Deuterium Magnetic Resonance Spectroscopy Quantifies Tumor Fraction in a Mouse Model of a Mixed Radiation Necrosis / GL261-Glioblastoma Lesion

• Published in: Molecular imaging and biology Vol. 26; no. 1; pp. 173 - 178
• Main Authors: Song, Kyu-Ho, Ge, Xia, Engelbach, John, Rich, Keith M., Ackerman, Joseph J. H., Garbow, Joel R.
• Format: Journal Article
• Language: English
• Published: Cham Springer International Publishing 01.02.2024; Springer Nature B.V
• Subjects: Animals; Brain cancer; Brain tumors; Deuteration; Deuterium; Disease Models, Animal; Glioblastoma; Glioblastoma - diagnostic imaging; Glucose; Glutamine; Glycolysis; Heavy water; Humans; Imaging; Intravenous administration; Lactic acid; Lactic Acid - metabolism; Lesions; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Medical imaging; Medicine; Medicine & Public Health; Metabolites; Mice; Necrosis; Neuroimaging; Oncology; Radiation; Radiology; Research Article; Spectroscopy; Spectrum analysis; Tumors; DMI; Deuterium metabolic imaging; GL261; GBM; Single voxel spectroscopy; Radiation necrosis
• ISSN: 1536-1632; 1860-2002; 1860-2002
• DOI: 10.1007/s11307-023-01837-2

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 ( 2 H) 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 O 2 ), a distinguishing characteristic of proliferating tumor, provides a quantitative readout of the tumor fraction (percent) in a mixed tumor/RN lesion. Procedures 2 H 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 2 H MRS voxel was placed over the mixed lesion as defined by contrast enhanced (CE) 1 H T1-weighted MRI. Following intravenous administration of [6,6- 2 H 2 ]glucose (Glc), 2 H MRS monitored the glycolytic conversion to [3,3- 2 H 2 ]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 1 H magnetization transfer experiments, vs. the total mixed-lesion volume. Metabolite 2 H MR spectral-amplitude values were converted to metabolite concentrations using the natural-abundance semi-heavy water ( 1 HO 2 H) resonance as an internal concentration standard. The 2 H 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 r 2  = 0.77. Conclusions This preclinical study supports the proposal that 2 H MR could occupy a well-defined secondary role when standard-of-care 1 H imaging is non-diagnostic regarding tumor presence and/or response to therapy.