Non-invasive molecular imaging methods capable of assessing tumor biology in-vivo were investigated to improve the clinical management of patients with glioma. In this study, we developed two hyperpolarized (HP) 13C-MRI techniques for clinical translation: one to evaluate blood-brain barrier (BBB) integrity and another to assess isocitrate dehydrogenase (IDH) mutation status in glioma. To evaluate BBB disruption, HP [13C,15N2]urea probe was developed, exploiting urea’s small molecular weight—approximately 15 times smaller than gadolinium-contrast agents—and its inability to cross an intact BBB. A dynamic 3D balanced SSFP acquisition was performed in healthy volunteers following intravenous injection of HP urea solution, enabling high-SNR visualization of arterial, capillary, and venous compartments. Quantitative analysis of vascular transit and spatial distribution established normative references for evaluating BBB integrity. HP 13C-urea MRI may offer superior sensitivity compared to current gadolinium-based methods by directly detecting subtle BBB disruptions as a positive-contrast signal within brain parenchyma, without requiring gadolinium administration, particularly in non-enhancing brain tumors. To evaluate the IDH mutation status of glioma, we developed HP [1-13C]alpha-ketoglutarate (aKG) MRI to monitor the metabolic reprogramming specific to this type of tumor, which involves the conversion of aKG to the oncometabolite 2-hydroxyglutarate (2HG). A dynamic 13C MRS utilizing a spectral-spatial RF pulse to independently excite aKG and its downstream metabolites was acquired following intravenous injection of HP aKG solution. Initial studies with HP [1-13C]aKG in healthy volunteers demonstrated safety and feasibility, showing glutamate production consistent with normal IDH activity. Subsequent studies in patients with IDH-mutant glioma revealed signals consistent with 2HG, suggesting feasibility for directly assessing mutant IDH activity in-vivo. Further validation is underway. Together, these developments highlight the significant clinical-research potential of HP 13C MRI for probing tumor vasculature and IDH-driven metabolism, offering complementary non-invasive biomarkers for improved diagnosis, treatment monitoring, and therapeutic stratification in glioma.
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