Deuterium Magnetic Resonance Spectroscopy Quantifies Tumor Fraction in a Mouse Model of a Mixed Radiation Necrosis / GL261-Glioblastoma Lesion
- 29.07.2023
- Research Article
- Verfasst von
- Kyu-Ho Song
- Xia Ge
- John Engelbach
- Keith M. Rich
- Joseph J. H. Ackerman
- Joel R. Garbow
- Erschienen in
- Molecular Imaging and Biology | Ausgabe 1/2024
Abstract
Purpose
Distinguishing recurrent brain tumor from treatment effects, including late time-to-onset radiation necrosis (RN), presents an on-going challenge in post-treatment imaging of neuro-oncology patients. Experiments were performed in a novel mouse model that recapitulates the relevant clinical histologic features of recurrent glioblastoma growing in a RN environment, the mixed tumor/RN model. The goal of this work was to apply single-voxel deuterium (2H) magnetic resonance spectroscopy (MRS), in concert with administration of deuterated glucose, to determine if the metabolic signature of aerobic glycolysis (Warburg effect: glucose → lactate in the presence of O2), a distinguishing characteristic of proliferating tumor, provides a quantitative readout of the tumor fraction (percent) in a mixed tumor/RN lesion.
Procedures
2H MRS employed the SPin-ECho full-Intensity Acquired Localized (SPECIAL) MRS pulse sequence and outer volume suppression at 11.74 T. For each subject, a single 2H MRS voxel was placed over the mixed lesion as defined by contrast enhanced (CE) 1H T1-weighted MRI. Following intravenous administration of [6,6-2H2]glucose (Glc), 2H MRS monitored the glycolytic conversion to [3,3-2H2]lactate (Lac) and glutamate + glutamine (Glu + Gln = Glx).
Results
Based on previous work, the tumor fraction of the mixed lesion was quantified as the ratio of tumor volume, defined by 1H magnetization transfer experiments, vs. the total mixed-lesion volume. Metabolite 2H MR spectral-amplitude values were converted to metabolite concentrations using the natural-abundance semi-heavy water (1HO2H) resonance as an internal concentration standard. The 2H MR-determined [Lac] / [Glx] ratio was strongly linearly correlated with tumor fraction in the mixed lesion (n = 9), Pearson’s r = 0.87, and 77% of the variation in the [Lac] / [Glx] ratio was due to tumor percent r2 = 0.77.
Conclusions
This preclinical study supports the proposal that 2H MR could occupy a well-defined secondary role when standard-of-care 1H imaging is non-diagnostic regarding tumor presence and/or response to therapy.
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- Titel
- Deuterium Magnetic Resonance Spectroscopy Quantifies Tumor Fraction in a Mouse Model of a Mixed Radiation Necrosis / GL261-Glioblastoma Lesion
- Verfasst von
-
Kyu-Ho Song
Xia Ge
John Engelbach
Keith M. Rich
Joseph J. H. Ackerman
Joel R. Garbow
- Publikationsdatum
- 29.07.2023
- Verlag
- Springer International Publishing
- Erschienen in
-
Molecular Imaging and Biology / Ausgabe 1/2024
Print ISSN: 1536-1632
Elektronische ISSN: 1860-2002 - DOI
- https://doi.org/10.1007/s11307-023-01837-2
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