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Osteoarthritis and cartilage2015; 23(9); 1613-1621; doi: 10.1016/j.joca.2015.05.004

Determining collagen distribution in articular cartilage using contrast-enhanced micro-computed tomography.

Abstract: Collagen distribution within articular cartilage (AC) is typically evaluated from histological sections, e.g., using collagen staining and light microscopy (LM). Unfortunately, all techniques based on histological sections are time-consuming, destructive, and without extraordinary effort, limited to two dimensions. This study investigates whether phosphotungstic acid (PTA) and phosphomolybdic acid (PMA), two collagen-specific markers and X-ray absorbers, could (1) produce contrast for AC X-ray imaging or (2) be used to detect collagen distribution within AC. Methods: We labeled equine AC samples with PTA or PMA and imaged them with micro-computed tomography (micro-CT) at pre-defined time points 0, 18, 36, 54, 72, 90, 180, 270 h during staining. The micro-CT image intensity was compared with collagen distributions obtained with a reference technique, i.e., Fourier-transform infrared imaging (FTIRI). The labeling time and contrast agent producing highest association (Pearson correlation, Bland-Altman analysis) between FTIRI collagen distribution and micro-CT -determined PTA distribution was selected for human AC. Results: Both, PTA and PMA labeling permitted visualization of AC features using micro-CT in non-calcified cartilage. After labeling the samples for 36 h in PTA, the spatial distribution of X-ray attenuation correlated highly with the collagen distribution determined by FTIRI in both equine (mean ± S.D. of the Pearson correlation coefficients, r = 0.96 ± 0.03, n = 12) and human AC (r = 0.82 ± 0.15, n = 4). Conclusions: PTA-induced X-ray attenuation is a potential marker for non-destructive detection of AC collagen distributions in 3D. This approach opens new possibilities in development of non-destructive 3D histopathological techniques for characterization of OA.
Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.
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Publication Date: 2015-05-21 PubMed ID: 26003951PubMed Central: PMC4565718DOI: 10.1016/j.joca.2015.05.004Google Scholar: Lookup
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  • Non-U.S. Gov't

Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

This research investigated how to assess the distribution of collagen within articular cartilage more efficiently using X-ray imaging. By labeling samples with collagen-specific markers and studying micro-Computed Tomography image intensities, it was found that the spatial distribution of X-ray attenuation strongly correlated with collagen distribution.

Research Background

  • The focus of the study was the evaluation of collagen distribution within articular cartilage (AC), a procedure that traditionally relies on time-consuming, destructive techniques such as histological sectioning.
  • The investigation centered on whether collagen-specific markers and X-ray absorbers, phosphotungstic acid (PTA) and phosphomolybdic acid (PMA), could enhance X-ray imaging contrast of AC or identify collagen distribution.

Research Methodology

  • Equine AC samples were labelled with either PTA or PMA.
  • These samples were then imaged using micro-computed tomography (micro-CT) at several predetermined time points.
  • The micro-CT image intensity was compared with collagen distributions derived from a reference technique known as Fourier-transform infrared imaging (FTIRI).
  • The contrast agent and labelling time that produced the highest correlation between FTIRI collagen distribution and micro-CT-determined PTA distribution was then selected for use with human AC.

Research Findings

  • Both PTA and PMA labelling enabled clear visualization of AC features using micro-CT in non-calcified cartilage.
  • After labelling samples for 36 hours with PTA, there was a high correlation between the spatial distribution of X-ray attenuation and the collagen distribution identified by FTIRI. This was the case for both equine and human AC.

Conclusion

  • PTA-induced X-ray attenuation has been identified as a potential marker for non-destructive detection of AC collagen distributions in three dimensions.
  • This approach presents new opportunities for the creation of non-destructive, 3D histopathological techniques for characterizing osteoarthritis (OA).

Cite This Article

APA
Nieminen HJ, Ylitalo T, Karhula S, Suuronen JP, Kauppinen S, Serimaa R, Hæggström E, Pritzker KP, Valkealahti M, Lehenkari P, Finnilä M, Saarakkala S. (2015). Determining collagen distribution in articular cartilage using contrast-enhanced micro-computed tomography. Osteoarthritis Cartilage, 23(9), 1613-1621. https://doi.org/10.1016/j.joca.2015.05.004

Publication

Osteoarthritis and cartilage
ISSN: 1522-9653
NlmUniqueID: 9305697
Country: England
Language: English
Volume: 23
Issue: 9
Pages: 1613-1621
PII: S1063-4584(15)01161-9

Researcher Affiliations

Nieminen, H J
  • Department of Physics, University of Helsinki, Helsinki, Finland; Research Center Group for Medical Imaging, Physics and Technology, Faculty of Medicine, University of Oulu, Oulu, Finland. Electronic address: heikki.nieminen@helsinki.fi.
Ylitalo, T
  • Department of Physics, University of Helsinki, Helsinki, Finland; Research Center Group for Medical Imaging, Physics and Technology, Faculty of Medicine, University of Oulu, Oulu, Finland. Electronic address: tuomo.ylitalo@helsinki.fi.
Karhula, S
  • Research Center Group for Medical Imaging, Physics and Technology, Faculty of Medicine, University of Oulu, Oulu, Finland. Electronic address: sakari.karhula@oulu.fi.
Suuronen, J-P
  • Department of Physics, University of Helsinki, Helsinki, Finland. Electronic address: jussi-petteri.suuronen@helsinki.fi.
Kauppinen, S
  • Research Center Group for Medical Imaging, Physics and Technology, Faculty of Medicine, University of Oulu, Oulu, Finland; Medical Research Center Oulu, Oulu University Hospital and University of Oulu, Finland. Electronic address: sami.kauppinen@oulu.fi.
Serimaa, R
  • Department of Physics, University of Helsinki, Helsinki, Finland. Electronic address: ritva.serimaa@helsinki.fi.
Hæggström, E
  • Department of Physics, University of Helsinki, Helsinki, Finland. Electronic address: edward.haeggstrom@helsinki.fi.
Pritzker, K P H
  • Department of Laboratory Medicine and Pathobiology, University of Toronto and Mount Sinai Hospital, Toronto, Canada. Electronic address: kenpritzker@gmail.com.
Valkealahti, M
  • Department of Surgery and Intensive Care, University of Oulu and Oulu University Hospital, Finland. Electronic address: maarit.valkealahti@ppshp.fi.
Lehenkari, P
  • Medical Research Center Oulu, Oulu University Hospital and University of Oulu, Finland; Department of Anatomy and Cell Biology, University of Oulu, Finland; Department of Surgery and Intensive Care, University of Oulu and Oulu University Hospital, Finland. Electronic address: petri.lehenkari@oulu.fi.
Finnilä, M
  • Research Center Group for Medical Imaging, Physics and Technology, Faculty of Medicine, University of Oulu, Oulu, Finland; Medical Research Center Oulu, Oulu University Hospital and University of Oulu, Finland. Electronic address: mikko.finnila@oulu.fi.
Saarakkala, S
  • Research Center Group for Medical Imaging, Physics and Technology, Faculty of Medicine, University of Oulu, Oulu, Finland; Medical Research Center Oulu, Oulu University Hospital and University of Oulu, Finland; Department of Diagnostic Radiology, Oulu University Hospital, Oulu, Finland. Electronic address: simo.saarakkala@oulu.fi.

MeSH Terms

  • Aged
  • Animals
  • Cartilage, Articular / chemistry
  • Collagen / analysis
  • Contrast Media
  • Horses
  • Humans
  • Male
  • Middle Aged
  • Molybdenum
  • Osteoarthritis / metabolism
  • Phosphoric Acids
  • Phosphotungstic Acid
  • Tissue Distribution
  • X-Ray Microtomography / methods

Grant Funding

  • 336267 / European Research Council

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