage treated with exogenous lysyl oxidase homolog 2

Dual contrast in computed tomography allows earlier characterization of articular cartilage over single contrast

Multi-scale imaging techniques to investigate solute transport across articular cartilage

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