Widespread elevated hyperpolarized 13C-lactate and 13C-bicarbonate signal in the brain of patients with brain metastases undergoing treatment

Abstract

Patients with brain metastases (BMs) experience altered neurological function due to cancer itself and treatment effects. Brain alterations may be underpinned by dysregulated cellular metabolism that can be measured with hyperpolarized [1- 13 C]pyruvate magnetic resonance imaging (HP [1- 13 C]pyruvate MRI). HP [1- 13 C]pyruvate MRI was used to detect altered brain metabolism in the normal appearing brain parenchyma of patients with BMs compared with healthy controls. Twelve patients with untreated BMs and 46 healthy controls were imaged with HP [1- 13 C]pyruvate MRI. The brain was parcellated into 132 regions and segmented into grey and white matter. Tumor-involved brain regions and hyperintense T2w FLAIR regions were excluded. Mean regional [1- 13 C]pyruvate, [1- 13 C]lactate, [ 13 C]bicarbonate, 13 C-lactate-to-pyruvate ratio, 13 C-bicarbonate-to-pyruvate ratio, 13 C-lactate-to-bicarbonate ratio, region volume, and grey and white matter density and volume were modeled using mixed effects linear regression. Patients exhibited a 65% (95% CI: 36% to 99%; p = 4 \(\times \) 10 -6 ) increase in the 13 C-lactate-to-pyruvate ratio and 54% (95% CI: 19% to 99%; p = 0.002) increase in the 13 C-bicarbonate-to-pyruvate ratio relative to controls. The superior parietal lobule showed the greatest increase in both metabolite ratios. Overall, frontal and parietal brain regions exhibited the greatest increases in 13 C-lactate-to-pyruvate and 13 C-bicarbonate-to-pyruvate ratios. Increased 13 C-metabolite ratios warrant further investigation to determine causes of this metabolic shift and its relation to clinical outcomes. Clinical Trial Registry: Registered on ClinicalTrials.gov on October 4, 2017 with trial registration number NCT03324360.