# Metabolic Imaging as Future Technology and Innovation in Brain-Tumour Surgery: A Systematic Review

## TL;DR

This paper reviews how hyperpolarized MRI can help visualize brain tumor metabolism, potentially improving surgery and treatment monitoring.

## Contribution

The study systematically evaluates hyperpolarized 13C-MRI for metabolic tumor characterization in brain cancer patients.

## Key findings

- The bicarbonate-to-pyruvate ratio significantly differentiates tumor from non-tumor tissue.
- High heterogeneity limits the generalizability of results due to small sample sizes and varied methods.
- Hyperpolarized MRI shows potential for intraoperative tumor identification but needs further validation.

## Abstract

Malignant brain tumors are known to undergo profound metabolic changes that drive their growth and resistance to therapy. Understanding these metabolic shifts in living patients remains a major challenge in oncology. This study explores the use of hyperpolarized magnetic resonance imaging, a novel method that enables non-invasive, real-time measurement of key metabolic pathways directly in the tumour. By focusing on conversion of pyruvate into lactate or bicarbonate, this approach may provide insights into tumour aggressiveness and treatment response. Our findings suggest that mapping tumour metabolism in this way could help (neuro-)oncologists and neurosurgeons to improve diagnostic precision, guide targeted and more precise resection therapy, and monitor disease progression more effectively in patients with intrinsic brain cancer.

Background: Standard imaging in neurosurgery often fails to visualize infiltrative tumor regions that extend beyond contrast enhancement. Metabolic imaging using hyperpolarized 13C-MRI may offer new intraoperative insights into tumor biology. Objective: To systematically assess the clinical and technical evidence on hyperpolarized MRI for metabolic tumour characterization in patients with malignant brain tumors. Eligibility criteria: We included original human studies reporting on hyperpolarized 13C-MRI for perioperative and diagnostic use in brain tumor patients. Reviews, animal studies, and technical-only reports were excluded. Information sources: Searches were conducted in PubMed, Embase, and Web of Science on 26 December 2024. Risk of bias: Methodological quality was assessed using the QUADAS-2 tool. Synthesis of results: A qualitative synthesis was performed, and where feasible, random-effects meta-analysis was used to calculate standardized mean differences (SMDs) and heterogeneity statistics. Results: Three studies (n = 15 patients) met inclusion criteria. The bicarbonate-to-pyruvate ratio showed a significant difference between tumor and non-tumour brain (SMD = 1.34, p = 0.002), whereas pyruvate-to-lactate ratio (kPL) values showed minimal difference (SMD = 0.06, p = 0.730). Asmall effect was observed for kPL between tumor and normal-appearing white matter (SMD = –0.33). One study provided qualitative data only. Overall heterogeneity was high (I2 = 69.4%). Limitations: Limitations include small sample sizes, heterogeneous methodologies, and limited availability of patient-level data. Interpretation: Hyperpolarized 13C-MRI shows metabolic differentiation between tumor and healthy tissue in certain parameters, especially bicarbonate metabolism. While promising, the technology requires further clinical validation before routine intraoperative application.