Assessment of Tumor Invasion Depth in Colorectal Carcinoma Using Multiphoton Microscopy

Wang, Shu; Chen, Jianxin; Yang, Yinghong; Jiang, Weizhong; Feng, Changyin; Guan, Guoxian; Zhuo, Shuangmu; Chen, Zhifen

doi:10.1109/jphot.2015.2420615

Cited by 12 publications

(3 citation statements)

References 29 publications

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“…A number of factors contribute to dysplastic transformation in colon epithelium, and it is important to fully understand disease progression in order to improve techniques and tools for screening, diagnosis, and treatment. While studies of collagen fiber structure using optical imaging in cancers such as cervical have been conducted [17], investigation of collagen structures in murine CRC studies has been understudied [36]. Multiphoton endoscopic imaging has shown to be a feasible technology for clinical translation due to its miniaturization and label-free image acquisition.…”

Section: Resultsmentioning

confidence: 99%

Differences in colonic crypt morphology of spontaneous and colitis-associated murine models via second harmonic generation imaging to quantify colon cancer development

et al. 2019

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Background Colorectal cancer remains the second leading cause of cancer death in the United States, and increased risk in patients with ulcerative colitis (a subset of inflammatory bowel disease) has motivated studies into early markers of dysplasia. The development of clinically translatable multiphoton imaging systems has allowed for the potential of in vivo label-free imaging of epithelial crypt structures via autofluorescence and/or second harmonic generation (SHG). SHG has been used to investigate collagen structures in various types of cancer, though the changes that colorectal epithelial collagen structures undergo during tumor development, specifically colitis-associated tumors, have not been fully investigated. Methods This study used two murine models, using A/J mice, one for spontaneous carcinoma and one for colitis-associated carcinoma, to investigate and quantify SHG image features that could potentially inform future study designs of endoscopic multiphoton imaging systems. The spontaneous tumor model comprised a series of six weekly injections of azoxymethane (AOM model). The colitis-associated tumor model comprised a single injection of AOM, followed by cycles of drinking water with dissolved dextran sodium sulfate salt (AOM-DSS model). SHG images of freshly resected murine colon were acquired with a multiphoton imaging system, and image features, such as crypt size, shape and distribution, were quantified using an automated algorithm. Results The comparison of quantified features of crypt morphology demonstrated the ability of our quantitative image feature algorithms to detect differences between spontaneous (AOM model) and colitis-associated (AOM-DSS model) murine colorectal tissue specimens. There were statistically significant differences in the mean and standard deviation of nearest neighbor (distance between crypts) and circularity between the Control cohort, AOM and AOM-DSS cohorts. We also saw significance between AOM and AOM-DSS cohorts when calculating nearest neighbor in images acquired at fixed depths. Conclusion The results provide insight into the ability of SHG imaging to yield relevant data about the crypt microstructure in colorectal epithelium, specifically the potential to distinguish between spontaneous and colitis-associated murine models using quantification of crypt shape and distribution, informing future design of translational multiphoton imaging systems and protocols. Electronic supplementary material The online version of this article (10.1186/s12885-019-5639-8) contains supplementary material, which is available to authorized users.

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Section: Resultsmentioning

confidence: 99%

Differences in colonic crypt morphology of spontaneous and colitis-associated murine models via second harmonic generation imaging to quantify colon cancer development

et al. 2019

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“…The fibrillar collagens, such as type I and type III have a highly crystalline triple‐helix structure which is not centrosymmetric; hence they are very effective generators of SHG signals (Cox et al ., ; Lutz et al ., ). In addition to SHG signals,fibrillar collagens can contribute to a TPEF signal and they have comparable SHG and TPEF signal yields at the same order of magnitude (Wang et al ., ). In this paper, employing nonlinear optical microscopy, MPM based on TPEF and SHG, the visualization of fibrillar collagen deposition within GBM was investigated.…”

Section: Introductionmentioning

confidence: 97%

Label‐free detection of fibrillar collagen deposition associated with vascular elements in glioblastoma multiforme by using multiphoton microscopy

Jiang

Wang

et al. 2016

Journal of Microscopy

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Glioblastoma multiforme (GBM-WHO grade IV) is the most common and the most aggressive form of brain tumors in adults with the median survival of 10-12 months. The diagnostic detection of extracellular matrix (ECM) component in the tumour microenvironment is of prognostic value. In this paper, the fibrillar collagen deposition associated with vascular elements in GBM were investigated in the fresh specimens and unstained histological slices by using multiphoton microscopy (MPM) based on two-photon excited fluorescence (TPEF) and second harmonic generation (SHG). Our study revealed the existence of fibrillar collagen deposition in the adventitia of remodelled large blood vessels and in glomeruloid vascular structures in GBM. The degree of fibrillar collagen deposition can be quantitatively evaluated by measuring the adventitial thickness of blood vessels or calculating the ratio of SHG pixel to the whole pixel of glomeruloid vascular structure in MPM images. These results indicated that MPM can not only be employed to perform a retrospective study in unstained histological slices but also has the potential to apply for in vivo brain imaging to understand correlations between malignancy of gliomas and fibrillar collagen deposition.

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“…information of the tissue can be further obtained through analysis. Currently, the MPM has been widely used in the imaging of gastric cancer [14], bowel cancer [15], breast cancer [16], and other diseases. The above studies have laid a foundation for the early application of MPM to human bile duct tissue to judge tumor boundaries.…”

Section: Introductionmentioning

confidence: 99%

Identification of the Tumor Boundary of Hilar Cholangiocarcinoma Based on Multiphoton Microscopy

et al. 2022

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Hilar cholangiocarcinoma (HCC) is a common malignant tumor of the biliary system. The structural characteristics of the bile duct tissue can reflect the changes in its function. The visualization of these specific features is of special significance for understanding the degree of invasion of HCC and tumor borders. Radical R0 resection is the only cure for HCC. Currently, the commonly used medical imaging diagnostic methods can only provide a rough tumor range and require a histopathological analysis. Multiphoton microscopy (MPM) not only has an ultra-high spatial resolution but is also extremely sensitive to collagen fibers with noncentrosymmetric structures. In this study, MPM is applied to image the boundaries of HCC tumors. First, the experimental results show that MPM can clearly reveal the existence of residual cancer cells at the surgical margin. Second, the density of the collagen fibers and the dispersion of the 2D direction angle of the collagen fibers of normal and cancerous tissues are further calculated quantitatively. The collagen fiber signals before and after cancer cell invasion into the different tissues are found to be different. Finally, through a logistic regression prediction curve, combined with the collagen fiber density and 2D direction angle as indicators, it is further judged whether the resection margin is negative, which is closely related to the prognosis of HCC. The experimental results indicate that MPM imaging can serve as a new tool for diagnosing whether the HCC tumor boundary reaches R0 resection.

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Assessment of Tumor Invasion Depth in Colorectal Carcinoma Using Multiphoton Microscopy

Cited by 12 publications

References 29 publications

Differences in colonic crypt morphology of spontaneous and colitis-associated murine models via second harmonic generation imaging to quantify colon cancer development

Differences in colonic crypt morphology of spontaneous and colitis-associated murine models via second harmonic generation imaging to quantify colon cancer development

Label‐free detection of fibrillar collagen deposition associated with vascular elements in glioblastoma multiforme by using multiphoton microscopy

Identification of the Tumor Boundary of Hilar Cholangiocarcinoma Based on Multiphoton Microscopy

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