Int J Biol Sci 2020; 16(8):1376-1387. doi:10.7150/ijbs.41579 This issue

Research Paper

Label-free multiphoton imaging to assess neoadjuvant therapy responses in breast carcinoma

Lianhuang Li1*✉, Zhonghua Han2*✉, Lida Qiu1 3*, Deyong Kang4, Zhenlin Zhan1, Haohua Tu5, Jianxin Chen1✉

1. Key Laboratory of OptoElectronic Science and Technology for Medicine of Ministry of Education, Fujian Provincial Key Laboratory for Photonics Technology, Fujian Normal University, Fuzhou 350007, P. R. China
2. Department of Breast Surgery, Fujian Medical University Union Hospital, Fuzhou 350001, P. R. China
3. College of Physics and Electronic Information Engineering, Minjiang University, Fuzhou 350108, P. R. China
4. Department of Pathology, Fujian Medical University Union Hospital, Fuzhou 350001, P. R. China
5. Beckman Institute for Advanced Science and Technology, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA
* These authors contributed equally to this work.

This is an open access article distributed under the terms of the Creative Commons Attribution License ( See for full terms and conditions.
Li L, Han Z, Qiu L, Kang D, Zhan Z, Tu H, Chen J. Label-free multiphoton imaging to assess neoadjuvant therapy responses in breast carcinoma. Int J Biol Sci 2020; 16(8):1376-1387. doi:10.7150/ijbs.41579. Available from

File import instruction


Graphic abstract

Neoadjuvant chemotherapy has been used increasingly in patients with early-stage or locally advanced breast carcinoma, and has been recommended as a general approach in locally advanced-stage diseases. Assessing therapy response could offer prognostic information to help determine subsequent nursing plan; particularly it is essential to identify responders and non-responders for the sake of helping develop follow-up treatment strategies. However, at present, diagnostic accuracy of preoperative clinical examination are still not satisfactory. Here we presented an alternate approach to monitor tumor and stroma changes associated with neoadjuvant therapy responses in breast carcinoma, with a great potential for becoming a new diagnostic tool—multiphoton microscopy. Imaging results showed that multiphoton imaging techniques have the ability to label-freely visualize tumor response such as tumor necrosis, and stromal response including fibrosis, mucinous response, inflammatory response as well as vascular hyperplasia in situ at cellular and subcellular levels. Moreover, using automated image analysis and a set of scoring methods, we found significant differences in the area of cell nucleus and in the content of collagen fibers between the pre-treatment and post-treatment breast carcinoma tissues. In summary, this study was conducted to pathologically evaluate the response of breast carcinoma to preoperative chemotherapy as well as to assess the efficacy of multiphoton microscopy in detecting these pathological changes, and experimental results demonstrated that this microscope may be a promising tool for label-free, real-time assessment of treatment response without the use of any exogenous contrast agents.

Keywords: breast carcinoma, neoadjuvant chemotherapy, treatment response, multiphoton imaging