Detection of extracellular matrix degradation in intervertebral disc degeneration by diffusion magnetic resonance spectroscopy

Abstract

Purpose: To investigate whether diffusion magnetic resonance spectroscopy (MRS) can detect the extracellular matrix (ECM) degradation during intervertebral disc degeneration (IVDD) by the increased mobility of ECM macromolecules such as proteoglycans and collagens.

Methods: Fresh bovine intervertebral discs were injected with papain solution to induce ECM degradation. The apparent diffusion coefficients (ADCs), T2 values, and contents of ECM macromolecules and water resonances were measured longitudinally in the nucleus pulposus.

Results: The macromolecule ADCs increased drastically at day 1 after papain injection, and continued increasing for 5 days. In contrast, the proteoglycan content exhibited a small and slow decrease after injection while the macromolecule T2 values, water T2, ADC, and content showed slight increase or no change. The protein gel electrophoresis analysis confirmed the gradually increased ECM fragmentation in accordance with the observed macromolecule ADC increases.

Conclusion: Diffusion MRS provides a new method to characterize the ECM degradation processes directly and sensitively. Macromolecule ADCs offer a potentially more sensitive and earlier marker for ECM degradation than the proteoglycan content and T2, and water MR properties during early IVDD. Such diffusion approach offers the possibility to directly monitor ECM integrity and degradation processes in vivo at molecular and microstructural levels in both preclinical and clinical settings.

Keywords: diffusion weighted MRS; extracellular matrix; intervertebral disc degeneration; magnetic resonance spectroscopy; proteoglycan.