Advanced Hyperpolarized ¹³C Metabolic Imaging Protocol for Patients with Gliomas: A Comprehensive Multimodal MRI Approach

Simple Summary: Dynamic hyperpolarized carbon-13 (HP-C-13) MRI is a novel molecular imaging technique that allows for real-time in vivo imaging of glycolysis and oxidative phosphorylation using [1-C-13]pyruvate as a non-radioactive and non-toxic metabolic probe. While HP-C-13 MRI has recently demonstrated the potential to capture Warburg-related metabolic dysregulation in patients with progressive/treatment-na & iuml;ve high-grade gliomas, further improvement in methodologies is still necessary to help monitor disease status and evaluate early predictors of therapeutic response. To this end, a multimodal H-1/HP-C-13 MRI protocol was implemented in this study, which incorporated advanced brain tumor MR acquisitions and improved HP-C-13 metabolic imaging methodologies for the serial monitoring of patients with glioma over the course of clinical treatment. This study aimed to implement a multimodal H-1/HP-C-13 imaging protocol to augment the serial monitoring of patients with glioma, while simultaneously pursuing methods for improving the robustness of HP-C-13 metabolic data. A total of 100 H-1/HP [1-C-13]-pyruvate MR examinations (104 HP-C-13 datasets) were acquired from 42 patients according to the comprehensive multimodal glioma imaging protocol. Serial data coverage, accuracy of frequency reference, and acquisition delay were evaluated using a mixed-effects model to account for multiple exams per patient. Serial atlas-based HP-C-13 MRI demonstrated consistency in volumetric coverage measured by inter-exam dice coefficients (0.977 +/- 0.008, mean +/- SD; four patients/11 exams). The atlas-derived prescription provided significantly improved data quality compared to manually prescribed acquisitions (n = 26/78; p = 0.04). The water-based method for referencing [1-C-13]-pyruvate center frequency significantly reduced off-resonance excitation relative to the coil-embedded [C-13]-urea phantom (4.1 +/- 3.7 Hz vs. 9.9 +/- 10.7 Hz; p = 0.0007). Significantly improved capture of tracer inflow was achieved with the 2-s versus 5-s HP-C-13 MRI acquisition delay (p = 0.007). This study demonstrated the implementation of a comprehensive multimodal H-1/HP-C-13 MR protocol emphasizing the monitoring of steady-state/dynamic metabolism in patients with glioma.