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Multi-parametric hyperpolarized 13C/1H imaging reveals Warburg-related metabolic dysfunction and associated regional heterogeneity in high-grade human gliomas.
Autry, Adam W; Vaziri, Sana; LaFontaine, Marisa; Gordon, Jeremy W; Chen, Hsin-Yu; Kim, Yaewon; Villanueva-Meyer, Javier E; Molinaro, Annette; Clarke, Jennifer L; Oberheim Bush, Nancy Ann; Xu, Duan; Lupo, Janine M; Larson, Peder E Z; Vigneron, Daniel B; Chang, Susan M; Li, Yan.
Affiliation
  • Autry AW; Department of Radiology and Biomedical Imaging, University of California, San Francisco, USA.
  • Vaziri S; Department of Radiology and Biomedical Imaging, University of California, San Francisco, USA.
  • LaFontaine M; Department of Radiology and Biomedical Imaging, University of California, San Francisco, USA.
  • Gordon JW; Department of Radiology and Biomedical Imaging, University of California, San Francisco, USA.
  • Chen HY; Department of Radiology and Biomedical Imaging, University of California, San Francisco, USA.
  • Kim Y; Department of Radiology and Biomedical Imaging, University of California, San Francisco, USA.
  • Villanueva-Meyer JE; Department of Radiology and Biomedical Imaging, University of California, San Francisco, USA; Department of Neurological Surgery, University of California, San Francisco, USA.
  • Molinaro A; Department of Neurological Surgery, University of California, San Francisco, USA; Department of Epidemiology and Biostatistics, University of California, San Francisco, USA.
  • Clarke JL; Department of Neurological Surgery, University of California, San Francisco, USA; Department of Neurology, University of California, San Francisco, USA.
  • Oberheim Bush NA; Department of Neurological Surgery, University of California, San Francisco, USA; Department of Neurology, University of California, San Francisco, USA.
  • Xu D; Department of Radiology and Biomedical Imaging, University of California, San Francisco, USA.
  • Lupo JM; Department of Radiology and Biomedical Imaging, University of California, San Francisco, USA.
  • Larson PEZ; Department of Radiology and Biomedical Imaging, University of California, San Francisco, USA.
  • Vigneron DB; Department of Radiology and Biomedical Imaging, University of California, San Francisco, USA; Department of Bioengineering and Therapeutic Science, University of California, San Francisco, USA.
  • Chang SM; Department of Neurological Surgery, University of California, San Francisco, USA.
  • Li Y; Department of Radiology and Biomedical Imaging, University of California, San Francisco, USA. Electronic address: yan.li@ucsf.edu.
Neuroimage Clin ; 39: 103501, 2023.
Article in En | MEDLINE | ID: mdl-37611371
ABSTRACT

BACKGROUND:

Dynamic hyperpolarized (HP)-13C MRI has enabled real-time, non-invasive assessment of Warburg-related metabolic dysregulation in glioma using a [1-13C]pyruvate tracer that undergoes conversion to [1-13C]lactate and [13C]bicarbonate. Using a multi-parametric 1H/HP-13C imaging approach, we investigated dynamic and steady-state metabolism, together with physiological parameters, in high-grade gliomas to characterize active tumor.

METHODS:

Multi-parametric 1H/HP-13C MRI data were acquired from fifteen patients with progressive/treatment-naïve glioblastoma [prog/TN GBM, IDH-wildtype (n = 11)], progressive astrocytoma, IDH-mutant, grade 4 (G4AIDH+, n = 2) and GBM manifesting treatment effects (n = 2). Voxel-wise regional analysis of the cohort with prog/TN GBM assessed imaging heterogeneity across contrast-enhancing/non-enhancing lesions (CEL/NEL) and normal-appearing white matter (NAWM) using a mixed effects model. To enable cross-nucleus parameter association, normalized perfusion, diffusion, and dynamic/steady-state (HP-13C/spectroscopic) metabolic data were collectively examined at the 13C resolution. Prog/TN GBM were similarly compared against progressive G4AIDH+ and treatment effects.

RESULTS:

Regional analysis of Prog/TN GBM metabolism revealed statistically significant heterogeneity in 1H choline-to-N-acetylaspartate index (CNI)max, [1-13C]lactate, modified [1-13C]lactate-to-[1-13C]pyruvate ratio (CELval > NELval > NAWMval); [1-13C]lactate-to-[13C]bicarbonate ratio (CELval > NELval/NAWMval); and 1H-lactate (CELval/NELval > NAWMundetected). Significant associations were found between normalized perfusion (cerebral blood volume, nCBV; peak height, nPH) and levels of [1-13C]pyruvate and [1-13C]lactate, as well as between CNImax and levels of [1-13C]pyruvate, [1-13C]lactate and modified ratio. GBM, by comparison to G4AIDH+, displayed lower perfusion %-recovery and modeled rate constants for [1-13C]pyruvate-to-[1-13C]lactate conversion (kPL), and higher 1H-lactate and [1-13C]pyruvate levels, while having higher nCBV, %-recovery, kPL, [1-13C]pyruvate-to-[1-13C]lactate and modified ratios relative to treatment effects.

CONCLUSIONS:

GBM consistently displayed aberrant, Warburg-related metabolism and regional heterogeneity detectable by novel HP-13C/1H imaging techniques.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Glioblastoma / Glioma Type of study: Risk_factors_studies Limits: Humans Language: En Journal: Neuroimage Clin Year: 2023 Document type: Article Affiliation country: Estados Unidos
Fulltext
Add to My VHL
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Glioblastoma / Glioma Type of study: Risk_factors_studies Limits: Humans Language: En Journal: Neuroimage Clin Year: 2023 Document type: Article Affiliation country: Estados Unidos