Zhong Tianzheng, Duan Yanhua, Li Kun, Qiu Jianfeng, Cheng Zhaoping, Lu Weizhao
School of Radiology, Shandong First Medical University & Shandong Academy of Medical Sciences, No. 619 Changcheng Road, Taian, 271016, China.
Department of Nuclear Medicine, The First Affiliated Hospital of Shandong First Medical University, Shandong Provincial Qianfoshan Hospital Affiliated to Shandong University, No.16766 Jingshi Road, Jinan, 250014, China.
Eur J Nucl Med Mol Imaging. 2025 May 9. doi: 10.1007/s00259-025-07324-w.
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.
目前缺乏用于非小细胞肺癌（NSCLC）肺脑相互作用及脑转移的影像学标志物。本研究旨在利用全身正电子发射断层扫描（PET）成像探索NSCLC对脑葡萄糖代谢的影响。
56名健康对照者（HCs）和42名NSCLC患者接受了全身PET成像。获取了NSCLC患者的血清肿瘤标志物浓度。基于肿瘤、淋巴结、转移（TNM）分期系统生成了NSCLC的伪时间序列数据。分别以标准化摄取值的最大值和平均值（SULmax和SULmean）、血清肿瘤标志物作为种子序列，构建了NSCLC与脑葡萄糖代谢之间的新型因果代谢协方差网络（CaMCN）。通过反向CaMCN分析评估可靠性。最后，对显示出由NSCLC引起因果关系的脑区进行事后分析。
CaMCN分析表明，NSCLC与后颅窝区域、解剖学“分水岭区域”以及额叶、颞叶和枕叶的灰白质交界处的葡萄糖摄取之间存在显著的因果关系。反向CaMCN分析显示与原始CaMCN结果有显著差异。事后分析显示，颞下回、丘脑、额上回、中央前回和中央后回的葡萄糖摄取在HCs和不同分期的NSCLC之间存在显著差异。
所提出的方法能够捕捉从NSCLC到脑代谢的因果关系，为NSCLC中的肺脑相互作用提供病理生理学见解。此外，所确定的脑区是NSCLC脑转移的常见发生区域，有望成为NSCLC脑转移的生物标志物。
