Discriminating different grades of cervical intraepithelial neoplasia based on label-free phasor fluorescence lifetime imaging microscopy

Xinyi Wang; Yulan Wang; Zixiao Zhang; Maojia Huang; Yiyan Fei; Jiong Ma; Lan Mi

doi:10.1364/BOE.386999

Discriminating different grades of cervical intraepithelial neoplasia based on label-free phasor fluorescence lifetime imaging microscopy

Biomed Opt Express. 2020 Mar 13;11(4):1977-1990. doi: 10.1364/BOE.386999. eCollection 2020 Apr 1.

Authors

Xinyi Wang^{1

2}, Yulan Wang^{3

2}, Zixiao Zhang¹, Maojia Huang¹, Yiyan Fei¹, Jiong Ma^{1

4

5

6}, Lan Mi^{1

7}

Affiliations

¹ Department of Optical Science and Engineering, Shanghai Engineering Research Center of Ultra-precision Optical Manufacturing, Key Laboratory of Micro and Nano Photonic Structures (Ministry of Education), Green Photoelectron Platform, Fudan University, 220 Handan Road, Shanghai 200433, China.
² Contributed equally.
³ Department of Gynecology, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430014, China.
⁴ Institute of Biomedical Engineering and Technology, Academy for Engineer and Technology, Fudan University, 220 Handan Road, Shanghai 200433, China.
⁵ The Multiscale Research Institute of Complex Systems (MRICS), School of Life Sciences, Fudan University, 220 Handan Road, Shanghai 200433, China.
⁶ jiongma@fudan.edu.cn.
⁷ lanmi@fudan.edu.cn.

Abstract

This study proposed label-free fluorescence lifetime imaging and phasor analysis methods to discriminate different grades of cervical intraepithelial neoplasia (CIN). The human cervical tissue lesions associated with cellular metabolic abnormalities were detected by the status changes of important coenzymes in cells and tissues, reduced nicotinamide adenine dinucleotide (phosphate) (NAD(P)H) and flavin adenine dinucleotide (FAD). Fluorescence lifetime imaging microscopy (FLIM) was used to study human cervical tissues, human cervical epithelial cells, and standard samples. Phasor analysis was applied to reveal the interrelation between the metabolic changes and cancer development, which can distinguish among different stages of cervical lesions from low risk to high risk. This approach also possessed high sensitivity, especially for healthy sites of CIN3 tissues, and indicated the dominance of the glycolytic pathway over oxidative phosphorylation in high-grade cervical lesions. This highly adaptive, sensitive, and rapid diagnostic tool exhibits a great potential for cervical precancer diagnosis.