Dataset Information

NIR-II Imaging and Sandwiched Plasmonic Biosensor for Ultrasensitive Intraoperative Definition of Tumor-Invaded Lymph Nodes.

ABSTRACT: Radical lymphadenectomy remains the cornerstone of preventing tumor metastasis through the lymphatic system. Current surgical resection of lymph nodes (LNs) based on fluorescence-guided surgery (FGS) suffers from low sensitivity/selectivity with only qualitative information, hampering accurate intraoperative decision-making. Herein, we develop a modularized theranostic system including NIR-II FGS and a sandwiched plasmonic chip (SPC). Intraoperative NIR-II FGS and detection of tumor-positive lymph nodes were performed on the gastric tumor to determine the feasibility of the modularized theranostic system in defining LN metastasis. Under the NIR-II imaging window, the orthotopic tumor and sentinel lymph nodes (SLNs) were successfully excised without ambient light interference in the operating room. Importantly, the SPC biosensor achieved 100% sensitivity and 100% specificity for tumor markers and realized rapid and high-throughput intraoperative SLN detection. We propose the synergetic design of combining the NIR-II FGS and suitable biosensor will substantially improve the efficiency of cancer diagnosis and therapy follow-up.

SUBMITTER: Wang Y

PROVIDER: S-EPMC10176571 | biostudies-literature | 2023 May

REPOSITORIES: biostudies-literature

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NIR-II Imaging and Sandwiched Plasmonic Biosensor for Ultrasensitive Intraoperative Definition of Tumor-Invaded Lymph Nodes.

Wang Yajun Y Nan Jingjie J Ma Huilong H Xu Jiajun J Guo Feifei F Wang Yufeng Y Liang Yongye Y Zhang Junhu J Zhu Shoujun S

Nano letters 20230418 9

Radical lymphadenectomy remains the cornerstone of preventing tumor metastasis through the lymphatic system. Current surgical resection of lymph nodes (LNs) based on fluorescence-guided surgery (FGS) suffers from low sensitivity/selectivity with only qualitative information, hampering accurate intraoperative decision-making. Herein, we develop a modularized theranostic system including NIR-II FGS and a sandwiched plasmonic chip (SPC). Intraoperative NIR-II FGS and detection of tumor-positive lym ...[more]

PMID: 37071592

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Project description:Background and objectivesSentinel lymph node (SLN) biopsy is a standard procedure for patients with breast cancer and normal axilla on imaging. Positive SLNs on histological examination can lead to a subsequent surgery for axillary lymph node clearance (ALNC). Here we report a non-destructive technique based on autofluorescence (AF) imaging and Raman spectroscopy for intra-operative assessment of SLNs excised in breast cancer surgery.MethodsA microscope integrating AF imaging and Raman spectroscopy modules was built to allow scanning of lymph node biopsy samples. During AF-Raman measurements, AF imaging determined optimal sampling locations for Raman spectroscopy measurements. After optimisation of the AF image analysis and training of classification models based on data from 85 samples, the AF-Raman technique was tested on an independent set of 81 lymph nodes comprising 58 fixed and 23 fresh specimens. The sensitivity and specificity of AF-Raman were calculated using post-operative histology as a standard of reference.ResultsThe independent test set contained 66 negative lymph nodes and 15 positive lymph nodes according to the reference standard, collected from 78 patients. For this set of specimens, the area under the receiver operating characteristic (ROC) curve for the AF-Raman technique was 0.93 [0.83-0.98]. AF-Raman was then operated in a regime that maximised detection specificity, producing a 94% detection accuracy: 80% sensitivity and 97% specificity. The main confounders for SLN metastasis were areas rich in histiocytes clusters, for which only few Raman spectra had been included in the training dataset.DiscussionThis preliminary study indicates that with further development and extension of the training dataset by inclusion of additional Raman spectra of histiocytes clusters and capsule, the AF-Raman may become a promising technique for intra-operative assessment of SLNs. Intra-operative detection of positive biopsies could avoid second surgery for axillary clearance.

Project description:Understanding how breast cancer (BC) grows in axillary lymph nodes (ALNs), and refining how therapies might halt that process, is clinically important. However, modelling the complex ALN microenvironment is difficult, and no human models exist at present. We harvested ALNs from ten BC patients, and perfused them at 37 °C ex vivo for up to 24 h. Controlled autologous testing showed that ALNs remain viable after 24 h of ex vivo perfusion: haematoxylin and eosin-stained histological appearance and proliferation (by Ki67 immunohistochemistry) did not change significantly over time for any perfused ALN compared with a control from time-point zero. Furthermore, targeted gene expression analysis (NanoString PanCancer IO360 panel) showed that only 21/750 genes were differentially expressed between control and perfused ALNs (|log2 FC| > 1 and q < 0.1): none were involved in apoptosis and metabolism, but rather all 21 genes were involved in immune function and angiogenesis. During perfusion, tissue acid-base balance remained stable. Interestingly, the flow rate increased (p < 0.001) in cancer-replaced (i.e. metastasis occupied more than 90% of the surface area on multiple levels) compared to cancer-free nodes (i.e. nodes with no metastasis on multiple sections). CXCL11 transcripts were significantly more abundant in cancer-replaced nodes, while CXCL12 transcripts were significantly more abundant in cancer-free nodes. These cytokines were also detected in the circulating perfusate. Monoclonal antibodies (nivolumab and trastuzumab) were administered into a further three ALNs to confirm perfusion efficacy. These drugs saturated the nodes; nivolumab even induced cancer cell death. Normothermic ALN perfusion is not only feasible but sustains the tumour microenvironment ex vivo for scientific investigation. This model could facilitate the identification of actionable immuno-oncology targets. © 2019 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.

Dataset Information

NIR-II Imaging and Sandwiched Plasmonic Biosensor for Ultrasensitive Intraoperative Definition of Tumor-Invaded Lymph Nodes.

Publications

NIR-II Imaging and Sandwiched Plasmonic Biosensor for Ultrasensitive Intraoperative Definition of Tumor-Invaded Lymph Nodes.

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