Label-Free Assessment of Premalignant Gastric Lesions Using Multimodal Nonlinear Optical Microscopy

In this paper, a nonlinear optical microscopy employing two-photon excited fluorescence and second-harmonic generation was used for the detection of premalignant gastric lesions. It was found that gland morphology and collagen structure in mucosa will change with the progression of gastric diseases from normal to intestinal metaplasia, to low-grade intraepithelial neoplasia, and to high-grade intraepithelial neoplasia, and this microscopy was able to directly distinguish these warning symptoms. Furthermore, two features were quantified from nonlinear optical images to demonstrate the changes of gland size and collagen content during the development process of preneoplastic lesions. These results clearly show that nonlinear optical microscopy can effectively differentiate normal and precancerous gastric tissues without contrast agents, which would be helpful for early diagnosis and treatment of gastric diseases. This study may provide the groundwork for further application of nonlinear optical microscopy in clinical practice.

[1]  S. Yoshida,et al.  Endoscopic mucosal resection for treatment of early gastric cancer , 2001, Gut.

[2]  Leslie M Loew,et al.  Second-harmonic imaging microscopy for visualizing biomolecular arrays in cells, tissues and organisms , 2003, Nature Biotechnology.

[3]  Shusen Xie,et al.  Recent advances in two-photon imaging: technology developments and biomedical applications , 2013 .

[4]  E. Gratton,et al.  Label-free fluorescence lifetime and second harmonic generation imaging microscopy improves quantification of experimental renal fibrosis. , 2016, Kidney international.

[5]  Shuangmu Zhuo,et al.  Establishing diagnostic features for identifying the mucosa and submucosa of normal and cancerous gastric tissues by multiphoton microscopy. , 2011, Gastrointestinal endoscopy.

[6]  Paul Campagnola,et al.  Second Harmonic Generation Imaging Distinguishes Both High-Grade Dysplasia and Cancer from Normal Colonic Mucosa , 2014, Digestive Diseases and Sciences.

[7]  S. Cross,et al.  In vivo real‐time confocal laser scanning endomicroscopic colonoscopy for the detection and characterization of colorectal neoplasia , 2008, The British journal of surgery.

[8]  Nonlinear optical microscopy for label-free detection of gastrointestinal neuroendocrine tumors , 2016, Lasers in Medical Science.

[9]  Bruce J Tromberg,et al.  Selective corneal imaging using combined second-harmonic generation and two-photon excited fluorescence. , 2002, Optics letters.

[10]  Brian Seed,et al.  Dynamic imaging of collagen and its modulation in tumors in vivo using second-harmonic generation , 2003, Nature Medicine.

[11]  Peng Wang,et al.  Confocal laser endomicroscopy for in vivo diagnosis of gastric intraepithelial neoplasia: a feasibility study. , 2010, Gastrointestinal endoscopy.

[12]  Sergey Plotnikov,et al.  Second harmonic generation microscopy for quantitative analysis of collagen fibrillar structure , 2012, Nature Protocols.

[13]  W. Webb,et al.  Live tissue intrinsic emission microscopy using multiphoton-excited native fluorescence and second harmonic generation , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[14]  M. Sporn,et al.  Treatment and prevention of intraepithelial neoplasia: an important target for accelerated new agent development. , 2002, Clinical cancer research : an official journal of the American Association for Cancer Research.

[15]  Ina Pavlova,et al.  In vivo imaging of unstained tissues using a compact and flexible multiphoton microendoscope. , 2012, Journal of biomedical optics.

[16]  J. Baak,et al.  Morphometric definition and grading of gastric intestinal metaplasia , 1990, The Journal of pathology.

[17]  A. Jemal,et al.  Cancer statistics in China, 2015 , 2016, CA: a cancer journal for clinicians.

[18]  Melissa C Skala,et al.  Multiphoton microscopy of endogenous fluorescence differentiates normal, precancerous, and cancerous squamous epithelial tissues. , 2005, Cancer research.

[19]  Jun Nagata,et al.  Multiphoton imaging can be used for microscopic examination of intact human gastrointestinal mucosa ex vivo. , 2008, Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association.

[20]  M. Sporn,et al.  Treatment and Prevention of Intraepithelial Neoplasia: An Important Target for Accelerated New Agent Development: Recommendations of the American Association for Cancer Research Task Force on the Treatment and Prevention of Intraepithelial Neoplasia , 2002 .

[21]  Silvia Sanduleanu,et al.  In vivo diagnosis and classification of colorectal neoplasia by chromoendoscopy-guided confocal laser endomicroscopy. , 2010, Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association.

[22]  S. Taghavi,et al.  Comparison of chromoendoscopy and conventional endoscopy in the detection of premalignant gastric lesions. , 2009, Canadian journal of gastroenterology = Journal canadien de gastroenterologie.

[23]  Shuangmu Zhuo,et al.  Visualization of Tumor Response to Neoadjuvant Therapy for Rectal Carcinoma by Nonlinear Optical Imaging , 2016, IEEE Journal of Selected Topics in Quantum Electronics.