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

Abstract

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.

In vivo diffusion MRS investigation of non‐water molecules in biological tissues

“…In skeletal muscle, ADC of IMCLs can probe the size changes of the small IMCL droplets in response to metabolic perturbations or disorders , while ADCs of ATP and PCr could probe the capacity of diffusion‐related cellular energy transport . In intervertebral disk, ECM macromolecule ADCs can serve as a marker of the integrity of ECM structure and the severity of ECM degeneration . In tumor tissue, 1 H diffusion MRS can characterize Cho, mobile lipid, and lactate ADCs, reflecting changes of tissue microstructure and physiology ; 13 C diffusion MRS could be a useful tool for monitoring the intracellular glycolytic metabolism .…”

Diffusion‐weighted stimulated echo acquisition mode (DW‐STEAM) MR spectroscopy to measure fat unsaturation in regions with low proton‐density fat fraction

“…Diffusion‐weighted (DW) MRS has recently been introduced to separate overlapping peaks in skeletal muscle and intervertebral disc MRS, relying on the differing diffusion behavior between the peaks of interest. Xiao and Wu and Brandejsky et al used a high b‐value DW‐MRS scan to separate and quantify intramyocellular lipid (IMCL) and extramyocellular lipid (EMCL) peaks in skeletal muscle MRS. Wang et al used a multiple b‐value DW‐MRS scan to quantify the carbohydrate peak overlapping with the water peak in the MRS of the intervertebral disc. The diffusion decay of water in most human tissues is around 100 times faster than that of lipids .…”

Early changes in the apparent diffusion coefficient and MMP‑9 expression of a cervical carcinoma U14 allograft model following irradiation

“…Sub-lethal doses of radiation may enhance MMP-9 promoter activity and expression through the phosphoinositide 3-kinase/protein kinase B/NF-κB signal transduction pathways (13,35). An early and significant increase in MMP-9 expression induced by irradiation facilitates ECM degradation (36). It has been suggested that gene knockdown of MMP-9 or RNA interference-mediated downregulation of radiation-induced MMP-9 may significantly reverse ADC reduction, and that increased expression of MMP-9 facilitates ECM degradation, leading to a decrease in cellularity and an increase in the water diffusion and ADC values of tumors (35).…”

“…The dilatation of the ECS is characterized by a loss of cellularity, degradation of the ECM, morphological changes such as cell-drink and occupancy effect, and inactivation of Na+/K+/ATP enzyme (38,39). It has been previously demonstrated that ECM degradation is associated with the increased mobility of ECM macromolecules, and that macromolecule ADCs offer potential sensitive and early markers for ECM degradation and the prospect of directly monitoring ECM degradation processes in vivo in clinical settings at the molecular and microstructural levels (36). These results support the hypothesis that ECS is crucial for determining the ADC values of tumors: The extracellular ADC values increased with increases in the ECS due to MMP-9-mediated degradation of the ECM following radiation treatment.…”