Multiparametric MR Investigation of Proteoglycan Diffusivity, T2 Relaxation, and Concentration in an Ex Vivo Model of Intervertebral Disc Degeneration

Abstract

Background: Proteoglycan (PG) is a major component of the intervertebral disc extracellular matrix (ECM) that acts to hydrate the disc nucleus. Early detection of PG degradation is valuable for both diagnosis and preclinical research of intervertebral disc degeneration (IVDD).

Purpose: To compare different MR techniques for detecting early degradative changes of PG in IVDD.

Study type: Prospective.

Phantom/specimen: Glycosaminoglycan (GAG) phantom/bovine discs with papain injection and human cadaveric discs.

Field strength/sequences: 7T/diffusion-weighted MR spectroscopy (DW-MRS), T₂ -weighted MRS (T₂ W-MRS), and chemical exchange saturation transfer (CEST) imaging.

Assessment: DW-MRS, T₂ W-MRS, and CEST imaging were applied longitudinally to measure PG diffusivity, T₂ value, overall content, and spatial distribution in the disc nucleus with enzyme-induced proteolytic ECM degradation (n = 8). Similar MR measurements were applied in GAG phantom and human cadaveric discs with different levels of degeneration (n = 6).

Statistical tests: T-tests were conducted to measure the differences of PG properties between pre- and post-enzyme injection. Linear regression and mixed-effects models were used to assess the associations among different PG properties as well as the degeneration grades in human cadaveric discs.

Results: In bovine discs, PG diffusivity increased most rapidly after the enzyme was injected into the disc nucleus (12 hours postinjection, t = 5.76, P = 0.0007). The PG T₂ value did not change significantly (t < 1.54, P > 0.17 for all timepoints) during ECM degradation and was not associated with PG diffusivity (t = 0.06, P = 0.95). PG distribution change was more rapid than overall PG content and was strongly associated with PG diffusivity increase (t = -9.25, P < 1 × 10^-8 ). In severely degenerated human cadaveric discs, the PG ADCs and T₂ values were both associated with degeneration grades.

Data conclusion: PG diffusivity is a direct biomarker for early ECM degradation, while PG distribution can be an indirect biomarker for early IVDD.

Level of evidence: 2 Technical Efficacy Stage: 2 J. Magn. Reson. Imaging 2020;51:1390-1400.

Keywords: T2-weighted MRS; chemical exchange saturation transfer; diffusion-weighted MRS; extracellular matrix; intervertebral disc degeneration; proteoglycan.