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The response to treatment has been shown to correlate closely with the prognosis. However, current evaluation systems only provide coarse assessment on limited information, due to the lack of accurate and reproducible approach for quantitation of different types of responses. In this study, a novel stain\u2010free, slide\u2010free multimodal multiphoton microscopy imaging technique was applied to image rectal cancer tissues after neoadjuvant therapies with high resolution and contrast. Qualitative and quantitative evaluation of tumor, stromal, and inflammatory responses were demonstrated which are consistent with current tumor regression grading system using American Joint Committee on Cancer criteria, showing the great potential of such approach to build a more informative grading system for accurate and standardizable assessment of neoadjuvant therapy in rectal cancer.<jats:inline-graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"graphic\/jbio202200079-gra-0001.png\" xlink:title=\"image\"\/><\/jats:p>","DOI":"10.1002\/jbio.202200079","type":"journal-article","created":{"date-parts":[[2022,6,30]],"date-time":"2022-06-30T15:11:30Z","timestamp":1656601890000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Evaluation of histopathological response to neoadjuvant therapy in rectal cancer using slide\u2010free, stain\u2010free multimodal multiphoton 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