Fluorescence Guidance Research Articles

Use of indocyanine green-human serum albumin complexes in fluorescence image-guided laparoscopic anatomical liver resection: a case series study (with video)

BackgroundThis study aimed to investigate the feasibility and efficacy of near-infrared fluorescence-guided laparoscopic anatomical hepatectomy (LAH) using a novel indocyanine green (ICG)-human serum albumin complex (HSA) in patients with hepatocellular carcinoma.MethodsClinical data of hepatocellular carcinoma patients who underwent ICG-HSA fluorescence-guided LAH at our center from January 2024 to April 2024 were prospectively collected and analyzed. Ultraviolet absorption spectroscopy was used to test the absorption and stability of ICG-HSA complex solutions under different conditions. After determining the optimal ratio, the complex was administered intravenously during surgery to perform negative staining via Glissonean pedicle isolation. LAH was performed along the fluorescence-demarcated boundaries.ResultsThirty-one patients were included (24 men; mean age, 54.61 ± 13.54 years). The median maximum tumor diameter was 2.80 (interquartile range [IQR], 2.00–4.00) cm. S8 segmentectomy (22.6%) and right posterior segmentectomy (19.4%) were the most common resections performed. Successful fluorescence negative staining was achieved in all patients using ICG and HSA at a 1:6 molar ratio at room temperature. Mean operation time was 297.58 ± 85.53 min, Median intraoperative blood loss was 100.0 mL (IQR, 50.0–200.0). The median surgical margin distance was 0.90 cm (IQR, 0.40–1.50). The postoperative complication rate was 45.2% (35.5% Clavien–Dindo grade I and 9.7% grade II). The median length of hospital stay was 5.0 days (IQR, 4.0–5.0).ConclusionICG-HSA-assisted LAH is safe and feasible. Compared with free ICG, the novel ICG-HSA complex exhibits better optical properties and in vivo stability, which can improve the accuracy of intraoperative liver segment localization and optimize the anatomical dissection plane. It has the potential to become an ideal fluorescent imaging agent for anatomical hepatectomy.Graphical abstractA In vitro binding experiments of indocyanine green (ICG) and human serum albumin (HSA) suggested that a 1:6 molar ratio and a configuration temperature of 37°C were optimal. B During surgery, after extrahepatic Glissonean isolation of the liver pedicle planned for resection, the ICG-HSA complex was administered through a peripheral vein using an infusion pump. C ICG-HSA metabolism comprises three stages: intravascular, liver, and systemic clearance. D The actual intraoperative fluorescence imaging and guidance effects of ICG-HSA in laparoscopic fluorescence negative-staining right hemihepatectomy.

Illuminate Resection Pathways with Fluorescence Guidance in Glioma Surgery: Case Reports and Systematic Review

Gliomas are the most common brain tumor in adults, with a poor prognosis despite intensive treatments. Complete surgical resection is difficult due to its infiltrative growth, but aggressive surgery improves outcomes. Fluorescence-guided surgery (FGS) is used to distinguish tumor tissue during surgery. 5-Aminolevulinic Acid (5-ALA) is a crucial fluorescent agent in FGS, transforming into a molecule that accumulates in tumor cells. We presented a 34-year-old female with a high-grade glioma in the left parietal lobe who underwent fluorescence-guided tumor resection using 5-ALA was reported. In addition, a review of the literature on fluorescence in glioma surgery, searching databases like PubMed and SCOPUS from 2021 to 2023, was performed. Fifteen papers were included in our review. This technique ensured gross-total tumor resection while preserving neurological function. FGS improves tumor identification, surgical outcomes, and survival.

Impact of indocyanine green on decision making for performing laparoscopic cortical sparing adrenalectomy.

Indocyanine green imaging (ICG) is an expansion technology that can contribute to the development of demanding techniques such as cortical-sparing adrenalectomy (CSA). The aim of this study was to determine in which cases CSA should be performed and when total adrenalectomy should be performed instead based on ICG fluorescence. Here, we present our experience through a series of cases and videos. Prospective and descriptive study on patients with surgical adrenal lesions who were proposed for CSA using ICG with near-infrared fluorescence imaging in our center. A first bolus of 6,25mg ICG was administered intravenously upon exposure of the retroperitoneal plane. Fluorescence was visualized using a Storz® NIR/ICG endoscopic system. Seven patients were proposed for CSA. After the application of ICG, a change in attitude was carried out in 71.4% of the cases (five of seven). In the two patients in whom CSA could be performed, the adrenal remnants were functional, and the resection margins of the surgical specimens were free of disease. The reasons why partial adrenalectomy could not be completed, and a total adrenalectomy was decided instead were the presence of a tumor located very close to the adrenal vein that prevented a correct remnant volume (n = 4) and one case of isofluorescent tumor with the adrenal parenchyma. ICG fluorescence guidance could help in the decision making to select patients intraoperatively for successful cortical preservation.

Pressure-enhanced sensing of tissue oxygenation via endogenous porphyrin: Implications for dynamic visualization of cancer in surgery

Fluorescence guidance is routinely used in surgery to enhance perfusion contrast in multiple types of diseases. Pressure-enhanced sensing of tissue oxygenation (PRESTO) via fluorescence is a technique extensively analyzed here, that uses an FDA-approved human precursor molecule, 5-aminolevulinic acid (ALA), to stimulate a unique delayed fluorescence signal that is representative of tissue hypoxia. The ALA precontrast agent is metabolized in most tissues into a red fluorescent molecule, protoporphyrin IX (PpIX), which has both prompt fluorescence, indicative of the concentration, and a delayed fluorescence, that is amplified in low tissue oxygen situations. Applied pressure from palpation induces transient capillary stasis and a resulting transient PRESTO contrast, dominant when there is near hypoxia. This study examined the kinetics and behavior of this effect in both normal and tumor tissues, with a prolonged high PRESTO contrast (contrast to background of 7.3) across 5 tumor models, due to sluggish capillaries and inhibited vasodynamics. This tissue function imaging approach is a fundamentally unique tool for real-time palpation-induced tissue response in vivo, relevant for chronic hypoxia, such as vascular diseases or oncologic surgery.

ROS-Responsive Nanoprobes for Bimodal Imaging-Guided Cancer Targeted Combinatorial Therapy.

Chemotherapy mediated by Reactive oxygen species (ROS)-responsive drug delivery systems can potentially mitigate the toxic side effects of chemotherapeutic drugs and significantly enhance their therapeutic efficacy. However, achieving precise targeted drug delivery and real-time control of ROS-responsive drug release at tumor sites remains a formidable challenge. Therefore, this study aimed to describe a ROS-responsive drug delivery system with specific tumor targeting capabilities for mitigating chemotherapy-induced toxicity while enhancing therapeutic efficacy under guidance of Fluorescence (FL) and Magnetic resonance (MR) bimodal imaging. Indocyanine green (ICG), Doxorubicin (DOX) prodrug pB-DOX and Superparamagnetic iron oxide (SPIO, Fe3O4) were encapsulated in poly(lactic-co-glycolic acid) (PLGA) by double emulsification method to prepare ICG/ pB-DOX/ Fe3O4/ PLGA nanoparticles (IBFP NPs). The surface of IBFP NPs was functionalized with mammaglobin antibodies (mAbs) by carbodiimide method to construct the breast cancer-targeting mAbs/ IBFP NPs (MIBFP NPs). Thereafter, FL and MR bimodal imaging ability of MIBFP NPs was evaluated in vitro and in vivo. Finally, the combined photodynamic therapy (PDT) and chemotherapy efficacy evaluation based on MIBFP NPs was studied. The multifunctional MIBFP NPs exhibited significant targeting efficacy for breast cancer. FL and MR bimodal imaging clearly displayed the distribution of the targeting MIBFP NPs in vivo. Upon near-infrared laser irradiation, the MIBFP NPs loaded with ICG effectively generated ROS for PDT, enabling precise tumor ablation. Simultaneously, it triggered activation of the pB-DOX by cleaving its sensitive moiety, thereby restoring DOX activity and achieving ROS-responsive targeted chemotherapy. Furthermore, the MIBFP NPs combined PDT and chemotherapy to enhance the efficiency of tumor ablation under guidance of bimodal imaging. MIBFP NPs constitute a novel dual-modality imaging-guided drug delivery system for targeted breast cancer therapy and offer precise and controlled combined treatment options.

HHEPATO-Cy5, a Bimodal Tracer for Image-Guided Hepatobiliary Surgery.

Liver cancer is a leading cause of cancer deaths worldwide. Surgical resection of superficial hepatic lesions is increasingly guided by the disrupted bile excretion of the fluorescent dye indocyanine green (ICG). To extend this approach to deeper lesions, a dedicated bimodal tracer that facilitates both fluorescence guidance and radioguidance was developed. Methods: A tracer comprising a methylated cyanine-5 (Cy5) fluorescent dye and a mercaptoacetyltriserine chelate (hHEPATO-Cy5) was synthesized and characterized. Cellular uptake and excretion were evaluated in hepatocyte cultures (2-dimensional culture and invitro lesion model), using a fluorescent bile salt, MitoTracker dye, and methylated Cy5 as a control. After radiolabeling, the pharmacokinetics of 99mTc-hHEPATO-Cy5 were assessed in mice over 24 h (percentage injected dose and percentage injected dose per gram of tissue, SPECT/CT imaging and fluorescence imaging). The ability to provide real-time fluorescence guidance during robot-assisted hepatobiliary surgery was evaluated in a porcine model using ICG as a reference. Results: The unique molecular signature of hHEPATO-Cy5 promotes hepatobiliary excretion. In vitro studies on hepatocytes showed that where methylated Cy5 remained internalized, hHEPATO-Cy5 showed fast clearance (10 min) similar to that of fluorescent bile salt. In vivo use of 99mTc-hHEPATO-Cy5 in mice revealed liver accumulation and rapid biliary clearance. The effectiveness of bile clearance was best exemplified by the 2-orders-of-magnitude reduction in count rate for the gallbladder (P = 0.008) over time. During hepatobiliary surgery in a porcine model, hHEPATO-Cy5 enabled fluorescence-based lesion identification comparable to that of ICG. Conclusion: The bimodal 99mTc-hHEPATO-Cy5 provides an effective means to identify liver lesions. Uniquely, it helps overcome the shortcomings of fluorescence-only approaches by allowing for an extension to in-depth radioguidance.

Towards machine learning-based quantitative hyperspectral image guidance for brain tumor resection

BackgroundComplete resection of malignant gliomas is hampered by the difficulty in distinguishing tumor cells at the infiltration zone. Fluorescence guidance with 5-ALA assists in reaching this goal. Using hyperspectral imaging, previous work characterized five fluorophores’ emission spectra in most human brain tumors.MethodsIn this paper, the effectiveness of these five spectra was explored for different tumor and tissue classification tasks in 184 patients (891 hyperspectral measurements) harboring low- (n = 30) and high-grade gliomas (n = 115), non-glial primary brain tumors (n = 19), radiation necrosis (n = 2), miscellaneous (n = 10) and metastases (n = 8). Four machine-learning models were trained to classify tumor type, grade, glioma margins, and IDH mutation.ResultsUsing random forests and multilayer perceptrons, the classifiers achieve average test accuracies of 84–87%, 96.1%, 86%, and 91% respectively. All five fluorophore abundances vary between tumor margin types and tumor grades (p < 0.01). For tissue type, at least four of the five fluorophore abundances are significantly different (p < 0.01) between all classes.ConclusionsThese results demonstrate the fluorophores’ differing abundances in different tissue classes and the value of the five fluorophores as potential optical biomarkers, opening new opportunities for intraoperative classification systems in fluorescence-guided neurosurgery.

The potential of indocyanine green fluorescence detection in surgical cut margin of breast conserving surgery.

Fluorescence-guided surgery (FGS) is a cutting-edge technology that uses near-infrared (NIR) fluorescence imaging to guide surgeons in surgery. Indocyanine green (ICG) is a fluorescent dye, which can be used for in vivo imaging of tumor cells. We aimed to explore the use of ICG fluorescence-guided technology as a rapid intraoperative margin assessment method for breast cancer surgery. In addition, we also compared the dose selection of ICG. This was a non-randomized prospective cohort study. Data were collected between August 2021 and October 2022 in the Division of Breast Surgery, Department of General Surgery, Nanjing Drum Tower Hospital, the Affiliated Hospital of Medical School, Nanjing University. Upon specimen removal, tumor margins were immediately analyzed by ICG fluorescence detection and then sent to the pathology department for intraoperative frozen section analysis and subsequent routine pathological examination. Abnormal margin rates were calculated and compared using intraoperative frozen section analysis and under the guidance of ICG fluorescence. The study included 69 cases of breast cancer patients who underwent tumor resection assisted by ICG fluorescence-guided technology, including 18 patients with a 0.5 mg/kg dose and 51 patients with a 1.0 mg/kg dose. According to the study findings, the ICG test achieved a sensitivity of 81.82% and a specificity of 75.82%. At a dose of 0.5 mg/kg, the sensitivity was 66.67% whereas the specificity was 93.33%. At the dose of 1 mg/kg, the sensitivity was 87.5%, and the specificity was 74.42%. Similarly, for intraoperative frozen section analysis, the sensitivity was 81.82%, but the specificity was enhanced to 94.83%. Positive surgical cut margin was not identified in 2/69 by ICG fluorescence and frozen section analysis respectively. The sensitivity of ICG fluorescence detection is comparable to that of frozen section analysis, but the specificity is poor. The sensitivity increased and the specificity decreased at 1 mg/kg compared to the 0.5 mg/kg dose. ICG fluorescence can be used as a supplementary tool for frozen section analysis. These findings support further development and clinical performance assessment of ICG fluorescence.

First-in-man study of the PSMA Minibody IR800-IAB2M for molecularly targeted intraoperative fluorescence guidance during radical prostatectomy

PurposeProstate-specific membrane antigen (PSMA) is increasingly used to image prostate cancer in clinical practice. We sought to develop and test a humanised PSMA minibody IAB2M conjugated to the fluorophore IRDye 800CW-NHS ester in men undergoing robot-assisted laparoscopic radical prostatectomy (RARP) to image prostate cancer cells during surgery.MethodsThe minibody was evaluated pre-clinically using PSMA positive/negative xenograft models, following which 23 men undergoing RARP between 2018 and 2020 received between 2.5 mg and 20 mg of IR800-IAB2M intravenously, at intervals between 24 h and 17 days prior to surgery. At every step of the procedure, the prostate, pelvic lymph node chains and extra-prostatic surrounding tissue were imaged with a dual Near-infrared (NIR) and white light optical platform for fluorescence in vivo and ex vivo. Histopathological evaluation of intraoperative and postoperative microscopic fluorescence imaging was undertaken for verification.ResultsTwenty-three patients were evaluated to optimise both the dose of the reagent and the interval between injection and surgery and secure the best possible specificity of fluorescence images. Six cases are presented in detail as exemplars. Overall sensitivity and specificity in detecting non-lymph-node extra-prostatic cancer tissue were 100% and 65%, and 64% and 64% respectively for lymph node positivity. There were no side-effects associated with administration of the reagent.ConclusionIntraoperative imaging of prostate cancer tissue is feasible and safe using IR800-IAB2M. Further evaluation is underway to assess the benefit of using the technique in improving completion of surgical excision during RARP.RegistrationISCRCTN10046036: https://www.isrctn.com/ISRCTN10046036.

Synergistic luminescent radicals and precursors as type-I photosensitizers for near-infrared fluorescence-guided tumor therapy

Near-infrared (NIR) fluorescence-guided photodynamic therapy (PDT) shows great potential as a cancer treatment modality. However, its application in solid tumors is limited by the scarcity of NIR molecules and the oxygen dependence of conventional photosensitizers. Here, two novel radical nanoparticles (TTM-3PDMAC:HTTM-3PDMAC@NPs and TTM-PDMAC:HTTM-PDMAC@NPs) are developed as type-I photosensitizers by combining luminescent radicals and their precursors. The unique encapsulation of these nanoparticles effectively addresses the limitations of radicals being insoluble and non-fluorescent in water, thus preserving the NIR emission of the radicals. Notably, the superoxide radicals generated by these nanoparticles upon light irradiation have been demonstrated to originate from both the radicals and their precursors. In vivo experiments demonstrated that TTM-3PDMAC:HTTM-3PDMAC@NPs exhibit significant efficacy in treating hypoxic tumor with minimal side effects. Overall, this PDT strategy based on synergistic combination of luminescent radicals and precursors provides novel insights for achieving accurate and efficient PDT under NIR fluorescence guidance.

Laparoscopic Anatomical Cranial Sub-segmentectomy of Segment VII (S7) with Super-Selective Intra-arterial Nano-ICG Positive Staining-Guided Trans-Parenchymal Approach.

With introduction of "cone unit," which is the smallest resectable anatomical area supplied by a tertiary branch of Glissonean pedicle, more precise subsegmental anatomical resection has been proposed.1 Super-selective intra-arterial ICG staining, delivering ICG and lipiodol mixing to arterial branch using interventional radiology, has been proved feasibility especially for complicated anatomy.2-6 It was difficult to uniformly mix water-soluble ICG with lipophilic lipiodol, rendering to inconsistency development of liver segment between angiography and laparoscopy. Nano-ICG is a uniform mixing of ICG and lipiodol.7 We demonstrated an exclusive "two-step" method to perform LAR for cranial S7 via super-selective intra-arterial nano-ICG staining guidance. A 70-year-old male was admitted. CT scan showed tumor was located in cranial S7 with 2.1*1.9cm. Preoperative AFP was 4.66ng/ml and PIVKA-II was 2332mAU/ml. The liver function was Child-Pugh class A and ICG-15R was 7.8%. Given that tumor was confined to cranial S7, precise anatomical sub-segmentectomy was warranted. This study was approved by the West China Hospital, Sichuan University Ethics Committee (approval number: 2023-2327). The operation was performed "two step." "First step" was super-selective intra-arterial nano-ICG embolization in intervention room, while "second step" was performed in operation room. ICG demarcation line was clearly identified even after 7hr. After full mobilization of right hemiliver, we performed transparenchymal approach to find and clamp pedicle of cranial S7 under fluorescence guidance. Operation time was 150min with 20ml of blood loss with uneventful course. Although LAR of S7 remains challenging, super-selective intra-arterial nano-ICG positive staining guidance might be a feasible and safe option.

Enhancing surgical outcomes: accurate identification and removal of prostate cancer with B7-H3-targeted NIR-II molecular imaging.

One of the main reasons for prostate cancer (PCa) recurrence is the difficulty in identifying and removing cancerous lesions during surgery. Accurately localizing and excising cancerous tissue remains a significant challenge. The second near-infrared window (NIR-II, 1000-1700nm) fluorescence offers enhanced resolution, a high signal-to-noise ratio, and the potential for deeper tissue penetration. However, this technology is not currently employed for intraoperative imaging of PCa. This study aims to construct a new NIR-II probe targeting B7-H3 (AbB7-H3-800CW) for accurate intraoperative identification and resection of PCa. Based on the differential expression of B7-H3 in PCa, we designed a novel imaging probe to accurately identify and guide the resection of preclinical PCa models and ex vivo human PCa tissues using NIR-II fluorescence imaging technology. Analyzing tissue samples from 60 clinical cases of PCa, along with benign prostatic hyperplasia and normal prostate tissue from 22 cases, we observed a significant difference in B7-H3 protein expression levels (P < 0.001). Subcutaneous and orthotopic mouse models of PCa were imaged using NIR-II fluorescence after AbB7-H3-800CW injection, showing promising results with successful tumor targeting and high-contrast images achieved within 24-48h post-injection. The imaging also enabled the detection of occult PCa lesions approximately 1mm in diameter. In addition, imaging analysis of human PCa and adjacent tissues using AbB7-H3-800CW incubation revealed that cancer tissues exhibited a significantly higher fluorescence intensity than adjacent tissues (P < 0.05), which was conducive to the evaluation of tumor resection margin in vitro. The findings revealed that B7-H3 was a compelling imaging target for PCa. The AbB7-H3-800CW molecular imaging probe is capable of accurately identifying PCa lesions and guiding their removal. This approach can potentially reduce the rate of surgical margins under NIR-II fluorescence guidance.

Fluorescence guidance using near-infrared fluorescent clips in robotic rectal surgery: a case series

PurposeTattoo markings are often used as preoperative markers for colorectal cancer. However, scattered ink markings adversely affect tumor site recognition intraoperatively; therefore, interventions for rectal cancer may lead to an inaccurate distal resection margin (DRM) and incomplete total mesorectal excision (TME). This is the first case series of fluorescence-guided robotic rectal surgery in which near-infrared fluorescence clips (NIRFCs) were used to localize rectal cancer lesions.MethodsWe enrolled 20 consecutive patients who underwent robotic surgery for rectal cancer between December 2022 and December 2023 in the current study. The primary endpoints were the rate of intraoperative clip detection and its usefulness for marking the tumor site. Secondary endpoints were oncological assessments, including DRM and the number of lymph nodes.ResultsClip locations were confirmed in 17 of 20 (85%) patients. NIRFCs were not detected in 3 out of 7 patients who underwent preoperative chemoradiation therapy. No adverse events, including bleeding or perforation, were observed at the time of clipping, and no clips were lost. The median DRM was 55 mm (range, 22–86 mm) for rectosigmoid (Rs), 33 mm (range, 16–60 mm) for upper rectum (Ra), and 20 mm (range, 17–30 mm) for low rectum (Rb). The median number of lymph nodes was 13 (range, 10–21).ConclusionThe rate of intraoperative clip detection, oncological assessment, including DRM, and the number of lymph nodes indicate that the utility of fluorescence-guided methods with NIRFCs is feasible for rectal cancer.

A rationally designed nuclei-targeting FAPI 04-based molecular probe with enhanced tumor uptake for PET/CT and fluorescence imaging.

Fibroblast activation protein inhibitor (FAPI) -based probes have been widely studied in the diagnosis of various malignant tumors with positron emission tomography/computed tomography (PET/CT). However, current imaging studies of FAPI-based probes face challenges in rapid clearance rate and potential false-negative results. Furthermore, FAPI has been rarely explored in optical imaging. Considering this, further modifications are imperative to improve the properties of FAPI-based probes to address existing limitations and broaden their application scenarios. In this study, we rationally introduced methylene blue (MB) to FAPIs, thereby imparting nuclei-targeting and fluorescence imaging capabilities to the probes. Furthermore, we evaluated the added value of FAPI-based fluorescence imaging to traditional PET/CT, exploring the potential application of FAPI-based probes in intraoperative fluorescence imaging. A new FAPI-based probe, namely NOTA-FAPI-MB, was designed for both PET/CT and fluorescence imaging by conjugation of MB. The targeting efficacy of the probe was evaluated on fibroblast activation protein (FAP)-transfected cell line and human primary cancer-associated fibroblasts (CAFs). Subsequently, PET/CT and fluorescence imaging were conducted on tumor-bearing mice. The tumor detection and boundary delineation were assessed by fluorescence imaging of tissues from hepatocellular carcinoma (HCC) patients. NOTA-FAPI-MB demonstrated exceptional targeting ability towards FAP-transfected cells and CAFs in comparison to NOTA-FAPI. This benefit arises from the cationic methylene blue (MB) affinity for anionic nucleic acids. PET/CT imaging of tumor-bearing mice revealed significantly higher tumor uptake of [18F]F-NOTA-FAPI-MB (standard uptake value of 2.20 ± 0.31) compared to [18F]F-FDG (standard uptake value of 1.66 ± 0.14). In vivo fluorescence imaging indicated prolonged retention at the tumor site, with retention lasting up to 24h. In addition, the fluorescent probes enabled more precise lesion detection and tumor margin delineation than clinically used indocyanine green (ICG), achieving a 100.0% (6/6) tumor-positive rate for NOTA-FAPI-MB while 33.3% (2/6) for ICG. These findings highlighted the potential of NOTA-FAPI-MB in guiding intraoperative surgical procedures. The NOTA-FAPI-MB was successfully synthesized, in which FAPI and MB simultaneously contributed to the targeting effect. Notably, the nuclear delivery mechanism of the probes improved intracellular retention time and targeting efficacy, broadening the imaging time window for fluorescence imaging. In vivo PET/CT demonstrated favorable performance of NOTA-FAPI-MB compared to [18F]F-FDG. This study highlights the significance of fluorescence imaging as an adjunct technique to PET/CT. Furthermore, the encouraging results obtained from the imaging of human HCC tissues hold promise for the potential application of NOTA-FAPI-MB in intraoperative fluorescent surgery guidance within clinical settings.

Awake magic: glioblastoma resection under 5-aminolevulinic acid guidance during awake craniotomy. A case report with video demonstration

An awake craniotomy's primary goal is to remove the tumor or damaged cells as much as possible without affecting the patient's capacity for clear thought or other crucial functions. This surgical procedure offers a better prognosis by balancing the maximum removal of lesions with the preservation of working zones. For patients with malignant gliomas, the current neurosurgical objective is for resection the large part of a tumor using contrast and not causing neurological deficits. Neurooncological patients are required to have further chemotherapy and radiotherapy, with a control MRI of the brain in 3 and 6 months. Real multidisciplinary work should be provided to improve each patient's quality of life and overall survival. This paper aims to report single case of successful awake craniotomy with fluorescence guidance and discuss the outcomes of the performed surgery.

Assessment of Laparoscopic Indocyanine Green Tracer-guided Lymphadenectomy After Neoadjuvant Chemotherapy for Locally Advanced Gastric Cancer: A Randomized Controlled Trial.

To assess the effectiveness of indocyanine green (ICG)-guided lymph node (LN) dissection during laparoscopic radical gastrectomy after neoadjuvant chemotherapy (NAC) in patients with locally advanced gastric cancer (LAGC). Studies on ICG imaging use in patients with LAGC on NAC are rare. Patients with gastric adenocarcinoma (clinical T2-4NanyM0) who received NAC were randomly assigned to receive ICG-guided laparoscopic radical gastrectomy or laparoscopic radical gastrectomy alone. Here, we reported the secondary endpoints including the quality of lymphadenectomy (total retrieved LNs and LN noncompliance) and surgical outcomes. Overall, 240 patients were randomized. Of whom, 236 patients were included in the primary analysis (118 in the ICG group and 118 in the non-ICG group). In the ICG group, the mean number of LNs retrieved was significantly higher than in the non-ICG group within the D2 dissection (48.2 vs 38.3, P < 0.001). The ICG fluorescence guidance significantly decreased the LN noncompliance rates (33.9% vs 55.1%, P = 0.001). In 165 patients without baseline measurable LNs, ICG significantly increased the number of retrieved LNs and decreased the LN noncompliance rate ( P < 0.05). For 71 patients with baseline measurable LNs, the quality of lymphadenectomy significantly improved in those who had a complete response ( P < 0.05) but not in those who did not ( P > 0.05). Surgical outcomes were comparable between the groups ( P > 0.05). ICG can effectively improve the quality of lymphadenectomy in patients with LAGC who underwent laparoscopic radical gastrectomy after NAC.

Single-Plane Retroperitoneoscopic Adrenalectomy Guided by Indocyanine Green Dye: An Optimized Step.

Background: The objective of this study was to explore the perioperative outcomes of single-plane posterior retroperitoneoscopic adrenalectomy (SPRA) guided by indocyanine green dye (ICG) fluorescence imaging. Methods: A retrospective analysis of patients who underwent SPRA from April to September 2023 in our center was conducted. Patients were divided into the ICG group and the non-ICG group, based on whether they received intraoperative ICG fluorescence guided or not. Baseline and perioperative data were recorded and analyzed by R software (R 4.3.1). Results: A total of 23 patients were enrolled in the study, with 12 in the ICG group and 11 in the non-ICG group. The demographics including age, gender, body mass index, or American Society of Anesthesiologists classification showed no significant differences between groups. There were obvious advantages in shortening adrenal gland localization time and total operative time, as well as reducing estimated blood loss in the ICG group compared with the non-ICG group (5.58 ± 0.36 minutes vs 7.55 ± 0.62 minutes, p < 0.001; 27.50 ± 5.46 minutes vs 45.00 ± 10.99 minutes, p < 0.001; 22.91 ± 7.57 mL vs 54.54 ± 18.90 mL, p < 0.001; respectively). Furthermore, patients in the ICG group exhibited significantly lower visual analog pain scale scores at 24 hours postoperatively and at discharge (p = 0.001 and p = 0.006, respectively). The oral intake intervals, hospital stays, and perioperative complications were comparable between groups. Conclusions: ICG-guided SPRA could be a safe and effective procedure for patients with adrenal tumors. This technique improves the accuracy and efficacy of adrenal gland localization and has shown benefits in perioperative outcomes. The use of ICG fluorescence guidance represents a promising clinical application.

Subsurface fluorescence time-of-flight imaging using a large-format single-photon avalanche diode sensor for tumor depth assessment.

Fluorescence guidance is used clinically by surgeons to visualize anatomical and/or physiological phenomena in the surgical field that are difficult or impossible to detect by the naked eye. Such phenomena include tissue perfusion or molecular phenotypic information about the disease being resected. Conventional fluorescence-guided surgery relies on long, microsecond scale laser pulses to excite fluorescent probes. However, this technique only provides two-dimensional information; crucial depth information, such as the location of malignancy below the tissue surface, is not provided. We developed a depth sensing imaging technique using light detection and ranging (LiDAR) time-of-flight (TOF) technology to sense the depth of target tissue while overcoming the influence of tissue optical properties and fluorescent probe concentration. The technology is based on a large-format (), binary, gated, single-photon avalanche diode (SPAD) sensor with an 18ps time-gate step, synchronized with a picosecond pulsed laser. The fast response of the sensor was developed and tested for its ability to quantify fluorescent inclusions at depth and optical properties in tissue-like phantoms through analytical model fitting of the fast temporal remission data. After calibration and algorithmic extraction of the data, the SPAD LiDAR technique allowed for sub-mm resolution depth sensing of fluorescent inclusions embedded in tissue-like phantoms, up to a maximum of 5mm in depth. The approach provides robust depth sensing even in the presence of variable tissue optical properties and separates the effects of fluorescence depth from absorption and scattering variations. LiDAR TOF fluorescence imaging using an SPAD camera provides both fluorescence intensity images and the temporal profile of fluorescence, which can be used to determine the depth at which the signal is emitted over a wide field of view. The proposed tool enables fluorescence imaging at a higher depth in tissue and with higher spatial precision than standard, steady-state fluorescence imaging tools, such as intensity-based near-infrared fluorescence imaging, optical coherence tomography, Raman spectroscopy, or confocal microscopy. Integration of this technique into a standard surgical tool could enable rapid, more accurate estimation of resection boundaries, thereby improving the surgeon's efficacy and efficiency, and ultimately improving patient outcomes.

Real-time fluorescence-guided adhesiolysis with indocyanine green in intra-abdominal surgery (with video)

Intra-abdominal adhesions have consistently posed a challenge for surgeons during procedures. This study aims to investigate the feasibility of utilizing indocyanine green (ICG) in conjunction with near-infrared imaging for the detection of intra-abdominal adhesions. In vitro, we analyzed factors affecting ICG fluorescence. We divided SD rats into groups to study ICG excretion in different digestive tract regions. Additionally, we reviewed surgical videos from previous cholecystectomy cases, categorizing them by ICG injection timing and assessing fluorescence imaging in various digestive tract regions. Finally, we preoperatively injected ICG into two cholecystectomized patients with abdominal adhesions, guiding intraoperative adhesiolysis with near-infrared fluorescence imaging. In vitro, we observed a significant influence of protein and ICG concentrations on ICG fluorescence intensity. Our rat experiments unveiled a strong and highly significant correlation (Kendall’s tau-b = 1, P < 0.001) between the timing of ICG injection and the farthest point of intestinal fluorescence. A retrospective case analysis further validated this finding (Kendall’s tau-b = 0.967, P < 0.001). Under the guidance of fluorescence navigation, two cholecystectomized patients with intra-abdominal adhesions successfully underwent adhesiolysis, and no postoperative complications occurred. The intraoperative combination of ICG with near-infrared fluorescence imaging effectively enhances the visibility of the liver, bile ducts, and various segments of the gastrointestinal tract while providing real-time navigation. This real-time fluorescence guidance has the potential to aid surgeons in the dissection of intra-abdominal adhesions.

Sodium-fluorescein-guided awake surgery for cerebral metastases located in eloquent brain areas: technical notes and preliminary experiences.

Awake craniotomy (AC) maximizes the resection of lesions in eloquent brain areas while preserving functionality. Tumor delineation with intraoperative use of sodium fluorescein (NaFl) facilitates total resection. When used with AC, it may allow for safe resection without increasing the risk of postoperative neurologic deficits. This study investigated the efficacy and safety of the combined use of NaFl and AC for maximum safe resection in patients with brain metastases. Patients who underwent AC due to brain metastasis in the Department of Neurosurgery of Uludağ University's Faculty of Medicine between January 1, 2018 and August 1, 2022, were retrospectively analyzed. The study comprised 2 patient groups: plain AC (pAC) and NaFl-guided AC (NaFlg-AC). Surgical outcomes related to fluorescence intensity, degree of resection, perioperative complications, and postoperative neurological factors were evaluated. The pAC group included 16 patients (12 males, 4 females), and the NaFlg-AC group comprised 21 (13 males, 7 females). The mean patient ages for males and females were 61.4 years (61.4 ± 9.5 years) and 60.4 years (60.6 ± 12 years), respectively. The most common origin of the metastatic lesion was the lung in both the pAC and NaFlg-AC groups (n = 12 vs. n = 14, respectively). Gross total resection (GTR) was achieved in 85.7% of the patients in the NaFlg-AC group, whereas the GTR rate was 68.7% in the pAC group. There was no significant difference in GTR rates between the 2 groups (p = 0.254). The mean duration of the resection time was significantly shorter in the NaFlg-AC group (45.95 ± 7.00 min vs. 57.5 ± 12.51 min; p = 0.002). The patients' Karnofsky Performance Status (KPS) score did not reach statistical significance at 6-month follow-up in either group compared to their preoperative baseline scores (p = 0.374). KPS did not show a significant difference between the 2 groups at any time. Fluorescence-guided resection in AC for metastatic tumors in sensory, motor, and cognitive areas is a feasible, safe, and convenient technique that significantly increases GTR rates and shortens operative time compared to conventional white light surgery without fluorescence guidance. It also does not increase the incidence of postoperative complications. With the combined use of AC and NaFl, ensuring clear and visible tumor margins during surgery and controlling patients' neurological function in real-time are possible.