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Purpose: Collagen features in breast tumor microenvironment is closely associated with the prognosis of patients. We aim to explore the prognostic significance of collagen features at breast tumor border by combining multiphoton imaging and imaging analysis. Methods: We used multiphoton microscopy (MPM) to label-freely image human breast tumor samples and then constructed an automatic classification model based on deep learning to identify collagen signatures from multiphoton images. We recognized three kinds of collagen signatures at tumor boundary (CSTB I-III) in a small-scale, and furthermore obtained a CSTB score for each patient based on the combined CSTB I-III by using the ridge regression analysis. The prognostic performance of CSTB score is assessed by the area under the receiver operating characteristic curve (AUC), Cox proportional hazard regression analysis, as well as Kaplan-Meier survival analysis. Results: As an independent prognostic factor, statistical results reveal that the prognostic performance of CSTB score is better than that of the clinical model combining three independent prognostic indicators, molecular subtype, tumor size, and lymph nodal metastasis (AUC, Training dataset: 0.773 vs. 0.749; External validation: 0.753 vs. 0.724; HR, Training dataset: 4.18 vs. 3.92; External validation: 4.98 vs. 4.16), and as an auxiliary indicator, it can greatly improve the accuracy of prognostic prediction. And furthermore, a nomogram combining the CSTB score with the clinical model is established for prognosis prediction and clinical decision making. Conclusion: This standardized and automated imaging prognosticator may convince pathologists to adopt it as a prognostic factor, thereby customizing more effective treatment plans for patients. [ABSTRACT FROM AUTHOR]

Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors arising in the digest tract. It brings a challenge to diagnosis because it is asymptomatic clinically. It is well known that tumor development is often accompanied by the changes in the morphology of collagen fibers. Nowadays, an emerging optical imaging technique, second-harmonic generation (SHG), can directly identify collagen fibers without staining due to its noncentrosymmetric properties. Therefore, in this study, we attempt to assess the feasibility of SHG imaging for detecting GISTs by monitoring the morphological changes of collagen fibers in tumor microenvironment. We found that collagen alterations occurred obviously in the GISTs by comparing with normal tissues, and furthermore, two morphological features from SHG images were extracted to quantitatively assess the morphological difference of collagen fibers between normal muscular layer and GISTs by means of automated image analysis. Quantitative analyses show a significant difference in the two collagen features. This study demonstrates the potential of SHG imaging as an adjunctive diagnostic tool for label-free identification of GISTs. [ABSTRACT FROM AUTHOR]

The tumor microenvironment (TME) is now recognized as an important participant of tumor progression. As the most abundant extracellular matrix component in TME, collagen plays an important role in tumor development. The imaging study of collagen morphological feature in TME is of great significance for understanding the state of tumor. Multiphoton microscopy (MPM), based on second harmonic generation (SHG) and two-photon excitation fluorescence (TPEF), can be used to monitor the morphological changes of biological tissues without labeling. In this study, we used MPM for large-scale imaging of early invasive breast cancer from the tumor center to normal tissues far from the tumor. We found that there were significant differences in collagen morphology between breast cancer tumor boundary, near tumor transition region and normal tissues far from the tumor. Furthermore, the morphological feature of eight collagen fibers was extracted to quantify the variation trend of collagen in three regions. These results may provide a new perspective for the optimal negative margin width of breast-conserving surgery and the understanding of tumor metastasis. [ABSTRACT FROM AUTHOR]

Background: Gastrointestinal stromal tumor (GIST) is currently regarded as a potentially malignant tumor, and early diagnosis is the best way to improve its prognosis. Therefore, it will be meaningful to develop a new method for auxiliary diagnosis of this disease. Methods: Here we try out a new means to detect GIST by combining two-photon imaging with automatic image processing strategy. Results: Experimental results show that two-photon microscopy has the ability to label-freely identify the structural characteristics of GIST such as tumor cells, desmoplastic reaction, which are entirely different from those from gastric adenocarcinoma. Moreover, an image processing approach is used to extract eight collagen morphological features from tumor microenvironment and normal muscularis, and statistical analysis demonstrates that there are significant differences in three features—fiber area, density and cross-link density. The three morphological characteristics may be considered as optical imaging biomarkers to differentiate between normal and abnormal tissues. Conclusion: With continued improvement and refinement of this technology, we believe that two-photon microscopy will be an efficient surveillance tool for GIST and lead to better management of this disease. [ABSTRACT FROM AUTHOR]

Worldwide, the most common malignancy in women is breast cancer. At present, the gold standard for breast cancer diagnosis, namely pathological analysis, cannot reach the subcellular level, and is unable to provide more physiological information. Multiphoton microscopy (MPM) has its unique advantages, such as label‐free detection, high resolution, low damage, deep imaging depth, low photobleaching and phototoxicity, and so on, which make up for the deficiences of traditional methods. This review mainly introduces the principle of MPM and its applications in breast diseases, especially in monitoring the occurrence, progression, metastasis, and therapy response of tumor. At the same time, the performance and progress of MPM combined with nanomaterials in breast cancer treatment are summarized. Finally, we propose the clinical challenges and future research directions of MPM. [ABSTRACT FROM AUTHOR]

Gastric cancer, one of the most common malignant tumors that can affect the digestive system, poses a serious threat to human life. The survival rate of gastric cancer patients depends on early detection and treatment. The widespread adoption of endoscopy has improved the detection rate of early gastric cancer. Accurate preoperative diagnosis of early gastric cancer is key to developing individualized treatment strategies. Here, nonlinear optical microscopy (NLOM) is used to differentiate between normal gastric mucosae and those with early gastric cancer. Furthermore, the quantitative relationship between submucosal infiltration depth and collagen signals in early gastric cancer is explored. First, the two-dimensional collagen direction angle was measured as an indicator to identify cancerous tissue. The orientation indexes of collagen fibers in normal and cancerous tissues were found to be 0.8511 ± 0.0839 and 0.6466 ± 0.07429 (P < 0.0001), respectively, indicating a significant decrease for the cancerous site. The backscattered second harmonic generation (SHG) signal corresponding to the collagen content and the three-dimensional collagen fiber orientation were then studied for early gastric cancer at different infiltration depths. The backscattered collagen SHG signal (a.u.) in the infiltrated lamina propria, muscularis mucosa, and submucosa were found to be 0.1850 ± 0.0393, 0.0870 ± 0.0189, and 0.0435 ± 0.0163, respectively. The 3D directional variance of collagen corresponding to the three infiltration depth sites were 0.6108 ± 0.0707, 0.6794 ± 0.0610, and 0.8200 ± 0.0618 (P < 0.05), respectively. Significant differences between the early gastric cancer collagen signals at different infiltration depths were observed. Our results indicate that NLOM can differentiate cancerous tissue from normal tissue, and thus diagnose early gastric cancer based on infiltration depth. NLOM provides a new evaluation method for the real-time in situ diagnosis of early gastric cancer and has important clinical significance for preparing accurate individualized treatment guidance. [ABSTRACT FROM AUTHOR]

Neoadjuvant chemotherapy has become a standard treatment for breast cancer as it has been shown to increase the rate of breast preservation and to improve outcome in patients. However, how to accurately detect residual tumors is still a challenge. In this work, we tried to use multiphoton imaging to look for residual breast tumors after preoperative therapy. Imaging results demonstrate that multiphoton microscopy can identify remaining tumor tissues and can even detect rarely residual tumor cells, which would be helpful for surgeons to accurately assess the surgical margin in real time to confirm negative margins during operation. We also performed a quantification analysis of the nuclear area of tumor cells before and after treatment with neoadjuvant chemotherapy. The measurement data show that the tumor cell nuclei after chemotherapy are significantly larger than those without treatment, and there is a statistically significant difference in the nuclear areas between the pre-treatment and post-treatment mammary carcinoma. Our pilot study indicates the potential utility of multiphoton imaging for detecting residual breast carcinoma tissues in fresh, ex vivo specimens without the use of exogenous contrast agents. We foresee real-time intraoperative applications of multiphoton microscopy in evaluating therapy response, and thereby helping clinicians develop individualized treatment plans. [ABSTRACT FROM AUTHOR]

Liquid-assisted hard tissue ablation by infrared lasers has extensive clinical application. However, detailed studies are still needed to explore the underlying mechanism. In the present study, the dynamic process of bubble evolution induced by Ho:YAG laser under water without and with bone tissue at different thickness layer were studied, as well as its effects on hard tissue ablation. The results showed that the Ho:YAG laser was capable of ablating hard bone tissue effectively in underwater conditions. The penetration of Ho:YAG laser can be significantly increased up to about 4 mm with the assistance of bubble. The hydrokinetic forces associated with the bubble not only contributed to reducing the thermal injury to peripheral tissue, but also enhanced the ablation efficiency and improve the ablation crater morphology. The data also presented some clues to optimal selection of irradiation parameters and provided additional knowledge of the bubble-assisted hard tissue ablation mechanism. [ABSTRACT FROM AUTHOR]

Background: Early gastric cancer is associated with a much better prognosis than advanced disease, and strategies to improve prognosis is strictly dependent on earlier detection and accurate diagnosis. Therefore, a label-free, non-invasive imaging technique that allows the precise identification of morphologic changes in early gastric cancer would be of considerable clinical interest.Methods: In this study, multiphoton microscopy (MPM) using two-photon excited fluorescence combined with second-harmonic generation was used for the identification of early gastric cancer.Results: This microscope was able to directly reveal improved cellular detail and stromal changes during the development of early gastric cancer. Furthermore, two features were quantified from MPM images to assess the cell change in size and stromal collagen change as gastric lesion developed from normal to early cancer.Conclusions: These results clearly show that multiphoton microscopy can be used to examine early gastric cancer at the cellular level without the need for exogenous contrast agents. This study would be helpful for early diagnosis and treatment of gastric cancer, and may provide the groundwork for further exploration into the application of multiphoton microscopy in clinical practice. [ABSTRACT FROM AUTHOR]