Abstract
Early identification of premalignant and malignant gastric mucosa is crucial to decrease the incidence and mortality of stomach cancer. Spectrum- and time-resolved multiphoton microscopy are capable of providing not only structural but also biochemical information at the subcellular level. Based on this multidimensional imaging technique, we performed a systematic investigation on fresh human tissue specimens at the typical stages of gastric carcinogenesis, including normal, chronic gastritis with erosion, chronic gastritis with intestinal metaplasia, and intestinal-type adenocarcinoma. The results demonstrate that this technique is available to characterize the three-dimensional subcellular morphological and biochemical properties of gastric mucosa and further provide quantitative indicators of different gastric disorders, by using endogenous contrast. With advances in multiphoton endoscopy, it has the potential to allow noninvasive, label-free, real-time histological and functional diagnosis of premalignant and malignant lesions of stomach in the future.
Highlights
Stomach cancer is the fifth most commonly diagnosed cancer and the third leading cause of cancer death worldwide [1, 2]. 90% of the stomach cancers are gastric adenocarcinomas [2, 3]
Gastric carcinogenesis is a long-term and multistep process, which generally involves a progression from normal mucosa through chronic gastritis, atrophic gastritis, and intestinal metaplasia, to dysplasia and carcinoma [4]
We report for the first time, the systematic investigation on human gastric carcinogenesis by spectrum- and time-resolved multiphoton microscopy (MPM) imaging of its multiple typical stages, including normal, chronic gastritis with erosion (CG-E), chronic gastritis with intestinal metaplasia (CG-IM), and intestinal-type adenocarcinoma (ITA)
Summary
Stomach cancer is the fifth most commonly diagnosed cancer and the third leading cause of cancer death worldwide [1, 2]. 90% of the stomach cancers are gastric adenocarcinomas [2, 3]. Confocal laser endomicroscopy with subcellular resolution (down to 0.7 μm) has emerged as a noninvasive on-site imaging modality of gastric mucosa, potentially bringing a revolutionary leap toward the in vivo diagnosis of gastric diseases [16, 17] This technique has been proven to be able to provide histology-like images of tissues, while avoiding the risks and costs of conventional biopsies [16]. As a more powerful imaging tool, multiphoton microscopy (MPM) based on two-photon excited fluorescence (TPEF) and second harmonic generation (SHG) has attracted lots of attention since it was developed [18, 19] This imaging modality is capable of producing images with similar details of standard histology by detecting intrinsic fluorescence chromophores, and possesses superior tissue penetration depth, reduced photobleaching and photodamage, and intrinsic three-dimensional (3D) sectioning ability [18,19,20]. Due to these attractive advantages over confocal laser microscopy, MPM has been widely applied in the investigation of normal and diseased gastrointestinal tissues [6, 8, 21,22,23]
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