Abstract
Objective The purpose of this study was to demonstrate the feasibility of using hyperpolarized carbon-13 (13C) metabolic imaging with [1-13C]-labeled pyruvate for evaluating real-time in vivo metabolism of orthotopic diffuse intrinsic pontine glioma (DIPG) xenografts. Materials and Methods 3D 13C 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 [1-13C]-pyruvate. Results Anatomical images from DIPG-bearing rats characteristically exhibited T2-hyperintensity throughout the cerebellum and pons that was not accompanied by contrast enhancement. Evaluation of real-time in vivo13C 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 T2 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 13C MRSI may serve as a noninvasive imaging technique for in vivo monitoring of biochemical processes in patients with DIPG.
Highlights
Di use intrinsic pontine glioma (DIPG) comprises a heterogeneous class of childhood brainstem cancers that defy molecular strati cation and surgical intervention because of their sensitive location
All animals were scanned on a 3Tclinical Magnetic resonance imaging (MRI) system (GE Healthcare, Waukesha, WI, USA) equipped with a customdesigned 1H/13C rat coil on approximately the 58th day after tumor implantation. e body temperature was maintained using a heated pad positioned inside the RF coil
Representative anatomical data from a rat injected with DIPG cells are shown in Figure 1, with panel (a) providing an overview of an orthotopic lesion around the brainstem on a sagittal T2-weighted image. e corresponding axial T2weighted image exhibited hyperintensity throughout the cerebellum and pons (Figure 1(b)), while no contrast enhancement was visible from the post-Gd T1-weighted image acquired at the same location (Figure 1(c))
Summary
Di use intrinsic pontine glioma (DIPG) comprises a heterogeneous class of childhood brainstem cancers that defy molecular strati cation and surgical intervention because of their sensitive location. E purpose of this study was to explore the feasibility of using hyperpolarized 13C metabolic imaging with [1-13C]-pyruvate for evaluating real-time in vivo metabolism of orthotopic DIPG xenografts.
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