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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Research Project (R01)
Project #
5R01AR052353-05
Application #
8242811
Study Section
Microscopic Imaging Study Section (MI)
Program Officer
Tyree, Bernadette
Project Start
2008-04-30
Project End
2014-03-31
Budget Start
2013-04-01
Budget End
2014-03-31
Support Year
5
Fiscal Year
2013
Total Cost
$422,505
Indirect Cost
$117,162
Name
Oakland University
Department
Physics
Type
Schools of Arts and Sciences
DUNS #
041808262
City
Rochester
State
MI
Country
United States
Zip Code
48309
Wang, Nian; Kahn, David; Badar, Farid et al. (2015) Molecular origin of a loading-induced black layer in the deep region of articular cartilage at the magic angle. J Magn Reson Imaging 41:1281-90
Peers, Sebastian C; Maerz, Tristan; Baker, Erin A et al. (2014) T1? magnetic resonance imaging for detection of early cartilage changes in knees of asymptomatic collegiate female impact and nonimpact athletes. Clin J Sport Med 24:218-25
Yin, Jianhua; Xia, Yang (2014) Proteoglycan concentrations in healthy and diseased articular cartilage by Fourier transform infrared imaging and principal component regression. Spectrochim Acta A Mol Biomol Spectrosc 133:825-30
Wang, Nian; Chopin, Edith; Xia, Yang (2013) The effects of mechanical loading and gadolinium concentration on the change of T1 and quantification of glycosaminoglycans in articular cartilage by microscopic MRI. Phys Med Biol 58:4535-47
Wang, Nian; Xia, Yang (2013) Anisotropic analysis of multi-component T2 and T1ýý relaxations in achilles tendon by NMR spectroscopy and microscopic MRI. J Magn Reson Imaging 38:625-33
Lee, Ji Hyun; Xia, Yang (2013) Quantitative zonal differentiation of articular cartilage by microscopic magnetic resonance imaging, polarized light microscopy, and Fourier-transform infrared imaging. Microsc Res Tech 76:625-32
Wang, Nian; Xia, Yang (2013) Experimental issues in the measurement of multi-component relaxation times in articular cartilage by microscopic MRI. J Magn Reson 235:15-25
Wang, Nian; Xia, Yang (2012) Depth and orientational dependencies of MRI T(2) and T(1ýý) sensitivities towards trypsin degradation and Gd-DTPA(2-) presence in articular cartilage at microscopic resolution. Magn Reson Imaging 30:361-70
Yin, Jianhua; Xia, Yang; Lu, Mei (2012) Concentration profiles of collagen and proteoglycan in articular cartilage by Fourier transform infrared imaging and principal component regression. Spectrochim Acta A Mol Biomol Spectrosc 88:90-6
Xia, Yang; Zheng, Shaokuan; Szarko, Matthew et al. (2012) Anisotropic properties of bovine nasal cartilage. Microsc Res Tech 75:300-6

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