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Correlation of HR-MAS Spectroscopy Derived Metabolite Concentrations With Collagen and Proteoglycan Levels and Thompson Grade in the Degenerative Disc

Keshari, Kayvan R. BS*; Lotz, Jeffrey C. PhD†; Kurhanewicz, John PhD*; Majumdar, Sharmila PhD*†


Study Design. A quantitative high-resolution magic angle spinning (HR-MAS) NMR study of human lumbar discs was conducted to determine biomarkers of disc degeneration.

Objectives. To correlate HR-MAS quantification of compounds relevant to human lumbar disc degeneration to conventional methods of disc grading such as Thompson grading and biochemical analysis.

Summary of Background Data. It has been shown that there is poor correlation between MRI and CT morphologic findings, spinal biomechanics, and patient symptoms in degenerative disc disease and low back pain. There is a need for an objective, quantitative measurement of biochemical status, morphology, and function.

Methods. A total of 17 cadaveric human lumbar intervertebral discs were harvested from patients ranging from 20 to 85 years of age. Quantitative HR-MAS data were acquired, and proteoglycan and collagen biochemical analyses were conducted on 3-mm biopsy punches taken from the anulus fibrosus and nucleus pulposus of each sample. HR-MAS data were fitted and analyzed for hydroxyproline (3.42 ppm), glycine (3.56 ppm), and the N-acetyl peak (2.04 ppm) associated with proteoglycans in comparison with an internal standard. These concentrations were then compared directly to biochemical analyses and Thompson grade.

Results. HR-MAS data correlated well with Thompson grade (P < 0.001). An increase was seen in the levels of unbound hydroxyproline and glycine in anular tissue, which is directly associated to collagen breakdown. This trend also correlates with the changes of total collagen measured by a collagen biochemical assay. HR-MAS also detected a decrease in concentration of nucleus pulposus proteoglycans with degeneration. This proteoglycan decrease was verified by a standard proteoglycan biochemical assay.

Conclusions. Changes in disc chemical composition can be accurately quantified using quantitative HR-MAS NMR spectroscopy ex vivo. This noninvasive method of qualitatively and quantitatively assessing disc degeneration supports the utility of these biomarkers and underlines the need for developing in vivo magnetic resonance spectroscopic imaging (MRSI) for characterizing intervertebral disc degeneration.

Quantitative high-resolution magic angle spinning (HR-MAS) NMR spectroscopy can be used to quantify compounds associated with intervertebral disc degeneration. This supports the feasibility of using magnetic resonance spectroscopic imaging in vivo to noninvasively determine the degree of disc degeneration.

From the Departments of *Radiology and †Orthopaedic Surgery, University of California, San Francisco, CA.

Acknowledgment date: October 18, 2004. First revision date: April 11, 2005. Acceptance date: September 16, 2005.

Supported by the National Health Institute (R21-AR51048, R01-AG17762).

The manuscript submitted does not contain information about medical device(s)/drug(s).

No funds were received in support of this work. No benefits in any form have been or will be received from a commercial party related directly or indirectly to the subject of this manuscript.

Address correspondence and reprint requests to Kayvan R. Keshari, BS, Musculoskeletal and Quantitative Imaging Research Group, Department of Radiology, University of California, San Francisco, 185 Berry St, Suite 350, Box 0946, San Francisco, CA 94107; E-mail:

© 2005 Lippincott Williams & Wilkins, Inc.