Directional interactions from non-small cell lung cancer to brain glucose metabolism revealed by total-body PET...

Imaging markers for lung-brain interaction and brain metastasis of non-small cell lung cancer (NSCLC) are lacking. This study aimed to explore the effect of NSCLC on brain glucose metabolism using total-body positron emission tomography (PET) imaging.

Fifty-six healthy controls (HCs) and 42 NSCLC patients underwent total-body PET imaging. Concentrations of serum tumor markers were obtained for NSCLC patients. Pseudo-time series data of NSCLC were generated based on the tumor, node, metastasis (TNM) staging system. A novel causal metabolic covariance network (CaMCN) between NSCLC and brain glucose metabolism was conducted with maximum and mean of standardized uptake value (SULmax and SULmean), serum tumor markers as the seed series, respectively. Reliability was evaluated by reverse CaMCN analysis. Finally, post-hoc analysis was performed on brain regions that exhibited causality from NSCLC.

CaMCN analysis demonstrated significant causality from NSCLC to glucose uptake of the posterior fossa regions, the anatomic "watershed areas" and the gray-white matter junction in the frontal, temporal and occipital lobes. Reverse CaMCN analysis demonstrated significant distinctions from the original CaMCN results. Post-hoc analysis revealed that glucose uptake in the inferior temporal gyrus, thalamus, superior frontal gyrus, precentral gyrus and postcentral gyrus exhibited significant differences among HCs and different stages of NSCLC.

The proposed method can capture causal relationships from NSCLC to brain metabolism, providing pathophysiological insights into the lung-brain interaction in NSCLC. Moreover, the identified brain regions were the areas where NSCLC brain metastases frequently occur, holding the promise as biomarkers for brain metastases of NSCLC.