Two-photon excitation fluorescence lifetime imaging microscopy and spectroscopy for cancer detection

摘要

Cancer incidence and mortality are rapidly growing worldwide, resulting in heavy social and economic burdens. Earlydetection as well as precise intraoperative diagnosis of cancers is crucial to improving the prognosis and thussignificantly decreasing the mortality. Two-photon excitation fluorescence lifetime imaging microscopy andspectroscopy not only shows the outstanding capability of label-free, intravital, high-resolution, three-dimensionalimaging but also allows the quantitative biochemical characterizing of live tissues. Benefiting from these advantages,this technology is promising for early detection and demarcation of malignant tumors. However, its full potential has notbeen extensively evaluated in clinical settings.Here, we assess the feasibility of using two-photon excitation fluorescence lifetime imaging microscopy andspectroscopy to identify various cancers, including esophageal cancer, gastric cancer, and brain cancer. In terms ofesophageal cancer, we compared the fresh human esophageal mucosal tissues of normal, squamous cell carcinoma, andadenocarcinoma. For gastric cancer, we performed a systematic investigation on fresh human gastric mucosal specimensat typical stages of gastric carcinogenesis. In addition, by developing a mouse chronic cranial window, we carried out apreliminary study on glioma margin identification in vivo. By extracting fluorescence spectrum and lifetime informationof endogenous fluorophores, qualitative and quantitative indicators which are found to have the potential to discriminatenormal, premalignant and different malignant lesions are derived.This study may shed new light on the early detection, precise intraoperative diagnosis, and classification ofdigestive tract cancers and brain cancers. With advances in endoscopy, two-photon excitation fluorescence lifetimeimaging microscopy and spectroscopy has the potential to become a noninvasive, label-free, real-time histological andfunctional cancer detection tool in the future.