Project description:Recently, fluorescence imaging following the preoperative intravenous injection of indocyanine green has been used in clinical settings to identify hepatic malignancies during surgery. The aim of this study was to evaluate the ability of photoacoustic tomography using indocyanine green as a contrast agent to produce representative fluorescence images of hepatic tumors by visualizing the spatial distribution of indocyanine green on ultrasonographic images. Indocyanine green (0.5 mg/kg, intravenous) was preoperatively administered to 9 patients undergoing hepatectomy. Intraoperatively, photoacoustic tomography was performed on the surface of the resected hepatic specimens (n = 10) under excitation with an 800 nm pulse laser. In 4 hepatocellular carcinoma nodules, photoacoustic imaging identified indocyanine green accumulation in the cancerous tissue. In contrast, in one hepatocellular carcinoma nodule and five adenocarcinoma foci (one intrahepatic cholangiocarcinoma and 4 colorectal liver metastases), photoacoustic imaging delineated indocyanine green accumulation not in the cancerous tissue but rather in the peri-cancerous hepatic parenchyma. Although photoacoustic tomography enabled to visualize spatial distribution of ICG on ultrasonographic images, which was consistent with fluorescence images on cut surfaces of the resected specimens, photoacoustic signals of ICG-containing tissues decreased approximately by 40% even at 4 mm depth from liver surfaces. Photoacoustic tomography using indocyanine green also failed to identify any hepatocellular carcinoma nodules from the body surface of model mice with non-alcoholic steatohepatitis. In conclusion, photoacoustic tomography has a potential to enhance cancer detectability and differential diagnosis by ultrasonographic examinations and intraoperative fluorescence imaging through visualization of stasis of bile-excreting imaging agents in and/or around hepatic tumors. However, further technical advances are needed to improve the visibility of photoacoustic signals emitted from deeply-located lesions.
Project description:Tumor-targeted fluorescent probes in the near-infrared spectrum can provide invaluable information about the location and extent of primary and metastatic tumors during intraoperative procedures to ensure no residual tumors are left in the patient's body. Even though the first fluorescence-guided surgery was performed more than 50 years ago, it is still not accepted as a standard of care in part due to the lack of efficient and non-toxic targeted probes approved by regulatory agencies around the world. Herein, we report protease-activated cationic gelatin nanoparticles encapsulating indocyanine green (ICG) for the detection of primary breast tumors in murine models with high tumor-to-background ratios. Upon intravenous administration, these nanoprobes remain optically silent due to the energy resonance transfer among the bound ICG molecules. As the nanoprobes extravasate and are exposed to the acidic tumor microenvironment, their positive surface charges increase, facilitating cellular uptake. The internalized nanoprobes are activated upon proteolytic degradation of gelatin to allow high contrast between the tumor and normal tissue. Since both gelatin and ICG are FDA-approved for intravenous administration, this activatable nanoprobe can lead to quick clinical adoption and improve the treatment of patients undergoing image-guided cancer surgery.
Project description:Soft tissue sarcomas (STS) are rare malignant tumors often associated with poor outcomes and high local recurrence rates. Current tools for intraoperative and definitive margin assessment include intraoperative frozen section and permanent pathology, respectively. Indocyanine green dye (ICG) is a historically safe fluorophore dye that has demonstrated efficacy for intraoperative margin assessment in the surgical management of both breast and gastrointestinal cancers. The utility of ICG in the surgical management of sarcoma surgery has primarily been studied in pre-clinical mouse models and warrants further investigation as a potential adjunct to achieving negative margins. This study is a prospective, non-randomized clinical study conducted on patients with confirmed or suspected STS. Patients younger than 18 years, with a prior adverse reaction to iodine or fluorescein, or with renal disease were excluded from the study. Intravenous ICG was infused approximately three hours prior to surgery at a dosage of 2.0-2.5 mg/kg, and following tumor resection, the excised tumor and tumor bed were imaged for fluorescence intensity. When scanning the tumor bed, a threshold of 77% calibrated to the region of maximum intensity in the resected tumor was defined as a positive ICG margin, according to published protocols from the breast cancer literature. ICG results were then compared with the surgeon's clinical impression of margin status and permanent pathology results. Out of 26 subjects recruited for the original study, 18 soft tissue sarcomas (STS) were included for analysis. Three subjects were excluded for having bone sarcomas, and five subjects were excluded due to final pathology, which was ultimately inconsistent with sarcoma. The average age of patients was 64.1 years old (range: 28-83), with an average ICG dose of 201.8 mg. In 56% (10/18) of patients, ICG margins were consistent with the permanent pathology margins, with 89% specificity. The use of ICG as an intraoperative adjunct to obtaining negative margins in soft tissue sarcoma surgery is promising. However, studies with larger sample sizes are warranted to further delineate the accuracy, optimal dosage, timing, and types of sarcoma in which this diagnostic tool may be most useful.
Project description:BackgroundThis study assessed the feasibility of near-infrared fluorescence imaging with indocyanine green (ICG) to identify the parathyroid glands (PGs) intraoperatively and to assess their perfusion after thyroid resection.MethodsPatients undergoing elective thyroidectomy were enrolled in this prospective study. An intravenous bolus of 7.5 mg ICG was administered twice: the first bolus to identify the PGs before resection of the thyroid and the second to assess vascularization of the PGs after resection.ResultsA total of 30 operations in 26 patients were included. In 17 surgeries (56.7%), fluorescence imaging was of added value, especially to confirm the presence of a suspected PG. No intraoperative or postoperative complications occurred because of the use of ICG.ConclusionNear-infrared fluorescence imaging with the use of ICG for intraoperative identification of the PGs and the assessment of its vascularization is feasible and safe and can provide more certainty about the location of the PGs.
Project description:BackgroundKidney transplantation is the most valuable renal replacement therapy. One of the most common urologic complications following kidney transplantation is ureter anastomosis leakage, which leads to high morbidity along with kidney graft loss. We hypothesized that indocyanine green (ICG) fluorescence videography can assess ureter perfusion after revascularization of transplanted kidneys.MethodsWe conducted a prospective cross-sectional study in end-stage renal disease patients who underwent deceased donor kidney transplantation at Ramathibodi Hospital from September 2019 to January 2020. The segments of transplanted ureters were categorized as having good or poor perfusion based on the percentage from ICG fluorescence videography images. Then the results from ICG fluorescence videography were compared with histopathology which is considered the gold standard.ResultsThirty-one sections of dissected ureters were evaluated from 10 patients. Compared with pathological diagnosis of ureteral ischemia, ICG videography had sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and positive likelihood ratio of 100%, 92.6%, 66.7%, 100%, and 14, respectively. Accuracy was 93.6%. The area under the curve of ICG fluorescence videography was 0.96. The average ureter length that maintained good perfusion was 14 cm from the ureteropelvic junction. Adverse events from ICG were not observed in this study.ConclusionsWe conclude that ICG fluorescence videography is beneficial for detection of early ureteral ischemia in kidney transplantation patients, with negligible adverse events. However, further studies with larger numbers of patients are necessary to confirm our results and clinical outcomes regarding complication rates.
Project description:BACKGROUND:Vascularized intranasal flaps are the primary reconstructive option for endoscopic skull base defects. Flap vascularity may be compromised by injury to the pedicle or prior endonasal surgery. There is currently no validated technique for intraoperative evaluation of intranasal flap viability. OBJECTIVE:To evaluate the efficacy of indocyanine green (ICG) near-infrared angiography in predicting the viability of pedicled intranasal flaps during endoscopic skull base surgery through a pilot study. METHODS:ICG near-infrared fluorescence endoscopy was performed during endoscopic endonasal surgery for skull base tumors. Intraoperative and postoperative data were collected regarding enhancement of the flap body and pedicle. Fluorescence was rated qualitatively. Postoperatively, flap perfusion was evaluated via MRI-contrast enhancement in addition to clinical outcomes (cerebrospinal fluid leak and endoscopic flap appearance). RESULTS:Thirty-eight patients underwent ICG fluorescence angiography. Both the body and pedicle enhanced in 20 patients (53%), while the pedicle only enhanced for 12 patients (32%), the body only for 3 (8%), and neither for 3 (8%). When both the pedicle and body enhanced with ICG, the rate of postoperative MRI contrast enhancement was 100% and the rate of flap necrosis was 0%. The sensitivity and specificity of flap pedicle ICG enhancement for predicting postoperative flap MRI enhancement were 97% and 67%, respectively. Two of 3 patients without enhancement developed flap necrosis. CONCLUSION:ICG fluorescence angiography of intraoperative flap perfusion is feasible and correlates well with outcomes of postoperative MRI flap enhancement and flap necrosis. Additional study is needed to further refine the imaging technique and optimally characterize the clinical utility.
Project description:Fluorescence imaging in the second near-infrared window (NIR-II) holds promise for real-time deep tissue imaging. In this work, we investigated the NIR-II fluorescence properties of a liposomal formulation of indocyanine green (ICG), a FDA-approved dye that was recently shown to exhibit NIR-II fluorescence. Fluorescence spectra of liposomal-ICG were collected in phosphate-buffered saline (PBS) and plasma. Imaging studies in an Intralipid® phantom were performed to determine penetration depth. In vivo imaging studies were performed to test real-time visualization of vascular structures in the hind limb and intracranial regions. Free ICG, NIR-I imaging, and cross-sectional imaging modalities (MRI and CT) were used as comparators. Fluorescence spectra demonstrated the strong NIR-II fluorescence of liposomal-ICG, similar to free ICG in plasma. In vitro studies demonstrated superior performance of liposomal-ICG over free ICG for NIR-II imaging of deep (≥4 mm) vascular mimicking structures. In vivo, NIR-II fluorescence imaging using liposomal-ICG resulted in significantly (p < 0.05) higher contrast-to-noise ratio compared to free ICG for extended periods of time, allowing visualization of hind limb and intracranial vasculature for up to 4 hours post-injection. In vivo comparisons demonstrated higher vessel conspicuity with liposomal-ICG-enhanced NIR-II imaging compared to NIR-I imaging.
Project description:The detection of all glands during total parathyroidectomy (TPTX) in secondary hyperparathyroidism (SHPT) patients is often difficult due to their variability in number and location. The objective of this study was to evaluate the feasibility of near-infrared fluorescence (NIRF) imaging using indocyanine green (ICG) for intraoperative parathyroid gland (PTG) localization in SHPT patients. Twenty-nine patients with SHPT were divided into two groups with or without intraoperative NIRF imaging. ICG was administered in patients undergoing intraoperative imaging, and the fluorescence of PTGs was assessed. Clinical and histopathologic variables were analyzed to determine factors associated with ICG uptake. Comparisons between NIRF and preoperative imaging, as well as differences between groups with or without NIRF imaging, were carried out to evaluate the efficacy of this technique. Most PTGs could be clearly identified, including one ectopic gland. The sensitivity of NIRF imaging is 91.1% in contrast to 81.82% for ultrasonography (US), 62.34% for 99mTc-MIBI and 85.71% for computed tomography (CT). In addition, intraoperative NIRF imaging can reduce the operation time and improve the complete resection rate compared with the group not using it. Intraoperative NIRF imaging using ICG during TPTX is technically feasible and reliable for assisting surgeons in detecting and confirming PTGs.
Project description: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. 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. 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. 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.
Project description:Background and objectiveAs a surgical tool, indocyanine green (ICG) is increasingly used in surgery, especially in gastric and colorectal surgery. The use of ICG fluorescence imaging can improve the accuracy of tumor resection and potentially improve surgical outcomes for cancer patients. However, there are still different opinions or controversies on the application of ICG in the literature and the administration of ICG is still not uniform. In this review, we summarize the current status of its application and ICG administration methods in gastrointestinal cancer and discuss its existing limitations and future research directions.MethodsLiterature published in the PubMed database from 1969 to 2022 was searched for using the keywords "Indocyanine green or near-infrared imaging or ICG", "gastric cancer", "gastroesophageal junction cancer", and "colorectal cancer" to summarize the main applications of ICG in gastrointestinal cancers.Key content and findingsICG guidance can rapidly determine tumor location and save operative time, and can also visualize lymph nodes (LNs) in real-time, helping surgeons to retrieve more LNs for better postoperative staging, but its use in identifying sentinel lymph node (SLN) in gastric cancer (GC) remains controversial due to false negatives. ICG fluorescent angiography has great potential in preventing colorectal anastomotic leakage, but there is a dearth of high-caliber research evidence. In addition, ICG has unique advantages in detecting colorectal liver micrometastasis. Notably, there is still no uniform administration method and dose of ICG.ConclusionsIn this review, we summarize the current status of ICG application in gastrointestinal cancer, and the current literature suggests that it is safe and effective and has the potential to change the clinical outcome of patients. Therefore, ICG should be routinely used in gastrointestinal cancers to improve the surgical outcomes of patients. In addition, this review summarizes the ICG administration in the literature, and we expect future guidelines to unitize and standardize the administration of ICG.