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Review
. 2022 Jan-Dec:21:15330338221133244.
doi: 10.1177/15330338221133244.

Application of Multiphoton Microscopic Imaging in Study of Gastric Cancer

Xiaoying Wang  1 , Di Zhang  2 , Xiaochun Zhang  3 , Yuting Xing  4 , Jihua Wu  1 , Xinke Sui  1 , Xin Huang  1 , Guoqing Chang  4 , Lianyong Li  1
Affiliations
Review

Application of Multiphoton Microscopic Imaging in Study of Gastric Cancer

Xiaoying Wang et al. Technol Cancer Res Treat. 2022 Jan-Dec.

Abstract

Multiphoton microscopy (MPM) imaging relies on the nonlinear interaction between ultrashort optical pulses and the samples to achieve image contrast. Featuring larger penetration depth, less phototoxicity, 3-dimensional sectioning capability, no need for labeling, MPM become a powerful medical imaging technique that can identify structural characteristics of tissues at the cellular and subcellular levels. In this review paper, we introduce the working principle of MPM imaging, present the current results of MPM imaging applied to the study of gastric tumors, and discuss the future prospects of this interdisciplinary research field.

Keywords: 2-photon excited fluorescence; 3-photon excited fluorescence; gastric cancer; multiphoton microscopy; second-harmonic generation; third-harmonic generation.

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Conflict of interest statement

The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Figures

Figure 1.
Figure 1.
MPM images and corresponding H&E-stained images of normal gastric tissue. Row 1: TPEF images (green), row 2: SHG images (red), row 3: overlaid TPEF/SHG images, row 4: corresponding H&E-stained images (20× magnification). Column 1: normal gastric mucosa. (a) TPEF image (blue arrows: fluorescent cytoplasm derived from NADH and FAD, pink arrows: nonfluorescent nuclear), (b) SHG image, (c) overlaid TPEF/SHG image (white curves: basement membrane, position1: epithelium and glands, position2: lamina propria, position3: muscularis mucosa), and (d) H&E-stained image. Column 2: normal gastric submucosa. € TPEF image (pink arrows: elastic fibers, white arrows: collagen bundles), (f) SHG image (blue arrows: collagen fibers, white arrows: collagen bundles), (g) overlaid TPEF/SHG image (triangle: blood vessels), (h) H&E-stained image. Column 3: normal gastric serosa. (i) TPEF image (white arrows: elastic fibers), (j) SHG image (blue arrows: collagen fibers), (k) overlaid TPEF/SHG (pink arrows: collagen bundles), (l) H&E-stained image. Scale bar: 100 μm. These images are adapted from He et al [55]. MPM, multiphoton microscopy; TPEF, 2-photon excited fluorescence; SHG, second-harmonic generation; FAD, flavin adenine dinucleotide; H&E, hematoxylin-eosin; NADH, reduced form of nicotinamide-adenine dinucleotid
Figure 2.
Figure 2.
MPM images and H&E image of normal gastric muscle tissues. (a) TPEF image, (b) SHG image, (c) overlaid TPEF/SHG image. Position1-3 mark external longitudinal muscle, midterm circular muscle, and internal oblique muscle, respectively. White arrows: septa in the muscle tissues. (d) H&E-stained image (20× magnification). Scale bar: 100 μm. Abbreviations: MPM, multiphoton microscopy; TPEF, 2-photon excited fluorescence; SHG, second-harmonic generation; H&E, hematoxylin-eosin
Figure 3.
Figure 3.
MPM images (first 3 rows, transverse view) and corresponding histology (last row, longitudinal view) of the normal and diseased human gastric antrum mucosa, the TPEF signal generated by NADH from the surface epithelium shown as green, and the SHG signal of collagen from the interstitial tissue of the lamina propria shown in blue. A column: normal, B column: chronic gastritis with erosion, C column: chronic gastritis with intestinal metaplasia, and D column: intestinal-type adenocarcinoma. The depth is labeled in the bottom left corner of each panel for TPEF images. Scale bar: 50 μm. This figure is adapted from Figure 4 in Li et al. Abbreviations: MPM, multiphoton microscopy; TPEF, 2-photon excited fluorescence; SHG, second-harmonic generation; NADH, reduced form of nicotinamide-adenine inucleotide
Figure 4.
Figure 4.
MPM images and H&E images of EGC. Column 1: EGC invading the mucosa alone (a: SHG image, b: TPEF image, c: overlaid TPEF/SHG image, d: H&E-stained image), white arrow: cancerous cells. Column 2: EGC invading into submucosa (e: SHG image, f: TPEF image, g: overlaid TPEF/SHG image, h: H&E-stained image), Yellow arrow: muscularis mucosae. Column 3: boundary between submucosal and muscular layers in EGC (i: SHG image, j: TPEF image, k: overlaid TPEF/SHG image, l: H&E-stained image), Yellow arrow: elastic fiber, white arrow: malignant tumors, blue arrow: muscularis propria. Scale bar: 100 μm. Abbreviations: EGC, early gastric cancer; MPM, multiphoton microscopy; TPEF, 2-photon excited fluorescence; ThPEF, 3-photon excited fluorescence; SHG, second-harmonic generation; H&E, hematoxylin-eosin.
Figure 5.
Figure 5.
TPEF/SHG/ThPEF/THG images of ex vivo human gastric tissue. (a) TPEF image; (b)SHG image; (c) ThPEF image; (d)THG image; (e)Merging of TPEF/SHG/ThPEF/THG images. pink arrow: elastic fiber; yellow arrow: collagen; white arrow: adipocyte. Scale bar: 100 μm. Abbreviations: TPEF, 2-photon excited fluorescence; ThPEF, 3-photon excited fluorescence; THG, third-harmonic generation; SHG, second-harmonic generation.
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