Pilot Study of Hyperpolarized ¹³C Metabolic Imaging in Pediatric Patients with Diffuse Intrinsic Pontine Glioma and Other CNS Cancers

Abstract

BACKGROUND AND PURPOSE: Pediatric CNS tumors commonly present challenges for radiographic interpretation on conventional MR imaging. This study sought to investigate the safety and tolerability of hyperpolarized carbon-13 (HP-13 C) metabolic imaging in pediatric patients with brain tumors. MATERIALS AND METHODS: Pediatric patients 3 to 18 years of age who were previously diagnosed with a brain tumor and could undergo MR imaging without sedation were eligible to enroll in this safety study of HP [1-13 C]pyruvate. Participants received a onetime injection of HP [1-13 C]pyruvate and were imaged using dynamic HP-13 C MR imaging. We assessed 2 dose levels: 0.34 mL/kg and the highest tolerated adult dose of 0.43 mL/kg. Participants were monitored throughout imaging and for 60 minutes postinjection, including pre-and postinjection electrocardiograms and vital sign measurements.

Current state of pediatric neuro-oncology imaging, challenges and future directions

“…Hyperpolarized carbon-13 (HP-13C) MR imaging presents a promising relatively new technique that allows noninvasive investigation of in vivo tumor metabolism by using dynamic nuclear polarization to transiently enhance the signal for molecular probes that can assess different aspects of tumor metabolism. A recent feasibility study in participants with diffuse intrinsic pontine glioma demonstrated the safety of HP [1-13C]pyruvate injection and characteristic conversion to [1-13C]lactate and [13C]bicarbonate in the brain as biomarkers of glycolysis and oxidative phosphorylation respectively; however, the study was closed prematurely due to poor accrual [93] . Despite promises of HP [1-13C] MRI, the short lifetime of 13C magnetization requires very tight study logistics which can be challenging in pediatric glioma patients.…”

MR‐Nucleomics: The study of pathological cellular processes with multinuclear magnetic resonance spectroscopy and imaging in vivo

“…Balanced steady state free precession and concentric rings are also acquisition techniques that have been proposed for 3D imaging (Figure 6). 151,152 Among these, despite the frequent practice of EPSI, [153][154][155] metabolite-specific techniques (e.g., spectral-spatial excitation pulse followed by nonspectroscopic readout) are increasingly used in clinical research with hyperpolarized 13 C. 152,156,157 This is probably because clinical scenarios usually have determined targeting metabolites, making the nonspectroscopic readout techniques more time-efficient for clinical scenarios. 9 This is also evidenced by the adoption of spiral-based Dixon methods, which essentially consist of the acquisition of an extremely concise spectrum.…”

Current human brain applications and challenges of dynamic hyperpolarized carbon-13 labeled pyruvate MR metabolic imaging

“…For brain studies, HP [1- 13 C]pyruvate has been applied in healthy controls [55,60]; patients with glioma [42,43,46], brain metastasis [42,63], and TBI [64]; and pediatric patients with CNS tumors [65]. In the following section, we will discuss these most recent clinical applications.…”

“…Other [1- 13 C]pyruvate HP 13 C MR metabolic brain imaging studies also include (1) safety and feasibility study in pediatric patients with CNS tumors (diffuse intrinsic pontine glioma, DIPG; craniopharyngioma; medulloblastoma) [ 65 ]. This study demonstrated preliminary safety profile in 6 patients at dosages of 0.34 and 0.43 mL/kg.…”

“…For example, DIPG is a tumor located in the weakly perfused brain stem. Higher ratios of [1- 13 C]lactate to [1- 13 C]pyruvate were seen in the lesion while [1- 13 C]pyruvate signal was relatively low [ 65 ]. In another case shown in Fig.…”