Search Results (12)

Background/Objectives: Motion artifacts significantly distort fluorescence measurements during surgical perfusion assessment, potentially leading to incorrect clinical decisions. This study evaluates the efficacy of automated motion compensation (MC) in quantitative indocyanine green (q-ICG) imaging to improve the accuracy of perfusion assessment. Methods: Frames from ICG perfusion assessment during 17 pancreaticoduodenectomies were analyzed. Regions of interest (ROIs) were systematically placed on each frame series, and automated MC was applied to track tissue movement. Performance was evaluated by comparing MC with surgeon-adjusted placement using multiple image quality metrics and analyzing perfusion metrics on time–intensity curves. Principal Component Analysis (PCA) was applied to explore whether image patterns could distinguish between successful and unsuccessful motion compensation. Results: Automated motion compensation successfully corrected motion artifacts in 67.5% of frame sequences, achieving comparable performance to surgeon-guided adjustments. PCA demonstrated clear separation between sufficient and insufficient corrections (AUC = 0.80). At the population level, MC did not significantly change perfusion slope (t(59) = 1.60, p = 0.11) or time-to-peak (Tmax; t(58) = 0.81, p = 0.42). Bland–Altman analysis showed a mean bias of −0.54 (SD = 3.32) for slope and 24.95 (SD = 238.40) for Tmax. At the individual level, 86.7% of slope and 79.7% of Tmax values differed by ≥10% after MC, with mean absolute percentage changes of 108.5% (median 37.8%) and 431.5% (median 65.9%), respectively. Conclusions: MC effectively reduces motion artifacts in fluorescence-guided perfusion assessment. By improving the precision of ICG-derived parameters, this technology enhances measurement reliability and represents an enabler for accurate intraoperative perfusion quantification. Full article

Indocyanine green near-infrared fluorescence (ICG-NIRF) imaging is widely used to assess tissue perfusion, yet its subjective interpretation limits correlation with postoperative parathyroid function. To address this, the Workflow model for ICG-angiography integrating Standardization and Quantification (WISQ) was developed. This exploratory prospective multicenter study evaluated the reproducibility of WISQ in adults undergoing total thyroidectomy at two Dutch university centres. Patients with contraindications to ICG or prior neck surgery were excluded. Intraoperative imaging used standardized camera settings with blood volume-adjusted ICG dosing, and perfusion curves were analyzed using predefined regions of interest. Eighty patients were included. Significant inter-centre variability was observed in maximum fluorescence intensity, inflow slope, and outflow slope (n = 30). At the lead centre, outflow was the most promising predictor of postoperative hypoparathyroidism (HPT) (median −0.33 [IQR −0.49–−0.15] a.f.u./s for HPT vs. −0.68 [−0.91–−0.41], n = 17, p = 0.08), although no parameter significantly predicted HPT. Repeated ICG injections consistently produced lower maximal intensities irrespective of injection rate, and reproducible curves were achieved only when ICG was freshly dissolved at 0.5 mg/mL instead of 2.5 mg/mL. These findings indicate that ICG concentration and injection technique influence perfusion kinetics and underscore the need to update WISQ with standardized injection dilution to improve its clinical utility. Full article

Background: Pain is a complex phenomenon characterized by unpleasant experiences with profound heterogeneity influenced by biological, psychological, and social factors. According to the National Health Interview Survey, 50.2 million U.S. adults (20.5%) experience pain on most days, with the annual cost of prescription medication for pain reaching approximately USD 17.8 billion. Theranostic pain nanomedicine therefore emerges as an attractive analgesic strategy with the potential for increased efficacy, reduced side-effects, and treatment personalization. Theranostic nanomedicine combines drug delivery and diagnostic features, allowing for real-time monitoring of analgesic efficacy in vivo using molecular imaging. However, clinical translation of these nanomedicines are challenging due to complex manufacturing methodologies, lack of standardized quality control, and potentially high costs. Quality by Design (QbD) can navigate these challenges and lead to the development of an optimal pain nanomedicine. Our lab previously reported a macrophage-targeted perfluorocarbon nanoemulsion (PFC NE) that demonstrated analgesic efficacy across multiple rodent pain models in both sexes. Here, we report PFC-free, biphasic nanoemulsions formulated with a biocompatible and non-immunogenic plant-based coconut oil loaded with a COX-2 inhibitor and a clinical-grade, indocyanine green (ICG) near-infrared fluorescent (NIRF) dye for parenteral theranostic analgesic nanomedicine. Methods: Critical process parameters and material attributes were identified through the FMECA (Failure, Modes, Effects, and Criticality Analysis) method and optimized using a 3 × 2 full-factorial design of experiments. We investigated the impact of the oil-to-surfactant ratio (w/w) with three different surfactant systems on the colloidal properties of NE. Small-scale (100 mL) batches were manufactured using sonication and microfluidization, and the final formulation was scaled up to 500 mL with microfluidization. The colloidal stability of NE was assessed using dynamic light scattering (DLS) and drug quantification was conducted through reverse-phase HPLC. An in vitro drug release study was conducted using the dialysis bag method, accompanied by HPLC quantification. The formulation was further evaluated for cell viability, cellular uptake, and COX-2 inhibition in the RAW 264.7 macrophage cell line. Results: Nanoemulsion droplet size increased with a higher oil-to-surfactant ratio (w/w) but was no significant impact by the type of surfactant system used. Thermal cycling and serum stability studies confirmed NE colloidal stability upon exposure to high and low temperatures and biological fluids. We also demonstrated the necessity of a solubilizer for long-term fluorescence stability of ICG. The nanoemulsion showed no cellular toxicity and effectively inhibited PGE2 in activated macrophages. Conclusions: To our knowledge, this is the first instance of a celecoxib-loaded theranostic platform developed using a plant-derived hydrocarbon oil, applying the QbD approach that demonstrated COX-2 inhibition. Full article

Background/Objectives: Indocyanine green fluorescence angiography (ICG-FA) enables the real-time visualization of tissue perfusion. However, objective research on microscope-integrated fluorescence angiography (FA) has not been conducted before. This study aims to evaluate the fluorescence light distribution in images formed by ICG-FA in two surgical microscopes using a phantom, and to provide recommendations for their application. Methods: An 11.8 by 6.8 cm ICG and Intralipid phantom was made to evaluate overall spatial fluorescence sensitivity in two surgical microscopes in multiple working distances (WDs) and magnification factors (MFs). The signal was quantified using a tailor-made software in Python 3.8.10. Results: A clear center–periphery effect was present in most settings in both microscopes, with the highest peripheral fluorescence signal loss in the lowest MF: 100% in the Tivato and 83% in the Pentero. Increasing the MF improved homogeneity, where the biggest difference was seen between the first and second MF. A 30 cm WD and 3.5× MF produced the most homogeneous images suitable for free-flap surgery. Manually opening the light beam diameter also reduced the center–periphery effect. Conclusions: Peripheral signal loss in microscope-integrated ICG-FA must be considered during clinical interpretation and for the quantification of tissue perfusion. In clinical practice during reconstructive free-flap surgery, a 30 cm WD, 3.5 MF, and manually opened light beam diameter should be applied to achieve the most homogeneous image. Full article

To obtain a quantitative parameter for the measurement of choroidal vascular hyperpermeability (CVH) on ultra-widefield indocyanine green angiography (UWICGA) using an objective analysis method in macular choroidal neovascularization (CNV). A total of 113 UWICGA images from 113 subjects were obtained, including with 25 neovascular age-related macular degeneration (nAMD), 37 with polypoidal choroidal vasculopathy (PCV) (19 with thin-choroid and 18 with thick-choroid), 33 with pachychoroid neovasculopathy (PNV), and 18 age-matched controls. CVH was quantified on a gray image by the subtraction of 2 synchronized UWICGA images of early and late phases. The measured CVH parameter was compared with human graders and among CNV subtypes and correlated with choroidal vascular density (CVD) and subfoveal choroidal thickness (SFCT). The mean CVH values were 28.58 ± 4.97, 33.36 ± 8.40, 33.61 ± 11.50, 42.19 ± 13.25, and 43.59 ± 7.86 in controls and patients with nAMD, thin-choroid PCV, thick-choroid PCV, and PNV, respectively (p < 0.001). CVH was higher in thick-choroid PCV and PNV compared to the other groups (all p ≤ 0.006). The measured CVH value positively correlated with those reported by human graders (p < 0.001), CVD, and SFCT (p = 0.001 and p < 0.001, respectively). CVH can be measured objectively using quantitative UWICGA analysis. The CVH parameter differs among macular CNV subtypes and correlates with CVD and SFCT. Full article

Near-infrared (NIR) imaging with indocyanine green (ICG) has proven to be useful in general, visceral, and transplant surgery. However, most studies have performed only qualitative assessments. Therefore, a systematic overview of all studies performing quantitative indocyanine green evaluation in general, visceral, and transplant surgeries should be conducted. Free term and medical subject heading (MeSH) term searches were performed in the Medline and Cochrane databases until October 2022. The main categories of ICG quantification were esophageal surgery (24.6%), reconstructive surgery (24.6%), and colorectal surgery (21.3%). Concordantly, anastomotic leak (41%) was the main endpoint, followed by the assessment of flap perfusion (23%) and the identification of structures and organs (14.8%). Most studies examined open surgery (67.6%) or laparoscopic surgery (23.1%). The analysis was mainly carried out using manufacturer software (44.3%) and open-source software (15.6%). The most frequently analyzed parameter was intensity over time for blood flow assessment, followed by intensity alone or intensity-to-background ratios for structure and organ identification. Intraoperative ICG quantification could become more important with the increasing impact of robotic surgery and machine learning algorithms for image and video analysis. Full article

While the sentinel lymph node concept is routinely applied in other surgical fields, no established and valid modality for lymph node mapping for esophageal cancer surgery currently exists. Near-infrared light fluorescence (NIR) using indocyanine green (ICG) has been recently proven to be a safe technology for peritumoral injection and consecutive lymph node mapping in small surgical cohorts, mostly without the usage of robotic technology. The aim of this study was to identify the lymphatic drainage pattern of esophageal cancer during highly standardized RAMIE and to correlate the intraoperative images with the histopathological dissemination of lymphatic metastases. Patients with clinically advanced stage squamous cell carcinoma or adenocarcinoma of the esophagus undergoing a RAMIE at our Center of Excellence for Surgery of the Upper Gastrointestinal Tract were prospectively included in this study. Patients were admitted on the day prior to surgery, and an additional EGD with endoscopic injection of the ICG solution around the tumor was performed. Intraoperative imaging procedures were performed using the Stryker 1688 or the FIREFLY fluorescence imaging system, and resected lymph nodes were sent to pathology. A total of 20 patients were included in the study, and feasibility and safety for the application of NIR using ICG during RAMIE were shown. NIR imaging to detect lymph node metastases can be safely performed during RAMIE. Further analyses in our center will focus on pathological analyses of ICG-positive tissue and quantification using artificial intelligence tools with a correlation of long-term follow-up data. Full article

Near infrared imaging (NIR) camera systems have been clinically deployed to visualize intravenous injected indocyanine green (ICG) spreading through the vascular bed, thereby creating the ability to assess tissue perfusion. While standardization is key to make fluorescence angiography (FA) comparable and reproducible, optical characteristics like field illumination homogeneity are often not considered. Therefore the aim of this study is to investigate light distribution and the center-periphery effect among five different NIR imaging devices in an indocyanine green phantom. A 13 × 13 cm fluorescence phantom was created by diluting ICG in Intralipid (representing 0.1 mg/kg dose in an 80 kg reference male), to evaluate the overall spatial collection efficiency with fluorescent modalities of five different NIR camera systems using a 0-degree laparoscope. The fluorescence signal from the phantom was quantified at a fixed distance of 16 cm using tailor-made software in Python. The results showed considerable variability in regard to light distribution among the five camera systems, especially toward the periphery of the field of view. In conclusion, NIR signal distribution varies between different systems and within the same displayed image. The fluorescence intensity diminishes peripherally away from the center of the field of view. These optical phenomena need to be considered when clinically interpreting the signal and in the development of computational fluorescence quantification. Full article

Background: Postoperative hypoparathyroidism is the most common complication after total thyroidectomy. Over the past years, optical imaging techniques, such as parathyroid autofluorescence, indocyanine green (ICG) angiography, and laser speckle contrast imaging (LSCI) have been employed to save parathyroid glands during thyroid surgery. This study provides an overview of the utilized methods of the optical imaging techniques during total thyroidectomy for parathyroid gland identification and preservation. Methods: PUBMED, EMBASE and Web of Science were searched for studies written in the English language utilizing parathyroid autofluorescence, ICG-angiography, or LSCI during total thyroidectomy to support parathyroid gland identification or preservation. Case reports, reviews, meta-analyses, animal studies, and post-mortem studies were excluded after the title and abstract screening. The data of the studies were analyzed qualitatively, with a focus on the methodologies employed. Results: In total, 59 articles were included with a total of 6190 patients. Overall, 38 studies reported using parathyroid autofluorescence, 24 using ICG-angiography, and 2 using LSCI. The heterogeneity between the utilized methodology in the studies was large, and in particular, regarding study protocols, imaging techniques, and the standardization of the imaging protocol. Conclusion: The diverse application of optical imaging techniques and a lack of standardization and quantification leads to heterogeneous conclusions regarding their clinical value. Worldwide consensus on imaging protocols is needed to establish the clinical utility of these techniques for parathyroid gland identification and preservation. Full article

Introduction: Image-guided surgery is becoming a new tool in colorectal surgery. Intraoperative visualisation of different structures using fluorophores helps during various steps of operations. In our report, we used two fluorophores—indocyanine green (ICG), and methylene blue (MB)—during different steps of colorectal surgery, using one camera system for two separate near-infrared wavelengths. Material and methods: Twelve patients who underwent complex open or laparoscopic colorectal surgeries were enrolled. Intravenous injections of MB and ICG at different time points were administered. Visualisation of intraoperative ureter position and fluorescent angiography for optimal anastomosis was performed. A retrospective analysis of patients treated in our departments during 2020 was performed, and data about ureter injury and anastomotic site complications were collected. Results: Intraoperative localisation of ureters with MB under fluorescent light was possible in 11 patients. The mean signal-to-background ratio was 1.58 ± 0.71. Fluorescent angiography before performing anastomosis using ICG was successful in all 12 patients, and none required a change in position of the planned colon resection for anastomosis. The median signal-to-background ratios was 1.25 (IQR: 1.22–1.89). Across both centres, iatrogenic injury of the ureter was found in 0.4% of cases, and complications associated with anastomosis was found in 5.5% of cases. Conclusions: Our study showed a substantial opportunity for using two different fluorophores in colorectal surgery, whereby the visualisation of one will not change the possible quantification analysis of the other. Using two separate dyes during one procedure may help in optimisation of the fluorescent properties of both dyes when using them for different applications. Visualisation of different structures by different fluorophores seems to be the future of image-guided surgery, and shows progress in optical technologies used in image-guided surgery. Full article

Indocyanine green (ICG) is a near infrared fluorescent tracer used in image-guided surgery to assist surgeons during resection. Despite appearing as a very promising tool for surgical oncology, its employment in this area is limited to lymph node mapping or to laparoscopic surgery, as it lacks tumor targeting specificity. Recently, a nanoformulation of this dye has been proposed with the aim toward tumor targeting specificity in order to expand its employment in surgical oncology. This nanosystem is constituted by 24 monomers of H-Ferritin (HFn), which self-assemble into a spherical cage structure enclosing the indocyanine green fluorescent tracer. These HFn nanocages were demonstrated to display tumor homing due to the specific interaction between the HFn nanocage and transferrin receptor 1, which is overexpressed in most tumor tissues. Here, we provide an ex vivo detailed comparison between the biodistribution of this nanotracer and free ICG, combining the results obtained with the Karl Storz endoscope that is currently used in clinical practice and the quantification of the ICG signal derived from the fluorescence imaging system IVIS Lumina II. These insights demonstrate the suitability of this novel HFn-based nanosystem in fluorescence-guided oncological surgery. Full article

The revelation of mechanisms of photodynamic therapy (PDT) at the cellular level as well as singlet oxygen (¹O₂) as a second messengers requires the quantification of intracellular ¹O₂. To detect singlet oxygen, directly measuring the phosphorescence emitted from ¹O₂ at 1270 nm is simple but limited for the low quantum yield and intrinsic efficiency of ¹O₂ emission. Another method is chemically trapping ¹O₂ and measuring fluorescence, absorption and Electron Spin Resonance (ESR). In this paper, we used indocyanine green (ICG), the only near-infrared (NIR) probe approved by the Food and Drug Administration (FDA), to detect ¹O₂ in vitro. Once it reacts with ¹O₂, ICG is decomposed and its UV absorption at 780 nm decreases with the laser irradiation. Our data demonstrated that ICG could be more sensitive and accurate than Singlet Oxygen Sensor Green reagent^® (SOSG, a commercialized fluorescence probe) in vitro, moreover, ICG functioned with Eosin Y while SOSG failed. Thus, ICG would reasonably provide the possibility to sense ¹O₂ in vitro, with high sensitivity, selectivity and suitability to most photosensitizers. Full article