Label-Free Identification of Early Gastrointestinal Neuroendocrine Tumors via Biomedical Multiphoton Microscopy and Automatic Image Analysis

Li, Lianhuang; Huang, Shenghui; Qiu, Lida; Jiang, Weizhong; Chen, Zhifen; Kang, Deyong; Tu, Haohua; Chen, Jianxin; Zhou, Yongjian

doi:10.1109/access.2020.3000289

Cited by 3 publications

(3 citation statements)

References 50 publications

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“…Figure 4 shows the different morphologic information provided by SHG (Figure 4B) and 2PEF (Figure 4C−F) imaging. There is a clear increase in cell density within the tumor regions shown in the 2PEF images while SHG shows the disorganized and thick stromal (S) changes near the tumor sites which is consistent with prior findings that exhibit desmoplastic changes occurring around tumor regions 49 . There is a loss of SHG signal and the appearance of thick collagenous encapsulation of the neoplasms.…”

Section: Resultssupporting

confidence: 88%

“…There is a clear increase in cell density within the tumor regions shown in the 2PEF images while SHG shows the disorganized and thick stromal (S) changes near the tumor sites which is consistent with prior findings that exhibit desmoplastic changes occurring around tumor regions. 49 There is a loss of SHG signal and the appearance of thick collagenous encapsulation of the neoplasms. In comparison, the 2PEF and SHG images of the neighboring BGs show clear contrast to the tumor in the organized arrangement of the glands with thin collagen walls composing their structure.…”

Section: Resultsmentioning

confidence: 99%

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Quantitative characterization of duodenal gastrinoma autofluorescence using multiphoton microscopy

et al. 2022

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Background: Duodenal gastrinomas (DGASTs) are neuroendocrine tumors that develop in the submucosa of the duodenum and produce the hormone gastrin. Surgical resection of DGASTs is complicated by the small size of these tumors and the tendency for them to develop diffusely in the duodenum. Endoscopic mucosal resection of DGASTs is an increasingly popular method for treating this disease due to its low complication rate but suffers from poor rates of pathologically negative margins. Multiphoton microscopy can capture high-resolution images of biological tissue with contrast generated from endogenous fluorescence (autofluorescence [AF]) through two-photon excited fluorescence (2PEF). Second harmonic generation is another popular method of generating image contrast with multiphoton microscopy (MPM) and is a lightscattering phenomenon that occurs predominantly from structures such as collagen in biological samples. Some molecules that contribute to AF change in abundance from processes related to the cancer disease process (e.g., metabolic changes, oxidative stress, and angiogenesis). Study Design/Materials and Methods: MPM was used to image 12 separate patient samples of formalin-fixed and paraffin-embedded duodenal gastrinoma slides with a second-harmonic generation (SHG) channel and four 2PEF channels. The excitation and emission profiles of each 2PEF channel were tuned to capture signal dominated by distinct fluorophores with well-characterized fluorescent spectra and known connections to the physiologic changes that arise in cancerous tissue. Results: We found that there was a significant difference in the relative abundance of signal generated in the 2PEF channels for regions of DGASTs in comparison to the neighboring tissues of the duodenum. Data generated from texture feature extraction of the MPM images were used in linear discriminant analysis models to create classifiers for tumor versus all other tissue types before and after principal component analysis (PCA). PCA improved the classifier accuracy and reduced the number of features required to achieve maximum accuracy. The linear discriminant classifier after PCA distinguished between tumor and other tissue types with an accuracy of 90.6%−93.8%. Conclusions: These results suggest that multiphoton microscopy 2PEF and SHG imaging is a promising label-free method for discriminating between DGASTs and normal duodenal tissue which has implications for future applications of in vivo assessment of resection margins with endoscopic MPM.

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Section: Resultssupporting

confidence: 88%

Section: Resultsmentioning

confidence: 99%

Quantitative characterization of duodenal gastrinoma autofluorescence using multiphoton microscopy

et al. 2022

View full text Add to dashboard Cite

show abstract

“…There is a clear increase in cell density within the tumor regions shown in the 2PEF images while SHG shows the disorganized and thick stromal (S) changes near the tumor sites which is consistent with prior findings of desmoplastic changes occurring around tumor regions. 41 There is a loss of SHG signal and the appearance of thick collagenous encapsulation of the neoplasms. In comparison, the 2PEF and SHG images of the neighboring Brunner’s glands (BGs) show clear contrast to the tumor in the organized arrangement of the glands with thin collagen walls composing their structure.…”

Section: Resultsmentioning

confidence: 99%

Quantitative Characterization of Duodenal Gastrinoma Autofluorescence using Multi-photon Microscopy

Sawyer

Knapp

2022

Preprint

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Duodenal gastrinomas (DGASTs) are neuroendocrine tumors that develop in the submucosa of the duodenum and produce the hormone, gastrin. Surgical resection of DGASTs is complicated by the small size of these tumors and the tendency for them to develop diffusely in the duodenum. Endoscopic mucosal resection of DGASTS is an increasingly popular method for treating this disease due to its low complication rate but suffers from poor rates of pathologically negative margins. Multiphoton microscopy (MPM) is capable of capturing high-resolution images of biological tissue with contrast generated from endogenous fluorescence (autofluorescence) through two-photon excited fluorescence (2PEF). Second harmonic generation (SHG) is another popular method of generating image contrast with MPM and is a light-scattering phenomenon that occurs predominantly from structures such as collagen in biological samples. Some molecules that contribute to autofluorescence change in abundance from processes related to the cancer disease process (e.g., metabolic changes, oxidative stress, angiogenesis). MPM was used to image 12 separate patient samples of formalin-fixed and paraffinized DGAST slides with a SHG channel 4 2PEF channels, each tuned to capture fluorescence from NADH, FAD, lipofuscin, and porphyrin. We found that there was a significant difference in the relative abundance of signal generated in the 2PEF in comparison to the neighboring tissues of the duodenum. Texture extraction was used to create linear discriminant classifiers for tumor vs all other tissue classes before and after principal component analysis (PCA) of the texture feature dataset. PCA improved the classifier accuracy and reduced the number of features required to achieve maximum accuracy of the classifier. The LDA classifier after PCA distinguished between tumor and other tissue types with an accuracy of 90.6 - 93.8%. These results suggest that MPM 2PEF and SHG imaging is a promising label-free method for discriminating between DGAST tumors and normal duodenal tissue which has implications for future applications of in vivo assessment of resection margins with endoscopic MPM.

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Optical second-harmonic generation imaging for identifying gastrointestinal stromal tumors

Zhang¹,

Huang²,

Kang³

et al. 2023

J. Innov. Opt. Health Sci.

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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.

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Label-Free Identification of Early Gastrointestinal Neuroendocrine Tumors via Biomedical Multiphoton Microscopy and Automatic Image Analysis

Cited by 3 publications

References 50 publications

Quantitative characterization of duodenal gastrinoma autofluorescence using multiphoton microscopy

Quantitative characterization of duodenal gastrinoma autofluorescence using multiphoton microscopy

Quantitative Characterization of Duodenal Gastrinoma Autofluorescence using Multi-photon Microscopy

Optical second-harmonic generation imaging for identifying gastrointestinal stromal tumors

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