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Indocyanine green fluorescence image processing techniques for breast cancer macroscopic demarcation.

ABSTRACT: Re-operation due to disease being inadvertently close to the resection margin is a major challenge in breast conserving surgery (BCS). Indocyanine green (ICG) fluorescence imaging could be used to visualize the tumor boundaries and help surgeons resect disease more efficiently. In this work, ICG fluorescence and color images were acquired with a custom-built camera system from 40 patients treated with BCS. Images were acquired from the tumor in-situ, surgical cavity post-excision, freshly excised tumor and histopathology tumour grossing. Fluorescence image intensity and texture were used as individual or combined predictors in both logistic regression (LR) and support vector machine models to predict the tumor extent. ICG fluorescence spectra in formalin-fixed histopathology grossing tumor were acquired and analyzed. Our results showed that ICG remains in the tissue after formalin fixation. Therefore, tissue imaging could be validated in freshly excised and in formalin-fixed grossing tumor. The trained LR model with combined fluorescence intensity (pixel values) and texture (slope of power spectral density curve) identified the tumor's extent in the grossing images with pixel-level resolution and sensitivity, specificity of 0.75 ± 0.3, 0.89 ± 0.2.This model was applied on tumor in-situ and surgical cavity (post-excision) images to predict tumor presence.

SUBMITTER: Leiloglou M

PROVIDER: S-EPMC9124184 | biostudies-literature | 2022 May

REPOSITORIES: biostudies-literature

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Indocyanine green fluorescence image processing techniques for breast cancer macroscopic demarcation.

Leiloglou Maria M Kedrzycki Martha S MS Chalau Vadzim V Chiarini Nicolas N Thiruchelvam Paul T R PTR Hadjiminas Dimitri J DJ Hogben Katy R KR Rashid Faiza F Ramakrishnan Rathi R Darzi Ara W AW Leff Daniel R DR Elson Daniel S DS

Scientific reports 20220521 1

Re-operation due to disease being inadvertently close to the resection margin is a major challenge in breast conserving surgery (BCS). Indocyanine green (ICG) fluorescence imaging could be used to visualize the tumor boundaries and help surgeons resect disease more efficiently. In this work, ICG fluorescence and color images were acquired with a custom-built camera system from 40 patients treated with BCS. Images were acquired from the tumor in-situ, surgical cavity post-excision, freshly excise ...[more]

PMID: 35597783

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Project description:Background: Indocyanine green (ICG)-guided near-infrared fluorescence (NIRF) has been recently adopted in pediatric minimally invasive surgery (MIS). This study aimed to report our experience with ICG-guided NIRF in pediatric laparoscopy and robotics and evaluate its usefulness and technique of application in different pediatric pathologies. Methods: ICG technology was adopted in 76 laparoscopic and/or robotic procedures accomplished in a single division of pediatric surgery over a 24-month period (January 2018-2020): 40 (37 laparoscopic, three robotic) left varicocelectomies with intra-operative lymphography; 13 (10 laparoscopic, three robotic) renal procedures: seven partial nephrectomies, three nephrectomies, and three renal cyst deroofings; 12 laparoscopic cholecystectomies; five robotic tumor excisions; three laparoscopic abdominal lymphoma excisions; three thoracoscopic procedures: two lobectomies and one lymph node biopsy for suspected lymphoma. The ICG solution was administered into a peripheral vein in all indications except for varicocele and lymphoma in which it was, respectively, injected into the testis body or the target organ. Regarding the timing of the administration, the ICG solution was administered intra-operatively in all indications except for cholecystectomy in which the ICG injection was performed 15-18 h before surgery. Results: No conversions to open or laparoscopy occurred. No adverse and allergic reactions to ICG or other postoperative complications were reported. Conclusions: Based upon our 2 year experience, we believe that ICG-guided NIRF is a very useful tool in pediatric MIS to perform a true imaged-guided surgery, allowing an easier identification of anatomic structures and an easier surgical performance in difficult cases. The most common applications in pediatric surgery include varicocele repair, difficult cholecystectomy, partial nephrectomy, lymphoma, and tumors excision but further indications will be soon discovered. ICG-enhanced fluorescence was technically easy to apply and safe for the patient reporting no adverse reactions to the product. The main limitation is represented by the specific equipment needed to apply ICG-guided NIRF in laparoscopic procedures, that is not available in all centers whereas the ICG system Firefly® is already integrated into the robotic platform.

Project description:Indocyanine green (ICG) has been used in clinical practice for more than 40 years and its safety and preferential accumulation in tumors has been reported for various tumor types, including colon cancer. However, reports on clinical assessments of ICG-based molecular endoscopy imaging for precancerous lesions are scarce. We determined visualization ability of ICG fluorescence endoscopy in colitis-associated colon cancer using 30 lesions from an azoxymethane/dextran sulfate sodium (AOM/DSS) mouse model and 16 colon cancer patient tissue-samples. With a total of 60 images (optical, fluorescence) obtained during endoscopy observation of mouse colon cancer, we used deep learning network to predict four classes (Normal, Dysplasia, Adenoma, and Carcinoma) of colorectal cancer development. ICG could detect 100% of carcinoma, 90% of adenoma, and 57% of dysplasia, with little background signal at 30 min after injection via real-time fluorescence endoscopy. Correlation analysis with immunohistochemistry revealed a positive correlation of ICG with inducible nitric oxide synthase (iNOS; r > 0.5). Increased expression of iNOS resulted in increased levels of cellular nitric oxide in cancer cells compared to that in normal cells, which was related to the inhibition of drug efflux via the ABCB1 transporter down-regulation resulting in delayed retention of intracellular ICG. With artificial intelligence training, the accuracy of image classification into four classes using data sets, such as fluorescence, optical, and fluorescence/optical images was assessed. Fluorescence images obtained the highest accuracy (AUC of 0.8125) than optical and fluorescence/optical images (AUC of 0.75 and 0.6667, respectively). These findings highlight the clinical feasibility of ICG as a detector of precancerous lesions in real-time fluorescence endoscopy with artificial intelligence training and suggest that the mechanism of ICG retention in cancer cells is related to intracellular nitric oxide concentration.

Project description:ObjectiveAchieving negative resection margin is critical but challenging in breast-conserving surgery. Fluorescence-guided surgery allows the surgeon to visualize the tumor bed in real-time and to facilitate complete resection. We envisioned that intraoperative real-time fluorescence imaging with a human serum albumin decorated indocyanine green probe could enable complete surgical removal of breast cancer in a mouse model.MethodsWe prepared the probe by conjugating indocyanine green (ICG) with human serum albumin (HSA). In vitro uptake of the HSA-ICG probe was compared between human breast cancer cell line MDA-MB-231 and normal breast epithelial cell line MCF 10A. In vivo probe selectivity for tumors was examined in nude mice bearing MDA-MB-231-luc xenografts and the FVB/N-Tg (MMTV-PyMT) 634Mul/J mice model with spontaneous breast cancer. A positive-margin resection mice model bearing MDA-MB-231-luc xenograft was established and the performance of the probe in assisting surgical resection of residual lesions was examined.ResultsA significantly stronger fluorescence intensity was detected in MDA-MB-231 cells than MCF 10A cells incubated with HSA-ICG. In vivo fluorescence imaging showed that HSA-ICG had an obvious accumulation at tumor site at 24 h with tumor-to-normal tissue ratio of 8.19 ± 1.30. The same was true in the transgenic mice model. The fluorescence intensity of cancer tissues was higher than that of non-cancer tissues (58.53 ± 18.15 vs 32.88 ± 11.34). During the surgical scenarios, the residual tumors on the surgical bed were invisible with the naked eye, but were detected and resected with negative margin under HSA-ICG guidance in all the mice (8/8). Recurrence rate among mice that underwent resection with HSA-ICG (0/8) was significantly lower than the rates among mice with ICG (4/8), as well as the control group under white light (7/7).ConclusionsThis study suggests that real-time in vivo visualization of breast cancer with an HSA-ICG fluorescent probe facilitates complete surgical resection of breast cancer in a mouse xenograft model.

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Indocyanine green fluorescence image processing techniques for breast cancer macroscopic demarcation.

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Indocyanine green fluorescence image processing techniques for breast cancer macroscopic demarcation.

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