Clinical Applications of Hyperpolarized Magnetic Resonance Imaging in Brain Tumors: Current Evidence and Future...

Brain tumors exhibit extensive metabolic reprogramming that supports proliferation, invasion, therapeutic resistance, and adaptation to dynamic microenvironmental conditions. These alterations provide opportunities for metabolic imaging approaches that extend beyond conventional anatomical neuroimaging. Hyperpolarized magnetic resonance imaging (hpMRI) has emerged as a novel metabolic imaging platform capable of non-invasively visualizing real-time cellular metabolism through dynamic nuclear polarization of carbon-13-labeled substrates. By dramatically enhancing magnetic resonance signal intensity, hpMRI enables interrogation of enzyme-specific metabolic pathways and provides unique insight into tumor energetics, metabolic heterogeneity, and treatment response. The distinct contribution of this review is an updated, brain tumor-specific, clinically oriented framework that integrates recent human evidence with longitudinal metabolic phenotyping, emerging pathway-specific probes, acquisition standardization, multimodal validation, and the remaining barriers to clinical implementation. Particular emphasis is placed on hyperpolarized [1-¹³C]pyruvate, which has demonstrated feasibility and safety in patients with gliomas and has enabled assessment of glycolytic metabolism, oxidative phosphorylation, tumor recurrence, and longitudinal treatment response. Serial changes in lactate and bicarbonate flux may also reflect evolution toward more glycolytic, heterogeneous, and treatment-resistant tumor phenotypes, supporting the potential prognostic value of hpMRI before conventional radiographic progression becomes evident. We also review emerging applications involving α-ketoglutarate metabolism, redox biology, glutathione cycling, perfusion imaging, and molecular characterization of clinically relevant alterations including IDH1, TERT, and c-MYC-associated metabolic programs. In addition, we discuss recent advances in acquisition methods, image standardization, and multimodal integration with conventional MRI and positron emission tomography. Although several technical and logistical challenges remain, hpMRI is an investigational, radiation-free metabolic imaging modality with potential applications in diagnosis, molecular stratification, and treatment monitoring; however, substantial technical, regulatory, logistical, and economic barriers currently limit routine clinical use, molecular stratification, therapeutic monitoring, and precision medicine approaches in neuro-oncology. Continued clinical translation and development of novel metabolic probes may further expand its role in brain tumors and other neurological diseases.