Intraoperative Near-infrared Fluorescence Research Articles

Intraoperative near-infrared fluorescence guided surgery using indocyanine green (ICG) may aid the surgical removal of benign bone and soft tissue tumours

BackgroundBenign bone and soft tissue tumours encompass a broad, heterogenous range of tumours with varying clinical characteristics. These are often managed surgically with either curettage or marginal excision, but unfortunately have high rates of local recurrence. Indocyanine green (ICG) is a fluorescent dye which can be used to identify solid malignancies intraoperatively but its use is not yet established in benign bone and soft tissue tumours. This study aims to assess whether these tumours fluoresce when administered with ICG pre-operatively and whether this helps surgeons to identify tumour intra-operatively. Patients and methodsPatients with locally aggressive benign bone and soft tissue tumours were administered with 25–75 mg of ICG preoperatively at the induction of anaesthesia. Fluorescence was imaged intraoperatively using the Stryker SPY-PHI camera. ResultsOf the 12 patients included, 11 tumours fluoresced. The surgeons felt the fluorescence guided the procedure in 7 out of the 11 cases which fluoresced. It was felt to be particularly useful in the curettage of bone tumours, in which curettage could be repeated until the absence of fluorescence on imaging. After 12 months, no patients had local recurrence of the tumour. There were no adverse events recorded in this study and surgeons found the technology acceptable. ConclusionsThe use of ICG for fluorescence guided surgery is a promising technology to improve outcomes of surgery for benign bone and soft tissue tumours. Further, longer term, study with a control arm is needed to identify whether it results in a reduction in the local recurrence rate.

Rising sun or strangled in the cradle？A narrative review of near-infrared fluorescence imaging-guided surgery for pancreatic tumors.

Near-infrared fluorescence (NIRF)-guided surgical navigation has become a promising and effective detection method in pancreatic tumor surgery. The imaging technique has gradually transitioned from the NIR-I region to the NIR-II region. Real-time assessment of the tumor boundary and determination of the ideal resection plane are essential for preserving the pancreatic parenchyma and its secretory functions. However, since the pancreatic parenchyma has a less rich blood supply than the liver, the application of contrast agents in pancreatic tumor surgery is still in its infancy. The application of indocyanine green (ICG) and methylene blue (MB) in intraoperative NIRF imaging of pancreatic tumors has become more mature, but due to the characteristics of non-specific imaging, the imaging efficiency and depth need to be improved. Many tumor-specific imaging agents have been designed, but most of them have not gone past animal trials because of their high development and imaging costs, biotoxicity, and other limitations. In this article, we review recent reports of ICG, MB and newly developed contrast agents and imaging devices. We focus on the current status and new developments in the application of these contrast agents and summarize the current clinical and preclinical studies on specific contrast agents. We synthesize relevant reports to discuss the difficulties and prospects of the application of fluorescent imaging agents in pancreatic tumors. We hope that reviewing previous studies and the current progress on contrast imaging technology will provide new perspectives for its future application and development in pancreatic tumor surgery, which should translate into better patient prognoses. The manuscript was written according to the Scale for the Assessment of Narrative Review Articles (SANRA).

Intraoperative near-infrared fluorescence visualization of anatomical structures in general surgical and urological practice

Aim: to analyze current literature on the assessment of intraoperative near-infrared fluorescence visualization of anatomical structures in general surgical and urological practice. The experience of using intraoperative near-infrared fluorescence visualization of anatomical structures in general surgical and urological practice is analyzed. The priority areas of the method application are defined, the recent clinical studies in various fields of surgery and urology are reviewed. Conclusions. The method of intraoperative near-infrared fluorescence imaging of anatomical structures with abundant vascularization and for assessing oncological prognosis is the most promising.

Optical precision in pancreatic cancer surgery: novel targeted fluorescent probe - cRGD-ZW800-1 for intraoperative near-infrared fluorescence imaging – a phase II feasibility trial

Optical precision in pancreatic cancer surgery: novel targeted fluorescent probe - cRGD-ZW800-1 for intraoperative near-infrared fluorescence imaging – a phase II feasibility trial

Advancements in Intraoperative Near-Infrared Fluorescence Imaging for Accurate Tumor Resection: A Promising Technique for Improved Surgical Outcomes and Patient Survival.

Clear surgical margins for solid tumor resection are essential for preventing cancer recurrence and improving overall patient survival. Complete resection of tumors is often limited by a surgeon's ability to accurately locate malignant tissues and differentiate them from healthy tissue. Therefore, techniques or imaging modalities are required that would ease the identification and resection of tumors by real-time intraoperative visualization of tumors. Although conventional imaging techniques such as positron emission tomography (PET), computed tomography (CT), magnetic resonance imaging (MRI), or radiography play an essential role in preoperative diagnostics, these cannot be utilized in intraoperative tumor detection due to their large size, high cost, long imaging time, and lack of cancer specificity. The inception of several imaging techniques has paved the way to intraoperative tumor margin detection with a high degree of sensitivity and specificity. Particularly, molecular imaging using near-infrared fluorescence (NIRF) based nanoprobes provides superior imaging quality due to high signal-to-noise ratio, deep penetration to tissues, and low autofluorescence, enabling accurate tumor resection and improved survival rates. In this review, we discuss the recent developments in imaging technologies, specifically focusing on NIRF nanoprobes that aid in highly specific intraoperative surgeries with real-time recognition of tumor margins.

164. INTRAOPERATIVE LYMPHATIC FLOW MAPPING USING INDOCYANINE GREEN PREDICTS LYMPH NODE METASTASIS IN ESOPHAGEAL CANCER PATIENTS NOT TREATED WITH NEOADJUVANT CHEMOTHERAPY

Abstract Background Lymphatic flow mapping using near-infrared fluorescence (NIR) imaging with indocyanine green (ICG) has been used for the intraoperative prediction of lymph node metastasis (LNM) in various cancers. Previous studies examined the feasibility of applying this technique to patients with esophageal cancer. However, a consistent method that yields sufficient diagnostic quality has yet to be confirmed. This study explored the diagnostic utility of our established lymphatic flow mapping protocol for predicting LNM in esophageal cancer. Methods We injected 0.5 mL of ICG (500 μg/mL) into the submucosal layer at four peritumoral points on the day before surgery for 54 patients. We performed lymphatic flow mapping intraoperatively using NIR imaging. After determining the NIR status and presence of metastases, evaluable lymph node stations on intraoperative NIR imaging and all resected lymph nodes were divided into four categories: ICG + meta+ (true positive), ICG + meta− (false positive), ICG − meta+ (false negative), and ICG − meta− (true negative). Logistic regression models were used to investigate the characteristics of patients with LNs or LN stations associated with high false-negative rates. Results The distribution of ICG+ and meta+ lymph node stations differed according to the primary tumor site. Sensitivity and specificity for predicting meta+ lymph nodes among ICG+ ones were 50% and 75%, respectively. Predicting meta+ lymph node stations among ICG+ stations improved these values to 66% and 77%, respectively. Undergoing neoadjuvant chemotherapy was an independent risk factor for having meta+ lymph nodes with false-negative diagnoses (odds ratio: 4.82; 95% confidence interval: 1.28–18.19). The sensitivity of our technique for predicting meta+ lymph nodes and meta+ lymph node stations in patients who did not undergo neoadjuvant chemotherapy was 79% and 83%, respectively. Conclusion Our NIR imaging protocol potentially helps to predict lymph node metastasis intraoperatively in patients with esophageal cancer undergoing esophagectomy who had not undergone neoadjuvant chemotherapy. This technique may effectively serve as a parameter for assessing the need for dissecting LNs in each station and determining whether it is applicable to reduce the extent of lymphadenectomy.

Artificial intelligence-based technology for enhancing the quality of simulation, navigation, and outcome prediction for hepatectomy

In the past decade, artificial intelligence (AI)-based technology has been applied to develop a simulation and navigation system and a model for predicting surgical outcomes in hepatobiliary surgery. To identify the intrahepatic vascular structure and accurate liver segmentation and volumetry, AI technology has been applied in three-dimensional (3D) simulation software. Recently, 3D and 4D printing have been used as innovative technologies for tissue and organ fabrication, medical education, and preoperative planning. AI can empower 3D and 4D printing technologies. Attempts have been made to use AI technology in augmented reality for navigating and performing intraoperative ultrasound. To predict surgical outcomes and postoperative early recurrence in patients with hepatocellular carcinoma, a deep learning model can be useful. Indocyanine green fluorescence imaging is used in hepatobiliary surgery to visualize the anatomy of the bile duct, hepatic tumors, and hepatic segmental areas. AI technology was applied to fuse intraoperative near-infrared fluorescence and visible images. Preoperative simulation, intraoperative navigation, and models to predict surgical outcomes using AI technology can be clinically applied in hepatobiliary surgery. As shown in reliable and robust clinical studies, AI can be a useful tool in clinical practice to improve the safety and efficacy of hepatobiliary surgery.

Comparison of indirect computed tomographic lymphography and near-infrared fluorescence sentinel lymph node mapping for integumentary canine mast cell tumors.

To compare the independent and combined use of indirect computed tomographic lymphography (ICTL) and near-infrared fluorescence (NIRF) for sentinel lymph node (SLN) mapping in dogs with integumentary mast cell tumors (MCT) and report the metastatic LN rate. Prospective clinical study. Twenty client-owned dogs. Dogs underwent preoperative ICTL, then intraoperative NIRF SLN mapping and excision of the anatomic lymph node (ALN) and/or SLN, and primary MCT. Technique agreement was complete if the same SLN was detected, and partial if the same SLN was detected along with additional SLN. No agreement occurred if the techniques detected different or no SLN. MCT were graded using two- and three-tier schemes, and LN were graded from HN0-3; HN2-3 were considered metastatic. Complete, partial, and no agreement between ICTL and NIRF was seen in 8/20 (40%), 8/20 (40%), and 4/20 (20%) dogs, respectively. Detection of ICTL-SLN and NIRF-SLN failed in 1/20 (5%) and 4/20 (20%), respectively. Tumors were grade II/low-grade in 19/20 (95%) and grade III/high-grade in 1/20 (5%) dogs. Nineteen out of 20 (95%) dogs had HN2-3 LN. Technique agreement of at least one SLN was seen in 16/20 (80%) dogs. Although most MCT were classified as intermediate to low grade, LN metastases were commonly detected. Combining ICTL and NIRF for MCT SLN mapping yields high SLN detection rates. Lymph node metastasis may be more common than previously reported for intermediate to low grade MCT.

Modified low-dose second window indocyanine green technique improves near-infrared fluorescence image-guided dermatofibrosarcoma protuberans resection: A randomized control trial.

Conventional second window indocyanine green (SWIG) technique has been widely attempted in near-infrared fluorescence (NIRF) imaging for intraoperative navigation of tumor radical resection. Nevertheless, the overuse of indocyanine green (ICG) led to an increased risk of drug lethal allergy and high medical cost. This prospective study was to explore clinical application of modified low-dose SWIG technique in guiding dermatofibrosarcoma protuberans (DFSPs) radical resection. Patients with DFSPs were randomly assigned to control and experimental group. The ICG was injected intravenously 24 h before surgery, at a dose of 3.5 mg/kg in the control group and 25 mg/patient in the experiment group, respectively. Intraoperative NIRF imaging included serial views of gross tumor, tumor bed and cross-sectional specimen. Although NIRF imaging of gross tumor and tumor bed in the experimental group demonstrated similar sensitivity and negative predictive value, the specificity and positive predictive value were obviously higher compared to control group. The tumor-to-background ratios of cross-sectional specimens in the experimental group was significantly higher than in the control group (P = 0.000). Data in both groups displayed that there was a positive correlation of tumor size in cross-sections between integrated histopathologic photomicrographs and NIRF imaging of specimen views (P = 0.000). NIRF imaging of cross-sectional specimens had a significant decrease in time cost, and an increase in the ability of examining more surgical margins (P = 0.000). This is the first study to demonstrate that a low-dose SWIG technique could improve the accuracy of near-infrared fluorescence image-guided dermatofibrosarcoma protuberans resection.Clinical Trial Registration: ChiCTR2100050174; date of registration: August 18, 2021 followed by "retrospectively registered".

An Acid Response IR780-Based Targeted Nanoparticle for Intraoperative Near-Infrared Fluorescence Imaging of Ovarian Cancer

IntroductionComplete resection of all visible disease (R0 resection) is critical for the treatment of ovarian cancer patients, and accurate real-time guidance provided by intraoperative near-infrared (NIR) fluorescence images is beneficial for achieving complete resection of all visible disease.MethodsBased on the optical properties of IR780 and the characteristics of the acidic tumor microenvironment, we develop a new smart nanoparticle (eg, FA-IR780&PFOB-SNPs) by using the pH response nano framework (FA-PEG-PLGA-PEOz) and adjusting the amount of IR780. The FA-IR780&PFOB-SNPs was characterized for morphology, microstructure, particle size, pH-response, drug-loading efficiency and biological safety. The ultraclear fluorescence Navigation Endoscopy System was applied to evaluate the tumor recognition of FA-IR780&PFOB-SNPs in vivo.ResultsThe structure of FA-IR780&PFOB-SNPs was stable in a neutral environment, and the near-infrared (NIR) fluorescence was turned off, while the structure of FA-IR780&PFOB-SNPs was degraded in the acidic tumour microenvironment, and the NIR fluorescence was turned on. Through the ovarian subcutaneous xenograft tumour and ovarian intraperitoneal xenograft tumour models, it was confirmed that FA-IR780&PFOB-SNPs could clearly display the boundaries of abdominal micron-sized tumours through near-infrared fluorescence imaging, with a TBR greater than 5.ConclusionThe FA-IR780&PFOB-SNPs have the potential to provide to ovarian cancer intraoperative near infrared fluorescence navigation during precision tumour resection to achieve R0 and improve the prognosis of ovarian cancer patients.

Application of near-infrared fluorescence imaging in lingual lymph node screening and drainage pattern observation for tongue cancer.

Objective: Lingual lymph node (LLN) metastasis is regarded as an indicator of unfavorable prognosis and a crucial sign of the high degree of primary tumor aggressiveness. However, detecting LLN metastasis is an important but frequently overlooked aspect of diagnosis and surgical treatment planning. The study aims to identify LLNs by intraoperative near-infrared (NIR) fluorescence imaging with indocyanine green absorbed into human serum albumin (ICG: HSA) and describe the presence of lymphatic drainage channels from the floor of the mouth in patients with tongue carcinoma. Materials and Methods: 21 patients diagnosed with cT1-T4 squamous cell carcinoma (SCC) of the tongue margin and scheduled to undergo tumor resection and unilateral neck dissection were enrolled. After exposing the neck, the patients were injected with 0.3 ml of ICG: HSA (500 μM) in three quadrants around the tumor, excluding the mucous membrane of the basal region cavity. Employing a near-infrared fluorescence imaging system, the fluorescence of levels I, II, III, and IV was measured during neck dissection. Results: LLNs were detected in four patients and were identified as metastatic LLNs in all 21 patients. The near-infrared fluorescence imaging system showed the existence of lymphatic drainage channels in the floor of the mouth. In patients receiving peritumoral injection of ICG: HSA, the mean fluorescence intensity (MFI)of metastatic lymph nodes (LNs) (178.4 ± 64.39, mean ± SD) was higher than that in non-metastatic LNs (132.0 ± 76.5, mean ± SD) (p < 0.05). Conclusion: NIR fluorescence imaging with ICG: HSA could be used for intraoperative identification of LLNs and assist in the determination of metastatic lymph nodes for tongue carcinoma patients. Additionally, this finding demonstrates the feasibility of near-infrared fluorescence imaging in defining lymphatic drainage channels in the head and neck.

Indocyanine Green-Guided Intraoperative Imaging to Facilitate Video-Assisted Retroperitoneal Debridement for Treating Acute Necrotizing Pancreatitis.

Video-assisted retroperitoneal debridement (VARD) is a feasible, minimally invasive necrosectomy method for treating severe acute necrotizing pancreatitis, if it does not resolve or is accompanied with infected necrosis in the retroperitoneum. As there are rarely any visually clear separating surface in white light image between necrotic debris and adjacent inflammatory normal tissues due to extensive retroperitoneal adhesions, VARD is accompanied with the risk of vascular injury, external pancreatico-cutaneous or enterocutaneous fistulae. In view of the above disadvantages, we apply real-time intraoperative near-infrared fluorescence imaging with indocyanine green (ICG) during VARD, which enables visualization of the well-perfused adjacent normal tissues. This modified technique (ICG-guided VARD) can provide a clear separating surface during debridement and reduce the risk of vascular or enteric injury. ICG-guided VARD may facilitate surgeons to perform safer debridement in treating severe acute necrotizing pancreatitis.

Impact of near-infrared fluorescence imaging with indocyanine green on structural sequelae of anastomotic leakage after laparoscopic intersphincteric resection of malignant rectal tumors.

Recent studies have indicated the potential benefit of intraoperative near-infrared fluorescence imaging (NIR-FI) with indocyanine green in reducing early anastomotic leakage in colorectal surgery. Nonetheless, whether NIR-FI is effective in reducing structural sequelae of anastomotic leakage (SSAL) remains unclear. The aim of the present study was to investigate the impact of NIR-FI on SSAL after laparoscopic intersphincteric resection (ISR) of malignant rectal tumors. This study was a retrospective single-center cohort study. A total of 293 consecutive patients who underwent elective laparoscopic ISR from May 2010 to August 2017 were included. Patients were divided into 2 groups; those who underwent elective laparoscopic ISR with lymphadenectomy for malignant rectal tumors using NIR-F (NIR-FI group) and those who underwent elective laparoscopic ISR with lymphadenectomy for malignant rectal tumors without using NIR-FI (control group). Thirty were excluded from the analyses (13 died, 7 had pelvic recurrence, and 10 were lost to follow-up). The primary endpoint was the rate of SSAL within 2years after the primary resection, whereas the secondary endpoint was the rate of natural defecation via the anus at 2years after the primary resection. Using various statistical analyses, such as propensity score matching, the rate of SSAL was compared between groups. A total of 263 patients were analyzed [177 males and 86 females, median age 61 (27-84) years]. Prior to propensity score matching (n = 263), NIR-FI was performed in 70 patients (26.6%) The rates of SSAL were 1.4% (1/70) in the NIR-FI group and 10.4% (20/193) in the control group (p = 0.02). After propensity score matching (n = 163), the rates of SSAL were 1.5% (1/66) in the NIR-FI group and 11.7% (12/103) in the control group (p = 0.02). Propensity score analyses, as well as simple regression analyses, revealed that NIR-FI was associated with a significantly lower risk of SSAL (OR 0.10-0.13; p = 0.03-0.05). NIR-FI is useful in reducing the rate of SSAL after laparoscopic ISR.

Tumor-Specific Imaging with Angiostamp800 or Bevacizumab-IRDye 800CW Improves Fluorescence-Guided Surgery over Indocyanine Green in Peritoneal Carcinomatosis

Complete surgical removal of lesions improves survival of peritoneal carcinomatosis and can be enhanced by intraoperative near-infrared fluorescence imaging. Indocyanine green (ICG) is the only near-infrared fluorescent dye approved for clinical use, but it lacks specificity for tumor cells, highlighting the need for tumor-selective targeting agents. We compared the tumor-specific near-infrared fluorescent probes Bevacizumab-IRDye 800CW and Angiostamp800, which target tumor angiogenesis and cancer cells, to ICG for fluorescence-guided surgery in peritoneal carcinomatosis of ovarian origin. The probes were administered to mice with orthotopic peritoneal carcinomatosis prior to conventional and fluorescence-guided surgery. The influence of neoadjuvant chemotherapy was also assessed. Conventional surgery removed 88.0 ± 1.2% of the total tumor load in mice. Fluorescence-guided surgery allowed the resection of additional nodules, enhancing the total tumor burden resection by 9.8 ± 0.7%, 8.5 ± 0.8%, and 3.9 ± 1.2% with Angiostamp800, Bevacizumab-IRDye 800CW and ICG, respectively. Interestingly, among the resected nodules, 15% were false-positive with ICG, compared to only 1.4% with Angiostamp800 and 3.5% with Bevacizumab-IRDye 800CW. Furthermore, conventional surgery removed only 69.0 ± 3.9% of the total tumor burden after neoadjuvant chemotherapy. Fluorescence-guided surgery with Angiostamp800 and Bevacizumab-IRDye 800CW increased the total tumor burden resection to 88.7 ± 4.3%, whereas ICG did not improve surgery at all. Bevacizumab-IRDye 800CW and Angiostamp800 better detect ovarian tumors and metastases than the clinically used fluorescent tracer ICG, and can help surgeons completely remove tumors, especially after surgery neoadjuvant chemotherapy.

Intraoperative Near-Infrared Fluorescence Imaging with Indocyanine Green for Identification of Gastrointestinal Stromal Tumors (GISTs), a Feasibility Study.

Simple SummarySurgical resection plays a pivotal role in the treatment of GIST patients. The current study aims to explore the use of near-infrared fluorescence imaging to optimize the intraoperative tumor identification of GISTs. For this purpose, the potential and limitations of the widely used, and non-specific, tracer indocyanine green were assessed in a multicenter study including 10 patients. Our results show that GISTs typically have similar fluorescence intensity to the surrounding tissue, within several minutes after the intravenous administration of indocyanine green. These findings justify future research into specific fluorescent tracers for GISTs, and set a reference for future intraoperative imaging trials.Background: Optimal intraoperative tumor identification of gastrointestinal stromal tumors (GISTs) is important for the quality of surgical resections. This study aims to assess the potential of near-infrared fluorescence (NIRF) imaging with indocyanine green (ICG) to improve intraoperative tumor identification. Methods: Ten GIST patients, planned to undergo resection, were included. During surgery, 10 mg of ICG was intravenously administered, and NIRF imaging was performed at 5, 10, and 15 min after the injection. The tumor fluorescence intensity was visually assessed, and tumor-to-background ratios (TBRs) were calculated for exophytic lesions. Results: Eleven GIST lesions were imaged. The fluorescence intensity of the tumor was visually synchronous and similar to the background in five lesions. In one lesion, the tumor fluorescence was more intense than in the surrounding tissue. Almost no fluorescence was observed in both the tumor and healthy peritoneal tissue in two patients with GIST lesions adjacent to the liver. In three GISTs without exophytic growth, no fluorescence of the tumor was observed. The median TBRs at 5, 10, and 15 min were 1.0 (0.4–1.2), 1.0 (0.5–1.9), and 0.9 (0.7–1.2), respectively. Conclusion: GISTs typically show similar fluorescence intensity to the surrounding tissue in NIRF imaging after intraoperative ICG administration. Therefore, intraoperatively administered ICG is currently not applicable for adequate tumor identification, and further research should focus on the development of tumor-specific fluorescent tracers for GISTs.

Intraoperative near-infrared fluorescence imaging can identify pelvic nerves in patients with cervical cancer in real time during radical hysterectomy

PurposeRadical hysterectomy combined with pelvic lymphadenectomy is the standard treatment for early-stage cervical cancer, but unrecognized pelvic nerves are vulnerable to irreversible damage during surgery. This early clinical trial investigated the feasibility and safety of intraoperative near-infrared (NIR) fluorescence imaging (NIR-FI) with indocyanine green (ICG) for identifying pelvic nerves during radical hysterectomy for cervical cancer.MethodsSixty-six adults with cervical cancer were enrolled in this prospective, open-label, single-arm, single-center clinical trial. NIR-FI was performed in vivo to identify genitofemoral (GN), obturator (ON), and hypogastric (HN) nerves intraoperatively. The primary endpoint was the presence of fluorescence in pelvic nerves. Secondary endpoints were the ICG distribution in a nerve specimen and potential underlying causes of fluorescence emission in pelvic nerves.ResultsIn total, 63 patients were analyzed. The ON was visualized bilaterally in 100% (63/63) of patients, with a mean fluorescence signal-to-background ratio (SBR) of 5.3±2.1. The GN was identified bilaterally in 93.7% (59/63) of patients and unilaterally in the remaining 4 patients, with a mean SBR of 4.1±1.9. The HN was identified bilaterally in 81.0% (51/63) of patients and unilaterally in 7.9% (5/63) of patients, with a mean SBR of 3.5±1.3. ICG fluorescence was detected in frozen sections of a nerve specimen, and was mainly distributed in axons. No ICG-related complications were observed.ConclusionThis early clinical trial demonstrated the feasibility and safety of NIR-FI to visualize pelvic nerves intraoperatively. Thus, NIR-FI may help surgeons adjust surgical decision-making, avoid nerve damage, and improve surgical outcomes.Trial registrationClinicalTrials.gov NCT04224467

Adaptive brightness fusion method for intraoperative near-infrared fluorescence and visible images

An adaptive brightness fusion method (ABFM) for near-infrared fluorescence imaging is proposed to adapt to different lighting conditions and make the equipment operation more convenient in clinical applications. The ABFM is designed based on the network structure of Attention Unet, which is an image segmentation technique. Experimental results show that ABFM has the function of adaptive brightness adjustment and has better fusion performance in terms of both perception and quantification. Generally, the proposed method can realize an adaptive brightness fusion of fluorescence and visible images to enhance the usability of fluorescence imaging technology during surgery.

Intraoperative Near-Infrared Fluorescence Guided Surgery Using Indocyanine Green (ICG) for the Resection of Sarcomas May Reduce the Positive Margin Rate: An Extended Case Series.

Simple SummarySarcomas are rare cancers that can arise all over the body, with many occurring in younger people. Treatment is usually based around surgery to remove the tumour. It is crucial to remove all of the tumour to minimise the chance of the tumour coming back. Currently, surgeons review scans of the tumour and plan the operation beforehand, but it can be difficult to relate the scans to what the surgeon sees during the operation. Currently, there are no established technologies to help them identify the tumour during the operation. Here we have given patients a harmless dye (indocyanine green) prior to the operation, which makes the tumour glow on a screen when seen by a camera during the operation, helping the surgeon to identify and remove the tumour. This resulted in the surgeon being able to remove all of the tumour more often, reducing the chances of it coming back.Background: Sarcomas are rare, aggressive cancers which can occur in any region of the body. Surgery is usually the cornerstone of curative treatment, with negative surgical margins associated with decreased local recurrence and improved overall survival. Indocyanine green (ICG) is a fluorescent dye which accumulates in sarcoma tissue and can be imaged intraoperatively using handheld near-infrared (NIR) cameras, theoretically helping guide the surgeon’s resection margins. Methods: Patients operated on between 20 February 2019 and 20 October 2021 for intermediate to high grade sarcomas at our centres received either conventional surgery, or were administered ICG pre-operatively followed by intra-operative NIR fluorescence guidance during the procedure. Differences between the unexpected positive margin rates were compared. Results: 115 suitable patients were identified, of which 39 received ICG + NIR fluorescence guided surgery, and 76 received conventional surgery. Of the patients given ICG, 37/39 tumours fluoresced, and surgeons felt the procedure was guided by the intra-operative images in 11 cases. Patients receiving ICG had a lower unexpected positive margin rate (5.1% vs. 25.0%, p = 0.01). Conclusions: The use of NIR fluorescence cameras in combination with ICG may reduce the unexpected positive margin rate for high grade sarcomas. A prospective, multi-centre randomised control trial is now needed to validate these results.

Assessment of deep inferior epigastric perforator flap perfusion with near-infrared fluorescence: A pilot study and description of a standardized working protocol

Fat necrosis (FN) is a common complication after autologous breast reconstruction (ABR) using a free flap, which can influence reconstruction outcome and patient satisfaction. Intraoperative near-infrared fluorescence imaging using indocyanine green (ICG) permits the visualization of flap perfusion. The aim of this study was to assess the effect of near-infrared fluorescence on FN incidence in patients undergoing an ABR with a deep inferior epigastric perforator flap (DIEP) and to propose a standard working protocol for this technique. In this prospective study, patients undergoing one-sided ABR with a DIEP were included. The standard DIEP procedure was complemented with near-infrared fluorescence imaging using the fluorescent tracer ICG to evaluate flap perfusion. This cohort was compared to a retrospective cohort of DIEP procedures without near-infrared fluorescence imaging. Patients and surgery characteristics, as well as postoperative complications, were registered and compared. In both cohorts, 24 patients were included. No significant differences were present between patients and surgery characteristics, including no difference in duration of surgery. In the prospective and retrospective group, the incidence of FN was 4.2% and 33%, respectively (p-value=0.023). Moreover, microsurgeons were positive about using near-infrared fluorescence as it either provided additional information about perfusion or confirmed the clinical assessment. Our pilot study showed a significant decrease of FN in patients undergoing an ABR with a DIEP when near-infrared fluorescence imaging was used to assess flap perfusion. This study provides a standardized working protocol for near-infrared fluorescence imaging. In the future, large multicenter studies should focus on the quantification of near-infrared fluorescence imaging.

Unexpected Binding of Tozuleristide "Tumor Paint" to Cerebral Vascular Malformations: A Potentially Novel Application of Fluorescence-Guided Surgery.

Fluorescence-guided surgery (FGS) is under investigation as a means to improve the extent of resection for primary central nervous system (CNS) tumors. Tozuleristide, known also as "Tumor Paint," is an investigational tumor-targeting agent covalently conjugated to a derivative of the fluorescent dye indocyanine green. To report the finding of avid intraoperative fluorescence of tozuleristide on cerebral vascular malformations. Our institution is participating in a phase 2/3 study of intraoperative near-infrared fluorescence detection of pediatric primary CNS tumors in patients receiving intravenous tozuleristide and imaged with the Canvas system. Our site enrolled 2 patients with intracranial lesions, suspected preoperatively of possibly being gliomas that proved to be cavernous vascular malformations after resection. Each lesion had a dark blue mulberry appearance and each fluoresced avidly with tozuleristide. Each was completely resected, and the patients recovered without deficit. Pathological assessment showed cavernous angioma for both cases. Tozuleristide fluorescence is postulated to result from binding to matrix metalloproteinase-2 and annexin A2, and literature review demonstrates expression of both these ligands on multiple cerebrovascular lesions, including cavernous malformations. This finding deserves further investigation to determine if tozuleristide "Tumor Paint" may have a wider role in the identification of non-neoplastic intracranial pathologies.