Multi-parametric hyperpolarized 13C/1H imaging reveals Warburg-related metabolic dysfunction and associated regional heterogeneity in high-grade human gliomas.

2023

https://researcherprofiles.org/profile/425624205

37611371

Autry AW, Vaziri S, LaFontaine M, Gordon JW, Chen HY, Kim Y, Villanueva-Meyer JE, Molinaro A, Clarke JL, Oberheim Bush NA, Xu D, Lupo JM, Larson PEZ, Vigneron DB, Chang SM, Li Y

Abstract

BACKGROUND

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

METHODS

Multi-parametric H/HP-C 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 (G4A, 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-C/spectroscopic) metabolic data were collectively examined at the C resolution. Prog/TN GBM were similarly compared against progressive G4A and treatment effects.

RESULTS

Regional analysis of Prog/TN GBM metabolism revealed statistically significant heterogeneity in H choline-to-N-acetylaspartate index (CNI), [1-C]lactate, modified [1-C]lactate-to-[1-C]pyruvate ratio (CEL > NEL > NAWM); [1-C]lactate-to-[C]bicarbonate ratio (CEL > NEL/NAWM); and H-lactate (CEL/NEL > NAWM). Significant associations were found between normalized perfusion (cerebral blood volume, nCBV; peak height, nPH) and levels of [1-C]pyruvate and [1-C]lactate, as well as between CNI and levels of [1-C]pyruvate, [1-C]lactate and modified ratio. GBM, by comparison to G4A, displayed lower perfusion %-recovery and modeled rate constants for [1-C]pyruvate-to-[1-C]lactate conversion (k), and higher H-lactate and [1-C]pyruvate levels, while having higher nCBV, %-recovery, k, [1-C]pyruvate-to-[1-C]lactate and modified ratios relative to treatment effects.

CONCLUSIONS

GBM consistently displayed aberrant, Warburg-related metabolism and regional heterogeneity detectable by novel HP-C/H imaging techniques.

Journal Issue

Volume 39