Adaptability of Articular Cartilage to External Loading by Microscopic Imaging

Summary

Principal Investigator: Y Xia
Affiliation: Oakland University
Country: USA
Abstract: DESCRIPTION (provided by applicant): Osteoarthritis (OA) is a major health concern affecting more than 20 million people in US. The disease is predominantly characterized by a gradual degeneration of the load-bearing tissue in joint, articular cartilage. Before the earliest clinical diagnosis of OA, a series of complex and depth-dependent events at various molecular and structural levels has already taken place inside cartilage. A lack of non-invasive and molecular-specific markers to detect the early degradation events in cartilage has so far prevented a fundamental understanding of the development of OA, as well as early diagnosis of and intervention in OA. Due to its multi-level hierarchical organization, multidisciplinary measurements that interrogate cartilage at different technical modalities are warranted. Due to its depth-dependent and heterogeneous structure, a thorough understanding of tissue's response to external loading requires microscopic imaging. Recently, we have successfully imaged the load-induced ultrastructural adaptability in cartilage using at high resolution. We use static loading as a tool to force the tissue to reach a new equilibrium with the environment in order to probe cartilage's intrinsic properties and structural adaptability in a depth-resolved manner in imaging. In essence, static loading becomes a controllable mechanism to induce additional contrast and to enhance weak contrast in our imaging work. The overarching goal of this proposal is to detect the early changes in the in situ molecular architecture of diseased articular cartilage. We hypothesize that the load-induced changes in cartilage at the structural and molecular levels can be detected by a combination of microscopic imaging modalities and that the degradation in cartilage due to diseases or mechanical injury could affect load-induced ultrastructural changes, which will be calibrated by immunohistochemistry imaging. The three specific aims of this study will determine a set of multidisciplinary parameters that detects various changes in tissue's response to static loading due to biochemical digestion, natural lesion, and repetitive/dynamic loading. In combination, this proposal will go beyond the level of describing and characterizing the imaging signals. It aims to put these imaging techniques to work as the predictors of disease progression, and monitors of injury and repair. Osteoarthritis, which is a major health concern affecting more than 20 million people in US, is predominantly characterized by a gradual degeneration of the load-bearing tissue in joint, articular cartilage. This project aims to detect the early changes in the in situ molecular architecture of diseased cartilage using a set of multidisciplinary microscopic imaging techniques.
Funding Period: ----------------2008 - ---------------2013-
more information: NIH RePORT

Top Publications

  1. pmc Molecular and morphological adaptations in compressed articular cartilage by polarized light microscopy and Fourier-transform infrared imaging
    Y Xia
    Department of Physics and Center for Biomedical Research, Oakland University, Rochester, MI 48309, USA
    J Struct Biol 164:88-95. 2008
  2. ncbi T1ρ magnetic resonance imaging for detection of early cartilage changes in knees of asymptomatic collegiate female impact and nonimpact athletes
    Sebastian C Peers
    Departments of Orthopaedic Surgery Orthopaedic Research and Diagnostic Radiology, Beaumont Health System, Royal Oak, Michigan and Department of Physics, Oakland University, Rochester, Michigan
    Clin J Sport Med 24:218-25. 2014
  3. pmc Experimental issues in the measurement of multi-component relaxation times in articular cartilage by microscopic MRI
    Nian Wang
    Department of Physics and Center for Biomedical Research, Oakland University, Rochester, MI 48309, USA
    J Magn Reson 235:15-25. 2013
  4. pmc The effects of mechanical loading and gadolinium concentration on the change of T1 and quantification of glycosaminoglycans in articular cartilage by microscopic MRI
    Nian Wang
    Department of Physics and Center for Biomedical Research, Oakland University, Rochester, MI 48309, USA
    Phys Med Biol 58:4535-47. 2013
  5. doi Quantitative zonal differentiation of articular cartilage by microscopic magnetic resonance imaging, polarized light microscopy, and Fourier-transform infrared imaging
    Ji Hyun Lee
    Department of Physics and Center for Biomedical Research, Oakland University, Rochester, Michigan 48309, USA
    Microsc Res Tech 76:625-32. 2013
  6. pmc Anisotropic analysis of multi-component T2 and T1ρ relaxations in achilles tendon by NMR spectroscopy and microscopic MRI
    Nian Wang
    Department of Physics and Center for Biomedical Research, Oakland University, Rochester, Michigan 48309, USA
    J Magn Reson Imaging 38:625-33. 2013
  7. doi Orientational dependent sensitivities of T2 and T1ρ towards trypsin degradation and Gd-DTPA2- presence in bovine nasal cartilage
    Nian Wang
    Department of Physics and Center for Biomedical Research, Oakland University, Rochester, MI 48309, USA
    MAGMA 25:297-304. 2012
  8. pmc Macromolecular concentrations in bovine nasal cartilage by Fourier transform infrared imaging and principal component regression
    Jianhua Yin
    Department of Physics and Center for Biomedical Research, Oakland University, Rochester, Michigan 48309, USA
    Appl Spectrosc 64:1199-208. 2010
  9. pmc Damages to the extracellular matrix in articular cartilage due to cryopreservation by microscopic magnetic resonance imaging and biochemistry
    Shaokuan Zheng
    Department of Physics and Center for Biomedical Research, Oakland University, Rochester, MI 48309, USA
    Magn Reson Imaging 27:648-55. 2009
  10. pmc Multi-components of T2 relaxation in ex vivo cartilage and tendon
    Shaokuan Zheng
    Department of Physics and Center for Biomedical Research, Oakland University, Rochester, MI 48309, USA
    J Magn Reson 198:188-96. 2009

Scientific Experts

  • Y Xia
  • Nian Wang
  • Shaokuan Zheng
  • Jianhua Yin
  • Sebastian C Peers
  • Ji Hyun Lee
  • Daniel Mittelstaedt
  • Aruna Bidthanapally
  • Farid Badar
  • S Zheng
  • Steffan Puwal
  • David Keyes
  • Anil Shetty
  • David Marcantonio
  • Joseph Guettler
  • Erin A Baker
  • Tristan Maerz
  • Edith Chopin
  • Mei Lu
  • Alex Shmelyov
  • Nick Casciani
  • Nick Duvoisin
  • Itamar Ilsar

Detail Information

Publications24

  1. pmc Molecular and morphological adaptations in compressed articular cartilage by polarized light microscopy and Fourier-transform infrared imaging
    Y Xia
    Department of Physics and Center for Biomedical Research, Oakland University, Rochester, MI 48309, USA
    J Struct Biol 164:88-95. 2008
    ..These depth-dependent adaptations to static loading in cartilage's morphological structure and chemical distribution could be useful in the future studies of the early diseased cartilage...
  2. ncbi T1ρ magnetic resonance imaging for detection of early cartilage changes in knees of asymptomatic collegiate female impact and nonimpact athletes
    Sebastian C Peers
    Departments of Orthopaedic Surgery Orthopaedic Research and Diagnostic Radiology, Beaumont Health System, Royal Oak, Michigan and Department of Physics, Oakland University, Rochester, Michigan
    Clin J Sport Med 24:218-25. 2014
    ..It was hypothesized that impact cohort would demonstrate greater changes than nonimpact cohort...
  3. pmc Experimental issues in the measurement of multi-component relaxation times in articular cartilage by microscopic MRI
    Nian Wang
    Department of Physics and Center for Biomedical Research, Oakland University, Rochester, MI 48309, USA
    J Magn Reson 235:15-25. 2013
    ..The transitions between a mono-component and multi-components in cartilage under various experimental conditions call for the extra caution in interpreting the relaxation results...
  4. pmc The effects of mechanical loading and gadolinium concentration on the change of T1 and quantification of glycosaminoglycans in articular cartilage by microscopic MRI
    Nian Wang
    Department of Physics and Center for Biomedical Research, Oakland University, Rochester, MI 48309, USA
    Phys Med Biol 58:4535-47. 2013
    ..It is concluded that the GAG quantification by MRI was accurate as long as the Gd concentration in the solution reached at least 0.2 mM (tissue not loaded) or 0.4 mM (tissue loaded)...
  5. doi Quantitative zonal differentiation of articular cartilage by microscopic magnetic resonance imaging, polarized light microscopy, and Fourier-transform infrared imaging
    Ji Hyun Lee
    Department of Physics and Center for Biomedical Research, Oakland University, Rochester, Michigan 48309, USA
    Microsc Res Tech 76:625-32. 2013
    ..A set of previously established criteria in cartilage imaging was revised. The new criteria could simultaneously correlate the thicknesses of the three consecutive subtissue zones in articular cartilage among these imaging techniques...
  6. pmc Anisotropic analysis of multi-component T2 and T1ρ relaxations in achilles tendon by NMR spectroscopy and microscopic MRI
    Nian Wang
    Department of Physics and Center for Biomedical Research, Oakland University, Rochester, Michigan 48309, USA
    J Magn Reson Imaging 38:625-33. 2013
    ..To study the anisotropic characteristics of both multi-component T2 and T1ρ relaxation times in tendon...
  7. doi Orientational dependent sensitivities of T2 and T1ρ towards trypsin degradation and Gd-DTPA2- presence in bovine nasal cartilage
    Nian Wang
    Department of Physics and Center for Biomedical Research, Oakland University, Rochester, MI 48309, USA
    MAGMA 25:297-304. 2012
    ..To study the orientational dependencies of T(2) and T(1ρ) in native and trypsin-degraded bovine nasal cartilage, with and without the presence of 1 mM Gd-DTPA(2-)...
  8. pmc Macromolecular concentrations in bovine nasal cartilage by Fourier transform infrared imaging and principal component regression
    Jianhua Yin
    Department of Physics and Center for Biomedical Research, Oakland University, Rochester, Michigan 48309, USA
    Appl Spectrosc 64:1199-208. 2010
    ..The use of PCR with FT-IRI offers an accurate tool to spatially determine the distributions of macromolecular concentration in cartilage...
  9. pmc Damages to the extracellular matrix in articular cartilage due to cryopreservation by microscopic magnetic resonance imaging and biochemistry
    Shaokuan Zheng
    Department of Physics and Center for Biomedical Research, Oakland University, Rochester, MI 48309, USA
    Magn Reson Imaging 27:648-55. 2009
    ..These imaging results were verified by the biochemical analysis...
  10. pmc Multi-components of T2 relaxation in ex vivo cartilage and tendon
    Shaokuan Zheng
    Department of Physics and Center for Biomedical Research, Oakland University, Rochester, MI 48309, USA
    J Magn Reson 198:188-96. 2009
    ..81-20.52% increase in T2 relaxation in articular cartilage, depending upon the angle at which the tissue specimen was oriented in the magnetic field...
  11. pmc The collagen fibril structure in the superficial zone of articular cartilage by microMRI
    S Zheng
    Department of Physics, Oakland University, Rochester, MI 48309, USA
    Osteoarthritis Cartilage 17:1519-28. 2009
    ..To investigate the fibril architecture of the collagen matrix in the superficial zone (SZ) of articular cartilage non-destructively by microscopic magnetic resonance imaging (microMRI) T(2) anisotropy...
  12. pmc The impact of the relaxivity definition on the quantitative measurement of glycosaminoglycans in cartilage by the MRI dGEMRIC method
    Shaokuan Zheng
    Department of Physics and Center for Biomedical Research, Oakland University, Rochester, Michigan 48309, USA
    Magn Reson Med 63:25-32. 2010
    ....
  13. pmc On the measurement of multi-component T2 relaxation in cartilage by MR spectroscopy and imaging
    Shaokuan Zheng
    Department of Physics and Center for Biomedical Research, Oakland University, Rochester, MI 48309, USA
    Magn Reson Imaging 28:537-45. 2010
    ....
  14. pmc Depth and orientational dependencies of MRI T(2) and T(1ρ) sensitivities towards trypsin degradation and Gd-DTPA(2-) presence in articular cartilage at microscopic resolution
    Nian Wang
    Department of Physics and Center for Biomedical Research, Oakland University, Rochester, MI 48309, USA
    Magn Reson Imaging 30:361-70. 2012
    ..An MRI experimental protocol based on two T(1ρ) measurements (without and with the presence of the Gd ions) was proposed to be a new imaging marker for cartilage degradation...
  15. pmc Concentration profiles of collagen and proteoglycan in articular cartilage by Fourier transform infrared imaging and principal component regression
    Jianhua Yin
    Department of Physics, Center for Biomedical Research, Oakland University, Rochester, MI 48309, USA
    Spectrochim Acta A Mol Biomol Spectrosc 88:90-6. 2012
    ....
  16. pmc Reversed laminar appearance of articular cartilage by T1-weighting in 3D fat-suppressed spoiled gradient recalled echo (SPGR) imaging
    Yang Xia
    Department of Physics and Center for Biomedical Research, Oakland University, Rochester, Michigan 48309, USA
    J Magn Reson Imaging 32:733-7. 2010
    ..To investigate the reversed intensity pattern in the laminar appearance of articular cartilage by 3D fat-suppressed spoiled gradient recalled echo (FS-SPGR) imaging in magnetic resonance imaging (MRI)...
  17. pmc Anisotropic properties of bovine nasal cartilage
    Yang Xia
    Department of Physics and Center for Biomedical Research, Oakland University, Rochester, Michigan 48309, USA
    Microsc Res Tech 75:300-6. 2012
    ..Collectively, the results in this project coherently indicate a marked structural anisotropy in cartilage from the nasal septum, where the long axis of the collagen fibrils is oriented in parallel with the medial axis...
  18. pmc Further studies on the anisotropic distribution of collagen in articular cartilage by μMRI
    Shaokuan Zheng
    Department of Physics and Center for Biomedical Research, Oakland University, Rochester, Michigan, USA
    Magn Reson Med 65:656-63. 2011
    ....
  19. pmc Quantitative determination of morphological and territorial structures of articular cartilage from both perpendicular and parallel sections by polarized light microscopy
    Daniel Mittelstaedt
    Department of Physics and Center for Biomedical Research, Oakland University, Rochester, MI 48309, USA
    Connect Tissue Res 52:512-22. 2011
    ....
  20. pmc Strain-dependent T1 relaxation profiles in articular cartilage by MRI at microscopic resolutions
    Yang Xia
    Department of Physics and Center for Biomedical Research, Oakland University, Rochester, Michigan 48309, USA
    Magn Reson Med 65:1733-7. 2011
    ..This finding has potential implications in the use of gadolinium contrast agent in clinical magnetic resonance imaging of cartilage (the dGEMRIC procedure), when the loading or loading history of patients is considered...
  21. pmc Depth-dependent anisotropies of amides and sugar in perpendicular and parallel sections of articular cartilage by Fourier transform infrared imaging
    Yang Xia
    Department of Physics and Center for Biomedical Research, Oakland University, Rochester, Michigan 48309, USA
    Microsc Res Tech 74:122-32. 2011
    ..Being sensitive to the orientation of the macromolecular structure in healthy articular cartilage aids the prospect of detecting the early onset of the tissue degradation that may lead to pathological conditions such as osteoarthritis...
  22. pmc Dependencies of multi-component T2 and T1ρ relaxation on the anisotropy of collagen fibrils in bovine nasal cartilage
    Nian Wang
    Department of Physics, Center for Biomedical Research, Oakland University, Rochester, MI 48309, USA
    J Magn Reson 212:124-32. 2011
    ....