Intervertebral disc degeneration is characterized by a progressive cascade of changes in organization and mechanical properties of annulus fibrosus (AF), nucleus pulposus (NP) and end plates (EP). In early degeneration, proteoglycan fragmentation in the NP leads to a decrease of water content, osmotic pressure and stiffness. Advanced stages of degeneration are characterized by a transition of the nucleus from a gelatinous material to a fibrous one, structural changes in the AF, followed by fissures and tears in the AF. Early diagnosis of disc degeneration is critical for the success of any biological treatment strategy. Currently, diagnosis of disc degeneration using clinical MRI only detects characteristics of advanced stages of degeneration. New MR-based techniques, such as sodium imaging, magnetization transfer, T1r and T2 maps, have been used to quantify early changes in NP composition. However, tissue mechanical properties are more sensitive than MR-based composition at detecting changes in the tissue microstructure. Despite the numerous studies reporting the mechanical implications of early disc generation, the mechanical properties of disc tissues haven't been measured in-vivo. The destructive nature of current mechanical testing techniques for orthopaedic tissues is prohibitive for in-vivo applications. Therefore, there is a need of non-invasive, non- destructive methods to measure disc mechanical properties to serve as a biomarker of degeneration. Magnetic Resonance Elastography is an MR-based technique to measure elastic properties of soft tissues that has been successfully used for the diagnosis of diseases that involve changes in the mechanical properties. The objective of this study is to apply Magnetic Resonance Elastography to measure elastic properties of the disc from intact disc segments and to correlate those properties with degeneration. Specifically, we propose to:
Aim 1 : Adapt MRE to measure elastic properties of in the intervertebral disc. 1A. Modify our 2D MRE set-up to obtain three-dimensional (3D) measurements of elastic properties of the intervertebral disc. Specifically, to modify the 2D MRI pulse sequence to acquire 3D data by adding a phase encoding gradient in the slice direction;design and build a gradient coil to apply a motion sensitizing gradient at high frequencies;modify an inverse method to calculate anisotropic AF elastic properties. 1B. Integrate all these components and validate the method by comparing MRE properties with those obtained by conventional tissue mechanical torsion tests.
Aim 2 : Measure and correlate mechanical properties of disc and degeneration. Measure mechanical properties of AF and NP of intact disc segments across a range of different degeneration levels. Correlate those properties with degeneration measured using the Pfirrmann grade and continuous scales such as T1r and T2 maps. Results from this correlation will determine the sensitivity of MRE to identify and diagnose early stages of degeneration in the disc. This work is significant in that it will provide a much-needed non-invasive method to quantify mechanical properties of the disc, as well as the basis and technical developments required for a future application of MRE to measure elastic properties of the disc in-vivo.

Public Health Relevance

Lumbar disc degeneration and associated low back pain are costly and devastating. Disc degeneration is characterized by a cascade of events that impair the disc mechanical properties. Early diagnosis of disc degeneration is critical for the success of any treatment strategy. The objective of this proposal is to adapt and use magnetic resonance elastography to measure mechanical properties of disc tissues in early stages of degeneration. This work is significant in that it will provide a much needed non-invasive, non-destructive method to quantify mechanical properties of the disc, as well as the basis and technical developments required for a future application of MRE to measure elastic properties of the disc in-vivo.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Exploratory/Developmental Grants (R21)
Project #
5R21AR061751-03
Application #
8293159
Study Section
Musculoskeletal Tissue Engineering Study Section (MTE)
Program Officer
Lester, Gayle E
Project Start
2011-07-01
Project End
2014-06-30
Budget Start
2012-07-01
Budget End
2014-06-30
Support Year
3
Fiscal Year
2012
Total Cost
$172,125
Indirect Cost
$59,625
Name
University of Delaware
Department
Biomedical Engineering
Type
Schools of Engineering
DUNS #
059007500
City
Newark
State
DE
Country
United States
Zip Code
19716
Cortes, Daniel H; Jacobs, Nathan T; DeLucca, John F et al. (2014) Elastic, permeability and swelling properties of human intervertebral disc tissues: A benchmark for tissue engineering. J Biomech 47:2088-94
Cortes, Daniel H; Magland, Jeremy F; Wright, Alexander C et al. (2014) The shear modulus of the nucleus pulposus measured using magnetic resonance elastography: a potential biomarker for intervertebral disc degeneration. Magn Reson Med 72:211-9
Cortes, Daniel H; Elliott, Dawn M (2012) Extra-fibrillar matrix mechanics of annulus fibrosus in tension and compression. Biomech Model Mechanobiol 11:781-90