Glucose fluxes in glycolytic and oxidative pathways detected in vivo by deuterium magnetic resonance spectroscopy reflect proliferation in mouse glioblastoma

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

• Level A · Stronger Clinical Evidence
• Level B · Emerging clinical evidence with positive signals
• Level C · Early human research exploring benefits
• Level D · Scientific groundwork from lab and animal studies
• Emerging · Emerging topic under active research

Abstract (original English)

Objectives Glioblastoma multiforme (GBM), the most aggressive glial brain tumors, can metabolize glucose through glycolysis and mitochondrial oxidation pathways. While specific dependencies on those pathways are increasingly associated with treatment response, detecting such GBM subtypes in vivo remains elusive. Here, we develop a dynamic glucose-enhanced deuterium spectroscopy (DGE 2 H-MRS) approach for differentially assessing glucose turnover rates through glycolysis and mitochondrial oxidation in mouse GBM and explore their association with histologic features of the tumor and its microenvironment. Materials and methods GL261 and CT2A glioma allografts were induced in immunocompetent mice and scanned in vivo at 9.4 Tesla, harnessing DGE 2 H-MRS with volume selection and Marchenko-Pastur PCA (MP-PCA) denoising to achieve high temporal resolution. Each tumor was also classified by histopathologic analysis and assessed for cell proliferation (Ki67 immunostaining), while the respective cell lines underwent in situ extracellular flux analysis to assess mitochondrial function. Results MP-PCA denoising of in vivo DGE 2 H-MRS data significantly improved the time-course detection (~2-fold increased Signal-to-Noise Ratio) and fitting precision (-19 ± 1 % Cramér-Rao Lower Bounds) of 2 H-labelled glucose, and glucose-derived glutamate-glutamine (Glx) and lactate pools in GL261 and CT2A

Evidence level

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

Browse all related research

Filter the research library by this study's title keywords, author, or publication year.