Two-photon imaging reveals histopathological changes in the gastric tumor microenvironment induced by neoadjuvant treatment.

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There is a close association between tumor response and survival in gastric cancer patients after receiving neoadjuvant treatment. An accurate and rapid assessment of therapeutic efficacy would be helpful for subsequent treatments and individual prognosis. At present, pathological examination is the gold standard for evaluating treatment response, however, it requires additional staining and the process is tedious, labor-intensive, as well as time-consuming. Here, we introduce a label-free imaging technique, two-photon imaging, to evaluate histopathological changes induced by pre-operative therapy, with a focus on assessing tumor regression as well as stromal response. Imaging data show that two-photon imaging allows label-free, rapid visualization of various aspects of pathological alterations in tumor microenvironment such as fibrotic reaction, inflammatory cell infiltration, mucinous response, isolated residual tumor cells. Moreover, a semi-automatic image processing approach is developed to extract the collagen morphological features, and statistical results show that there are significant differences in collagen area, length, width, cross-link space between the gastric cancer tissues with and without treatment. With the advent of a portable, miniaturized two-photon imaging device, we have enough reason to believe that this technique will become as an important auxiliary diagnostic tool in assessing neoadjuvant treatment response and thereby tailoring the most appropriate therapy strategies for the patients.