Measuring Tumor Metabolism in Pediatric Diffuse Intrinsic Pontine Glioma Using Hyperpolarized Carbon-13 MR Metabolic Imaging

OBJECTIVE: The purpose of this study was to demonstrate the feasibility of using hyperpolarized carbon-13 ((13)C) metabolic imaging with [1-(13)C]-labeled pyruvate for evaluating real-time in vivo metabolism of orthotopic diffuse intrinsic pontine glioma (DIPG) xenografts. MATERIALS AND METHODS: 3D (13)C magnetic resonance spectroscopic imaging (MRSI) data were acquired on a 3T scanner from 8 rats that had been implanted with human-derived DIPG cells in the brainstem and 5 healthy controls, following injection of 2.5 mL (100 mM) hyperpolarized [1-(13)C]-pyruvate. RESULTS: Anatomical images from DIPG-bearing rats characteristically exhibited T(2)-hyperintensity throughout the cerebellum and pons that was not accompanied by contrast enhancement. Evaluation of real-time in vivo(13)C spectroscopic data revealed ratios of lactate-to-pyruvate (p < 0.002), lactate-to-total carbon (p < 0.002), and normalized lactate (p < 0.002) that were significantly higher in T(2) lesions harboring tumor relative to corresponding values of healthy normal brain. Elevated levels of lactate in lesions demonstrated a distinct metabolic profile that was associated with infiltrative, viable tumor recapitulating the histopathology of pediatric DIPG. CONCLUSIONS: Results from this study characterized pyruvate and lactate metabolism in orthotopic DIPG xenografts and suggest that hyperpolarized (13)C MRSI may serve as a noninvasive imaging technique for in vivo monitoring of biochemical processes in patients with DIPG.