Article
Metabolomic profiling with 1H NMR spectroscopy to predict disc degeneration in the human cervical spine
Vorhersagemöglichkeit der Degeneration der humanenHalswirbelsäule mittels Metabolom Analyse mit 1H-NMR-Spektroskopie
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Published: | June 26, 2020 |
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Objective: Recently, imaging techniques providing metabolic representations of the tissue, such as magnetic resonance spectroscopy (MRS), are used to characterize disc degeneration. Only few studies focus on cervical intervertebral disc (IVD) degeneration. The purpose of this study is to identify promising biomarkers, detectable non-invasively by MRS in the patient, to provide novel in vivo imaging opportunities of discogenic pain in the human cervical spine.
Methods: Thirty biopsies of cervical pathological ID (Ranging-age: 20 -74 years) were dissected into annulus fibrosus (AF) and nucleus pulposus (NP). Water-soluble metabolites were extracted with the dual-phase method using methanol:chloroform:water (1:1:1). By 1H NMR spectroscopy the complete water-soluble metabolome was analysed on a HR 700 MHz spectrometer. Differences in metabolic composition of AP and NP were calculated and related to the degree of disc degeneration (I-V Miyazaki grading system, MGS). Significances were calculated with ANOVA analyses and Bonferroni’s multiple comparison tests.
Results: We detected changes in a variety of well-studied metabolites including lactate (Lac), choline (Cho), creatine (Cre), chondroitin (Chond), glutamine (Gln), glutamate (Glu), Tyrosine (Tyr), Glycine (Gly), and Succinate (Suc). We observed significantly (p < 0.0001) increased concentrations of Chond and significantly (p < 0.005) decreased concentrations of Cre, Gln, and Cho in NF compared to AF tissue. Strikingly, the difference in relative Chond between NP and AF was highest in Grade 3 and significantly (p-value < 0.05) decreased with increasing MGS (4 and 5). Moreover, we calculated several metabolic ratios and compared to MGS. Furthermore, we could detect a linear trend between the MGS and the extent of the observed differences in metabolite ratios (p < 0.05).
Conclusion: By means of assessing metabolic biomarkers with non-invasive 1H MRS spectroscopy, early stages of IVD degeneration could be detected. Especially the identified metabolic ratios such as Lac/Cre, Chon/Cre, Glu/Cre, or Cho/Cre, have potential for prediction of severity of the disc degeneration.