Green light for liver function monitoring using indocyanine green? An overview of current clinical applications.

PubMed

Vos, J J; Wietasch, J K G; Absalom, A R; Hendriks, H G D; Scheeren, T W L

2014-12-01

The dye indocyanine green is familiar to anaesthetists, and has been studied for more than half a century for cardiovascular and hepatic function monitoring. It is still, however, not yet in routine clinical use in anaesthesia and critical care, at least in Europe. This review is intended to provide a critical analysis of the available evidence concerning the indications for clinical measurement of indocyanine green elimination as a diagnostic and prognostic tool in two areas: its role in peri-operative liver function monitoring during major hepatic resection and liver transplantation; and its role in critically ill patients on the intensive care unit, where it is used for prediction of mortality, and for assessment of the severity of acute liver failure or that of intra-abdominal hypertension. Although numerous studies have demonstrated that indocyanine green elimination measurements in these patient populations can provide diagnostic or prognostic information to the clinician, 'hard' evidence - i.e. high-quality prospective randomised controlled trials - is lacking, and therefore it is not yet time to give a green light for use of indocyanine green in routine clinical practice. © 2014 The Association of Anaesthetists of Great Britain and Ireland.

A pilot study of lymph node mapping with indocyanine green in robotic gastrectomy for gastric cancer.

PubMed

Lan, Yuan-Tzu; Huang, Kuo-Hung; Chen, Ping-Hsien; Liu, Chien-An; Lo, Su-Shun; Wu, Chew-Wun; Shyr, Yi-Ming; Fang, Wen-Liang

2017-01-01

Robotic gastrectomy has become increasingly popular in the treatment of gastric cancer, especially in Asian countries. The use of indocyanine green fluorescence has been reported in lymphatic mapping for gastric cancer in laparoscopic gastrectomy; however, there have been few reports regarding the use of indocyanine green in robotic gastrectomy. From January 2011 to March 2016, a total of 79 patients underwent robotic gastrectomy for gastric cancer. Among them, intraoperative subserosal injection (n = 9) or preoperative submucosal injection (n = 5) of indocyanine green with near-infrared imaging was performed in 14 patients, and the other 65 patients underwent robotic gastrectomy without the use of indocyanine green. There was no significant difference in the operative time, total number of retrieved lymph nodes, operative blood loss, and postoperative hospital stay between the patients who underwent robotic gastrectomy with or without indocyanine green fluorescence. For each lymph node station, there was significantly more number of retrieved lymph nodes in the indocyanine green group than in the no-indocyanine green group at the greater curvature side of the low body (#4d) to the infrapyloric region (#6) of the stomach. Five of the 14 patients who received an indocyanine green injection for lymphatic mapping had lymph node metastasis, and metastatic lymph nodes were located in the lymph node stations as detected by indocyanine green fluorescence during surgery. Indocyanine green fluorescence with near-infrared imaging is feasible and is a promising method of lymphatic mapping in robotic gastrectomy for gastric cancer. In future studies, larger patient numbers and long-term follow-up are required.

Sentinel lymph node biopsy under fluorescent indocyanin green guidance: Initial experience

PubMed Central

Aydoğan, Fatih; Arıkan, Akif Enes; Aytaç, Erman; Velidedeoğlu, Mehmet; Yılmaz, Mehmet Halit; Sager, Muhammet Sait; Çelik, Varol; Uras, Cihan

2016-01-01

Objective: Sentinel lymph node biopsy can be applied by using either blue dye or radionuclide method or both in breast cancer. Fluorescent imaging with indocyanine green is a new defined method. This study evaluates the applicability of sentinel lymph node biopsy via fluorescent indocyanine green. Material and Methods: IC-VIEW (Pulsion Medical Systems AG, Munich, Germany) infrared visualization system was used for imaging. Two mL of indocyanine green was injected to visualize sentinel lymph nodes. After injection, subcutaneous lymphatics were traced and sentinel lymph nodes were found with simultaneous imaging. Sentinel lymph nodes were excised under fluorescent light guidance, and excised lymph nodes were examined histopathologically. Patients with sentinel lymph node metastases underwent axillary dissection. Results: Four patients with sentinel lymph node biopsy due to breast cancer were included in the study. Sentinel lymph nodes were visualized with indocyanine green in all patients. The median number of excised sentinel lymph node was 2 (2–3). Two patients with lymph node metastasis underwent axillary dissection. No metastasis was detected in lymph nodes other than the sentinel nodes in patients with axillary dissection. There was no complication during and after the operation related to the method. Conclusion: According to our limited experience, sentinel lymph node biopsy under fluorescent indocyanine green guidance, which has an advantage of simultaneous visualization, is technically feasible. PMID:26985159

Indocyanine Green Fluorescence Navigation Thoracoscopic Metastasectomy for Pulmonary Metastasis of Hepatocellular Carcinoma.

PubMed

Kawakita, Naoya; Takizawa, Hiromitsu; Kondo, Kazuya; Sakiyama, Shoji; Tangoku, Akira

2016-12-20

Indocyanine green can selectively accumulate in primary hepatocellular carcinoma (HCC) and extrahepatic metastases. We report a patient who underwent resection of pulmonary metastasis of HCC using a thoracoscopic near-infrared imaging system and fluorescent navigation surgery. A 66-year-old man with suspicion of pulmonary metastasis of HCC was referred to our hospital. Indocyanine green was injected intravenously at a dose of 0.5 mg/kg body weight, 20 h before thoracoscopic surgery. An endoscopic indocyanine green near-infrared fluorescence imaging system showed clear blue fluorescence, indicating pulmonary metastasis of HCC in a lingular segment. We performed wide wedge resection using the fluorescence image for navigation to confirm the surgical margins. The specimen was histologically confirmed as a pulmonary metastasis of HCC. In conclusion, thoracoscopic indocyanine green near-infrared fluorescence imaging for pulmonary metastases of HCC is useful in identifying tumor locations and ensuring resection margins.

Indocyanine green SPY elite-assisted sentinel lymph node biopsy in cutaneous melanoma.

PubMed

Korn, Jason M; Tellez-Diaz, Alejandra; Bartz-Kurycki, Marisa; Gastman, Brian

2014-04-01

Sentinel lymph node biopsy is the standard of care for intermediate-depth and high-risk thin melanomas. Recently, indocyanine green and near-infrared imaging have been used to aid in sentinel node biopsy. The present study aimed to determine the feasibility of sentinel lymph node biopsy with indocyanine green SPY Elite navigation and to critically evaluate the technique compared with the standard modalities. A retrospective review of 90 consecutive cutaneous melanoma patients who underwent sentinel lymph node biopsy was performed. Two cohorts were formed: group A, which had sentinel lymph node biopsy performed with blue dye and radioisotope; and group B, which had sentinel lymph node biopsy performed with radioisotope and indocyanine green SPY Elite navigation. The cohorts were compared to assess for differences in localization rates, sensitivity and specificity of sentinel node identification, and length of surgery. The sentinel lymph node localization rate was 79.4 percent using the blue dye method, 98.0 percent using the indocyanine green fluorescence method, and 97.8 percent using the radioisotope/handheld gamma probe method. Indocyanine green fluorescence detected more sentinel lymph nodes than the vital dye method alone (p = 0.020). A trend toward a reduction in length of surgery was noted in the SPY Elite cohort. Sentinel lymph node mapping and localization in cutaneous melanoma with the indocyanine green SPY Elite navigation system is technically feasible and may offer several advantages over current modalities, including higher sensitivity and specificity, decreased number of lymph nodes sampled, decreased operative time, and potentially lower false-negative rates. Diagnostic, II.

Dose-dependent photochemical/photothermal toxicity of indocyanine green-based therapy on three different cancer cell lines.

PubMed

Ruhi, Mustafa Kemal; Ak, Ayşe; Gülsoy, Murat

2018-03-01

The Food and Drug Administration-approved Indocyanine Green can be used as a photosensitizer to kill cancer cells selectively. Although indocyanine green is advantageous as a photosensitizer in terms of strong absorption in the near-infrared region, indocyanine green-based cancer treatment is still not approved as a clinical method. Some reasons for this are aggregation at high concentrations, rapid clearance of the photosensitizer from the body, low singlet oxygen quantum yield, and the uncertainty concerning its action mechanism. This in vitro study focuses on two of these points: "what is the cell inhibition mechanism of indocyanine green-based therapy?" and "how the dose-dependent aggregation problem of indocyanine green alters its cell inhibition efficiency?" The following experiments were conducted to provide insight into these points. Nontoxic doses of indocyanine green and near-infrared laser were determined. The aggregation behavior of indocyanine green was verified through experiments. The singlet oxygen quantum yield of indocyanine green at different concentrations were calculated. Various indocyanine green and energy densities of near-infrared light were applied to prostate cancer, neuroblastoma, and colon cancer cells. An MTT assay was performed at the end of the first, second, and third days following the treatments to determine the cell viability. Temperature changes in the medium during laser exposure were recorded. ROS generation following the treatment was verified by using a Total Reactive Oxygen Species detection kit. An apoptosis detection test was performed to establish the cell death mechanism and, finally, the cellular uptakes of the three different cells were measured. According to the results, indocyanine green-based therapy causes cell viability decrease for three cancer cell lines by means of excessive reactive oxygen species production. Different cells have different sensitivities to the therapy possibly because of the differentiation

Optimal back-extrapolation method for estimating plasma volume in humans using the indocyanine green dilution method.

PubMed

Polidori, David; Rowley, Clarence

2014-07-22

The indocyanine green dilution method is one of the methods available to estimate plasma volume, although some researchers have questioned the accuracy of this method. We developed a new, physiologically based mathematical model of indocyanine green kinetics that more accurately represents indocyanine green kinetics during the first few minutes postinjection than what is assumed when using the traditional mono-exponential back-extrapolation method. The mathematical model is used to develop an optimal back-extrapolation method for estimating plasma volume based on simulated indocyanine green kinetics obtained from the physiological model. Results from a clinical study using the indocyanine green dilution method in 36 subjects with type 2 diabetes indicate that the estimated plasma volumes are considerably lower when using the traditional back-extrapolation method than when using the proposed back-extrapolation method (mean (standard deviation) plasma volume = 26.8 (5.4) mL/kg for the traditional method vs 35.1 (7.0) mL/kg for the proposed method). The results obtained using the proposed method are more consistent with previously reported plasma volume values. Based on the more physiological representation of indocyanine green kinetics and greater consistency with previously reported plasma volume values, the new back-extrapolation method is proposed for use when estimating plasma volume using the indocyanine green dilution method.

Novel Indocyanine Green-Phytate Colloid Technique for Sentinel Node Detection in Head and Neck: Mouse Study.

PubMed

Araki, Koji; Mizokami, Daisuke; Tomifuji, Masayuki; Yamashita, Taku; Ohnuki, Kazunobu; Umeda, Izumi O; Fujii, Hirofumi; Kosuda, Shigeru; Shiotani, Akihiro

2014-08-01

Sentinel node navigation surgery using real-time, near-infrared imaging with indocyanine green is becoming popular by allowing head and neck surgeons to avoid unnecessary neck dissection. The major drawback of this method is its quick migration through the lymphatics, limiting the diagnostic time window and undesirable detection of downstream nodes. We resolved this problem by mixing indocyanine green (ICG) with phytate colloid to retard its migration and demonstrated its feasibility in a nude mouse study. Experimental prospective animal study. Animal laboratory. Indocyanine green at 3 concentrations was tested to determine the optimal concentration for sentinel lymph node detection in a mouse model. Effect of indocyanine green with phytate colloid mixture solutions was also analyzed. Indocyanine green or mixture solution at different mixing ratios were injected into the tongue of nude mice and near-infrared fluorescence images were captured sequentially for up to 48 hours. The brightness of fluorescence in the sentinel lymph node and lymph nodes further downstream were assessed. Indocyanine green concentration >50 μg/mL did not improve sentinel lymph node detection. The addition of phytate colloid to indocyanine green extended the period when sentinel lymph node was detectable. Second echelon lymph nodes were not imaged in mice injected with the mixture, while these were visualized in mice injected with indocyanine green alone. This novel technique of ICG-phytate colloid mixture allows prolonged diagnostic time window, prevention of downstream subsequent nodes detection, and improved accuracy for the detection of true sentinel lymph nodes. © American Academy of Otolaryngology—Head and Neck Surgery Foundation 2014.

Optimal back-extrapolation method for estimating plasma volume in humans using the indocyanine green dilution method

PubMed Central

2014-01-01

Background The indocyanine green dilution method is one of the methods available to estimate plasma volume, although some researchers have questioned the accuracy of this method. Methods We developed a new, physiologically based mathematical model of indocyanine green kinetics that more accurately represents indocyanine green kinetics during the first few minutes postinjection than what is assumed when using the traditional mono-exponential back-extrapolation method. The mathematical model is used to develop an optimal back-extrapolation method for estimating plasma volume based on simulated indocyanine green kinetics obtained from the physiological model. Results Results from a clinical study using the indocyanine green dilution method in 36 subjects with type 2 diabetes indicate that the estimated plasma volumes are considerably lower when using the traditional back-extrapolation method than when using the proposed back-extrapolation method (mean (standard deviation) plasma volume = 26.8 (5.4) mL/kg for the traditional method vs 35.1 (7.0) mL/kg for the proposed method). The results obtained using the proposed method are more consistent with previously reported plasma volume values. Conclusions Based on the more physiological representation of indocyanine green kinetics and greater consistency with previously reported plasma volume values, the new back-extrapolation method is proposed for use when estimating plasma volume using the indocyanine green dilution method. PMID:25052018

Indocyanine green-loaded hollow mesoporous silica nanoparticles as an activatable theranostic agent

NASA Astrophysics Data System (ADS)

Hong, Suk ho; Kim, Hyunjin; Choi, Yongdoo

2017-05-01

Here we report indocyanine green (ICG)-loaded hollow mesoporous silica nanoparticles (ICG@HMSNP) as an activatable theranostic platform. Near-infrared fluorescence and singlet oxygen generation of ICG@HMSNP was effectively quenched (i.e. turned off) in its native state because of the fluorescence resonance energy transfer between ICG molecules. Therefore, ICG@HMSNP was nonfluorescent and nonphototoxic in the extracellular region. After the nanoparticles entered the cancer cells via endocytosis, they became highly fluorescent and phototoxic. In addition, intracellular uptake of ICG@HMSNP was 2.75 times higher than that of free ICG, resulting in an enhanced phototherapy of cancer.

Visualisation of the distributions of melanin and indocyanine green in biological tissues

DOE Office of Scientific and Technical Information (OSTI.GOV)

Genina, E A; Fedosov, I V; Bashkatov, A N

2008-03-31

A double-wavelength laser scanning microphotometer with the high spectral and spatial resolutions is developed for studying the distribution of endogenic and exogenic dyes in biological tissues. Samples of hair and skin biopsy with hair follicles stained with indocyanine green are studied. The spatial distribution of indocyanine green and melanin in the biological tissue is determined from the measured optical transmittance. (laser biology)

Gastric Tube Reconstruction with Superdrainage Using Indocyanine Green Fluorescence During Esophagectomy

PubMed Central

KITAGAWA, HIROYUKI; NAMIKAWA, TSUTOMU; IWABU, JUN; HANAZAKI, KAZUHIRO

2017-01-01

We report a case of gastric tube reconstruction with superdrainage using indocyanine green fluorescence during esophagectomy for esophageal cancer. A 53-year-old man with a history of early esophageal cancer treated with endoscopic mucosal dissection experienced esophageal cancer recurrence. There was no evidence of lymph node involvement or distant metastasis on computed tomography; therefore, we performed thoracoscopic esophagectomy. After thoracoscopic esophagectomy, we created a gastric tube. When pulling up the gastric tube through the post-mediastinum route, a root of the right gastroepiploic vein was injured. We subsequently performed superdrainage to avoid congestion of the gastric tube with omental vein and pre-tracheal vein anastomosis at the neck, and confirmed venous flow using the indocyanine green fluorescence method. No postoperative anastomotic leakage was observed, and the patient was discharged 22 days after surgery. Thus, we recommend the indocyanine green fluorescence method in cases involving superdrainage during esophagectomy. PMID:28882975

Lethal photosensitization of wound-associated microbes using indocyanine green and near-infrared light.

PubMed

Omar, Ghada S; Wilson, Michael; Nair, Sean P

2008-07-01

The increase in resistance to antibiotics among disease-causing bacteria necessitates the development of alternative antimicrobial approaches such as the use of light-activated antimicrobial agents (LAAAs). Light of an appropriate wavelength activates the LAAA to produce cytotoxic species which can then cause bacterial cell death via loss of membrane integrity, lipid peroxidation, the inactivation of essential enzymes, and/or exertion of mutagenic effects due to DNA modification. In this study, the effect of the LAAA indocyanine green excited with high or low intensity light (808 nm) from a near-infrared laser (NIR) on the viability of Staphylococcus aureus, Streptococcus pyogenes and Pseudomonas aeruginosa was investigated. All species were susceptible to killing by the LAAA, the bactericidal effect being dependent on both the concentration of indocyanine green and the light dose. Indocyanine green photosensitization using both high (1.37 W cm(-2)) and low (0.048 W cm(-2)) intensity NIR laser light was able to achieve reductions of 5.6 log10 (>99.99%) and 6.8 log10 (>99.99%) in the viable counts of Staph. aureus and Strep. pyogenes (using starting concentrations of 106-107 CFU ml(-1)). Kills of 99.99% were obtained for P. aeruginosa (initial concentration 108-109 CFU ml(-1)) photosensitized by the high intensity light (1.37 W cm(-2)); while a kill of 80% was achieved using low intensity irradiation (0.07 W cm(-2)). The effects of L-tryptophan (a singlet oxygen scavenger) and deuterium oxide (as an enhancer of the life span of singlet oxygen) on the survival of Staph. aureus was also studied. L-tryptophan reduced the proportion of Staph. aureus killed; whereas deuterium oxide increased the proportion killed suggesting that singlet oxygen was involved in the killing of the bacteria. These findings imply that indocyanine green in combination with light from a near-infrared laser may be an effective means of eradicating bacteria from wounds and burns.

Intravenous injection of indocyanine green results in an artificial transient desaturation by pulse oximetry.

PubMed

Ediriwickrema, Lilangi S; Francis, Jasmine H; Arslan-Carlon, Vittoria; Dalecki, Paul H; Brodie, Scott E; Marr, Brian P; Abramson, David H

2015-01-01

To describe a case series of transient oxygen desaturation measured by pulse oximetry during the intravenous infusion of indocyanine green to enhance transpupillary thermotherapy in treating retinoblastoma after ophthalmic artery chemosurgery. Retrospective descriptive case series. The intravenous administration of indocyanine green for ophthalmic angiography resulted in a transient drop in oxygen saturation as measured by Nellcor fingertip pulse oximetry in three children with retinoblastoma receiving indocyanine green-guided transpupillary thermotherapy. The magnitude of reduction ranged from 92% to 94% from an initial reading of 99% to 100% in each case, with an average duration of 3 minutes. Concurrent measurement of blood pressure, pulse, and expired CO2 showed no changes during this process. Administration of intravenous indocyanine green resulted in a transient desaturation by oximetry during transpupillary thermotherapy for children with retinoblastoma under anesthesia because of the fluorescent dye's absorption of red light in a manner similar to that of deoxygenated hemoglobin, thereby leading to transient instrument misinterpretation and miscalculation of arterial oxygenation.

Gastric Tube Reconstruction with Superdrainage Using Indocyanine Green Fluorescence During Esophagectomy.

PubMed

Kitagawa, Hiroyuki; Namikawa, Tsutomu; Iwabu, Jun; Hanazaki, Kazuhiro

2017-01-01

We report a case of gastric tube reconstruction with superdrainage using indocyanine green fluorescence during esophagectomy for esophageal cancer. A 53-year-old man with a history of early esophageal cancer treated with endoscopic mucosal dissection experienced esophageal cancer recurrence. There was no evidence of lymph node involvement or distant metastasis on computed tomography; therefore, we performed thoracoscopic esophagectomy. After thoracoscopic esophagectomy, we created a gastric tube. When pulling up the gastric tube through the post-mediastinum route, a root of the right gastroepiploic vein was injured. We subsequently performed superdrainage to avoid congestion of the gastric tube with omental vein and pre-tracheal vein anastomosis at the neck, and confirmed venous flow using the indocyanine green fluorescence method. No postoperative anastomotic leakage was observed, and the patient was discharged 22 days after surgery. Thus, we recommend the indocyanine green fluorescence method in cases involving superdrainage during esophagectomy. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

In vivo visualization and ex vivo quantification of experimental myocardial infarction by indocyanine green fluorescence imaging

PubMed Central

Sonin, Dmitry; Papayan, Garry; Pochkaeva, Evgeniia; Chefu, Svetlana; Minasian, Sarkis; Kurapeev, Dmitry; Vaage, Jarle; Petrishchev, Nickolay; Galagudza, Michael

2016-01-01

The fluorophore indocyanine green accumulates in areas of ischemia-reperfusion injury due to an increase in vascular permeability and extravasation of the dye. The aim of the study was to validate an indocyanine green-based technique of in vivo visualization of myocardial infarction. A further aim was to quantify infarct size ex vivo and compare this technique with the standard triphenyltetrazolium chloride staining. Wistar rats were subjected to regional myocardial ischemia (30 minutes) followed by reperfusion (n = 7). Indocyanine green (0.25 mg/mL in 1 mL of normal saline) was infused intravenously for 10 minutes starting from the 25th minute of ischemia. Video registration in the near-infrared fluorescence was performed. Epicardial fluorescence of indocyanine green corresponded to the injured area after 30 minutes of reperfusion. Infarct size was similar when determined ex vivo using traditional triphenyltetrazolium chloride assay and indocyanine green fluorescent labeling. Intravital visualization of irreversible injury can be done directly by fluorescence on the surface of the heart. This technique may also be an alternative for ex vivo measurements of infarct size. PMID:28101408

In vivo visualization and ex vivo quantification of experimental myocardial infarction by indocyanine green fluorescence imaging.

PubMed

Sonin, Dmitry; Papayan, Garry; Pochkaeva, Evgeniia; Chefu, Svetlana; Minasian, Sarkis; Kurapeev, Dmitry; Vaage, Jarle; Petrishchev, Nickolay; Galagudza, Michael

2017-01-01

The fluorophore indocyanine green accumulates in areas of ischemia-reperfusion injury due to an increase in vascular permeability and extravasation of the dye. The aim of the study was to validate an indocyanine green-based technique of in vivo visualization of myocardial infarction. A further aim was to quantify infarct size ex vivo and compare this technique with the standard triphenyltetrazolium chloride staining. Wistar rats were subjected to regional myocardial ischemia (30 minutes) followed by reperfusion (n = 7). Indocyanine green (0.25 mg/mL in 1 mL of normal saline) was infused intravenously for 10 minutes starting from the 25th minute of ischemia. Video registration in the near-infrared fluorescence was performed. Epicardial fluorescence of indocyanine green corresponded to the injured area after 30 minutes of reperfusion. Infarct size was similar when determined ex vivo using traditional triphenyltetrazolium chloride assay and indocyanine green fluorescent labeling. Intravital visualization of irreversible injury can be done directly by fluorescence on the surface of the heart. This technique may also be an alternative for ex vivo measurements of infarct size.

Application of a biodegradable macromolecular contrast agent in dynamic contrast enhanced MRI for assessing the efficacy of indocyanine green enhanced photothermal cancer therapy

PubMed Central

Feng, Yi; Emerson, Lyska; Jeong, Eun-Kee; Parker, Dennis L.; Lu, Zheng-Rong

2009-01-01

Purpose To investigate the effectiveness of a polydisulfide-based biodegradable macromolecular contrast agent, (Gd-DTPA)-cystamine copolymers (GDCC), in assessing the efficacy of indocyanine green enhanced photothermal cancer therapy using dynamic contrast enhanced MRI (DCE-MRI). Materials and Methods Breast cancer xenografts in mice were injected with indocyanine green and irradiated with laser. The efficacy was assessed using DCE-MRI with GDCC of 40 KDa (GDCC-40) at 4 hours and 7 days after the treatment. The uptake of GDCC-40 by the tumors was fit to a two-compartment model to obtain tumor vascular parameters, including fractional plasma volume (fPV), endothelium transfer coefficient (KPS), and permeability surface area product (PS). Results GDCC-40 resulted in similar tumor vascular parameters at three doses with larger standard deviations at lower doses. The values of fPV, KPS and PS of the treated tumors were smaller (p < 0.05) than those of untreated tumors at 4 hours after the treatment and recovered to pretreatment values (p > 0.05) at 7 days after the treatment. Conclusion DCE-MRI with GDCC-40 is effective for assessing tumor early response to dye-enhanced photothermal therapy and detecting tumor relapse after the treatment. GDCC-40 has a potential to non-invasively monitor anticancer therapies with DCE-MRI. PMID:19629979

BIRDSHOT CHORIORETINITIS LESIONS ON INDOCYANINE GREEN ANGIOGRAPHY AS AN INDICATOR OF DISEASE ACTIVITY.

PubMed

Cao, Jennifer H; Silpa-Archa, Sukhum; Freitas-Neto, Clovis A; Foster, C Stephen

2016-09-01

To determine whether classical indocyanine green angiography lesions in patients with birdshot chorioretinitis can be used to monitor disease activity. A retrospective case series was performed on 26 eyes in 26 consecutive patients with birdshot chorioretinitis who had at least one indocyanine green angiography performed during disease activity and another during disease quiescence. Using Photoshop, the mean number, area, and area per spot on indocyanine green angiography were compared between disease activity and quiescence using a paired ratio test. The mean total lesion number, area, and area per spot during disease activity were 75.27 spots, 24,525 pixels, and 364 pixels/spots, respectively. The mean total lesion number, area, and area per spot size during disease quiescence were 28.35 spots (P < 0.01), 7,411 pixels (P < 0.01), and 279 pixels/spot (P = 0.12), respectively. There was a statistically significant decrease in the mean total area and number of lesions between the time of disease activity and disease quiescence (P < 0.01). Our results suggest that indocyanine green angiography has a role not only in diagnosis but also in monitoring treatment effectiveness; lesions can be reversible with treatment and their reappearance may be an indicator of disease relapse.

LASER BIOLOGY: Visualisation of the distributions of melanin and indocyanine green in biological tissues

NASA Astrophysics Data System (ADS)

Genina, E. A.; Fedosov, I. V.; Bashkatov, A. N.; Zimnyakov, D. A.; Altshuler, G. B.; Tuchin, V. V.

2008-03-01

A double-wavelength laser scanning microphotometer with the high spectral and spatial resolutions is developed for studying the distribution of endogenic and exogenic dyes in biological tissues. Samples of hair and skin biopsy with hair follicles stained with indocyanine green are studied. The spatial distribution of indocyanine green and melanin in the biological tissue is determined from the measured optical transmittance.

Comparative study of the bactericidal effects of indocyanine green- and methyl aminolevulinate-based photodynamic therapy on Propionibacterium acnes as a new treatment for acne.

PubMed

Choi, Seung-Hwan; Seo, Jeong-Wan; Kim, Ki-Ho

2018-05-03

Acne vulgaris is one of the most common dermatological problems, and its therapeutic options include topical and systemic retinoids and antibiotics. However, increase in problems associated with acne treatment, such as side-effects from conventional agents and bacterial resistance to antibiotics, has led to greater use of photodynamic therapy. The purpose of this study was to compare the bactericidal effects of indocyanine green- and methyl aminolevulinate-based photodynamic therapy on Propionibacterium acnes. P. acnes were cultured under anaerobic conditions; then they were divided into three groups (control, treated with indocyanine green and treated with methyl aminolevulinate) and illuminated with different lights (630-nm light-emitting diode, 805-nm diode laser and 830-nm light-emitting diode). The bactericidal effects were evaluated by comparing each group's colony-forming units. The cultured P. acnes were killed with an 805-nm diode laser and 830-nm light-emitting diode in the indocyanine green group. No bactericidal effects of methyl aminolevulinate-based photodynamic therapy were identified. The clinical efficacy of indocyanine green-based photodynamic therapy in 21 patients was retrospectively analyzed. The Korean Acne Grading System was used to evaluate treatment efficacy, which was significantly decreased after treatment. The difference in the efficacy of the 805-nm diode laser and 830-nm light-emitting diode was not statistically significant. Although the methyl aminolevulinate-based photodynamic therapy showed no bactericidal effect, the indocyanine green-based photodynamic therapy has bactericidal effect and clinical efficacy. © 2018 Japanese Dermatological Association.

Phototoxic effect of conjugates of plasmon-resonance nanoparticles with indocyanine green dye on Staphylococcus aureus induced by IR laser radiation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tuchina, E S; Tuchin, Valerii V; Khlebtsov, B N

2011-04-30

The effect of IR laser radiation ({lambda} = 805 - 808 nm) on the bacteria of the strain Staphylococcus aureus 209 P, incubated in indocyanine green solutions, is studied, as well as that of colloid gold nanoshells, nanocages and their conjugates with indocyanine green. It is found that the S. aureus 209 P cells are equally subjected to the IR laser radiation ({lambda} = 805 nm) after preliminary sensitisation with indocyanine green and gold nanoparticles separately and with conjugates of nanoparticles and indocyanine green. The enhancement of photodynamic and photothermal effects by 5 % is observed after 30 min ofmore » laser illumination ({lambda} = 808 nm) of bacteria, treated with conjugates of indocyanine green and nanocages. (optical technologies in biophysics and medicine)« less

Uptake of indocyanine green by hamster sebaceous glands

NASA Astrophysics Data System (ADS)

McMillan, Kathleen; Lo, Kai-Ming; Wang, Zhi

2001-05-01

Photothermal injury to the sebaceous glands is a potential curative treatment for the common skin disease acne vulgaris. Accumulation of the exogenous chromophore indocyanine green in the sebaceous glands may be accomplished using an emulsion or liposomal formulation applied to the skin surface. An emulsion containing 0.09% by weight indocyanine green (ICG) was applied to the epidermis of hamster ears ex vivo and the flank organ in vivo. Fluorescence microscopy demonstrated selective accumulation of ICG in the underlying sebaceous glands. The concentration of ICG that may be expected to accumulate in sebaceous glands of humans was then estimated on the basis of the gland size and orifice area, for the case of topical application of a more concentrated 1% ICG liposomal formulation. Monte Carlo modeling and heat transfer calculations showed that the sebaceous glands containing the exogenous chromophore may be selectively damaged by pulsed 810 nm laser radiation in conjunction with cryogen spray cooling.

Indocyanine green laser angiography improves deep inferior epigastric perforator flap outcomes following abdominal suction lipectomy.

PubMed

Casey, William J; Connolly, Katharine A; Nanda, Alisha; Rebecca, Alanna M; Perdikis, Galen; Smith, Anthony A

2015-03-01

The reliability of deep inferior epigastric artery perforator (DIEP) flap reconstruction following abdominal liposuction is controversial. The authors' early cases were technically successful; however, they experienced high partial flap loss and fat necrosis rates. The authors sought to compare DIEP flap outcomes in the setting of prior liposuction after the use of intraoperative indocyanine green angiography compared to when flaps were assessed on clinical grounds alone. A retrospective review of a consecutive series of DIEP flaps following liposuction at a single institution was performed, comparing those evaluated on clinical grounds alone and those in which indocyanine green angiography was used intraoperatively. Outcomes measured included anastomotic complications, total flap loss, partial flap loss, fat necrosis, and postoperative abdominal wounds. Thirteen DIEP flaps following prior liposuction were performed on 11 patients from July of 2003 through January of 2014. All patients had preoperative imaging with duplex ultrasound or computed tomographic angiography to analyze perforator suitability before surgical exploration. Seven flaps were evaluated intraoperatively on clinical grounds alone. Six flaps were assessed and modified based on indocyanine green angiography. All flaps were successful; however, partial flap loss and fat necrosis rates dropped from 71.4 percent to 0 percent when indocyanine green angiography was used intraoperatively (p = 0.02). Indocyanine green angiography is an excellent vascular imaging modality for intraoperative use to assess flap perfusion, and improves outcomes in DIEP flaps when harvested after prior abdominal suction lipectomy.

Sentinel Lymphadenectomy in Vulvar Cancer Using Near-Infrared Fluorescence From Indocyanine Green Compared With Technetium 99m Nanocolloid.

PubMed

Soergel, Philipp; Hertel, Hermann; Nacke, Anna Kaarina; Klapdor, Rüdiger; Derlin, Thorsten; Hillemanns, Peter

2017-05-01

Nowadays, sentinel diagnostic is performed using technetium 99m (Tc) nanocolloid as a radioactive marker and sometimes patent blue. In the last years, indocyanine green has been evaluated for sentinel diagnostic in different tumor entities. Indocyanine green is a fluorescent molecule that emits a light signal in the near-infrared band after excitation. Our study aimed to evaluate indocyanine green compared with the criterion-standard Tc-nanocolloid. We included patients with primary, unifocal vulvar cancer of less than 4 cm with clinically node-negative groins in this prospective trial. Sentinel diagnostic was carried out using Tc-nanocolloid, indocyanine green, and patent blue. We examined each groin for light signals from the near-infrared band, for radioactivity, and for blue staining. A sentinel lymph node was defined as a Tc-nanocolloid-positive lymph node. All sentinel lymph nodes and all additional blue or fluorescent lymph nodes were excised and tested and then sent for histologic examination. In all, 27 patients were included in whom we found 91 sentinel lymph nodes in 52 groins. All these lymph nodes were positive for indocyanine green, also giving a sensitivity of 100% (95% confidence interval [CI], 96.0%-100%) compared with Tc-nanocolloid. Eight additional lymph nodes showed indocyanine green fluorescence but no Tc positivity, so that the positive predictive value was 91.9% (95% confidence interval, 84.6%-96.5%). In 1 patient, a false-negative sentinel missed by all 3 modalities was found. Our results show that indocyanine green is a promising approach for inguinal sentinel identification in vulvar cancer with a similar sensitivity as radioactive Tc-nanocolloid and worth to be evaluated in further studies.

Enhancement of high-resolution photoacoustic imaging with indocyanine green-conjugated carbon nanotubes

NASA Astrophysics Data System (ADS)

Phuc Nguyen, Van; Oh, Yunok; Ha, Kanglyeol; Oh, Junghwan; Kang, Hyun Wook

2015-07-01

The current study indicates the feasibility of photoacoustic imaging (PAI) enhanced with contrast agents. A single-element ultrasound transducer (20 MHz) was used to detect PA signals for image reconstruction. To improve PA sensitivity, single-walled carbon nanotubes (SWNTs) conjugated with indocyanine green (ICG) were injected into samples at various concentrations. PA signal amplitudes linearly increased with SWNT-ICG concentration owing to strong light absorption. Compared with SWNTs, SWNT-ICG augmented the signal intensity by approximately 2-fold (concentration: 300 nM). The enhanced optical absorption can allow the application of SWNT-ICG to enable PAI for specifically identifying tumors with high sensitivity.

Use of indocyanine green and sodium fluorescein for anterior segment angiography in ophthalmologically normal cats.

PubMed

Pirie, Chris G; Alario, Anthony

2015-10-01

To assess and compare results of anterior segment angiography of ophthalmologically normal cats following IV injection with indocyanine green and sodium fluorescein dyes. 10 client-owned cats. Anterior segment angiography was performed in anesthetized cats following administration of 0.25% indocyanine green (1.0 mg/kg, IV) or 10% sodium fluorescein (20 mg/kg, IV) solution. All cats received both treatments. Imaging (1 eye/cat) was performed with a full-spectrum digital single-lens reflex camera equipped with an adaptor (1 image/s for 30 seconds) immediately following IV dye injection and 1, 2, 3, 4, and 5 minutes after injection. Onset and duration of arterial, capillary, and venous phases of iris vasculature were identified and compared statistically between treatments. Degree of iridal pigmentation, leakage of dye from iris vasculature, and image quality were subjectively assessed. No differences were found in onset or duration of vascular phases between treatments. Visibility of the iris vasculature was not impaired by poor or moderate iridal pigmentation with either method. Indocyanine green provided subjectively better vascular detail and image contrast than sodium fluorescein. No vascular dye leakage was observed following indocyanine green administration. Leakage of dye from blood vessels in the stroma (in 10 cats) and presence of dye in the anterior chamber (in 5 cats) were detected after sodium fluorescein administration. Images obtained with either fluorescent dye were considered to be of diagnostic quality. Lack of leakage following indocyanine green administration suggested this treatment may have better diagnostic utility for anterior segment angiography. The photographic equipment used provided a cost-effective alternative to existing imaging systems.

Changes of choroidal neovascularization in indocyanine green angiography after intravitreal ranibizumab injection.

PubMed

Lee, Ji Eun; Kim, Hyun Woong; Lee, Sang Joon; Lee, Joo Eun

2015-05-01

To investigate vascular structural changes of choroidal neovascularization (CNV) followed by intravitreal ranibizumab injections using indocyanine green angiography. A total of 31 patients with exudative age-related macular degeneration and CNV whose structures were identifiable in indocyanine green angiography were included. Ranibizumab was injected into the vitreous cavity once a month for 3 months and then as needed for the next 3 months prospectively. Indocyanine green angiography was performed at baseline, 3, and 6 months. Early to midphase images of the indocyanine green angiography in the details of vascular structure of the CNV were discerned the best were used in the image analysis. Vascular structures of CNV were described as arteriovenular and capillary components, and structural changes were assessed. Arteriovenular components were observed in 29 eyes (94%). Regression of the capillary components was observed in most cases. Although regression of arteriovenular component was noted in 14 eyes (48%), complete resolution was not observed. The eyes were categorized into 3 groups according to CNV structural changes: the regressed (Group R, 10 eyes, 31%), the matured (Group M, 7 eyes, 23%), and the growing (Group G, 14 eyes, 45%). In Group R, there was no regrowth of CNV found at 6 months. In Group M, distinct vascular structures were observed at 3 months and persisted without apparent changes at 6 months. In Group G, growth or reperfusion of capillary components from the persisting arteriovenular components was noted at 6 months. Both capillary and arteriovenular components were regressed during monthly ranibizumab injections. However, CNV regrowth was observed in a group of patients during the as-needed treatment phase.

Indocyanine green angiography in posterior uveitis

PubMed Central

Agrawal, Rupesh V; Biswas, Jyotirmay; Gunasekaran, Dinesh

2013-01-01

Literature review for indocyanine green angiography and evaluate the role of indocyanine green angiogram (ICGA) in patients with posterior uveitis seen at a tertiary referral eye care centre. Detailed review of the literature on ICGA was performed. Retrospective review of medical records of patients with posterior uveitis and dual fundus and ICGA was done after institutional board approval. Eighteen patients (26 eyes) had serpiginous choroiditis out of which 12 patients had active choroiditis and six patients had healed choroiditis, six patients (12 eyes) had ampiginous choroiditis, six patients (12 eyes) had acute multifocal posterior placoid pigment epitheliopathy, eight patients (10 eyes) had multifocal choroiditis, four patients (eight eyes) had presumed ocular histoplasmosis syndrome, four patients (eight eyes) had presumed tuberculous choroiditis, two patients (four eyes) had multiple evanescent white dot syndrome and two patients (four eyes) had Vogt Koyanagi Harada (VKH) syndrome. The most characteristic feature noted on ICGA was the presence of different patterns of hypofluorescent dark spots, which were present at different stages of the angiogram. ICGA provides the clinician with a powerful adjunctive tool in choroidal inflammatory disorders. It is not meant to replace already proven modalities such as the fluorescein angiography, but it can provide additional information that is useful in establishing a more definitive diagnosis in inflammatory chorioretinal diseases associated with multiple spots. It still needs to be determined if ICGA can prove to be a follow up parameter to evaluate disease progression. PMID:23685486

Labeling of indocyanine green with carrier-free iodine-123

DOEpatents

Ansari, Azizullah N.; Lambrecht, Richard M.; Redvanly, Carol S.; Wolf, Alfred P.

1976-01-01

The method of labeling indocyanine green (ICG) with carrier-free iodine-123 comprising the steps of condensing xenon-123 on crystals of ICG followed by permitting decay of the .sup.123 Xe a sufficient length of time to produce .sup.123 I-electronically excited ions and atoms which subsequently label ICG.

Indocyanine Green Angiography Use in Breast Reconstruction: A National Analysis of Outcomes and Cost in 110,320 Patients.

PubMed

Chattha, Anmol; Bucknor, Alexandra; Chen, Austin D; Lee, Bernard T; Lin, Samuel J

2018-04-01

Indocyanine green angiography has gained popularity in breast reconstruction for its ability to assess mastectomy skin and tissue flap viability. The authors aim to analyze trends and outcomes associated with indocyanine green angiography use in breast reconstruction. Using 2012 to 2014 data from the Healthcare Cost and Utilization Project National Inpatient Sample, Agency for Healthcare Research and Quality, the authors identified breast reconstructions performed with or without indocyanine green angiography use. Trends over time were assessed using the Cochran-Armitage test. Outcomes were assessed using logistic regression and generalized linear modeling. Over the study period, 110,320 patients underwent breast reconstruction: 107,005 (97.0 percent) without and 3315 (3.0 percent) with indocyanine green angiography use. Usage increased over time: 750 patients (1.9 percent) in 2012, increasing to 1275 patients (3.7 percent) in 2013 (p < 0.001). Smokers (p = 0.018), hypertensive patients (p = 0.046), obese patients (p < 0.001), and those with a higher comorbidity index (p < 0.001) were more likely to undergo indocyanine green angiography. Autologous reconstruction was more frequently combined with its use compared with tissue expander reconstruction (4.5 percent versus 2.1 percent; p < 0.001). There was a significant increase in the odds of débridement associated with its use (OR, 1.404; p < 0.001; 95 percent CI, 1.201 to 1.640). Indocyanine green angiography use in breast reconstruction has increased in recent years and is associated with higher débridement rates. These rates may indicate changing trends for clinicians when deciding whether to débride tissue during breast reconstruction. Therapeutic, III.

Indocyanine green fluorescence angiography for quantitative evaluation of in situ parathyroid gland perfusion and function after total thyroidectomy.

PubMed

Lang, Brian Hung-Hin; Wong, Carlos K H; Hung, Hing Tsun; Wong, Kai Pun; Mak, Ka Lun; Au, Kin Bun

2017-01-01

Because the fluorescent light intensity on an indocyanine green fluorescence angiography reflects the blood perfusion within a focused area, the fluorescent light intensity in the remaining in situ parathyroid glands may predict postoperative hypocalcemia risk after total thyroidectomy. Seventy patients underwent intraoperative indocyanine green fluorescence angiography after total thyroidectomy. Any parathyroid glands with a vascular pedicle was left in situ while any parathyroid glands without pedicle or inadvertently removed was autotransplanted. After total thyroidectomy, an intravenous 2.5 mg indocyanine green fluorescence angiography was given and real-time fluorescent images of the thyroid bed were recorded using the SPY imaging system (Novadaq, Ontario, Canada). The fluorescent light intensity of each indocyanine green fluorescence angiography as well as the average and greatest fluorescent light intensity in each patient were calculated. Postoperative hypocalcemia was defined as adjusted calcium <2.00 mmol/L within 24 hours. The fluorescent light intensity between discolored and normal-looking indocyanine green fluorescence angiographies was similar (P = .479). No patients with a greatest fluorescent light intensity >150% developed postoperative hypocalcemia while 9 (81.8%) patients with a greatest fluorescent light intensity ≤150% did. Similarly, no patients with an average fluorescent light intensity >109% developed PH while 9 (30%) with an average fluorescent light intensity ≤109% did. The greatest fluorescent light intensity was more predictive than day-0 postoperative hypocalcemia (P = .027) and % PTH drop day-0 to 1 (P < .001). Indocyanine green fluorescence angiography is a promising operative adjunct in determining residual parathyroid glands function and predicting postoperative hypocalcemia risk after total thyroidectomy. Copyright © 2016 Elsevier Inc. All rights reserved.

A Review of Indocyanine Green Fluorescent Imaging in Surgery

PubMed Central

Alander, Jarmo T.; Kaartinen, Ilkka; Laakso, Aki; Pätilä, Tommi; Spillmann, Thomas; Tuchin, Valery V.; Venermo, Maarit; Välisuo, Petri

2012-01-01

The purpose of this paper is to give an overview of the recent surgical intraoperational applications of indocyanine green fluorescence imaging methods, the basics of the technology, and instrumentation used. Well over 200 papers describing this technique in clinical setting are reviewed. In addition to the surgical applications, other recent medical applications of ICG are briefly examined. PMID:22577366

[Use of indocyanine green angiography in oncological and reconstructive breast surgery].

PubMed

Struk, S; Honart, J-F; Qassemyar, Q; Leymarie, N; Sarfati, B; Alkhashnam, H; Mazouni, C; Rimareix, F; Kolb, F

2018-02-01

The Indocyanine green (ICG) is a soluble dye that is eliminated by the liver and excreted in bile. When illuminated by an near-infrared light, the ICG emits fluorescence in the near-infrared spectrum, which can be captured by a near-infrared camera-handled device. In case of intravenous injection, ICG may be used as a marker of skin perfusion. In case of interstitial injection, it may be useful for lymphatic network mapping. In oncological and reconstructive breast surgery, ICG is used for sentinel lymph node identification, to predict mastectomy skin flap necrosis, to assess the perfusion of free flaps in autologous reconstruction and for diagnosis and treatment of upper limb secondary lymphedema. Intraoperative indocyanine green fluorescence might also be used to guide the excision of nonpalpable breast cancer. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

A Comparison of the Regional Circulation in the Feet between Dialysis and Non-Dialysis Patients using Indocyanine Green Angiography.

PubMed

Nishizawa, M; Igari, K; Kudo, T; Toyofuku, T; Inoue, Y; Uetake, H

2017-09-01

Peripheral artery disease in dialysis cases is more prone to critical limb ischemia compared to non-dialysis cases, with a significantly high rate of major amputation of the lower limbs. Lesions are distributed on the more distal side in dialysis critical limb ischemia cases. The aim of this study was to investigate the usefulness of indocyanine green angiography to determine differences in the regional circulation in the foot between dialysis and non-dialysis patients. The subjects included 62 cases, among which 20 were dialysis patients and 42 were non-dialysis patients. We compared the indocyanine green angiography parameters for regions of interest in the dialysis and non-dialysis groups, which included the magnitude of intensity from indocyanine green onset to maximum intensity (Imax), the time from indocyanine green onset to maximum intensity (Tmax), the time elapsed from the fluorescence onset to half the maximum intensity (T1/2), and the time from maximum intensity to declining to 90% of the maximum intensity (Td90%). These indocyanine green angiography parameters were measured at region of interest 1 (the Chopart joint), region of interest 2 (the Lisfranc joint), and region of interest 3 (the distal region of the first metatarsal bone). In the comparison between the dialysis and non-dialysis groups, a significant difference was observed regarding Tmax, T1/2, and Td90%, especially in region of interest 3. In this study, we show that regional tissue perfusion is more deteriorated in dialysis patients compared with non-dialysis patients using indocyanine green angiography. Tmax, T1/2, and Td90% could be useful clinical parameters to compare ischemic severity of the lower limb between dialysis and non-dialysis patients.

A comparison of free autologous breast reconstruction with and without the use of laser-assisted indocyanine green angiography: a cost-effectiveness analysis.

PubMed

Chatterjee, Abhishek; Krishnan, Naveen M; Van Vliet, Michael M; Powell, Stephen G; Rosen, Joseph M; Ridgway, Emily B

2013-05-01

Laser-assisted indocyanine green angiography is a U.S. Food and Drug Administration-approved technology used to assess tissue viability and perfusion. Its use in plastic and reconstructive surgery to assess flap perfusion in autologous breast reconstruction is relatively new. There have been no previous studies evaluating the cost-effectiveness of this new technology compared with the current practice of clinical judgment in evaluating tissue perfusion and viability in free autologous breast reconstruction in patients who have undergone mastectomy. A comprehensive literature review was performed to identify the complication rate of the most common complications with and without laser-assisted indocyanine green angiography in free autologous breast reconstruction after mastectomy. These probabilities were combined with Medicare Current Procedural Terminology provider reimbursement codes (cost) and utility estimates for common complications from a survey of 10 plastic surgeons to fit into a decision model to evaluate the cost-effectiveness of laser-assisted indocyanine green angiography. The decision model revealed a baseline cost difference of $773.66 and a 0.22 difference in the quality-adjusted life-years, yielding an incremental cost-utility ratio of $3516.64 per quality-adjusted life year favoring laser-assisted indocyanine green angiography. Sensitivity analysis showed that using laser-assisted indocyanine green angiography was more cost-effective when the complication rate without using laser-assisted indocyanine green angiography (clinical judgment alone) was 4 percent or higher. The authors' study demonstrates that laser-assisted indocyanine green angiography is a cost-effective technology under the most stringent acceptable thresholds when used in immediate free autologous breast reconstruction.

Indocyanine Green Guided Pelvic Lymph Node Dissection: An Efficient Technique to Classify the Lymph Node Status of Patients with Prostate Cancer Who Underwent Radical Prostatectomy.

PubMed

Ramírez-Backhaus, Miguel; Mira Moreno, Alejandra; Gómez Ferrer, Alvaro; Calatrava Fons, Ana; Casanova, Juan; Solsona Narbón, Eduardo; Ortiz Rodríguez, Isabel María; Rubio Briones, José

2016-11-01

We evaluated the effectiveness of indocyanine green guided pelvic lymph node dissection for the optimal staging of prostate cancer and analyzed whether the technique could replace extended pelvic lymph node dissection. A solution of 25 mg indocyanine green in 5 ml sterile water was transperineally injected. Pelvic lymph node dissection was started with the indocyanine green stained nodes followed by extended pelvic lymph node dissection. Primary outcome measures were sensitivity, specificity, predictive value and likelihood ratio of a negative test of indocyanine green guided pelvic lymph node dissection. A total of 84 patients with a median age of 63.55 years and a median prostate specific antigen of 8.48 ng/ml were included in the study. Of these patients 60.7% had intermediate risk disease and 25% had high or very high risk disease. A median of 7 indocyanine green stained nodes per patient was detected (range 2 to 18) with a median of 22 nodes excised during extended pelvic lymph node dissection. Lymph node metastasis was identified in 25 patients, 23 of whom had disease properly classified by indocyanine green guided pelvic lymph node dissection. The most frequent location of indocyanine green stained nodes was the proximal internal iliac artery followed by the fossa of Marcille. The negative predictive value was 96.7% and the likelihood ratio of a negative test was 8%. Overall 1,856 nodes were removed and 603 were stained indocyanine green. Pathological examination revealed 82 metastatic nodes, of which 60% were indocyanine green stained. The negative predictive value was 97.4% but the likelihood ratio of a negative test was 58.5%. Indocyanine green guided pelvic lymph node dissection correctly staged 97% of cases. However, according to our data it cannot replace extended pelvic lymph node dissection. Nevertheless, its high negative predictive value could allow us to avoid extended pelvic lymph node dissection if we had an accurate intraoperative lymph

Intraoperative Fluorescence Imaging for Detection of Sentinel Lymph Nodes and Lymphatic Vessels during Open Prostatectomy using Indocyanine Green.

PubMed

Yuen, Keiji; Miura, Tetsuya; Sakai, Iori; Kiyosue, Akiko; Yamashita, Masuo

2015-08-01

We investigated the feasibility and validity of intraoperative fluorescence imaging using indocyanine green for the detection of sentinel lymph nodes and lymphatic vessels during open prostatectomy. Indocyanine green was injected into the prostate under transrectal ultrasound guidance just before surgery. Intraoperative fluorescence imaging was performed using a near-infrared camera system in 66 consecutive patients with clinically localized prostate cancer after a 10-patient pilot test to optimize indocyanine green dosing, observation timing and injection method. Lymphatic vessels were visualized and followed to identify the sentinel lymph nodes. Confirmatory pelvic lymph node dissection including all fluorescent nodes and open radical prostatectomy were performed in all patients. Lymphatic vessels were successfully visualized in 65 patients (98%) and sentinel lymph nodes in 64 patients (97%). Sentinel lymph nodes were located in the obturator fossa, internal and external iliac regions, and rarely in the common iliac and presacral regions. A median of 4 sentinel lymph nodes per patient was detected. Three lymphatic pathways, the paravesical, internal and lateral routes, were identified. Pathological examination revealed metastases to 9 sentinel lymph nodes in 6 patients (9%). All pathologically positive lymph nodes were detected as sentinel lymph nodes using this imaging. No adverse reactions due to the use of indocyanine green were observed. Intraoperative fluorescence imaging using indocyanine green during open prostatectomy enables the detection of lymphatic vessels and sentinel lymph nodes with high sensitivity. This novel method is technically feasible, safe and easy to apply with minimal additional operative time. Copyright © 2015 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

[Use of indocyanine green angiography in reconstructive surgery: Brief review].

PubMed

Echalier, C; Pluvy, I; Pauchot, J

2016-12-01

The success of flap surgery is highly dependant of vascularisation, according to the principle of dermal and subdermal perfusion. This principle requires compatible dimensions for the survival of the flap. Indocyanine green angiography (ICG), a technique enabling an assessment of vascularization by fluorescence, has received a considerable impetus during the last two decades. The purpose of this article was to conduct a review on this technique and to evaluate its relevance in flap surgery. We reviewed all articles referenced on PubMed from 1995 till 2015 using a search combining the terms 'indocyanine green', 'flap', 'near-infrared', 'fluorescence', 'imaging' OR 'angiography'. One hundred fifty five articles were found and among those thirty-four were selected. ICG is a reliable technique to locate perforants vessels, to determine the outlines of the flat and evaluate its per- and postoperative viability and to appraise anastomoses. This technique allows a reliable and real-time assessment of potential necrotic areas and an improvement in the detection of complications compared to conventional techniques. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Dual-Channel Endoscopic Indocyanine Green Fluorescence Angiography for Clipping of Cerebral Aneurysms.

PubMed

Cho, Won-Sang; Kim, Jeong Eun; Kang, Hyun-Seung; Ha, Eun Jin; Jung, Minwoong; Lee, Choonghee; Shin, Il Hyung; Kang, Uk

2017-04-01

Neuroendoscopy is useful for assessing status of perforators, parent arteries, and aneurysms beyond the straight line of microscopic view during aneurysm clipping. We aimed to evaluate the clinical usefulness of our endoscopic indocyanine green angiography (ICGA) system, which can simultaneously display visible light and indocyanine green fluorescent images. Surgical clipping of 16 unruptured aneurysms in 10 patients was performed via the keyhole approach. Using our endoscopic ICGA and commercial microscopic ICGA systems, we prospectively compared 10 targeted cerebral aneurysms at the posterior communicating (n = 4) and anterior choroidal (n = 6) arteries. Microscopic ICGA and endoscopic ICGA were feasible during surgery. Microscopic ICGA displayed 50% of branch orifices, 100% of branch trunks, and 20% of exact clip positions, whereas endoscopic ICGA showed 100% of these. Based on endoscopic ICGA findings such as incomplete clipping and compromise of parent arteries or branches, clips were repositioned in 2 cases, and additional clips were applied in 2 cases. Complete occlusion and residual neck states were achieved in 6 and 4 aneurysms after surgery. There were no neurologic deficits within 3 months after surgery except for frontalis palsy and anosmia in each patient. The endoscopic ICGA system with dual imaging of visible light and indocyanine green fluorescence was very useful for assessing geometry of aneurysms and surrounding vessels before clipping and for evaluating completeness of clip position after clipping. Copyright © 2017 Elsevier Inc. All rights reserved.

Indocyanine green fluorescence angiography for free flap monitoring: A pilot study.

PubMed

Hitier, Marine; Cracowski, Jean-Luc; Hamou, Cynthia; Righini, Christian; Bettega, Georges

2016-11-01

We evaluated the feasibility and the tolerance of repeated fluorescent indocyanine green angiography in free flap monitoring, and determined the intraoperative predictive values of flap vitality. The free flap failure rate has been significantly reduced, but free flap loss still occurs and remains a costly disaster. Repeated clinical examinations are commonly used for flap monitoring, but they can be unreliable because of their subjectivity. Laser-induced fluorescence of indocyanine green is a new method for assessing tissue perfusion. 20 patients undergoing microsurgical reconstruction were monitored by indocyanine green fluorescence angiography, intraoperatively, and during 4 days after surgery, with 18 injections. Monitoring was made by clinical examination, and then compared to angiographic findings. The vascular complication rate was 15% (3/20) with 2 cases of venous thrombosis and one case of partial necrosis of the flap skin paddle. Both cases of venous thrombosis were salvaged by secondary surgery. There was no total flap loss. ICG angiography allowed detecting each intra and postoperative complication, earlier than clinical examination. The mean per-operative intensity of fluorescence was significantly lower in flaps with vascular complications (23.8 GL/ms; p = 0.008). The postoperative slope (p = 0.02) and amplitude (p = 0.03) of the fluorescent signal were both significantly lower than for uncomplicated flaps, before surgical revision. These 2 parameters came back to normal values after secondary surgery. There was no adverse effect of ICG despite the repeated injections. ICG angiography is a feasible and safe technique for the detection of free flap vascular complications. Copyright © 2016 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.

In vitro efficiency and mechanistic role of indocyanine green as photodynamic therapy agent for human melanoma

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mamoon, A.M.; Miller, L.; Gamal-Eldeen, A. M.

2009-05-02

Photodynamic therapy (PDT) is a promising treatment for superficial cancer. However, poor therapeutic results have been reported for melanoma, due to the high melanin content. Indocyanine green (ICG) has near infrared absorption (700-800 nm) and melanins do not absorb strongly in this area. This study explores the efficiency of ICG as a PDT agent for human melanoma, and its mechanistic role in the cell death pathway. Human skin melanoma cells (Sk-Mel-28) were incubated with ICG and exposed to a low power Ti:Sapphire laser. Synchrotron-assisted Fourier transform infrared microspectroscopy and hierarchical cluster analysis were used to assess the cell damage andmore » changes in lipid, protein, and nucleic acids. The cell death pathway was determined by analysis of cell viability and apoptosis and necrosis markers. In the cell death pathway, {sup 1}O{sub 2} generation evoked rapid multiple consequences that trigger apoptosis after laser exposure for only 15min including the release of cytochrome c, the activation of total caspases, caspase-3, and caspase-9, the inhibition of NF-{Kappa}B P65, and the enhancement of DNA fragmentation, and histone acetylation. ICG/PDT can efficiently and rapidly induce apoptosis in human melanoma cells and it can be considered as a new therapeutic approach for topical treatment of melanoma.« less

Indocyanine green fluorescence imaging in the surgical management of liver cancers: current facts and future implications.

PubMed

Lim, C; Vibert, E; Azoulay, D; Salloum, C; Ishizawa, T; Yoshioka, R; Mise, Y; Sakamoto, Y; Aoki, T; Sugawara, Y; Hasegawa, K; Kokudo, N

2014-04-01

Imaging detection of liver cancers and identification of the bile ducts during surgery, based on the fluorescence properties of indocyanine green, has recently been developed in liver surgery. The principle of this imaging technique relies on the intravenous administration of indocyanine green before surgery and the illumination of the surface of the liver by an infrared camera that simultaneously induces and collects the fluorescence. Detection by fluorescence is based on the contrast between the (fluorescent) tumoral or peri-tumoral tissues and the healthy (non-fluorescent) liver. Results suggest that indocyanine green fluorescence imaging is capable of identification of new liver cancers and enables the characterization of known hepatic lesions in real time during liver resection. The purpose of this paper is to present the fundamental principles of fluorescence imaging detection, to describe successively the practical and technical aspects of its use and the appearance of hepatic lesions in fluorescence, and to expose the diagnostic and therapeutic perspectives of this innovative imaging technique in liver surgery. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

Prussian blue/serum albumin/indocyanine green as a multifunctional nanotheranostic agent for bimodal imaging guided laser mediated combinatorial phototherapy.

PubMed

Sahu, Abhishek; Lee, Jong Hyun; Lee, Hye Gyeong; Jeong, Yong Yeon; Tae, Giyoong

2016-08-28

Developing novel nanotheranostic agent using only clinically approved materials is highly desirable and challenging. In this study, we combined three clinically approved materials, Prussian blue (PB), serum albumin (BSA), and indocyanine green (ICG), by a simple and biocompatible method to prepare a multifunctional theranostic PB-BSA-ICG nanoparticle. The multifunctional nanoparticle system could provide dual mode magnetic resonance (MR) and near infrared (NIR) fluorescence imaging as well as combined photothermal and photodynamic (PTT-PDT) therapy in response to a single NIR laser. This nanoparticle showed an excellent stability in physiological solutions and could suppress the photo-instability of ICG. In the absence of light, the nanoparticles showed no cytotoxicity, but significant cell death was induced through combined PTT-PDT effect after irradiation with NIR laser light. A high tumor accumulation and minimal nonspecific uptake by other major organs of PB-BSA-ICG nanoparticle were observed in vivo, analyzed by T1-weighted MR and NIR fluorescence bimodal imaging in tumor xenograft mice after intravenous injection. The nanoparticles efficiently suppressed the tumor growth through combinatorial phototherapy with no tumor recurrence upon a single NIR laser irradiation. These results demonstrated that PB-BSA-ICG is potentially an interesting nanotheranostic agent for imaging guided cancer therapy by overcoming the limitations of each technology and enhancing the therapeutic efficiency as well as reducing side effects. Copyright © 2016 Elsevier B.V. All rights reserved.

Imaging the urinary pathways in mice by liposomal indocyanine green.

PubMed

Portnoy, Emma; Nizri, Eran; Golenser, Jacob; Shmuel, Miriam; Magdassi, Shlomo; Eyal, Sara

2015-07-01

Intraoperative ureter identification can assist in the prevention of ureteral injury and consequently improve surgery outcomes. Our aim was to take advantage of the altered pharmacokinetics of liposomal indocyanine green (ICG), the only FDA-approved near-infrared (NIR) dye, for imaging of ureters during surgeries. ICG was passively adsorbed to liposomes. NIR whole mice body and isolated tissue imaging were used to study liposomal ICG properties vs. free ICG. In vivo, the urinary bladder could be clearly observed in most of the liposome-treated mice. Liposomal encapsulation of ICG enhanced ureteral emission up to 1.9 fold compared to free ICG (P<0.01). Increase in liposomal micropolarity and microviscosity and differential scanning calorimetry supported ICG localization within the liposomal bilayer. Our findings suggest that liposomal ICG could be utilized for ureteral imaging intra-operatively, thus potentially improving surgical outcomes. Iatrogenic ureteral injury is a serious complication of abdominal surgery and intra-operative recognition of the ureters is usually the best method of injury prevention. In this article, the authors developed liposomal indocyanine green, which could be excreted via the urinary system and investigated its in-vivo use in mice. Copyright © 2015 Elsevier Inc. All rights reserved.

Indocyanine green fluorescence-navigated thoracoscopic anatomical segmentectomy

PubMed Central

Okumura, Sakae; Nakao, Masayuki; Matsuura, Yosuke; Nakagawa, Ken

2017-01-01

Background To evaluate the feasibility and efficacy of thoracoscopic anatomical segmentectomy (TS-S) using three-dimensional computed tomography (3D-CT) reconstruction and indocyanine green-fluorescence (ICGF) navigation. Methods Twenty TS-S procedures were performed for 15 primary lung cancers and 5 metastatic lung tumors. Preoperatively we evaluated the target segmental pulmonary artery and created a virtual intersegmental plane using 3D-CT reconstruction. Intraoperatively, the target segmental artery and bronchus were divided, and after intravenous systemic injection of indocyanine green (ICG, 0.25 mg/kg), ICGF of the non-target segments (NTS) was observed using infrared thoracoscopy (KARL STORZ Endoskope Japan K.K., Tokyo, Japan). We marked the border between target and NTS with electrocautery and divided the lung parenchyma along this border using electrocautery or staples. Strength of contrast between target and NTS was quantified as contrast index (CI) and compared over time. Results ICGF provided demarcation of sufficient clarity and duration to mark the lung surface in 19 patients (95%). TS-S was successfully performed in all patients. Mean operative duration was 186 min (90–310 min) and mean blood loss was 30 mL (0–107 mL). Demarcation appeared 20 s (10–100 s) after injection of ICG, and ICGF lasted 180 s (90–300 s). CI peaked 30 s after the appearance of ICGF and decreased over time. Effective contrast continued for 70 s (30–116 s), which was sufficient to mark the line of demarcation. There were no complications attributable to this method. Conclusions ICGF navigation is a safe and effective technique for TS-S. PMID:29078643

Management of Spinal Arteriovenous Fistulae with Intraarterial Indocyanine Green Angiography: A Case Report.

PubMed

Caglar, Y Sukru; Ozdemir, Mevci; Kahilogullari, Gokmen; Bozkurt, Melih; Attar, Ayhan

2018-01-01

We describe herein intraoperative effectiveness of indocyanine green (ICG) video angiography to confirm dural arteriovenous fistulae. A 62-year-old man with a residual symptomatic dural arteriovenous fistula that was previously embolized at another institution is presented. On neurological examination, the motor strength in his both lower extremities was documented as grade 4 and the patella reflex was slightly increased. After verifying the presence of abnormal early venous drainage and retrograde flow with indocyanine green video angiography, the fistula was repaired. Postoperatively there was no additional neurologic deficit. Five days after the operation, the patient was discharged. Intraoperative ICG video angiography provides non-invasive and realtime information, reduction of spinal cord ischemic damage, rapid identification of feeding artery and confirmation of its complete disconnection during surgery, reduction of operative time, and improved outcome with no radiation hazard.

Fluorescein and Indocyanine Green Angiography for Uveitis

PubMed Central

Herbort, Carl P

2009-01-01

In recent years enormous progress has been achieved in investigational procedures for uveitis. Imaging is one such example with the advent of new methods such as indocyanine green angiography, ultrasound biomicroscopy and optical coherence tomography to cite only the most important. This tremendous increase in precision and accuracy in the assessment of the level and degree of inflammation and its monitoring comes in parallel with the development of extremely potent and efficacious therapies. In view of these developments, our whole attitude in the appraisal and investigation of the uveitis patient has to be adapted and correctly reoriented integrating the recent developments and this is no different for ocular angiography. PMID:20404985

Indocyanine Green-Loaded Liposomes for Light-Triggered Drug Release.

PubMed

Lajunen, Tatu; Kontturi, Leena-Stiina; Viitala, Lauri; Manna, Moutusi; Cramariuc, Oana; Róg, Tomasz; Bunker, Alex; Laaksonen, Timo; Viitala, Tapani; Murtomäki, Lasse; Urtti, Arto

2016-06-06

Light-triggered drug delivery systems enable site-specific and time-controlled drug release. In previous work, we have achieved this with liposomes containing gold nanoparticles in the aqueous core. Gold nanoparticles absorb near-infrared light and release the energy as heat that increases the permeability of the liposomal bilayer, thus releasing the contents of the liposome. In this work, we replaced the gold nanoparticles with the clinically approved imaging agent indocyanine green (ICG). The ICG liposomes were stable at storage conditions (4-22 °C) and at body temperature, and fast near-infrared (IR) light-triggered drug release was achieved with optimized phospholipid composition and a 1:50 ICG-to-lipid molar ratio. Encapsulated small molecular calcein and FITC-dextran (up to 20 kDa) were completely released from the liposomes after light exposure for 15 s. Location of ICG in the PEG layer of the liposomes was simulated with molecular dynamics. ICG has important benefits as a light-triggering agent in liposomes: fast content release, improved stability, improved possibility of liposomal size control, regulatory approval to use in humans, and the possibility of imaging the in vivo location of the liposomes based on the fluorescence of ICG. Near-infrared light used as a triggering mechanism has good tissue penetration and safety. Thus, ICG liposomes are an attractive option for light-controlled and efficient delivery of small and large drug molecules.

Indocyanine green-enhanced fluorescence in laparoscopic sleeve gastrectomy.

PubMed

Frattini, Francesco; Lavazza, Matteo; Mangano, Alberto; Amico, Francesco; Rausei, Stefano; Rovera, Francesca; Boni, Luigi; Dionigi, Gianlorenzo

2015-05-01

The aim of this study is to present our preliminary experience with indocyanine green fluorescence (IGF) imaging in laparoscopic sleeve gastrectomy. After dissection of the greater curve sleeve, gastrectomy is performed using a linear articulated stapler. Once the stomach is resected, an indocyanine green solution is prepared and injected in a periferic vein. A laparoscopic system with a high-definition camera system connected to a laparoscope equipped with a specific filter for optimal detection of the near-infrared fluorescence was used at all times as previously reported in a paper of Boni et al. A methylene blue test is routinely performed after near-infrared fluorescence, and a routine gastrografin upper gastrointestinal study is performed on postoperative day 2. We retrospectively identified 15 patients undergoing laparoscopic sleeve gastrectomy between April and October 2014. IGF imaging was used for all patients. A regular and homogeneous perfusion was observed along the entire gastric sleeve including the esophago-gastric junction. On the contrary, the excised specimen appeared devascularized at IGF imaging as expected. Intraoperative methylene blue test was negative in all cases. The contrast swallow did not document any leak. Neither clinical leak nor other complications occurred postoperatively (minimum follow-up of 2 months). IGF is a recent development in minimally invasive surgery. In this preliminary experience, IGF results resemble to intraoperative methylene blue test and postoperative contrast swallow ones. IGF allows a real-time assessment and gives a direct image of tissue perfusion and vascularization. Moreover, IGF may be helpful to explain the exact pathogenesis of gastric leak.

Targeted Near-Infrared Fluorescence Imaging of Atherosclerosis: Clinical and Intracoronary Evaluation of Indocyanine Green.

PubMed

Verjans, Johan W; Osborn, Eric A; Ughi, Giovanni J; Calfon Press, Marcella A; Hamidi, Ehsan; Antoniadis, Antonios P; Papafaklis, Michail I; Conrad, Mark F; Libby, Peter; Stone, Peter H; Cambria, Richard P; Tearney, Guillermo J; Jaffer, Farouc A

2016-09-01

This study sought to determine whether indocyanine green (ICG)-enhanced near-infrared fluorescence (NIRF) imaging can illuminate high-risk histologic plaque features of human carotid atherosclerosis, and in coronary atheroma of living swine, using intravascular NIRF-optical coherence tomography (OCT) imaging. New translatable imaging approaches are needed to identify high-risk biological signatures of atheroma. ICG is a U.S. Food and Drug Administration-approved NIRF imaging agent that experimentally targets plaque macrophages and lipid in areas of enhanced endothelial permeability. However, it is unknown whether ICG can target atheroma in patients. Eight patients were enrolled in the BRIGHT-CEA (Indocyanine Green Fluorescence Uptake in Human Carotid Artery Plaque) trial. Five patients were injected intravenously with ICG 99 ± 25 min before clinically indicated carotid endarterectomy. Three saline-injected endarterectomy patients served as control subjects. Excised plaques underwent analysis by intravascular NIRF-OCT, reflectance imaging, microscopy, and histopathology. Next, following ICG intravenous injection, in vivo intracoronary NIRF-OCT and intravascular ultrasound imaged 3 atheroma-bearing coronary arteries of a diabetic, cholesterol-fed swine. ICG was well tolerated; no adverse clinical events occurred up to 30 days post-injection. Multimodal NIRF imaging including intravascular NIRF-OCT revealed that ICG accumulated in all endarterectomy specimens. Plaques from saline-injected control patients exhibited minimal NIRF signal. In the swine experiment, intracoronary NIRF-OCT identified ICG uptake in all intravascular ultrasound-identified plaques in vivo. On detailed microscopic evaluation, ICG localized to plaque areas exhibiting impaired endothelial integrity, including disrupted fibrous caps, and within areas of neovascularization. Within human plaque areas of endothelial abnormality, ICG was spatially related to localized zones of plaque macrophages and

Analysis of the neuronal marker protein gene product 9.5 in internal limiting membranes after indocyanine-green assisted peeling.

PubMed

Peters, Swaantje; Tatar, Olcay; Spitzer, Martin S; Szurman, Peter; Aisenbrey, Sabine; Lüke, Matthias; Adam, Annemarie; Yoeruek, Efdal; Grisanti, Salvatore

2009-02-01

Indocyanine green-assisted internal limiting membrane (ILM) peeling was suspected to disrupt the innermost layer of the neural retina. We examined whether surgically excised specimens contain remnants of neuronal tissue. Ten patients with macular hole underwent pars plana vitrectomy and indocyanine green-assisted ILM peeling. A total of 0.1 mL of a 0.5% indocyanine green solution was applied for 15 seconds. The ILM specimens were prepared for immunohistochemistry, using a polyclonal antibody against protein gene product 9.5. Protein gene product 9.5 is a pan-neuronal marker labeling human neuronal cells. Appropriate controls to show selectivity of the antibody were performed on neuronal tissue of donor eyes. One ILM was prepared for electron microscopy. A selective expression of protein gene product 9.5 was found in neuronal fibers of the retina and optic nerve of donor eyes. Only 1 of the 10 surgical ILM specimens showed a minimal focal positivity for protein gene product 9.5. No neuronal tissue was detected on the ILM by electron microscopy. Focal expression of protein gene product 9.5 in only 1 of 10 surgical ILM specimens argues against a general indocyanine green-related disruption of the innermost retinal layers. However, higher concentrations of the dye, longer incubation times or different solvents than used in this study may lead to different results.

Endoscopic near-infrared dental imaging with indocyanine green: a pilot study.

PubMed

Li, Zhongqiang; Yao, Shaomian; Xu, Jian; Wu, Ye; Li, Chunhong; He, Ziying

2018-06-01

Current dental diagnosis, especially tooth abnormalities, relies largely on X-ray-based imaging, a technique that requires specialized skills and suffers from ionizing radiation. Here, we present a pilot study in rats of an efficient, ionizing-radiation-free and easy-to-use alternative for dental imaging. Postnatal rats at different ages were injected with indocyanine green and molars were imaged by a laboratory-designed endoscopic near-infrared (NIR) dental imaging system. The results indicate that the endoscopic NIR dental imaging can be used to observe the morphology of postnatal rat molars, especially at early postnatal stages when morphology of the molar is indistinguishable under visible conditions. A small abnormal cusp was observed and distinguished from the normal cusps by the NIR dental imaging system. Dental structures, such as unerupted molars, can be imaged as soon as 10 min after the injection of indocyanine green; imaging after 24 h shows improved imaging contrast. Overall, the endoscopic NIR fluorescence dental imaging system described here may be useful in dental research; this technique may serve as a safe, real-time imaging tool for dental diagnosis and treatment beyond experimental systems in the future. © 2018 New York Academy of Sciences.

Tumor homing indocyanine green encapsulated micelles for near infrared and photoacoustic imaging of tumors.

PubMed

Uthaman, Saji; Bom, Joon-suk; Kim, Hyeon Sik; John, Johnson V; Bom, Hee-Seung; Kim, Seon-Jong; Min, Jung-Joon; Kim, Il; Park, In-Kyu

2016-05-01

Photoacoustic imaging (PAI) is an emerging analytical modality that is under intense preclinical development for the early diagnosis of various medical conditions, including cancer. However, the lack of specific tumor targeting by various contrast agents used in PAI obstructs its clinical applications. In this study, we developed indocyanine green (ICG)-encapsulated micelles specific for the CD 44 receptor and used in near infrared and photoacoustic imaging of tumors. ICG was hydrophobically modified prior to loading into hyaluronic acid (HA)-based micelles utilized for CD 44 based-targeting. We investigated the physicochemical characteristics of prepared HA only and ICG-encapsulated HA micelles (HA-ICG micelles). After intravenous injection of tumor-bearing mice, the bio-distribution and in vivo photoacoustic images of ICG-encapsulated HA micelles accumulating in tumors were also investigated. Our study further encourages the application of this HA-ICG-based nano-platform as a tumor-specific contrast agent for PAI. © 2016 Wiley Periodicals, Inc.

Fluorescence imaging of the nanoparticles modified with indocyanine green

NASA Astrophysics Data System (ADS)

Gareev, K. G.; Babikova, K. Y.; Postnov, V. N.; Naumisheva, E. B.; Korolev, D. V.

2017-11-01

The comparative research of silica, the magnetite and magnetite-silica nanoparticles modified with fluorescent dyes using gas-phase and liquid-phase methods was conducted. At the content of fluorescent dye comparable in size a particular spectrophotometric method, nanoparticles with fluorescein have up to 1000 times larger overall luminous efficiency. It is revealed that magnetic nanoparticles are characterized by a smaller light efficiency in comparison with silica particles, at the same time particles of a magnetite are most effective at modification with fluorescein, and magnetite-silica particles - at modification with indocyanine green.

Assessment of incomplete clipping of aneurysms intraoperatively by a near-infrared indocyanine green-video angiography (Niicg-Va) integrated microscope.

PubMed

Imizu, S; Kato, Y; Sangli, A; Oguri, D; Sano, H

2008-08-01

The objective of this article was to assess the clinical use and the completeness of clipping with total occlusion of the aneurysmal lumen, real-time assessment of vascular patency in the parent, branching and perforating vessels, intraoperative assessment of blood flow, image quality, spatial resolution and clinical value in difficult aneurysms using near infrared indocyanine green video angiography integrated on to an operative Pentero neurosurgical microscope (Carl Zeiss, Oberkochen Germany). Thirteen patients with aneurysms were operated upon. An infrared camera with near infrared technology was adapted on to the OPMI Pentero microscope with a special filter and infrared excitation light to illuminate the operating field which was designed to allow passage of the near infrared light required for excitation of indocyanine green (ICG) which was used as the intravascular marker. The intravascular fluorescence was imaged with a video camera attached to the microscope. ICG fluorescence (700-850 nm) from a modified microscope light source on to the surgical field and passage of ICG fluorescence (780-950 nm) from the surgical field, back into the optical path of the microscope was used to detect the completeness of aneurysmal clipping Incomplete clipping in three patients (1 female and 2 males) with unruptured complicated aneurysms was detected using indocyanine green video angiography. There were no adverse effects after injection of indocyanine green. The completeness of clipping was inadequately detected by Doppler ultrasound miniprobe and rigid endoscopy and was thus complemented by indocyanine green video angiography. The operative microscope-integrated ICG video angiography as a new intraoperative method for detecting vascular flow, was found to be quick, reliable, cost-effective and possibly a substitute or adjunct for Doppler ultrasonography or intraoperative DSA, which is presently the gold standard. The simplicity of the method, the speed with which the

NIRS and indocyanine-green-determined muscle blood flow during exercise in humans

NASA Astrophysics Data System (ADS)

Boushel, Robert; Ide, Kojiro; Moller-Sorensen, Hasse; Fernandes, Alvito; Pott, Frank; Secher, Niels H.

1998-01-01

We present a method for determination of muscle blood flow (MBF) using near infrared spectroscopy (NIRS) with indocyanine green (ICG) as the tracer. MBF was quantified using the integrated arterial [ICG] and the accumulation of ICG in muscle. MBF was determined together with ICG-assessed cardiac output (CO) at rest and during incremental cycling. To further modify CO, the same work loads were performed after cardio-selective beta blockade by metoprolol. In one subject both MBF (9 to 110 ml (DOT) 100 g-1 (DOT) min-1) and CO increased linearly with work rate (8 to 19 l (DOT) min-1). Under beta blockade, both the increase in MBF and CO were lower: 5 to 70 ml (DOT) 100 g-1 (DOT) min-1 and 5 to 161 DOT min-1, respectively. During exercise with and without beta blockade, MBF increased with work load to represent a larger proportion of CO. Also, NIRS could detect an attenuated increase in MBF manifest by the restrained CO during leg exercise after cardio-selective beta blockade. Both observations indicate that NIRS detection of indocyanine green provides an estimate of muscle blood flow over the range from rest to intense exercise.

NIRS and indocyanine-green-determined muscle blood flow during exercise in humans

NASA Astrophysics Data System (ADS)

Boushel, Robert; Ide, Kojiro; Moller-Sorensen, Hasse; Fernandes, Alvito; Pott, Frank; Secher, Niels H.

1997-12-01

We present a method for determination of muscle blood flow (MBF) using near infrared spectroscopy (NIRS) with indocyanine green (ICG) as the tracer. MBF was quantified using the integrated arterial [ICG] and the accumulation of ICG in muscle. MBF was determined together with ICG-assessed cardiac output (CO) at rest and during incremental cycling. To further modify CO, the same work loads were performed after cardio-selective beta blockade by metoprolol. In one subject both MBF (9 to 110 ml (DOT) 100 g-1 (DOT) min-1) and CO increased linearly with work rate (8 to 19 l (DOT) min-1). Under beta blockade, both the increase in MBF and CO were lower: 5 to 70 ml (DOT) 100 g-1 (DOT) min-1 and 5 to 161 DOT min-1, respectively. During exercise with and without beta blockade, MBF increased with work load to represent a larger proportion of CO. Also, NIRS could detect an attenuated increase in MBF manifest by the restrained CO during leg exercise after cardio-selective beta blockade. Both observations indicate that NIRS detection of indocyanine green provides an estimate of muscle blood flow over the range from rest to intense exercise.

Indocyanine green-incorporating nanoparticles for cancer theranostics

PubMed Central

Wang, Haolu; Li, Xinxing; Tse, Brian Wan-Chi; Yang, Haotian; Thorling, Camilla A.; Liu, Yuxin; Touraud, Margaux; Chouane, Jean Batiste; Liu, Xin; Roberts, Michael S.; Liang, Xiaowen

2018-01-01

Indocyanine green (ICG) is a near-infrared dye that has been used in the clinic for retinal angiography, and defining cardiovascular and liver function for over 50 years. Recently, there has been an increasing interest in the incorporation of ICG into nanoparticles (NPs) for cancer theranostic applications. Various types of ICG-incorporated NPs have been developed and strategically functionalised to embrace multiple imaging and therapeutic techniques for cancer diagnosis and treatment. This review systematically summaries the biodistribution of various types of ICG-incorporated NPs for the first time, and discusses the principles, opportunities, limitations, and application of ICG-incorporated NPs for cancer theranostics. We believe that ICG-incorporated NPs would be a promising multifunctional theranostic platform in oncology and facilitate significant advancements in this research-active area. PMID:29507616

Enhancement of indocyanine green stability and cellular uptake by incorporating cationic lipid into indocyanine green-loaded nanoemulsions.

PubMed

Lee, Eun-Hye; Kim, Jin-Ki; Lim, Joon-Seok; Lim, Soo-Jeong

2015-12-01

Indocyanine green (ICG) is a near-infrared optical dye approved by the Food and Drug Administration. ICG has been investigated as a simultaneous color and fluorescence-imaging tracer for the intraoperative identification of sentinel lymph nodes, but its use has recently expanded to include application as a photosensitizer for the local photodynamic/thermal treatment of identified lymph node metastases. The current study was designed to develop an ICG-loaded nanoemulsion as an effective agent for both the diagnosis and treatment of lymph node metastases. Incorporating the cationic lipid stearylamine (SA) together with ICG in the shell of nanoemulsions did not affect the loaded ICG concentration, but changed the surface charge of nanoemulsions from a negative to a positive value and improved the physical stability of nanoemulsions. Loading ICG into SA-incorporated nanoemulsions more effectively blocked the aggregation and degradation of ICG compared to loading in SA-free nanoemulsions. SA incorporation also enhanced tumor cell uptake of ICG-loaded nanoemulsions, resulting in greater cell killing upon light irradiation. After subcutaneous injection into the footpad of mice, SA-incorporated nanoemulsions increased the concentration of ICG accumulated in popliteal lymph nodes to a greater extent than SA-free nanoemulsions without affecting the kinetics of lymph node uptake of nanoemulsions. These multiple beneficial effects of incorporating SA in nanoemulsions are likely attributable to the electrostatic interaction between anionic ICG and cationic SA, as well as the change in the nanoemulsion surface charge from negative to positive. Our findings indicate that SA-incorporated nanoemulsions are promising ICG carriers for combined diagnosis and treatment of lymph node metastases. Copyright © 2015 Elsevier B.V. All rights reserved.

Indocyanine green as effective antibody conjugate for intracellular molecular targeted photodynamic therapy

NASA Astrophysics Data System (ADS)

Wang, Sijia; Hüttmann, Gereon; Rudnitzki, Florian; Diddens-Tschoeke, Heyke; Zhang, Zhenxi; Rahmanzadeh, Ramtin

2016-07-01

The fluorescent dye indocyanine green (ICG) is clinically approved and has been applied for ophthalmic and intraoperative angiography, measurement of cardiac output and liver function, or as contrast agent in cancer surgery. Though ICG is known for its photochemical effects, it has played a minor role so far in photodynamic therapy or techniques for targeted protein-inactivation. Here, we investigated ICG as an antibody-conjugate for the selective inactivation of the protein Ki-67 in the nucleus of cells. Conjugates of the Ki-67 antibody TuBB-9 with different amounts of ICG were synthesized and delivered into HeLa and OVCAR-5 cells through conjugation to the nuclear localization sequence. Endosomal escape of the macromolecular antibodies into the cytoplasm was optically triggered by photochemical internalization with the photosensitizer BPD. The second light irradiation at 690 nm inactivated Ki-67 and subsequently caused cell death. Here, we show that ICG as an antibody-conjugate can be an effective photosensitizing agent. Best effects were achieved with 1.8 ICG molecules per antibody. Conjugated to antibodies, the ICG absorption peaks vary proportionally with concentration. The absorption of ICG above 650 nm within the optical window of tissue opens the possibility of selective Ki-67 inactivation deep inside of tissues.

Utility of Indocyanine Green Fluorescence Imaging for Intraoperative Localization in Reoperative Parathyroid Surgery.

PubMed

Sound, Sara; Okoh, Alexis; Yigitbas, Hakan; Yazici, Pinar; Berber, Eren

2015-10-27

Due to the variations in anatomic location, the identification of parathyroid glands may be challenging. Although there have been advances in preoperative imaging modalities, there is still a need for an accurate intraoperative guidance. Indocyanine green (ICG) is a new agent that has been used for intraoperative fluorescence imaging in a number of general surgical procedures. Its utility for parathyroid localization in humans has not been reported in the literature. We report 3 patients who underwent reoperative neck surgery for primary hyperparathyroidism. Using a video-assisted technique with intraoperative ICG fluorescence imaging, the parathyroid glands were recognized and removed successfully in all cases. Surrounding soft tissue structures remained nonfluorescent, and could be distinguished from the parathyroid glands. This report suggests a potential utility of ICG imaging in intraoperative localization of parathyroid glands in reoperative neck surgery. Future work is necessary to assess its benefit for first-time parathyroid surgery. © The Author(s) 2015.

Investigation of porous silicon nanopowders functionalized by antibiotic Kanamycin, fluorophore Indocyanine Green

NASA Astrophysics Data System (ADS)

Bespalova, K.; Somov, P. A.; Spivak, Yu M.

2017-11-01

Porous silicon nanopowders for target drug delivery were obtained by electrochemical anodic etching in a hydrofluoric acid solution using the monocrystalline silicon n-type conductivity. Porous silicon powders were obtained by sonification of porous silicon layers. The powders were functionalized by antibiotic Kanamycin and fluorophore Indocyanine Green by the passive adsorption method. The peculiarities of absorption spectra in 190-600 nm region were revealed for functionalized porous silicon powders dispersions in water.

Indocyanine green videoangiography methodological variations: review.

PubMed

Simal-Julián, Juan A; Miranda-Lloret, Pablo; Evangelista-Zamora, Rocio; Sanromán-Álvarez, Pablo; Pérez de San Román, Laila; Pérez-Borredá, Pedro; Beltrán-Giner, Andrés; Botella-Asunción, Carlos

2015-01-01

Indocyanine green videoangiography (ICGVA) procedures have become widespread within the spectrum of microsurgical techniques for neurovascular pathologies. We have conducted a review to identify and assess the impact of all of the methodological variations of conventional ICGVA applied in the field of neurovascular pathology that have been published to date in the English literature. A total of 18 studies were included in this review, identifying four primary methodological variants compared to conventional ICGVA: techniques based on the transient occlusion, intra-arterial ICG administration via catheters, use of endoscope system with a filter to collect florescence of ICG, and quantitative fluorescence analysis. These variants offer some possibilities for resolving the limitations of the conventional technique (first, the vascular structure to be analyzed must be exposed and second, vascular filling with ICG follows an additive pattern) and allow qualitatively superior information to be obtained during surgery. Advantages and disadvantages of each procedure are discussed. More case studies with a greater number of patients are needed to compare the different procedures with their gold standard, in order to establish these results consistently.

A standardized model for predicting flap failure using indocyanine green dye

NASA Astrophysics Data System (ADS)

Zimmermann, Terence M.; Moore, Lindsay S.; Warram, Jason M.; Greene, Benjamin J.; Nakhmani, Arie; Korb, Melissa L.; Rosenthal, Eben L.

2016-03-01

Techniques that provide a non-invasive method for evaluation of intraoperative skin flap perfusion are currently available but underutilized. We hypothesize that intraoperative vascular imaging can be used to reliably assess skin flap perfusion and elucidate areas of future necrosis by means of a standardized critical perfusion threshold. Five animal groups (negative controls, n=4; positive controls, n=5; chemotherapy group, n=5; radiation group, n=5; chemoradiation group, n=5) underwent pre-flap treatments two weeks prior to undergoing random pattern dorsal fasciocutaneous flaps with a length to width ratio of 2:1 (3 x 1.5 cm). Flap perfusion was assessed via laser-assisted indocyanine green dye angiography and compared to standard clinical assessment for predictive accuracy of flap necrosis. For estimating flap-failure, clinical prediction achieved a sensitivity of 79.3% and a specificity of 90.5%. When average flap perfusion was more than three standard deviations below the average flap perfusion for the negative control group at the time of the flap procedure (144.3+/-17.05 absolute perfusion units), laser-assisted indocyanine green dye angiography achieved a sensitivity of 81.1% and a specificity of 97.3%. When absolute perfusion units were seven standard deviations below the average flap perfusion for the negative control group, specificity of necrosis prediction was 100%. Quantitative absolute perfusion units can improve specificity for intraoperative prediction of viable tissue. Using this strategy, a positive predictive threshold of flap failure can be standardized for clinical use.

Molecular Targeted Fluorescence-Guided Intraoperative Imaging of Bladder Cancer Nodal Drainage Using Indocyanine Green During Radical and Partial Cystectomy.

PubMed

Patel, Manish N; Hemal, Ashok K

2016-10-01

Optical imaging is a relatively inexpensive, fast, and sensitive addition to a surgeon's arsenal for the non-invasive detection of malignant dissemination. Optical cameras in the near infrared spectrum are able to successfully identify injected indocyanine green in lymphatic channels and sentinel lymph nodes. The use of this technology is now being used in the operating room to help with lymph node dissection and improve the prognosis of patients diagnosed with muscle invasive bladder cancer. Indocyanine green has the potential for many more applications due to its versatility. In the future, there is a potential to use it for lymphangiography during nephroureterctomy for upper tract urothelial carcinoma, adrenal surgery for partial or radical adrenalectomy. Further investigations at multiple centers will validate this technique and its efficiency.

Sentinel Node Biopsy for the Head and Neck Using Contrast-Enhanced Ultrasonography Combined with Indocyanine Green Fluorescence in Animal Models: A Feasibility Study.

PubMed

Kogashiwa, Yasunao; Sakurai, Hiroyuki; Akimoto, Yoshihiro; Sato, Dai; Ikeda, Tetsuya; Matsumoto, Yoshifumi; Moro, Yorihisa; Kimura, Toru; Hamanoue, Yasuhiro; Nakamura, Takehiro; Yamauchi, Koichi; Saito, Koichiro; Sugasawa, Masashi; Kohno, Naoyuki

2015-01-01

Sentinel node navigation surgery is gaining popularity in oral cancer. We assessed application of sentinel lymph node navigation surgery to pharyngeal and laryngeal cancers by evaluating the combination of contrast-enhanced ultrasonography and indocyanine green fluorescence in animal models. This was a prospective, nonrandomized, experimental study in rabbit and swine animal models. A mixture of indocyanine green and Sonazoid was used as the tracer. The tracer mixture was injected into the tongue, larynx, or pharynx. The sentinel lymph nodes were identified transcutaneously by infra-red camera and contrast-enhanced ultrasonography. Detection time and extraction time of the sentinel lymph nodes were measured. The safety of the tracer mixture in terms of mucosal reaction was evaluated macroscopically and microscopically. Sentinel lymph nodes were detected transcutaneously by contrast-enhanced ultrasonography alone. The number of sentinel lymph nodes detected was one or two. Despite observation of contrast enhancement of Sonazoid for at least 90 minutes, the number of sentinel lymph nodes detected did not change. The average extraction time of sentinel lymph nodes was 4.8 minutes. Indocyanine green fluorescence offered visual information during lymph node biopsy. The safety of the tracer was confirmed by absence of laryngeal edema both macro and microscopically. The combination method of indocyanine green fluorescence and contrast-enhanced ultrasonography for detecting sentinel lymph nodes during surgery for head and neck cancer seems promising, especially for pharyngeal and laryngeal cancer. Further clinical studies to confirm this are warranted.

Indocyanine green angiography of juvenile X-linked retinoschisis.

PubMed

Souied, Eric H; Goritsa, Anna; Querques, Giuseppe; Coscas, Gabriel; Soubrane, Gisele

2005-09-01

In juvenile X-linked retinoschisis (XLRS), fluorescein angiography is usually unremarkable and contributes poorly to the diagnosis. However, indocyanine green (ICG) angiography features in eyes that are affected with XLRS were not yet described. Retrospective observational case series. A complete ophthalmologic examination that included ICG angiography was performed on three unrelated male patients (six eyes) who were 15, 22, and 48 years old. A distinct hyperfluorescent stellate pattern in the macular area that was associated with radial lines of hypofluorescence that were centered on the foveola was observed on the early phase of ICG examination (six of six eyes). This feature disappeared on the late phase of ICG examination. On these six XLRS eyes, early phases of ICG examination revealed an unusual radial aspect on the macula. This finding suggests that ICG angiography may be useful for the diagnosis of XLRS.

Whom should we SPY? A cost analysis of laser-assisted indocyanine green angiography in prevention of mastectomy skin flap necrosis during prosthesis-based breast reconstruction.

PubMed

Kanuri, Arjun; Liu, Allen S; Guo, Lifei

2014-04-01

Skin flap necrosis is the most common complication following prosthesis-based breast reconstruction. Many studies have reported on the efficacy of laser-assisted indocyanine green angiography (SPY Elite System) in detecting flap necrosis. A cost-effectiveness analysis of laser-assisted indocyanine green angiography is lacking. The authors performed a retrospective review of all consecutive immediate postmastectomy prosthesis-based reconstructions at the Brigham and Women's Hospital over a 7-year 10-month period. The rate of mastectomy skin flap necrosis and related implant loss was determined for the entire cohort and for the subgroups of patients at increased risk for developing this complication: smokers, obese patients, and patients with large breasts. Cost of treating implant loss and skin flap necrosis was calculated based on the average treatment courses and costs at the authors' institution. The cost of the SPY was obtained from LifeCell Corp. From January of 2004 through October of 2011, 79 of 710 prosthesis-based breast reconstructions (11.1 percent) developed mastectomy skin flap necrosis requiring excision and reclosure. Performing laser-assisted indocyanine green angiography on the entire cohort would result in an additional cost of $1537.30 per case of flap necrosis prevented. If laser-assisted indocyanine green angiography was performed on only these high-risk subgroups, the cost savings per case of flap necrosis prevented is $2098.80 for smokers, $5162.30 for patients with a body mass index greater than 30, and $1892.70 for patients with mastectomy weight greater than 800 g. Laser-assisted indocyanine green angiography is not cost-effective as a preventative measure for flap necrosis if used indiscriminately on all patients undergoing prosthesis-based breast reconstructions, but it is cost-effective for high-risk patients, such as smokers, obese patients, and patients with large breasts.

Dynamic indocyanine green angiography measurements

NASA Astrophysics Data System (ADS)

Holmes, Timothy; Invernizzi, Alessandro; Larkin, Sean; Staurenghi, Giovanni

2012-11-01

Dynamic indocyanine green imaging uses a scanning laser ophthalmoscope and a fluorescent dye to produce movies of the dye-filling pattern in the retina and choroid of the eye. It is used for evaluating choroidal neovascularization. Movies are examined to identify the anatomy of the pathology for planning treatment and to evaluate progression or response to treatment. The popularity of this approach is affected by the complexity and difficulty in interpreting the movies. Software algorithms were developed to produce images from the movies that are easy to interpret. A mathematical model is formulated of the flow dynamics, and a fitting algorithm is designed that solves for the flow parameters. The images provide information about flow and perfusion, including regions of change between examinations. Imaged measures include the dye fill-time, temporal dispersion, and magnitude of the dye dilution temporal curves associated with image pixels. Cases show how the software can help to identify clinically relevant anatomy such as feeder vessels, drain vessels, capillary networks, and normal choroidal draining vessels. As a potential tool for research into the character of neovascular conditions and treatments, it reveals the flow dynamics and character of the lesion. Future varieties of this methodology may be used for evaluating the success of engineered tissue transplants, surgical flaps, reconstructive surgery, breast surgery, and many other surgical applications where flow, perfusion, and vascularity of tissue are important.

Doxorubicin and Indocyanine Green Loaded Hybrid Bicelles for Fluorescence Imaging Guided Synergetic Chemo/Photothermal Therapy.

PubMed

Lin, Li; Liang, Xiaolong; Xu, Yunxue; Yang, Yongbo; Li, Xiaoda; Dai, Zhifei

2017-09-20

Hybrid bicelles have been demonstrated to have great potential for hydrophobic drug delivery. Herein, we report a near-infrared light-driven, temperature-sensitive hybrid bicelles co-encapsulating hydrophobic doxorubicin (DOX) and indocyanine green (ICG) (DOX/ICG@HBs). Encapsulation of ICG into the lipid bilayer membrane of DOX/ICG@HBs results in higher photostability than free ICG. DOX/ICG@HBs exhibited temperature-regulated drug release behavior and significant photothermal cytotoxicity. After tail vein injection, such discotic nanoparticles of DOX/ICG@HBs were found to accumulate selectively at the tumor site and act as an efficient probe to enhance fluorescence imaging greatly. The in vivo experiments showed that the DOX/ICG@HBs-mediated chemo- and photothermal combination therapy was more cytotoxic to tumor cells than the photothermal treatment or the chemotherapy alone due to the synergistic effect, reducing the occurrence of tumor metastasis. Therefore, DOX/ICG@HBs can act as a powerful nanotheranostic agent for chemo/photothermal therapy of cancer under the guidance of near-infrared fluorescence imaging.

Lipid nanoparticle vectorization of indocyanine green improves fluorescence imaging for tumor diagnosis and lymph node resection.

PubMed

Navarro, Fabrice P; Berger, Michel; Guillermet, Stéphanie; Josserand, Véronique; Guyon, Laurent; Neumann, Emmanuelle; Vinet, Françoise; Texier, Isabelle

2012-10-01

Fluorescence imaging is opening a new era in image-guided surgery and other medical applications. The only FDA approved contrast agent in the near infrared is IndoCyanine Green (ICG), which despites its low toxicity, displays poor chemical and optical properties for long-term and sensitive imaging applications in human. Lipid nanoparticles are investigated for improving ICG optical properties and in vivo fluorescence imaging sensitivity. 30 nm diameter lipid nanoparticles (LNP) are loaded with ICG. Their characterization and use for tumor and lymph node imaging are described. Nano-formulation benefits dye optical properties (6 times improved brightness) and chemical stability (>6 months at 4 degrees C in aqueous buffer). More importantly, LNP vectorization allows never reported sensitive and prolonged (>1 day) labeling of tumors and lymph nodes. Composed of human-use approved ingredients, this novel ICG nanometric formulation is foreseen to expand rapidly the field of clinical fluorescence imaging applications.

Fabrication of Indocyanine Green and 2H, 3H-perfluoropentane loaded microbubbles for fluorescence and ultrasound imaging

NASA Astrophysics Data System (ADS)

He, Yutong; Wu, Qiang; Ma, Rong; Chang, Shufang; Shao, Pengfei; Xu, Ronald

2016-03-01

As a near-infrared (NIR) fluorescence dye, Indocyanine Green (ICG) has not gained broader clinical applications, owing to its multiple limitations such as concentration-dependent aggregation, low fluorescence quantum yield, poor physicochemical stability and rapid elimination from the body. In the meanwhile, 2H,3H-perfluoropentane (H-PFP) has been widely studied in ultrasound imaging as a vehicle for targeted delivery of contrast agents and drugs. We synthesized a novel dual-modal fluorescence and ultrasound contrast agent by encapsulating ICG and H-PFP in lipid microbubbles using a liquid-driven coaxial flow focusing (LDCFF) process. Uniform microbubbles with the sizes ranging from 1-10um and great ICG loading efficiency was achieved by this method. Our benchtop experiments showed that ICG/H-PFP microbubbles exhibited less aggregation, increased fluorescence intensity and more stable photostability compared to free ICG aqueous solution. Our phantom experiments demonstrated that ICG/H-PFP microbubbles enhanced the imaging contrasts in fluorescence imaging and ultrasonography. Our animal experiments indicated that ICG/H-PFP microbubbles extended the ICG life time and facilitated dual mode fluorescence and ultrasound imaging in vivo.

Indocyanine Green Enables Near-Infrared Fluorescence Imaging of Lipid-Rich, Inflamed Atherosclerotic Plaques

PubMed Central

Vinegoni, Claudio; Botnaru, Ion; Aikawa, Elena; Calfon, Marcella A.; Iwamoto, Yoshiko; Folco, Eduardo J.; Ntziachristos, Vasilis; Weissleder, Ralph; Libby, Peter; Jaffer, Farouc A.

2011-01-01

New high-resolution molecular and structural imaging strategies are needed to visualize high-risk plaques that are likely to cause acute myocardial infarction, because current diagnostic methods do not reliably identify at-risk subjects. While molecular imaging agents are available for lower-resolution detection of atherosclerosis in large arteries, a lack of imaging agents coupled to high-resolution modalities has limited molecular imaging of atherosclerosis in the smaller coronary arteries [AU: ok? YES]. Here, we have demonstrated that indocyanine green (ICG), an FDA-approved near-infrared fluorescence (NIRF) emitting compound, targets atheromas within 20 minutes of injection and provides sufficient signal enhancement for in vivo detection of lipid-rich, inflamed, coronary-sized plaques in atherosclerotic rabbits. In vivo NIRF sensing was achieved with an intravascular wire in the aortae, a vessel of comparable caliber to human coronary arteries. Ex vivo fluorescence reflectance imaging studies showed high plaque target-to-background ratios in atheroma-bearing rabbits injected with ICG, compared to atheroma-bearing rabbits injected with saline. In vitro studies using human macrophages established that ICG preferentially targets lipid-loaded macrophages. In an early clinical study of human atheroma specimens from four patients, we found that ICG colocalized with plaque macrophages and lipids. The atheroma-targeting capability of ICG has the potential to accelerate the clinical development of NIRF molecular imaging of high-risk plaques in humans. PMID:21613624

Indocyanine green-based fluorescent angiography in breast reconstruction

PubMed Central

Chae, Michael P.; Rozen, Warren Matthew

2016-01-01

Background Fluorescent angiography (FA) has been useful for assessing blood flow and assessing tissue perfusion in ophthalmology and other surgical disciplines for decades. In plastic surgery, indocyanine green (ICG) dye-based FA is a relatively novel imaging technology with high potential in various applications. We review the various FA detector systems currently available and critically appraise its utility in breast reconstruction. Methods A review of the published English literature dating from 1950 to 2015 using databases, such as PubMed, Medline, Web of Science, and EMBASE was undertaken. Results In comparison to the old fluorescein dye, ICG has a superior side effect profile and can be accurately detected by various commercial devices, such as SPY Elite (Novadaq, Canada), FLARE (Curadel LLC, USA), PDE-Neo (Hamamatsu Photonics, Japan), Fluobeam 800 (Fluoptics, France), and IC-View (Pulsion Medical Systems AG, Germany). In breast reconstruction, ICG has established as a safer, more accurate tracer agent, in lieu of the traditional blue dyes, for detection of sentinel lymph nodes with radioactive isotopes (99m-Technetium). In prosthesis-based breast reconstruction, intraoperative assessment of the mastectomy skin flap to guide excision of hypoperfused areas translates to improved clinical outcomes. Similarly, in autologous breast reconstructions, FA can be utilized to detect poorly perfused areas of the free flap, evaluate microvascular anastomosis for patency, and assess SIEA vascular territory for use as an alternative free flap with minimal donor site morbidity. Conclusions ICG-based FA is a novel, useful tool for various applications in breast reconstruction. More studies with higher level of evidence are currently lacking to validate this technology. PMID:27047782

Utility of indocyanine green videoangiography in subcortical arteriovenous malformation resection.

PubMed

Rustemi, Oriela; Scienza, Renato; Della Puppa, Alessandro

2017-07-01

Subcortical arteriovenous malformations (AVMs) are surgically challenging. Localization is crucial for eloquent areas, and complete resection evaluation is uncertain. Indocyanine green videoangiography (ICG-VA) can assist this surgery. An illustrative video of a subcortical frontoparietal bleeding AVM resection assisted by ICG-VA is presented. A bleeding arterial feeder aneurysm was embolized in the acute phase to protect against rebleeding. ICG-VA helped to detect the AVM's superficial arterialized draining vein, distinguishing it from normal cortical veins. This enabled a customized sulcus approach. ICG-VA showed normalized flow through the previously arterialized vein, confirming the AVM's complete resection. This applies when there is a single drainage remaining. The video can be found here: https://youtu.be/L7yJEE66kV0 .

Indocyanine green fluorescence in second near-infrared (NIR-II) window

PubMed Central

Bhavane, Rohan; Ghaghada, Ketan B.; Vasudevan, Sanjeev A.; Kaay, Alexander; Annapragada, Ananth

2017-01-01

Indocyanine green (ICG), a FDA approved near infrared (NIR) fluorescent agent, is used in the clinic for a variety of applications including lymphangiography, intra-operative lymph node identification, tumor imaging, superficial vascular imaging, and marking ischemic tissues. These applications operate in the so-called “NIR-I” window (700–900 nm). Recently, imaging in the “NIR-II” window (1000–1700 nm) has attracted attention since, at longer wavelengths, photon absorption, and scattering effects by tissue components are reduced, making it possible to image deeper into the underlying tissue. Agents for NIR-II imaging are, however, still in pre-clinical development. In this study, we investigated ICG as a NIR-II dye. The absorbance and NIR-II fluorescence emission of ICG were measured in different media (PBS, plasma and ethanol) for a range of ICG concentrations. In vitro and in vivo testing were performed using a custom-built spectral NIR assembly to facilitate simultaneous imaging in NIR-I and NIR-II window. In vitro studies using ICG were performed using capillary tubes (as a simulation of blood vessels) embedded in Intralipid solution and tissue phantoms to evaluate depth of tissue penetration in NIR-I and NIR-II window. In vivo imaging using ICG was performed in nude mice to evaluate vascular visualization in the hind limb in the NIR-I and II windows. Contrast-to-noise ratios (CNR) were calculated for comparison of image quality in NIR-I and NIR-II window. ICG exhibited significant fluorescence emission in the NIR-II window and this emission (similar to the absorption profile) is substantially affected by the environment of the ICG molecules. In vivo imaging further confirmed the utility of ICG as a fluorescent dye in the NIR-II domain, with the CNR values being ~2 times those in the NIR-I window. The availability of an FDA approved imaging agent could accelerate the clinical translation of NIR-II imaging technology. PMID:29121078

Eradication of C. albicans and T. rubrum with photoactivated indocyanine green, Citrus aurantifolia essential oil and fluconazole.

PubMed

Fekrazad, Reza; Poorsattar Bejeh Mir, Arash; Ghasemi Barghi, Vadood; Shams-Ghahfarokhi, Masoomeh

2015-06-01

We aimed to evaluate the efficacy of alternative therapies rather than the current antifungal conventional therapy and with assessing the hypothesis of photoactivation of citrus essential oil, fluconazole and Indocyanine green to treat two common mucocutaneous fungal infections. Suspensions of Candida albicans and Tricophyton rubrum containing 10(6)cells/ml was prepared. Equal samples were treated with infrared (IR) laser irradiation (810 nm, 55 J/cm(2)) in the presence of Indocyanine green (Emundo, 1 mg/ml) (IRLE), photoactivated Citrus aurantifolia essential oil (EO) with sequential exposure to natural and tungsten lights (CE), control non-activated essential oil (CC), laser alone (IRL), indocyanine green alone (E) and neither of treatments as the control group (C). Additional fluconazole (FL, 25.6 μg/ml) and IR activated fluconazole (IRLFL) groups were designed for T. rubrum fungi. Inoculums were serially diluted to 10(-2) and 10(-4) and streaked on Sabouraud dextrose agar plates. Final outcomes were assessed as the percent of reduction. Cell reduction rates (%) in C. albicans groups were 99.99 (CE), 91.67 (IRLE), 86.67 (CC), 72.37 (E) and 67.27 (RL). Whereas, a 99.99 (CE), 89.99 (CC), 74.5 (IRLE), 64.5 (E), 38.5 (IRLF), 37.5 (RL), and 31 (FL) percent eradication was achieved in T. rubrum groups. Photoactivation of Citrus EO increased the killing capability by 10-13%. A modest 7.5% augmented effect was observed with IR activation of Fluconazole. Both Citrus EO and photothermal-photodynamic therapy with ICG and IR diode laser exhibited remarkable lethal effect on fungal cells. Candida viable cells are more susceptible to laser only and ICG only treatments than Tricophyton cells. Copyright © 2015 Elsevier B.V. All rights reserved.

Assessing pharmacokinetics of indocyanine green-loaded nanoparticle in tumor with a dynamic diffuse fluorescence tomography system

NASA Astrophysics Data System (ADS)

Zhang, Yanqi; Yin, Guoyan; Zhao, Huijuan; Ma, Wenjuan; Gao, Feng; Zhang, Limin

2018-02-01

Real-time and continuous monitoring of drug release in vivo is an important task in pharmaceutical development. Here, we devoted to explore a real-time continuous study of the pharmacokinetics of free indocyanine green (ICG) and ICG loaded in the shell-sheddable nanoparticles in tumor based on a dynamic diffuse fluorescence tomography (DFT) system: A highly-sensitive dynamic DFT system of CT-scanning mode generates informative and instantaneous sampling datasets; An analysis procedure extracts the pharmacokinetic parameters from the reconstructed time curves of the mean ICG concentration in tumor, using the Gauss-Newton scheme based on two-compartment model. Compared with the pharmacokinetic parameters of free ICG in tumor, the ICG loaded in the shell-sheddable nanoparticles shows efficient accumulation in tumor. The results demonstrate our proposed dynamic-DFT can provide an integrated and continuous view of the drug delivery of the injected agents in different formulations, which is helpful for the development of diagnosis and therapy for tumors.

Indocyanine Green-Encapsulated Hybrid Polymeric Nanomicelles for Photothermal Cancer Therapy.

PubMed

Jian, Wei-Hong; Yu, Ting-Wei; Chen, Chien-Ju; Huang, Wen-Chia; Chiu, Hsin-Cheng; Chiang, Wen-Hsuan

2015-06-09

Indocyanine green (ICG), an FDA approved medical near-infrared (NIR) imaging agent, has been extensively used in cancer theranosis. However, the limited aqueous photostability, rapid body clearance, and poor cellular uptake severely restrict its practical applications. For these problems to be overcome, ICG-encapsulated hybrid polymeric nanomicelles (PNMs) were developed in this work through coassociation of the amphiphilic diblock copolymer poly(lactic-co-glycolic acid)-b-poly(ethylene glycol) (PLGA-b-PEG) and hydrophobic electrostatic complexes composed of ICG molecules and branched poly(ethylenimine) (PEI). The ICG-encapsulated hybrid PNMs featured a hydrophobic PLGA/ICG/PEI core stabilized by hydrophilic PEG shells. The encapsulation of electrostatic ICG/PEI complexes into the compact PLGA-rich core not only facilitated the ICG loading but also promoted its aqueous optical stability. The effects of the chain length of PEI in combination with ICG on the physiochemical properties of PNMs and their drug leakage were also investigated. PEI(10k) (10 kDa) could form highly robust and dense complexes with ICG, and thus prominently reduced ICG outflow from the PNMs. The results of in vitro cellular uptake and cytotoxicity studies revealed that the ICG/PEI(10k)-loaded PNMs significantly promoted cellular uptake of ICG by HeLa cells due to their near-neutral surface, and thereby augmented the NIR-triggered hyperthermia effect in destroying cancer cells. These findings strongly indicate that the ICG/PEI10k-loaded PNMs have significant potential for attaining effective cancer imaging and photothermal therapy.

[Sentinel node detection using optonuclear probe (gamma and fluorescence) after green indocyanine and radio-isotope injections].

PubMed

Poumellec, M-A; Dejode, M; Figl, A; Darcourt, J; Haudebourg, J; Sabah, Y; Voury, A; Martaens, A; Barranger, E

2016-04-01

Assess the biopsy's feasibility of the sentinel lymph node biopsy (SLNB) using optonuclear probe after of indocyanine green (ICG) and radio-isotope (RI) injections. Twenty-one patients with a localized breast cancer and unsuspicious axillary nodes underwent a SLNB after both injections of ICG and radio-isotope. One or more SLN were identified on the 21 patients (identification rate of 100%). The median number SLN was 2 (1-3). Twenty SLN were both radio-actives and fluorescents (54.1%), 11 fluorescent only (29.7%) and 6 were only radio-actives (16.2%). Seven patients had a metastatic SLN (8 SLN overall). Among them, only one had a micrometastasic SLN, 5 others had a macrometastatic SLN and one patient had two macrometastatic SLNs. Among the 8 metastatic SLN, 5 were both fluorescent and radioactive, 2 were only fluorescent and 1 was only radioactive. Detection SLN using optonuclear probe after indocyanine green and radio-isotope injections is effective and could be, after validation by randomized trial, a reliable alternative to the blue dye injection for teams who consider that combined detection as the reference. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Indocyanine green fluorescence-guided surgery after IV injection in metastatic colorectal cancer: A systematic review.

PubMed

Liberale, G; Bourgeois, P; Larsimont, D; Moreau, M; Donckier, V; Ishizawa, T

2017-09-01

Indocyanine green fluorescence-guided surgery (ICG-FGS) has emerged as a potential new imaging modality for improving the detection of hepatic, lymph node (LN), and peritoneal metastases in colorectal cancer (CRC) patients. The aim of this paper is to review the available literature in the clinical setting of ICG-FGS for tumoral detection in various fields of metastatic colorectal disease. PubMed and Medline literature databases were searched for original articles on the use of ICG in the setting of clinical studies on colorectal cancer. The search terms used were "near-infrared fluorescence", "intraoperative imaging", "indocyanine green", "human" and "colorectal cancer". ICG fluorescence imaging (ICG-FI) is clearly supported as an intraoperative technique that allows the detection of additional superficial hepatic metastases of CRC. Data on the role of ICG-FI in the intraoperative detection of peritoneal metastases and LN metastases are scarce but encouraging and ICG-FI could potentially improve the staging and treatment of these patients. ICG-FI is a promising imaging technique in the detection of small infraclinic LN, hepatic, and peritoneal metastatic deposits that may allow better staging and more complete surgical resection with a potential prognostic benefit for patients. Copyright © 2017 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.

Effect of ranibizumab on high-speed indocyanine green angiography and minimum intensity projection optical coherence tomography findings in neovascular age-related macular degeneration.

PubMed

Nicholson, Benjamin P; Nigam, Divya; Toy, Brian; Stetson, Paul F; Agrón, Elvira; Jacobs-El, Naima; Cunningham, Denise; Cukras, Catherine; Wong, Wai; Wiley, Henry; Chew, Emily; Ferris, Frederick; Meyerle, Catherine B

2015-01-01

The purpose of this 1-year prospective study was to investigate how induction/pro re nata ranibizumab intravitreal treatment of eyes with neovascular age-related macular degeneration affects the anatomy of choroidal neovascularization (CNV) and the overlying outer retinal tissue. High-speed indocyanine green (HS-ICG) angiography measurements provided quantification of the CNV size in 60 patients followed for 1 year. Minimum intensity projection optical coherence tomography (MinIP OCT), a novel algorithm assessing minimum optical intensity between the internal limiting membrane and retinal pigment epithelium, measured the area of outer retinal disruption overlying the CNV. Fluorescein angiography was also assessed to evaluate late retinal leakage. After 1 year, the mean area of CNV measured with indocyanine green angiography decreased by 5.8%. The mean area of MinIP OCT of outer retinal disruption overlying the CNV decreased by 4.2%. Mean area of fluorescein angiography leakage decreased by 6.3%. Both the area of outer retinal disruption measured with MinIP OCT and the area of leakage on fluorescein angiography typically exceeded the area of CNV on indocyanine green angiography at baseline and 1 year. Choroidal neovascularization treated with induction/pro re nata intravitreal ranibizumab for 1 year essentially remained static. Minimum intensity projection optical coherence tomography suggests that the area of outer retinal disruption overlying the CNV may be greater than the CNV itself and often correlates with the leakage area on fluorescein angiography. Additionally, there was minimal change in the area of outer retinal disruption on MinIP OCT even when fluid resolved. Measurements of the extent of CNV lesions based on indocyanine green angiography and MinIP OCT may provide useful outcome variables to help assess the CNV complex longitudinally and warrant further validation.

Indocyanine green-laser thermolysis of acne vulgaris

NASA Astrophysics Data System (ADS)

Genina, Elina A.; Bashkatov, Alexey N.; Simonenko, Georgy V.; Tuchin, Valery V.; Yaroslavsky, Ilya V.; Altshuler, Gregory B.

2005-08-01

The near-infrared (NIR) laser radiation due to its high penetration depth is widely used in phototherapy and photothermolysis. In application to skin appendages a high selectivity of laser treatment is needed to prevent light action on surrounding tissues. Indocyanine Green (ICG) dye may provide a high selectivity of treatment due to effective ICG uploading by a target and its narrow band of considerable absorption just at the wavelength of the NIR diode laser. The goal of this study is to demonstrate the efficacy of the NIR diode laser photothermolysis in combination with topical application of ICG suggested for treatment of acne vulgaris. Two volunteers with back-located acne were enrolled. Skin sites of subjects were stained by ICG and irradiated by NIR laser-diode light (803 or 809 nm). The individual acne lesions were photothermally treated at 18 W/cm2 (803 nm, 0.5 sec) without skin surface cooling or at 200 W/cm2 (809 nm, 0.5 sec) with cooling. The results of the observations during a month after the treatment have shown that ICG stained acne inflammatory elements were destructed for light exposures of 0.5 sec.

Indocyanine Green Videoangiography in Negative: Spinal Dural Arteriovenous Fistula.

PubMed

Simal Julián, Juan Antonio; Miranda Lloret, Pablo; Sanromán Álvarez, Pablo; Pérez de San Román, Laila; Beltrán Giner, Andrés; Botella Asunción, Carlos

2015-08-01

Introduction This work reports the first indocyanine green videoangiography (IGV) in negative published with video format support. This technique, so called because its first phase is performed with occlusion of the vessel suspected of being pathologic, is used for the diagnosis of spinal arteriovenous fistula (sDAVF). Case Report The authors present the case of a 68-year-old man with an sDAVF fed by the right T7 segmentary artery. IGV was initially performed with the presumptive fistula feeder occluded for less than 1 minute, which provided both diagnostic and postexclusion control in one procedure. This technique therefore is reversible by not prolonging vascular exclusion times. Discussion IGV in negative is an extremely visual and intuitive procedure that represents an improvement over conventional IGV. Conclusion Studies with larger sample sizes are necessary to determine whether IGV in negative can further reduce the need for postoperative digital subtraction angiography.

Indocyanine green for intraoperative localization of ureter.

PubMed

Siddighi, Sam; Yune, Junchan Joshua; Hardesty, Jeffrey

2014-10-01

Intraurethral injection of indocyanine green (ICG; Akorn, Lake Forest, IL) and visualization under near-infrared (NIR) light allows for real-time delineation of the ureter. This technology can be helpful to prevent iatrogenic ureteral injury during pelvic surgery. Patients were scheduled to undergo robot-assisted laparoscopic sacrocolpopexy. Before the robotic surgery started, the tip of a 6-F ureteral catheter was inserted into the ureteral orifice. Twenty-five milligrams of ICG was dissolved in 10-mL of sterile water and injected through the open catheter. The same procedure was repeated on the opposite side. The ICG reversibly stained the inside lining of the ureter by binding to proteins on urothelial layer. During the course of robotic surgery, the NIR laser on the da Vinci Si surgical robot (Intuitive Surgical, Inc, Sunnyvale, CA) was used to excite ICG molecules, and infrared emission was captured by the da Vinci filtered lens system and electronically converted to green color. Thus, the ureter fluoresced green, which allowed its definitive identification throughout the entire case. In all cases of >10 patients, we were able to visualize bilateral ureters with this technology, even though there was some variation in brightness that depended on the depth of the ureter from the peritoneal surface. For example, in a morbidly obese patient, the ureters were not as bright green. There were no intraoperative or postoperative adverse effects attributable to ICG administration for up to 2 months of observation. In our experience, this novel method of intraurethral ICG injection was helpful to identify the entire course of ureter and allowed a safe approach to tissues that were adjacent to the urinary tract. The advantage of our technique is that it requires the insertion of just the tip of ureteral catheter. Despite our limited cohort of patients, our findings are consistent with previous reports of the excellent safety profile of intravenous and intrabiliary ICG

PDI using nebulized indocyanine green for pneumonia treatment

NASA Astrophysics Data System (ADS)

Geralde, Mariana C.; Kassab, Giulia; Inada, Natalia M.; Kurachi, Cristina; Bagnato, Vanderlei S.

2018-02-01

Infectious pneumonia is a major cause of morbidity/mortality, mainly due to the increasing rate of microorganisms resistant to antibiotics. Photodynamic Inactivation (PDI) is emerging as a promising treatment option, which effects are based on oxidative stress, targeting several biomolecules and probably preventing potential resistant strains. In previous studies, the in vitro inactivation of Streptococcus pneumoniae using indocyanine green (ICG) and infrared (IR) light source (780 nm) was successful, and achieving satisfactory reduction of colony-forming units (CFU/mL). In the present study, a proof-of-principle protocol was designed to treat lung infections by PDI using extracorporeal irradiation with a 780 nm laser device and nebulized ICG as photosensitizer. Balb/c mice were infected with S. pneumoniae and PDI was performed two days after infection using 800 μM of nebulized ICG and extracorporeal irradiation. Our results indicate that IR-extracorporeal PDI using nebulized ICG may be considered a potential pneumonia treatment, and pulmonary decontamination with PDI may be used as a single therapy or as an adjuvant for antibiotics.

Indocyanine green videoangiography "in negative": definition and usefulness in spinal dural arteriovenous fistulae.

PubMed

Simal Julián, Juan Antonio; Miranda Lloret, Pablo; López González, Antonio; Evangelista Zamora, Rocío; Botella Asunción, Carlos

2013-05-01

Indocyanine green videoangiography (IGV) has proven its effectiveness in the field of exovascular neurosurgery, both in the intracranial and spinal compartment, but is necessary to define a systematic process for the performance of the IGV to facilitate its interpretation during the procedure. We have defined and applied the concept of videoangiography "in negative" (INIGV) to spinal dural arteriovenous fistulae (dAVF) for the detection and treatment of arteriovenous shunts, so called because the first phase is performed with the vessel suggestive of being pathological occluded. A Pentero-operating microscope with near-infrared IGV-integrated system (Carl Zeiss Co., Germany) was used. At our institution, 24 patients were treated for a spinal dAVF between 1995 and 2011, only in the last 4 cases, INIGV was performed. We describe the IGV in negative procedure and show the most illustrative cases. In all cases, the fistula occlusion was confirmed by postoperative selective digital subtraction angiography (DSA). INIGV demonstrate its capacity in detecting vessels not actually arterialized that should be respected and avoid some of the main limitations of the conventional IGV. This is a technical description about an Indocyanine green (ICG) videoangiographic procedure modification that is superior to merely performing ICG before and after clipping of a dAVF. The INIGV results are rapid and easy to interpret procedure and provide great advantages to the dAVF treatment. Nevertheless, further studies are needed with a larger sample size to determine if INIGV may reduce the need to perform immediate postoperative DSA.

A Classic Near-Infrared Probe Indocyanine Green for Detecting Singlet Oxygen.

PubMed

Tang, Cheng-Yi; Wu, Feng-Yao; Yang, Min-Kai; Guo, Yu-Min; Lu, Gui-Hua; Yang, Yong-Hua

2016-02-06

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.

Improvement of the sentinel lymph node detection rate of cervical sentinel lymph node biopsy using real-time fluorescence navigation with indocyanine green in head and neck skin cancer.

PubMed

Nakamura, Yasuhiro; Fujisawa, Yasuhiro; Nakamura, Yoshiyuki; Maruyama, Hiroshi; Furuta, Jun-ichi; Kawachi, Yasuhiro; Otsuka, Fujio

2013-06-01

The standard technique using lymphoscintigraphy, blue dye and a gamma probe has established a reliable method for sentinel node biopsy for skin cancer. However, the detection rate of cervical sentinel lymph nodes (SLN) is generally lower than that of inguinal or axillary SLN because of the complexity of lymphatic drainage in the head and neck region and the "shine-through" phenomenon. Recently, indocyanine green fluorescence imaging has been reported as a new method to detect SLN. We hypothesized that fluorescence navigation with indocyanine green in combination with the standard technique would improve the detection rate of cervical sentinel nodes. We performed cervical sentinel node biopsies using the standard technique in 20 basins of 18 patients (group A) and using fluorescence navigation in combination with the standard technique in 12 basins of 16 patients (group B). The mean number of sentinel nodes was two per basin (range, 1-4) in group A and three per basin (range, 1-5) in group B. The detection rate of sentinel nodes was 83% (29/35) in group A and 95% (36/38) in group B. The false-negative rate was 6% (1/18 patients) in group A and 0% in group B. Fluorescence navigation with indocyanine green may improve the cervical sentinel node detection rate. However, greater collection of data regarding the usefulness of cervical sentinel node biopsy using indocyanine green is necessary. © 2013 Japanese Dermatological Association.

[Evaluation of green indocyanine interest compared to Technetium in sentinel lymph node detection in breast cancer].

PubMed

Guenane, Y; Gorj, M; Nguyen, V; Revol, M; Mazouz-Dorval, S

2016-12-01

Axillary sentinel lymph node (SN) biopsy by using indocyanine green (ICG) fluorescence for breast cancer is a recent technique. However, compared to Technetium-99m (Tc), which is the reference technique, its efficiency has received little testing. Between December 2013 and January 2014, 40 patients with node-negative breast cancer underwent SN biopsy by injecting sub areolar Tc in preoperative stage and injecting sub areolar ICG in intraoperative stage. SN were previously identified and resected by using ICG coupled with infrared camera. After resection of fluorescent SN, we check its radioactivity with a gamma probe (isotopic method). In case of residual radioactive labeling in the axillary crease, we remove the remaining SN. We have retrospectively analyzed the SN detection concordance rates of these two methods. In total we resected 53 SN, among which 48 (90.6%) were indocyanine green positive and 53 (100%) Tc positive. The remaining 5 SN were all ICG negative and Tc positive. Using ICG has not caused any side effect. SN detection for breast cancer by using ICG fluorescence is a promising, reliable technique which nonetheless requires a degree of expertise before reaching similar results as the Tc technique. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Indocyanine green loaded liposome nanocarriers for photodynamic therapy using human triple negative breast cancer cells.

PubMed

Shemesh, Colby S; Hardy, Claire W; Yu, David S; Fernandez, Brian; Zhang, Hailing

2014-06-01

The goal of the current research is to evaluate the potential of photodynamic therapy (PDT) in the treatment of triple negative breast cancer (TNBC) with the development of a theranostic thermosensitive liposome platform to deliver indocyanine green (ICG) as the near-infrared (NIR) photosensitizer excited by an 808 nm diode laser. In the PDT protocol, an optimized thermosensitive liposome formulation is investigated to formulate ICG as the photosensitizer, which is exited by laser light at the wavelength of 808 nm delivered by a fiber-coupled laser system. ICG in both free solution and thermosensitive liposomal formulation were evaluated as the NIR photosensitizer and compared in the PDT treatment on a panel of triple negative breast cancer cell lines along with the nontumorigenic mammary epithelial cell line MCF-10A. In addition to cytotoxicity, and clonogenic survival assessment, the role of DNA double strand break damage was evaluated. Both MTT and clonogenic assays revealed that PDT using ICG inhibited the growth of several TNBC cell lines as well as the non-tumorigenic human breast epithelial cell line MCF-10A; and the liposomal formulation of ICG did not compromise the in vitro treatment potency, though free ICG performed slightly more effective in certain cell lines, but was not statistically significant. Cell viability was dose dependent in regards to ICG concentration and irradiation energy. Interestingly, PDT using the described protocol was more potent to inhibit the growth of MDA-MB-468 and HCC-1806 cells, coinciding with the observation that these cells are more sensitive toward DNA damaging agents. In comparison, cell lines HCC-70, BT-549, and MCF-10A were found to have less of an inhibitory effect. Furthermore, substantial DNA double strand breaks (DSBs) were observed 30 min after the PDT treatment via a γ-H2AX staining assay. PDT induced DNA damage has the potential to lead to mutagenicity, which may have various responses depending on the repair

Indocyanine green staining facilitates detection of bleb leakage during trabeculectomy.

PubMed

Okazaki, Teruhiko; Kiuchi, Takahiro; Kawana, Keisuke; Oshika, Tetsuro

2007-03-01

To report a new technique to visualize bleb leakage using indocyanine green (ICG) staining during trabeculectomy. The ICG solution was widely applied over the filtering bleb including the conjunctival wound before completion of trabeculectomy. This procedure was performed in 48 eyes of 44 consecutive patients undergoing trabeculectomy between December 2004 and October 2005. Without staining, bleb leakage was not identified by the direct observation under the operating microscope. ICG staining clearly visualized aqueous leakage from the bleb in 5 eyes (10.4%). The bleb leakage in these eyes was easily repaired with 10-0 nylon sutures, and no eyes, including these 5 cases, showed bleb leakage after surgery. There were no intraoperative and postoperative complications related to ICG application. The application of ICG during trabeculectomy is a simple and useful technique to facilitate detection and repair of the bleb leakage.

[Indocyanine green angiography in "multiple evanescent white dot syndrome" (MEWDS)].

PubMed

Desarnaulds, A B; Borruat, F X; Herbort, C P; de Courten, C

1998-05-01

Multiple evanescent white dot syndrome (MEWDS) is a benign acquired chorioretinal disorder occurring mostly in young adults. Its pathophysiology is unknown. To describe the results of indocyanine green angiography (ICGA) in MEWDS. Four patients with MEWDS were investigated by ICGA. In all cases, ICGA revealed numerous choroidal hypofluorescent lesions that largely outnumbered the lesions visible with either fundoscopy or fluorescein angiography. Three cases showed a blind spot enlargement on perimetry associated with the presence of a large peripapillary hypofluorescent zone on ICGA. Three cases showed macular granularity on fundoscopy correlating with a significant subfoveal hypfluorescent lesion on ICGA. Evolution was always favorable with disappearance of the hypofluorescent choroidal lesions. Our results confirm that MEWDS is primarily a choroidal disorder. The blind spot enlargement and the macular granularity, frequently detected in MEWDS, result from larger peripapillary and subfoveal choroidal lesions.

Application of indocyanine green-fluorescence imaging to full-thickness cholecystectomy.

PubMed

Morita, Kiyomi; Ishizawa, Takeaki; Tani, Keigo; Harada, Nobuhiro; Shimizu, Atsushi; Yamamoto, Satoshi; Takemura, Nobuyuki; Kaneko, Junichi; Aoki, Taku; Sakamoto, Yoshihiro; Sugawara, Yasuhiko; Hasegawa, Kiyoshi; Kokudo, Norihiro

2014-05-01

Fluorescence imaging using indocyanine green (ICG) has recently been applied to laparoscopic surgery to identify cancerous tissues, lymph nodes, and vascular anatomy. Here we report the application of ICG-fluorescence imaging to visualize the boundary between the liver and subserosal tissues of the gallbladder during laparoscopic full-thickness cholecystectomy. A patient with a potentially malignant gallbladder lesion was administered 2.5-mg intravenous ICG just before laparoscopic full-thickness cholecystectomy. Intraoperative fluorescence imaging enabled the real-time delineation of both extrahepatic bile duct anatomy and hepatic parenchyma throughout the procedure, which resulted in complete removal of subserosal tissues between liver and gallbladder. Safe and feasible ICG-fluorescence imaging can be widely applied to laparoscopic hepatobiliary surgery by utilizing a biliary excretion property of ICG. © 2014 Japan Society for Endoscopic Surgery, Asia Endosurgery Task Force and Wiley Publishing Asia Pty Ltd.

Oxygen and indocyanine green loaded phase-transition nanoparticle-mediated photo-sonodynamic cytotoxic effects on rheumatoid arthritis fibroblast-like synoviocytes.

PubMed

Tang, Qin; Cui, Jianyu; Tian, Zhonghua; Sun, Jiangchuan; Wang, Zhigang; Chang, Shufang; Zhu, Shenyin

2017-01-01

Photodynamic therapy and sonodynamic therapy are developing, minimally invasive, and site-specific modalities for cancer therapy. A combined strategy PSDT (photodynamic therapy followed by sonodynamic therapy) has been proposed in this study. Here, we aimed to develop novel biodegradable poly(DL-lactide- co -glycolic acid) phase-transition nanoparticles simultaneously loaded with oxygen and indocyanine green (OI-NPs) and to investigate the cytotoxic effects and the potential mechanisms of OI-NP-mediated PSDT on MH7A synoviocytes. The OI-NPs were prepared using a modified double emulsion method and the physicochemical properties were determined. The cellular uptake of OI-NPs was detected by confocal microscopy and flow cytometry. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromide assay, flow cytometry, and Hoechst 33342/propidium iodide double staining were used to determine the cytotoxic effect of OI-NP-mediated PSDT on MH7A cells. Fluorescence microscope and fluorescence microplate reader were used to detect reactive oxygen species (ROS) generation. The OI-NPs were a stable and efficient carrier to deliver oxygen and indocyanine green, and enhanced cellular uptake was observed in MH7A cells with the nanoparticles. OI-NP-mediated PSDT caused more serious cell damage and more evident cell apoptosis, compared with other groups. Furthermore, increased generation of intracellular ROS was detected in MH7A cells treated with PSDT. Interestingly, the OI-NP-mediated PSDT-induced cell viability loss was effectively rescued by pretreatment with the ROS scavenger N -acetylcysteine. Multifunctional OI-NPs were successfully developed and characterized for the combined delivery of oxygen and indocyanine green, and OI-NP-mediated PSDT would be a potential cytotoxic treatment for MH7A cells. This study may provide a novel strategy for the treatment of RA and develop a model of theranostic application through phase-transition nanoparticle-mediated PSDT in the future.

Oxygen and indocyanine green loaded phase-transition nanoparticle-mediated photo-sonodynamic cytotoxic effects on rheumatoid arthritis fibroblast-like synoviocytes

PubMed Central

Tang, Qin; Cui, Jianyu; Tian, Zhonghua; Sun, Jiangchuan; Wang, Zhigang; Chang, Shufang; Zhu, Shenyin

2017-01-01

Background Photodynamic therapy and sonodynamic therapy are developing, minimally invasive, and site-specific modalities for cancer therapy. A combined strategy PSDT (photodynamic therapy followed by sonodynamic therapy) has been proposed in this study. Here, we aimed to develop novel biodegradable poly(DL-lactide-co-glycolic acid) phase-transition nanoparticles simultaneously loaded with oxygen and indocyanine green (OI-NPs) and to investigate the cytotoxic effects and the potential mechanisms of OI-NP–mediated PSDT on MH7A synoviocytes. Methods The OI-NPs were prepared using a modified double emulsion method and the physicochemical properties were determined. The cellular uptake of OI-NPs was detected by confocal microscopy and flow cytometry. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromide assay, flow cytometry, and Hoechst 33342/propidium iodide double staining were used to determine the cytotoxic effect of OI-NP–mediated PSDT on MH7A cells. Fluorescence microscope and fluorescence microplate reader were used to detect reactive oxygen species (ROS) generation. Results The OI-NPs were a stable and efficient carrier to deliver oxygen and indocyanine green, and enhanced cellular uptake was observed in MH7A cells with the nanoparticles. OI-NP–mediated PSDT caused more serious cell damage and more evident cell apoptosis, compared with other groups. Furthermore, increased generation of intracellular ROS was detected in MH7A cells treated with PSDT. Interestingly, the OI-NP–mediated PSDT-induced cell viability loss was effectively rescued by pretreatment with the ROS scavenger N-acetylcysteine. Conclusion Multifunctional OI-NPs were successfully developed and characterized for the combined delivery of oxygen and indocyanine green, and OI-NP–mediated PSDT would be a potential cytotoxic treatment for MH7A cells. This study may provide a novel strategy for the treatment of RA and develop a model of theranostic application through phase

The feasibility of detecting cerebral blood flow direction using the indocyanine green video angiography.

PubMed

Murai, Yasuo; Nakagawa, Syunsuke; Matano, Fumihiro; Shirokane, Kazutaka; Teramoto, Akira; Morita, Akio

2016-10-01

The intraoperative confirmation of blood flow direction is necessary in cerebral vascular surgery. Using indocyanine green video angiography (ICG-VAG) with the FLOW 800 system, we examined the transit time of the blood vessel of interest and semiquantitatively evaluated the delay time (T1/2max) from indocyanine green (ICG) injection into the donor artery in reconstructive surgery and the middle cerebral artery (MCA) in aneurysmal surgery. The direction of cerebral blood flow (CBF), which can often be confirmed by ICG-VAG, may be more difficult to determine with faster blood flow. Here, we report our findings regarding the feasibility of detecting CBF direction using the FLOW 800 system. Twenty patients undergoing superficial temporal artery (STA) to MCA anastomosis for carotid occlusive disease and 13 patients with a small MCA aneurysm clipping were evaluated using the T1/2max, semiquantitative method with the FLOW 800 system. In STA-MCA anastomosis cases, the regions of interest (ROIs) included: the proximal donor STA and a region more than 10 mm on the distal side of the donor STA near the anastomosis site. In MCA aneurysms, the ROIs included the proximal M1 and distal M2 sides of the MCA aneurysm. T1/2max was significantly shorter for the proximal sites compared to the distal sites for all subjects (ps < 0.01). T1/2max was shorter for all subjects in the proximal sites. The direction of CBF can be determined using the FLOW 800 system.

Effectiveness of Intraoperative Indocyanine Green Videoangiography in Avoiding Failure in Proximal Clipping for Dissecting Vertebral Artery Aneurysm Associated with Double Origin of the Posterior Inferior Cerebellar Artery.

PubMed

Omoto, Koji; Motoyama, Yasushi; Shida, Yoichi; Nakagawa, Ichiro; Park, Young-Soo; Nakase, Hiroyuki

2016-06-01

Double origin of the posterior inferior cerebellar artery (PICA) is rarely reported but is associated with cerebral aneurysm and dissection. Such aneurysms and dissections with unusual anatomic dispositions present the surgeon or physician with difficulties during treatment. A 65-year-old man presented with severe subarachnoid hemorrhage caused by a left dissecting VA, which was treated with proximal clipping. No aberrant origin of the PICA was recognized on initial imaging. Dissecting VA was confirmed from mural discoloration and obliterated by clip application proximal to the dissection. However, the dissecting VA that should have been eliminated from the circulation was still depicted on indocyanine green videoangiography. Meticulous inspection revealed an aberrant branch connecting the VA with the PICA. Termination of the dissecting VA was accomplished by division of the aberrant stem of the PICA and was confirmed by indocyanine green videoangiography. Despite its rarity, the possibility of a double origin of the PICA should be considered when treating a dissecting VA. Missing a small aberrant origin of the PICA would lead to treatment failure but can be detected by indocyanine green videoangiography during open direct surgery. Copyright © 2016 Elsevier Inc. All rights reserved.

Vaporization and recondensation dynamics of indocyanine green-loaded perfluoropentane droplets irradiated by a short pulse laser

NASA Astrophysics Data System (ADS)

Yu, Jaesok; Chen, Xucai; Villanueva, Flordeliza S.; Kim, Kang

2016-12-01

Phase-transition droplets have been proposed as promising contrast agents for ultrasound and photoacoustic imaging. Short pulse laser activated perfluorocarbon-based droplets, especially when in a medium with a temperature below their boiling point, undergo phase changes of vaporization and recondensation in response to pulsed laser irradiation. Here, we report and discuss the vaporization and recondensation dynamics of perfluoropentane droplets containing indocyanine green in response to a short pulsed laser with optical and acoustic measurements. To investigate the effect of temperature on the vaporization process, an imaging chamber was mounted on a temperature-controlled water reservoir and then the vaporization event was recorded at 5 million frames per second via a high-speed camera. The high-speed movies show that most of the droplets within the laser beam area expanded rapidly as soon as they were exposed to the laser pulse and immediately recondensed within 1-2 μs. The vaporization/recondensation process was consistently reproduced in six consecutive laser pulses to the same area. As the temperature of the media was increased above the boiling point of the perfluoropentane, the droplets were less likely to recondense and remained in a gas phase after the first vaporization. These observations will help to clarify the underlying processes and eventually guide the design of repeatable phase-transition droplets as a photoacoustic imaging contrast agent.

Fluorescence spectroscopy using indocyanine green for lymph node mapping

NASA Astrophysics Data System (ADS)

Haj-Hosseini, Neda; Behm, Pascal; Shabo, Ivan; Wârdell, Karin

2014-02-01

The principles of cancer treatment has for years been radical resection of the primary tumor. In the oncologic surgeries where the affected cancer site is close to the lymphatic system, it is as important to detect the draining lymph nodes for metastasis (lymph node mapping). As a replacement for conventional radioactive labeling, indocyanine green (ICG) has shown successful results in lymph node mapping; however, most of the ICG fluorescence detection techniques developed are based on camera imaging. In this work, fluorescence spectroscopy using a fiber-optical probe was evaluated on a tissue-like ICG phantom with ICG concentrations of 6-64 μM and on breast tissue from five patients. Fiber-optical based spectroscopy was able to detect ICG fluorescence at low intensities; therefore, it is expected to increase the detection threshold of the conventional imaging systems when used intraoperatively. The probe allows spectral characterization of the fluorescence and navigation in the tissue as opposed to camera imaging which is limited to the view on the surface of the tissue.

Formulation of long-wavelength indocyanine green nanocarriers

NASA Astrophysics Data System (ADS)

Pansare, Vikram J.; Faenza, William J.; Lu, Hoang; Adamson, Douglas H.; Prud'homme, Robert K.

2017-09-01

Indocyanine green (ICG), a Food and Drug Administration (FDA)-approved fluorophore with excitation and emission wavelengths inside the "optical imaging window," has been incorporated into nanocarriers (NCs) to achieve enhanced circulation time, targeting, and real-time tracking in vivo. While previous studies transferred ICG exogenously into NCs, here, a one-step rapid precipitation process [flash nanoprecipitation (FNP)] creates ICG-loaded NCs with tunable, narrow size distributions from 30 to 180 nm. A hydrophobic ion pair of ICG-tetraoctylammonium or tetradodecylammonium chloride is formed either in situ during FNP or preformed then introduced into the FNP feed stream. The NCs are formulated with cores comprising either vitamin E (VE) or polystyrene (PS). ICG core loadings of 30 wt. % for VE and 10 wt. % for PS are achieved. However, due to a combination of molecular aggregation and Förster quenching, maximum fluorescence (FL) occurs at 10 wt. % core loading. The FL-per-particle scales with core diameter to the third power, showing that FNP enables uniform volume encapsulation. By varying the ICG counter-ion ratio, encapsulation efficiencies above 80% are achieved even in the absence of ion pairing, which rises to 100% with 1∶1 ion pairing. Finally, while ICG ion pairs are shown to be stable in buffer, they partition out of NC cores in under 30 min in the presence of physiological albumin concentrations.

Neurotoxic effects of indocyanine green -cerebellar granule cell culture viability study

PubMed Central

Toczylowska, Beata; Zieminska, Elzbieta; Goch, Grazyna; Milej, Daniel; Gerega, Anna; Liebert, Adam

2014-01-01

The aim of this study was to examine neurotoxicity indocyanine green (ICG). We assessed viability of primary cerebellar granule cell culture (CGC) exposed to ICG to test two mechanisms that could be the first triggers causing neuronal toxicity: imbalance in calcium homeostasis and the degree of oligomerization of ICG molecules. We have observed this imbalance in CGC after exposure to 75-125μΜ ICG and dose and application sequence dependent protective effect of Gadovist on surviving neurons in vitro when used with ICG. Spectroscopic studies suggest the major cause of toxicity of the ICG is connected with oligomers formation. ICG at concentration of 25 μM (which is about 4 times higher than the highest concentration of ICG in the brain applied in in-vivo human studies) is not neurotoxic in the cell culture. PMID:24688815

Shortwave infrared fluorescence imaging with the clinically approved near-infrared dye indocyanine green.

PubMed

Carr, Jessica A; Franke, Daniel; Caram, Justin R; Perkinson, Collin F; Saif, Mari; Askoxylakis, Vasileios; Datta, Meenal; Fukumura, Dai; Jain, Rakesh K; Bawendi, Moungi G; Bruns, Oliver T

2018-04-24

Fluorescence imaging is a method of real-time molecular tracking in vivo that has enabled many clinical technologies. Imaging in the shortwave IR (SWIR; 1,000-2,000 nm) promises higher contrast, sensitivity, and penetration depths compared with conventional visible and near-IR (NIR) fluorescence imaging. However, adoption of SWIR imaging in clinical settings has been limited, partially due to the absence of US Food and Drug Administration (FDA)-approved fluorophores with peak emission in the SWIR. Here, we show that commercially available NIR dyes, including the FDA-approved contrast agent indocyanine green (ICG), exhibit optical properties suitable for in vivo SWIR fluorescence imaging. Even though their emission spectra peak in the NIR, these dyes outperform commercial SWIR fluorophores and can be imaged in the SWIR, even beyond 1,500 nm. We show real-time fluorescence imaging using ICG at clinically relevant doses, including intravital microscopy, noninvasive imaging in blood and lymph vessels, and imaging of hepatobiliary clearance, and show increased contrast compared with NIR fluorescence imaging. Furthermore, we show tumor-targeted SWIR imaging with IRDye 800CW-labeled trastuzumab, an NIR dye being tested in multiple clinical trials. Our findings suggest that high-contrast SWIR fluorescence imaging can be implemented alongside existing imaging modalities by switching the detection of conventional NIR fluorescence systems from silicon-based NIR cameras to emerging indium gallium arsenide-based SWIR cameras. Using ICG in particular opens the possibility of translating SWIR fluorescence imaging to human clinical applications. Indeed, our findings suggest that emerging SWIR-fluorescent in vivo contrast agents should be benchmarked against the SWIR emission of ICG in blood.

Laser-assisted indocyanine green dye angiography accurately predicts the split-thickness graft timing of integra artificial dermis.

PubMed

Fourman, Mitchell S; Phillips, Brett T; Fritz, Jason R; Conkling, Nicole; McClain, Steve A; Simon, Marcia; Dagum, Alexander B

2014-08-01

The use of an artificial dermal substitute such as Integra-a bilaminate combination of thin silicone and cross-linked bovine tendon collagen and chondroitin-6-sulfate-has become a popular method to address large surface area wounds or smaller, complex wounds devoid of a vascular bed. The incorporation of Integra depends on a vascular wound bed or periphery and can take 4 weeks or longer to occur. If the Integra has not fully incorporated at the time of placement of the split-thickness graft, complete graft loss may result. The availability of a minimally invasive method to assess the incorporation of Integra would be of great value. Two 5 × 10-cm paraspinal full-thickness wounds were created on 3 female swine. Wounds were randomly assigned full-thickness skin graft or Integra (Plainsboro, NJ) treatment. Both types of grafts were placed after the application of fibrin glue (Tisseel, Deerfield, Ill) to the wound bed. Laser Doppler imaging (LDI) (Moor), indocyanine green dye (ICG) angiography (LifeCell SPY), and clinical scoring were performed weekly for a period of 8 weeks after grafting. At 4 weeks, the silicone layer of the Integra was removed, and a culture of autologous keratinocytes was applied. A 4-mm punch biopsy sample of each graft was taken 1, 2, 4, 6, 7, and 8 weeks postoperatively for histologic analysis. Both ICG angiography and LDI perfusion measurements noted an increase in perfusion at the Integra graft site that peaked 3 weeks after grafting, corresponding with the start of neovascularization and the optimal time for the application of a split-thickness skin graft. indocyanine green dye angiography measurements exhibit greater reproducibility between animals at late time points as compared with LDI. This decrease in LDI precision is directly related to increases in scar tissue thickness of greater than 5 mm as determined via histologic analysis and corresponds with the accepted maximum penetration depth of the LDI laser. Indocyanine green dye

Optical measurement of mouse strain differences in cerebral blood flow using indocyanine green

PubMed Central

Kang, Hye-Min; Sohn, Inkyung; Kim, Seunggyu; Kim, Daehwan; Jung, Junyang; Jeong, Joo-Won; Park, Chan

2015-01-01

C57BL/6 mice have more cerebral arterial branches and collaterals than BALB/c mice. We measured and compared blood flow dynamics of the middle cerebral artery (MCA) in these two strains, using noninvasive optical imaging with indocyanine green (ICG). Relative maximum fluorescence intensity (Imax) and the time needed for ICG to reach Imax in the MCA of C57BL/c were lower than that in BALB/c mice. Moreover, the mean transit time was significantly lower in C57BL/6 than in BALB/c mice. These data suggest that the higher number of arterial branches and collaterals in C57BL/6 mice yields a lower blood flow per cerebral artery. PMID:25833343

Review of fluorescence guided surgery systems: identification of key performance capabilities beyond indocyanine green imaging

NASA Astrophysics Data System (ADS)

DSouza, Alisha V.; Lin, Huiyun; Henderson, Eric R.; Samkoe, Kimberley S.; Pogue, Brian W.

2016-08-01

There is growing interest in using fluorescence imaging instruments to guide surgery, and the leading options for open-field imaging are reviewed here. While the clinical fluorescence-guided surgery (FGS) field has been focused predominantly on indocyanine green (ICG) imaging, there is accelerated development of more specific molecular tracers. These agents should help advance new indications for which FGS presents a paradigm shift in how molecular information is provided for resection decisions. There has been a steady growth in commercially marketed FGS systems, each with their own differentiated performance characteristics and specifications. A set of desirable criteria is presented to guide the evaluation of instruments, including: (i) real-time overlay of white-light and fluorescence images, (ii) operation within ambient room lighting, (iii) nanomolar-level sensitivity, (iv) quantitative capabilities, (v) simultaneous multiple fluorophore imaging, and (vi) ergonomic utility for open surgery. In this review, United States Food and Drug Administration 510(k) cleared commercial systems and some leading premarket FGS research systems were evaluated to illustrate the continual increase in this performance feature base. Generally, the systems designed for ICG-only imaging have sufficient sensitivity to ICG, but a fraction of the other desired features listed above, with both lower sensitivity and dynamic range. In comparison, the emerging research systems targeted for use with molecular agents have unique capabilities that will be essential for successful clinical imaging studies with low-concentration agents or where superior rejection of ambient light is needed. There is no perfect imaging system, but the feature differences among them are important differentiators in their utility, as outlined in the data and tables here.

Review of fluorescence guided surgery systems: identification of key performance capabilities beyond indocyanine green imaging

PubMed Central

DSouza, Alisha V.; Lin, Huiyun; Henderson, Eric R.; Samkoe, Kimberley S.; Pogue, Brian W.

2016-01-01

Abstract. There is growing interest in using fluorescence imaging instruments to guide surgery, and the leading options for open-field imaging are reviewed here. While the clinical fluorescence-guided surgery (FGS) field has been focused predominantly on indocyanine green (ICG) imaging, there is accelerated development of more specific molecular tracers. These agents should help advance new indications for which FGS presents a paradigm shift in how molecular information is provided for resection decisions. There has been a steady growth in commercially marketed FGS systems, each with their own differentiated performance characteristics and specifications. A set of desirable criteria is presented to guide the evaluation of instruments, including: (i) real-time overlay of white-light and fluorescence images, (ii) operation within ambient room lighting, (iii) nanomolar-level sensitivity, (iv) quantitative capabilities, (v) simultaneous multiple fluorophore imaging, and (vi) ergonomic utility for open surgery. In this review, United States Food and Drug Administration 510(k) cleared commercial systems and some leading premarket FGS research systems were evaluated to illustrate the continual increase in this performance feature base. Generally, the systems designed for ICG-only imaging have sufficient sensitivity to ICG, but a fraction of the other desired features listed above, with both lower sensitivity and dynamic range. In comparison, the emerging research systems targeted for use with molecular agents have unique capabilities that will be essential for successful clinical imaging studies with low-concentration agents or where superior rejection of ambient light is needed. There is no perfect imaging system, but the feature differences among them are important differentiators in their utility, as outlined in the data and tables here. PMID:27533438

Clinical use of endovenous indocyanine green during rectosigmoid segmental resection for endometriosis.

PubMed

Seracchioli, Renato; Raimondo, Diego; Arena, Alessandro; Zanello, Margherita; Mabrouk, Mohamed

2018-06-01

To describe a new use of endovenous indocyanine green (ICG) to allow real-time visualization of bowel perfusion in women with recto-sigmoid endometriosis who may be candidates for segmental resection. Step-by-step explanation of this method using descriptive text and educational video. Tertiary level referral academic center. A nulliparous 36-year-old woman affected by a large rectal endometriotic nodule was referred for severe dysmenorrhea, dyspareunia, hematochezia, and dyschezia, despite progestinic therapy. An intravenous injection of 1.5 mL solution containing 3.75 mg dose of ICG for intraoperative fluorescence imaging. Evaluation of blood perfusion of bowel and rectal endometriosis nodule. Evaluation of neoanastomosis vascularization after bowel resection. The procedure of endometriosis removal was performed using the daVinciXi surgical platform (Intuitive Surgical, Sunnyvale, CA). After ovarian endometriosis removal and adhesiolysis, we identified the endometriosis nodule on the anterior surface of the rectum. Pararectal, rectovaginal, and retrorectal spaces were dissected with a nerve-sparing technique. Indocyanine green was administered through a peripheral line. A near-infrared camera head enabled vision of the colorant after latency of a few seconds. We observed the ischemic area around the rectal nodule and perfusion areas upstream and downstream from the lesion. We selected the transecting line for rectal resection, taking account of this objective evaluation, beyond the limits of macroscopic disease. After direct mechanical anastomosis, we checked the rectal vascularization with ICG. To the best of our knowledge, this is the first reported use of endovenous ICG during a bowel resection for deep endometriosis. Endovenous ICG is proposed during surgery for rectosigmoid endometriosis to assess the perfusion of the bowel and select the transecting line. With ICG fluorescence imaging, we can objectively evaluate whether blood supply to the anastomosis is

The hyper-fluorescent transitional bands in ultra-late phase of indocyanine green angiography in chronic central serous chorioretinopathy.

PubMed

Hua, Rui; Yao, Kai; Xia, Fan; Li, Jun; Guo, Lei; Yang, Guoxing; Tao, Jun

2016-03-01

Chronic central serous chorioretinopathy (CSCR) is regarded as a type of severe diffuse retinal pigment epitheliopathy. There is an atrophic tract at level of retinal pigment epithelium (RPE) due to hyper-permeability of choroidal vessels, along with photoreceptor (PR) atrophy. Indocyanine green angiography (ICGA) is considered a gold standard for diagnosis. The purpose of this work is to investigate the hyper-fluorescent transitional bands (HFTB) between hypo-fluorescent and normal regions of the retina in the ultra-late phase of ICGA in CSCR. 26 chronic CSCR eyes and 12 relative normal eyes received spectral domain optical coherence tomography (SD-OCT), and ICGA at the 24th hour after indocyanine green (ICG) intravenous injection. In the ultra-late phase, images showed homogenous fluorescence in all normal eyes. On the contrary, geographical hypofluorescent lesions with atrophy of RPE was noted in 26 chronic CSCR eyes. Moreover, HFTB with intact RPE and disrupted PR was detected in 20 out of 26 chronic CSCR eyes (76.9%). The HFTB may indicate the early damage in chronic CSCR. Ultra-late ICGA can monitor not only metabolic status by endogenous melanin, but also membrane function in RPE by exogenous ICG molecule. © 2015 Wiley Periodicals, Inc.

Intraoperative Near-Infrared Fluorescence Imaging using indocyanine green in colorectal carcinomatosis surgery: Proof of concept.

PubMed

Barabino, G; Klein, J P; Porcheron, J; Grichine, A; Coll, J-L; Cottier, M

2016-12-01

This study assesses the value of using Intraoperative Near Infrared Fluorescence Imaging and Indocyanine green to detect colorectal carcinomatosis during oncological surgery. In colorectal carcinomatosis cancer, two of the most important prognostic factors are completeness of staging and completeness of cytoreductive surgery. Presently, intraoperative assessment of tumoral margins relies on palpation and visual inspection. The recent introduction of Near Infrared fluorescence image guidance provides new opportunities for surgical roles, particularly in cancer surgery. The study was a non-randomized, monocentric, pilot "ex vivo" blinded clinical trial validated by the ethical committee of University Hospital of Saint Etienne. Ten patients with colorectal carcinomatosis cancer scheduled for cytoreductive surgery were included. Patients received 0.25 mg/kg of Indocyanine green intravenously 24 h before surgery. A Near Infrared camera was used to detect "ex-vivo" fluorescent lesions. There was no surgical mortality. Each analysis was done blindly. In a total of 88 lesions analyzed, 58 were classified by a pathologist as cancerous and 30 as non-cancerous. Among the 58 cancerous lesions, 42 were correctly classified by the Intraoperative Near-Infrared camera (sensitivity of 72.4%). Among the 30 non-cancerous lesions, 18 were correctly classified by the Intraoperative Near-Infrared camera (specificity of 60.0%). Near Infrared fluorescence imaging is a promising technique for intraoperative tumor identification. It could help the surgeon to determine resection margins and reduce the risk of locoregional recurrence. Copyright © 2016 Elsevier Ltd, BASO ~ the Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.

Cabazitaxel and indocyanine green co-delivery tumor-targeting nanoparticle for improved antitumor efficacy and minimized drug toxicity.

PubMed

Tai, Xiaowei; Wang, Yang; Zhang, Li; Yang, Yuting; Shi, Kairong; Ruan, Shaobo; Liu, Yayuan; Gao, Huile; Zhang, Zhirong; He, Qin

2017-02-01

Cabazitaxel (CBX) is an effective antineoplastic agent for the treatment of many kinds of cancers. However, the poor water solubility remains a serious deterrent to the utilization of CBX as a commercial drug. In this study, we designed a strategy that integrated CBX into albumin nanoparticles (ANs) formed with human serum albumin (HSA) to improve the water solubility and targeting ability. Meanwhile, we utilized a photothermal agent-indocyanine green (ICG), which could cooperate with CBX to enhance the antitumor effect. The obtained ANs containing ICG and CBX (AN-ICG-CBX) exhibited good mono-dispersity. In vitro cytotoxicity study showed the effectiveness of CBX and ICG, respectively, whereas AN-ICG-CBX with irradiation exhibited the most efficient antiproliferative ability (83.7%). In vivo safety evaluation studies demonstrated the safety of AN-ICG-CBX. Furthermore, the in vivo antitumor study indicated that the AN-ICG-CBX with irradiation achieved higher tumor inhibition rate (91.3%) compared with CBX-encapsulated AN (AN-CBX) (83.3%) or ICG-encapsulated AN (AN-ICG) plus irradiation (60.1%) in 4T1 tumor-bearing mice. To sum up, a safety and effective formulation AN-ICG-CBX was developed in this study and successfully reduced the drug toxicity, improved the targeting efficiency and enhanced the therapeutic effects, becoming a promising candidate for clinical application.

Indocyanine green fluorescence imaging in hepatobiliary surgery.

PubMed

Majlesara, Ali; Golriz, Mohammad; Hafezi, Mohammadreza; Saffari, Arash; Stenau, Esther; Maier-Hein, Lena; Müller-Stich, Beat P; Mehrabi, Arianeb

2017-03-01

Indocyanine green (ICG) is a fluorescent dye that has been widely used for fluorescence imaging during hepatobiliary surgery. ICG is injected intravenously, selectively taken up by the liver, and then secreted into the bile. The catabolism and fluorescence properties of ICG permit a wide range of visualization methods in hepatobiliary surgery. We have characterized the applications of ICG during hepatobiliary surgery into: 1) liver mapping, 2) cholangiography, 3) tumor visualization, and 4) partial liver graft evaluation. In this literature review, we summarize the current understanding of ICG use during hepatobiliary surgery. Intra-operative ICG fluorescence imaging is a safe, simple, and feasible method that improves the visualization of hepatobiliary anatomy and liver tumors. Intravenous administration of ICG is not toxic and avoids the drawbacks of conventional imaging. In addition, it reduces post-operative complications without any known side effects. ICG fluorescence imaging provides a safe and reliable contrast for extra-hepatic cholangiography when detecting intra-hepatic bile leakage following liver resection. In addition, liver tumors can be visualized and well-differentiated hepatocellular carcinoma tumors can be accurately identified. Moreover, vascular reconstruction and outflow can be evaluated following partial liver transplantation. However, since tissue penetration is limited to 5-10mm, deeper tissue cannot be visualized using this method. Many instances of false positive or negative results have been reported, therefore further characterization is required. Copyright © 2016 Elsevier B.V. All rights reserved.

Formulation of long-wavelength indocyanine green nanocarriers.

PubMed

Pansare, Vikram J; Faenza, William J; Lu, Hoang; Adamson, Douglas H; Prud'homme, Robert K

2017-09-01

Indocyanine green (ICG), a Food and Drug Administration (FDA)-approved fluorophore with excitation and emission wavelengths inside the "optical imaging window," has been incorporated into nanocarriers (NCs) to achieve enhanced circulation time, targeting, and real-time tracking in vivo. While previous studies transferred ICG exogenously into NCs, here, a one-step rapid precipitation process [flash nanoprecipitation (FNP)] creates ICG-loaded NCs with tunable, narrow size distributions from 30 to 180 nm. A hydrophobic ion pair of ICG-tetraoctylammonium or tetradodecylammonium chloride is formed either in situ during FNP or preformed then introduced into the FNP feed stream. The NCs are formulated with cores comprising either vitamin E (VE) or polystyrene (PS). ICG core loadings of 30 wt. % for VE and 10 wt. % for PS are achieved. However, due to a combination of molecular aggregation and Förster quenching, maximum fluorescence (FL) occurs at 10 wt. % core loading. The FL-per-particle scales with core diameter to the third power, showing that FNP enables uniform volume encapsulation. By varying the ICG counter-ion ratio, encapsulation efficiencies above 80% are achieved even in the absence of ion pairing, which rises to 100% with 1∶1 ion pairing. Finally, while ICG ion pairs are shown to be stable in buffer, they partition out of NC cores in under 30 min in the presence of physiological albumin concentrations. (2017) COPYRIGHT Society of Photo-Optical Instrumentation Engineers (SPIE).

Synthesis and characterization of a glycine-modified heptamethine indocyanine dye for in vivo cancer-targeted near-infrared imaging

PubMed Central

Liu, Tao; Luo, Shenglin; Wang, Yang; Tan, Xu; Qi, Qingrong; Shi, Chunmeng

2014-01-01

Near-infrared (NIR) fluorescent sensors have emerged as promising molecular tools for cancer imaging and detection in living systems. However, cancer NIR fluorescent sensors are very challenging to develop because they are required to exhibit good specificity and low toxicity as an eligible contrast agent. Here, we describe the synthesis of a new heptamethine indocyanine dye (NIR-27) modified with a glycine at the end of each N-alkyl side chain, and its biological characterization for in vivo cancer-targeted NIR imaging. In addition to its high specificity, NIR-27 also shows lower cytotoxicity than indocyanine green, a nonspecific NIR probe widely used in clinic. These characteristics suggest that NIR-27 is a promising prospect as a new NIR fluorescent sensor for sensitive cancer detection. PMID:25246770

Development of ultrasound-assisted fluorescence imaging of indocyanine green.

PubMed

Morikawa, Hiroyasu; Toyota, Shin; Wada, Kenji; Uchida-Kobayashi, Sawako; Kawada, Norifumi; Horinaka, Hiromichi

2017-01-01

Indocyanine green (ICG) accumulation in hepatocellular carcinoma means tumors can be located by fluorescence. However, because of light scattering, it is difficult to detect ICG fluorescence from outside the body. We propose a new fluorescence imaging method that detects changes in the intensity of ICG fluorescence by ultrasound-induced temperature changes. ICG fluorescence intensity decreases as the temperature rises. Therefore, it should theoretically be possible to detect tissue distribution of ICG using ultrasound to heat tissue, moving the point of ultrasound transmission, and monitoring changes in fluorescence intensity. A new probe was adapted for clinical application. It consisted of excitation light from a laser, fluorescence sensing through a light pipe, and heating by ultrasound. We applied the probe to bovine liver to image the accumulation of ICG. ICG emits fluorescence (820 nm) upon light irradiation (783 nm). With a rise in temperature, the fluorescence intensity of ICG decreased by 0.85 %/°C. The distribution of fluorescent ICG was detected using an ultrasonic warming method in a new integrated probe. Modulating fluorescence by changing the temperature using ultrasound can determine where ICG accumulates at a depth, highlighting its potential as a means to locate hepatocellular carcinoma.

Fluorescence lifetime-based contrast enhancement of indocyanine green-labeled tumors

NASA Astrophysics Data System (ADS)

Kumar, Anand T. N.; Carp, Stefan A.; Yang, Jing; Ross, Alana; Medarova, Zdravka; Ran, Chongzhao

2017-04-01

Although the development of tumor-targeted fluorescent probes is a major area of investigation, it will be several years before these probes are realized for clinical use. Here, we report an approach that employs indocyanine-green (ICG), a clinically approved, nontargeted dye, in conjunction with fluorescence lifetime (FLT) detection to provide high accuracy for tumor-tissue identification in mouse models of subcutaneous human breast and brain tmors. The improved performance relies on the distinct FLTs of ICG within tumors versus tissue autofluorescence and is further aided by the well-known enhanced permeability and retention of ICG in tumors and the clearance of ICG from normal tissue several hours after intravenous injection. We demonstrate that FLT detection can provide more than 98% sensitivity and specificity, and a 10-fold reduction in error rates compared to intensity-based detection. Our studies suggest the significant potential of FLT-contrast for accurate tumor-tissue identification using ICG and other targeted probes under development, both for intraoperative imaging and for ex-vivo margin assessment of surgical specimens.

Indocyanine Green Liposomes for Diagnosis and Therapeutic Monitoring of Cerebral Malaria.

PubMed

Portnoy, Emma; Vakruk, Natalia; Bishara, Ameer; Shmuel, Miriam; Magdassi, Shlomo; Golenser, Jacob; Eyal, Sara

2016-01-01

Cerebral malaria (CM) is a major cause of death of Plasmodium falciparum infection. Misdiagnosis of CM often leads to treatment delay and mortality. Conventional brain imaging technologies are rarely applicable in endemic areas. Here we address the unmet need for a simple, non-invasive imaging methodology for early diagnosis of CM. This study presents the diagnostic and therapeutic monitoring using liposomes containing the FDA-approved fluorescent dye indocyanine green (ICG) in a CM murine model. Increased emission intensity of liposomal ICG was demonstrated in comparison with free ICG. The Liposomal ICG's emission was greater in the brains of the infected mice compared to naïve mice and drug treated mice (where CM was prevented). Histological analyses suggest that the accumulation of liposomal ICG in the cerebral vasculature is due to extensive uptake mediated by activated phagocytes. Overall, liposomal ICG offers a valuable diagnostic tool and a biomarker for effectiveness of CM treatment, as well as other diseases that involve inflammation and blood vessel occlusion.

In Vivo Imaging of the Human Retinal Pigment Epithelial Mosaic Using Adaptive Optics Enhanced Indocyanine Green Ophthalmoscopy

PubMed Central

Tam, Johnny; Liu, Jianfei; Dubra, Alfredo; Fariss, Robert

2016-01-01

Purpose The purpose of this study was to establish that retinal pigment epithelial (RPE) cells take up indocyanine green (ICG) dye following systemic injection and that adaptive optics enhanced indocyanine green ophthalmoscopy (AO-ICG) enables direct visualization of the RPE mosaic in the living human eye. Methods A customized adaptive optics scanning light ophthalmoscope (AOSLO) was used to acquire high-resolution retinal fluorescence images of residual ICG dye in human subjects after intravenous injection at the standard clinical dose. Simultaneously, multimodal AOSLO images were also acquired, which included confocal reflectance, nonconfocal split detection, and darkfield. Imaging was performed in 6 eyes of three healthy subjects with no history of ocular or systemic diseases. In addition, histologic studies in mice were carried out. Results The AO-ICG channel successfully resolved individual RPE cells in human subjects at various time points, including 20 minutes and 2 hours after dye administration. Adaptive optics-ICG images of RPE revealed detail which could be correlated with AO dark-field images of the same cells. Interestingly, there was a marked heterogeneity in the fluorescence of individual RPE cells. Confirmatory histologic studies in mice corroborated the specific uptake of ICG by the RPE layer at a late time point after systemic ICG injection. Conclusions Adaptive optics-enhanced imaging of ICG dye provides a novel way to visualize and assess the RPE mosaic in the living human eye alongside images of the overlying photoreceptors and other cells. PMID:27564519

In Vivo Imaging of the Human Retinal Pigment Epithelial Mosaic Using Adaptive Optics Enhanced Indocyanine Green Ophthalmoscopy.

PubMed

Tam, Johnny; Liu, Jianfei; Dubra, Alfredo; Fariss, Robert

2016-08-01

The purpose of this study was to establish that retinal pigment epithelial (RPE) cells take up indocyanine green (ICG) dye following systemic injection and that adaptive optics enhanced indocyanine green ophthalmoscopy (AO-ICG) enables direct visualization of the RPE mosaic in the living human eye. A customized adaptive optics scanning light ophthalmoscope (AOSLO) was used to acquire high-resolution retinal fluorescence images of residual ICG dye in human subjects after intravenous injection at the standard clinical dose. Simultaneously, multimodal AOSLO images were also acquired, which included confocal reflectance, nonconfocal split detection, and darkfield. Imaging was performed in 6 eyes of three healthy subjects with no history of ocular or systemic diseases. In addition, histologic studies in mice were carried out. The AO-ICG channel successfully resolved individual RPE cells in human subjects at various time points, including 20 minutes and 2 hours after dye administration. Adaptive optics-ICG images of RPE revealed detail which could be correlated with AO dark-field images of the same cells. Interestingly, there was a marked heterogeneity in the fluorescence of individual RPE cells. Confirmatory histologic studies in mice corroborated the specific uptake of ICG by the RPE layer at a late time point after systemic ICG injection. Adaptive optics-enhanced imaging of ICG dye provides a novel way to visualize and assess the RPE mosaic in the living human eye alongside images of the overlying photoreceptors and other cells.

Effect of indocyanine green angiography using infrared fundus camera on subsequent dark adaptation and electroretinogram.

PubMed

Wen, Feng; Yu, Minzhong; Wu, Dezheng; Ma, Juanmei; Wu, Lezheng

2002-07-01

To observe the effect of indocyanine green angiography (ICGA) with infrared fundus camera on subsequent dark adaptation and the Ganzfeld electroretinogram (ERG), the ERGs of 38 eyes with different retinal diseases were recorded before and after ICGA during a 40-min dark adaptation period. ICGA was performed with Topcon 50IA retina camera. Ganzfeld ERG was recorded with Neuropack II evoked response recorder. The results showed that ICGA did not affect the latencies and the amplitudes in ERG of rod response, cone response and mixed maximum response (p>0.05). It suggests that ICGA using infrared fundus camera could be performed prior to the recording of the Ganzfeld ERG.

Biodistribution of Encapsulated Indocyanine Green in Healthy Mice

PubMed Central

Yaseen, Mohammad A.; Yu, Jie; Jung, Bongsu; Wong, Michael S.; Anvari, Bahman

2009-01-01

Indocyanine Green (ICG) is a fluorescent probe used in various optically-mediated diagnostic and therapeutic applications. However, utility of ICG remains limited by its unstable optical properties and non-specific localization. We have encapsulated ICG within electrostatically-assembled mesocapsules (MCs) to explore its potential for targeted optical diagnosis and therapy. In this study, we investigate how the surface coating and size of the MCs influences ICG's biodistribution in vivo. ICG was administered intravenously to Swiss Webster mice as a free solution or encapsulated within either 100 nm diameter MCs coated with dextran; 500 nm diameter MCs coated with dextran; or 100 nm diameter MCs coated with 10 nm ferromagnetic iron oxide nanoparticles, themselves coated with polyethylene glycol. ICG was extracted from harvested blood and organs at various times and its amount quantified with fluorescence measurements. MCs containing ICG accumulated in organs of the reticuloendothelial system, namely the liver and spleen, as well as the lungs. The circulation kinetics of ICG remained unaffected by encapsulation; however, the deposition within organs other than the liver suggests a different biodistribution mechanism. Results suggest that the capsules' coating influences their biodistribution to a greater extent than their size. The MC encapsulation system allows for delivery of ICG to organs other than the liver, enabling the potential development of new optical imaging and therapeutic strategies. PMID:19799463

Nanotubes-Embedded Indocyanine Green-Hyaluronic Acid Nanoparticles for Photoacoustic-Imaging-Guided Phototherapy.

PubMed

Wang, Guohao; Zhang, Fan; Tian, Rui; Zhang, Liwen; Fu, Guifeng; Yang, Lily; Zhu, Lei

2016-03-02

Phototherapy is a light-triggered treatment for tumor ablation and growth inhibition via photodynamic therapy (PDT) and photothermal therapy (PTT). Despite extensive studies in this area, a major challenge is the lack of selective and effective phototherapy agents that can specifically accumulate in tumors to reach a therapeutic concentration. Although recent attempts have produced photosensitizers complexed with photothermal nanomaterials, the tedious preparation steps and poor tumor efficiency of therapy still hampers the broad utilization of these nanocarriers. Herein, we developed a CD44 targeted photoacoustic (PA) nanophototherapy agent by conjugating Indocyanine Green (ICG) to hyaluronic acid nanoparticles (HANPs) encapsulated with single-walled carbon nanotubes (SWCNTs), resulting in a theranostic nanocomplex of ICG-HANP/SWCNTs (IHANPT). We fully characterized its physical features as well as PA imaging and photothermal and photodynamic therapy properties in vitro and in vivo. Systemic delivery of IHANPT theranostic nanoparticles led to the accumulation of the targeted nanoparticles in tumors in a human cancer xenograft model in nude mice. PA imaging confirmed targeted delivery of the IHANPT nanoparticles into tumors (T/M ratio = 5.19 ± 0.3). The effect of phototherapy was demonstrated by low-power laser irradiation (808 nm, 0.8 W/cm(2)) to induce efficient photodynamic effect from ICG dye. The photothermal effect from the ICG and SWCNTs rapidly raised the tumor temperature to 55.4 ± 1.8 °C. As the result, significant tumor growth inhibition and marked induction of tumor cell death and necrosis were observed in the tumors in the tumors. There were no apparent systemic and local toxic effects found in the mice. The dynamic thermal stability of IHANPT was studied to ensure that PTT does not affect ICG-dependent PDT in phototherapy. Therefore, our results highlight imaging property and therapeutic effect of the novel IHANPT theranostic nanoparticle for CD44

Indocyanine green video angiography predicts outcome of extravasation injuries.

PubMed

Haslik, Werner; Pluschnig, Ursula; Steger, Günther G; Zielinski, Christoph C; Schrögendorfer, K F; Nedomansky, Jakob; Bartsch, Rupert; Mader, Robert M

2014-01-01

Extravasation of cytotoxic drugs is a serious complication of systemic cancer treatment. Still, a reliable method for early assessment of tissue damage and outcome prediction is missing. Here, we demonstrate that the evaluation of blood flow by indocyanine green (ICG) angiography in the extravasation area predicts for the need of surgical intervention. Twenty-nine patients were evaluated by ICG angiography after extravasation of vesicant or highly irritant cytotoxic drugs administered by peripheral i.v. infusion. Tissue perfusion as assessed by this standardized method was correlated with clinical outcome. The perfusion index at the site of extravasation differed significantly between patients with reversible tissue damage and thus healing under conservative management (N = 22) versus those who needed surgical intervention due to the development of necrosis (N = 7; P = 0.0001). Furthermore, in patients benefiting from conservative management, the perfusion index was significantly higher in the central extravasation area denoting hyperemia, when compared with the peripheral area (P = 0.0001). In this patient cohort, ICG angiography as indicator of local perfusion within the extravasation area was of prognostic value for tissue damage. ICG angiography could thus be used for the early identification of patients at risk for irreversible tissue damage after extravasation of cytotoxic drugs.

Indocyanine-green-loaded microballoons for biliary imaging in cholecystectomy

NASA Astrophysics Data System (ADS)

Mitra, Kinshuk; Melvin, James; Chang, Shufang; Park, Kyoungjin; Yilmaz, Alper; Melvin, Scott; Xu, Ronald X.

2012-11-01

We encapsulate indocyanine green (ICG) in poly[(D,L-lactide-co-glycolide)-co-PEG] diblock (PLGA-PEG) microballoons for real-time fluorescence and hyperspectral imaging of biliary anatomy. ICG-loaded microballoons show superior fluorescence characteristics and slower degradation in comparison with pure ICG. The use of ICG-loaded microballoons in biliary imaging is demonstrated in both biliary-simulating phantoms and an ex vivo tissue model. The biliary-simulating phantoms are prepared by embedding ICG-loaded microballoons in agar gel and imaged by a fluorescence imaging module in a Da Vinci surgical robot. The ex vivo model consists of liver, gallbladder, common bile duct, and part of the duodenum freshly dissected from a domestic swine. After ICG-loaded microballoons are injected into the gallbladder, the biliary structure is imaged by both hyperspectral and fluorescence imaging modalities. Advanced spectral analysis and image processing algorithms are developed to classify the tissue types and identify the biliary anatomy. While fluorescence imaging provides dynamic information of movement and flow in the surgical region of interest, data from hyperspectral imaging allow for rapid identification of the bile duct and safe exclusion of any contaminant fluorescence from tissue not part of the biliary anatomy. Our experiments demonstrate the technical feasibility of using ICG-loaded microballoons for biliary imaging in cholecystectomy.

Efficacy of Indocyanine Green Angiography on Microsurgical Subinguinal Varicocelectomy.

PubMed

Shibata, Yasuhiro; Kurihara, Sota; Arai, Seiji; Kato, Haruo; Suzuki, Tomomi; Miyazawa, Yoshiyuki; Koike, Hidekazu; Ito, Kazuto; Nakamura, Tetsuya; Suzuki, Kazuhiro

2017-08-01

Microsurgical subinguinal varicocelectomy is one of the best treatment modalities for varicoceles related to male infertility and scrotal pain. However, the difficulty in identifying testicular arteries, which should be spared, is a limitation of this technique. To visualize and identify the testicular arteries in spermatic cord during the operation, we examined the efficacy of intraoperative indocyanine green angiography (ICGA), which is regularly used in microsurgical neurosurgery. After the exposure of the spermatic cord blood vessels, ICG was injected intravenously under a surgical microscope for observing infrared fluorescence in patients to identify and isolate the testicular artery. The testicular artery was clearly identified by ICGA and was able to separate under ICGA view. Thereafter, the varicose veins were repeatedly ligated, while preserving a few lymphatic vessels and the spermatic duct. The preserved arteries were confirmed by repeated ICGA at the end of microsurgical operation. The number of arteries identified by ICGA was greater than the number detected by preoperative computed tomography angiogram. Microsurgical subinguinal varicocelectomy using intraoperative ICGA facilitated safe and quick surgery by enabling the visualization of the spermatic cord blood vessels. This is the first report to indicate the usefulness of vessel visualization by ICGA during microsurgical subinguinal varicocelectomy.

Effects of clofibrate and indocyanine green on the hepatobiliary disposition of acetaminophen and its metabolites in male CD-1 mice.

PubMed

Chen, C; Hennig, G E; McCann, D J; Manautou, J E

2000-11-01

1. The effects of clofibrate (CFB) and indocyanine green (ICG) on the biliary excretion of acetaminophen (APAP) and its metabolites were investigated. 2. Male CD-1 mice were pretreated with 500 mg CFB/kg, i.p. for 10 days. Controls received corn oil vehicle only. After overnight fasting, common bile duct-cannulated mice were challenged with a non-toxic dose of APAP (1 mmol/kg, i.v.). 3. CFB pretreatment did not affect bile flow rate, nor did it affect the cumulative biliary excretion of APAP and its conjugated metabolites. 4. Additional CFB or corn oil pretreated mice were given 30 mumol indocyanine green (ICG)/kg, i.v., immediately before APAP dosing. ICG is a non-metabolizable organic anion that is completely excreted into the bile through a canalicular transport process for organic anions. 5. ICG significantly decreased the bile flow rate and biliary concentration of APAP-glutathione, APAP-glucuronide and APAP-mercapturate within the first hour after dosing without affecting the biliary concentration of APAP. 6. The results indicate that CFB pretreatment does not affect the total amount of APAP and its metabolites excreted in bile. They also suggest that the biliary excretion of several conjugated metabolites of APAP share the same excretory pathway with the organic anion ICG.

Photodynamic therapy using nanoparticle loaded with indocyanine green for experimental peritoneal dissemination of gastric cancer

PubMed Central

Tsujimoto, Hironori; Morimoto, Yuji; Takahata, Risa; Nomura, Shinsuke; Yoshida, Kazumichi; Horiguchi, Hiroyuki; Hiraki, Shuichi; Ono, Satoshi; Miyazaki, Hiromi; Saito, Daizo; Hara, Isao; Ozeki, Eiichi; Yamamoto, Junji; Hase, Kazuo

2014-01-01

Although there have been multiple advances in the development of novel anticancer agents and operative procedures, prognosis of patients with advanced gastric cancer remains poor, especially in patients with peritoneal metastasis. In this study, we established nanoparticles loaded with indocyanine green (ICG) derivatives: ICG loaded lactosomes (ICGm) and investigated the diagnostic and therapeutic value of photodynamic therapy (PDT) using ICGm for experimental peritoneal dissemination of gastric cancer. Experimental peritoneal disseminated xenografts of human gastric cancer were established in nude mice. Three weeks after intraperitoneal injection of the cancer cells, either ICGm (ICGm-treated mice) or ICG solution (ICG-treated mice) was injected through the tail vein. Forty-eight hours after injection of the photosensitizer, in vivo and ex vivo imaging was carried out. For PDT, 48 h after injection of the photosensitizer, other mice were irradiated through the abdominal wall, and the body weight and survival rate were monitored. In vivo imaging revealed that peritoneal tumors were visualized through the abdominal wall in ICGm-treated mice, whereas only non-specific fluorescence was observed in ICG-treated mice. The PDT reduced the total weight of the disseminated nodules and significantly improved weight loss and survival rate in ICGm-treated mice. In conclusion, ICGm can be used as a novel diagnostic and therapeutic nanodevice in peritoneal dissemination of gastric cancer. PMID:25287817

Breast necrosis secondary to vasopressor extravasation: management using indocyanine green angiography and omental flap closure.

PubMed

Hagopian, Thomas M; Ghareeb, Paul A; Arslanian, Brian H; Moosavi, Benjamin L; Carlson, Grant W

2015-01-01

Extravasation is a rare but serious complication of vasopressor administration. A 60-year-old female who underwent ascending and hemiarch repair of the aorta along with aortic valve replacement developed extensive right breast and chest wall necrosis after vasopressor extravasation from an internal jugular vein central line. The patient underwent a total mastectomy due to deep tissue necrosis detected by laser-assisted indocyanine green dye angiography, and eventually required omental flap reconstruction to obtain adequate sternal coverage. This case represents a previously unreported complication of internal jugular central line extravasation of vasopressors with resultant breast and chest wall necrosis, and highlights the utility of the omentum in chest wall reconstruction. © 2015 Wiley Periodicals, Inc.

Use of indocyanine green angiography in microsurgical subinguinal varicocelectomy - lessons learned from our initial experience.

PubMed

Cho, Chak-Lam; Ho, Kwan-Lun; Chan, Wayne Kwun-Wai; Chu, Ringo Wing-Hong; Law, In-Chak

2017-01-01

Microsurgical subinguinal varicocelectomy (MSV) is generally considered the gold standard nowadays in view of the lower risk of complications and recurrence. To achieve complete ligation of veins while preserving testicular artery (TA) during the procedure remains challenging despite the application of high power optical magnification and micro-Doppler ultrasonography. The use of intraoperative indocyanine green angiography (ICGA) with infrared fluorescence operative micro-scope in MSV potentially lowers the incidence of TA injury and shortens the learning curve of nov-ice surgeons. We present our initial experience in the application of the technique in nine patients and explore the potential of the new adjunct. Copyright® by the International Brazilian Journal of Urology.

Direct Gallbladder Indocyanine Green Injection Fluorescence Cholangiography During Laparoscopic Cholecystectomy.

PubMed

Graves, Claire; Ely, Sora; Idowu, Olajire; Newton, Christopher; Kim, Sunghoon

2017-10-01

Intravenous injection of indocyanine green (ICG) is used to illuminate extrahepatic biliary anatomy. Fluorescence of biliary structures may lower surgical complications that can arise due to inadvertent injury to the common bile duct. We describe a method of injecting ICG directly into the gallbladder to define the cystic duct and common bile duct anatomy. A standard laparoscopic cholecystectomy was performed using a laparoscope with near-infrared imaging capability. Before dissection, the gallbladder was punctured with a cholangiogram catheter or a pigtail catheter to aspirate the bile within the gallbladder. The aspirated bile is mixed with ICG solution, which is reinjected into the gallbladder to fluoresce the gallbladder, cystic duct, and common bile duct structures. Eleven patients underwent direct gallbladder ICG injection for fluorescence cholangiography during cholecystectomy. Direct gallbladder ICG injection clearly defined the extrahepatic biliary anatomy, including the cystic duct-common bile duct junction, by fluorescence. In addition, the dissection plane between the gallbladder and the liver is highlighted with the gallbladder ICG fluorescence. Direct gallbladder ICG injection provides immediate visualization of extrahepatic biliary structures and clarifies the dissection plane between the gallbladder and the liver bed.

Indocyanine green-mediated photobiomodulation on human osteoblast cells.

PubMed

Ateş, Gamze Bölükbaşı; Ak, Ayşe; Garipcan, Bora; Gülsoy, Murat

2018-05-09

Photobiomodulation (PBM) and photodynamic therapy (PDT) share similar mechanisms but have opposite aims. Increased levels of reactive oxygen species (ROS) in the target tissue in response to light combined photosensitizer (PS) application may lead to cell proliferation or oxidative damage depending on the ROS amount. The purpose of the present study is to investigate the effect of indocyanine green (ICG)-mediated PBM on osteoblast cells by measuring cell viability, proliferation, alkaline phosphatase (ALP) activity, mineralization, and gene expressions of three phenotypic osteoblast markers. A diode laser irradiating at 809 nm (10 W output power, 50 mW/cm 2 power density) was used at 0.5, 1, and 2 J/cm 2 energy densities (10, 20, and 40 s respectively) was applied following ICG incubation. No inhibitory effect was observed in cell viability and proliferation according to the (4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) and Alamar Blue assays. ICG-mediated PBM did not alter cell viability but increased ALP activity and enhanced mineralization of existing osteoblasts. These results were also confirmed by real-time polymerase chain reaction (RT-PCR) analysis of osteoblastic markers. PS can be combined to PBM not only to damage the malignant cells as aimed in PDT studies, but also to promote cellular activity. The findings of this in vitro study may contribute to in vivo studies and ICG-mediated PBM can have promising outcomes in bone healing and regeneration therapies in future.

Estimation of regional cerebral blood flow distribution in infants by multichannel near-infrared spectroscopy with indocyanine green

NASA Astrophysics Data System (ADS)

Kusaka, Takashi; Isobe, Kenichi; Nagano, Keiko; Okubo, Kensuke; Yasuda, Saneyuki; Kawada, Kou; Itoh, Susumu; Onishi, Shoju; Oda, Ichiro; Wada, Yukihisa; Konishi, Ikuo; Tsunazawa, Yoshio

2001-06-01

This is the report on the use of multichannel near-infrared spectroscopy (MNIRS) with indocyanine green (ICG) to determine regional cerebral blood flow (rCBF) distribution disturbance in infants. We measured rCBF in an infant with subdural hemorrhage after surgical removal of a subdural hematoma. A probe consisting of 12 optical fibers, 6 for transmission and 6 for detection, was set on the right and then left temporal regions of the head of the infant, and 16 measuring points were determined. Changes in ICG concentration were recorded using MNIRS (near infrared optical imaging system, OMM-2000, Shimadzu Corp., Japan).

Near-infrared fluorescence imaging and photodynamic therapy with indocyanine green lactosome has antineoplastic effects for hepatocellular carcinoma.

PubMed

Tsuda, Takumi; Kaibori, Masaki; Hishikawa, Hidehiko; Nakatake, Richi; Okumura, Tadayoshi; Ozeki, Eiichi; Hara, Isao; Morimoto, Yuji; Yoshii, Kengo; Kon, Masanori

2017-01-01

Anticancer agents and operating procedures have been developed for hepatocellular carcinoma (HCC) patients, but their prognosis remains poor. It is necessary to develop novel diagnostic and therapeutic strategies for HCC to improve its prognosis. Lactosome is a core-shell-type polymeric micelle, and enclosing labeling or anticancer agents into this micelle enables drug delivery. In this study, we investigated the diagnostic and therapeutic efficacies of indocyanine green (ICG)-loaded lactosome for near-infrared fluorescence (NIF) imaging and photodynamic therapy (PDT) for HCC. The human HCC cell line HuH-7 was treated with ICG or ICG-lactosome, followed by PDT, and the cell viabilities were measured (in vitro PDT efficiency). For NIF imaging, HuH-7 cells were subcutaneously transplanted into BALB/c nude mice, followed by intravenous administration of ICG or ICG-lactosome. The transplanted animals were treated with PDT, and the antineoplastic effects were analyzed (in vivo PDT efficiency). PDT had toxic effects on HuH-7 cells treated with ICG-lactosome, but not ICG alone. NIF imaging revealed that the fluorescence of tumor areas in ICG-lactosome-treated animals was higher than that of contralateral regions at 24 h after injection and thereafter. PDT exerted immediate and continuous phototoxic effects in the transplanted mice treated with ICG-lactosome. Our results demonstrate that ICG-lactosome accumulated in xenograft tumors, and that PDT had antineoplastic effects on these malignant implants. NIF imaging and PDT with ICG-lactosome could be useful diagnostic and/or therapeutic strategies for HCC.

Encapsulation of indocyanine green into cell membrane capsules for photothermal cancer therapy.

PubMed

Sheng, Guoping; Chen, Ying; Han, Lijie; Huang, Yong; Liu, Xiaoli; Li, Lanjuan; Mao, Zhengwei

2016-10-01

Although indocyanine green (ICG) has promising applications in photothermal therapy (PPT) because of its low toxicity and high efficiency in inducing heat and singlet oxygen formation in response to near-infrared light with a wavelength of approximately 800nm, its clinical application has been restricted because of its rapid body clearance and poor water stability. Therefore, cell membrane capsules (CMCs) derived from mammalian cells were used to encapsulate negatively charged ICG by temporarily permeating the plasma membrane and resealing using positively charged doxorubicin hydrochloride (DOX). The resulting CMCs@DOX/ICG exhibited a spherical shape, with a diameter of approximately 800nm. The DOX and ICG encapsulation was confirmed by the UV-vis spectrum; a very small amount of DOX (0.8μg) and a very high amount of ICG (∼110μg) were encapsulated in 200μg CMCs. Encapsulation in the CMCs leads to sustained release of ICG, especially in the presence of positively charged DOX. The temperature enhancement and generation of ROS by ICG encapsulated in CMCs were confirmed upon laser irradiation in vitro, leading to cell death. CMCs@DOX/ICG also can significantly enhance the retention of ICG in a tumor after intratumoral injection in vivo. As a result, combination treatment with CMCs@DOX/ICG and laser irradiation demonstrated much better anticancer efficacy than that of free DOX/ICG and CMCs@ICG. The encapsulation of ICG into CMCs, especially with the assistance of DOX, significantly slows down the body clearance of ICG, with a retained PPT effect against tumors, an important step forward in the practical application of ICG in cancer therapy. In this study, cell membrane capsules (CMCs) derived from mammalian cells were used to encapsulate negatively charged indocyanine green (ICG) by temporarily permeating the plasma membrane and resealing, in the presence of positively charged doxorubicin hydrochloride (DOX). The resulting CMCs@DOX/ICG exhibited a spherical shape

Visualization of Skin Perfusion by Indocyanine Green Fluorescence Angiography—A Feasibility Study

PubMed Central

Steinbacher, Johannes; Yoshimatsu, Hidehiko; Meng, Stefan; Hamscha, Ulrike M.; Chan, Chun-Sheng; Weninger, Wolfgang J.; Wu, Chieh-Tsai; Cheng, Ming-Huei

2017-01-01

Summary: Plastic and reconstructive surgery relies on the knowledge of angiosomes in the raising of microsurgical flaps. Growing interest in muscle-sparing perforator flaps calls for reliable methods to assess the clinical feasibility of new donor sites in anatomical studies. Several injection techniques are known for the evaluation of vascular territories. Indocyanine green–based fluorescence angiography has found wide application in the clinical assessment of tissue perfusion. In this article, the use of indocyanine green–based fluorescence angiography for the assessment of perforasomes in anatomical studies is described for the first time. PMID:29062637

Comparison of Indocyanine Green Angiography and Laser Speckle Contrast Imaging for the Assessment of Vasculature Perfusion

PubMed Central

Towle, Erica L.; Richards, Lisa M.; Kazmi, S. M. Shams; Fox, Douglas J.; Dunn, Andrew K.

2013-01-01

BACKGROUND Assessment of the vasculature is critical for overall success in cranial vascular neurological surgery procedures. Although several methods of monitoring cortical perfusion intraoperatively are available, not all are appropriate or convenient in a surgical environment. Recently, 2 optical methods of care have emerged that are able to obtain high spatial resolution images with easily implemented instrumentation: indocyanine green (ICG) angiography and laser speckle contrast imaging (LSCI). OBJECTIVE To evaluate the usefulness of ICG and LSCI in measuring vessel perfusion. METHODS An experimental setup was developed that simultaneously collects measurements of ICG fluorescence and LSCI in a rodent model. A 785-nm laser diode was used for both excitation of the ICG dye and the LSCI illumination. A photothrombotic clot model was used to occlude specific vessels within the field of view to enable comparison of the 2 methods for monitoring vessel perfusion. RESULTS The induced blood flow change demonstrated that ICG is an excellent method for visualizing the volume and type of vessel at a single point in time; however, it is not always an accurate representation of blood flow. In contrast, LSCI provides a continuous and accurate measurement of blood flow changes without the need of an external contrast agent. CONCLUSION These 2 methods should be used together to obtain a complete understanding of tissue perfusion. PMID:22843129

[Unilateral pleural effusion caused by vessel perforation due to peripherally inserted central catheter: Indocyanine green as a diagnostic tool].

PubMed

Álvarez-Baena, L; Duque, P; Ramos, R; Zarain Obrador, L; Fernández-Quero, L

2016-01-01

A peripherally inserted central catheter (PICC) was inserted into a 44-year-old man to provide parenteral nutrition in a protein-calorie malnutrition secondary to a benign pyloric stenosis. On the fifth day while monitoring the catheter, the patient presented with a massive whitish pleural effusion after undergoing gastric endoscopy in order to treat pyloric stenosis. Chylothorax was initially suspected, and the patient was admitted to a recovery unit. Indocyanine green was administered through the PICC, obtaining a greenish discoloration in the pleural effusion 30 min later. This led to the diagnosis of a pleural effusion caused by a vessel perforation due to the PICC, leading to parenteral nutrition extravasation. Thoraco-abdominal computed tomography was performed, which confirmed an innominate vein perforation due to the PICC. PICC insertion may be associated with severe complications, such as central vessel perforation, and therefore the correct position of a central catheter should be always checked. Intravenous computed tomography contrast is the gold standard for central vascular perforation diagnosis. However if a pleural effusion occurs in this context, it is possible to use a dye, which administered intravenously can lead us to the correct diagnosis in situ. Indocyanine green was used for this purpose in this case. Copyright © 2015 Sociedad Española de Anestesiología, Reanimación y Terapéutica del Dolor. Publicado por Elsevier España, S.L.U. All rights reserved.

Evaluation of lymph flow patterns in splenic flexural colon cancers using laparoscopic real-time indocyanine green fluorescence imaging.

PubMed

Watanabe, Jun; Ota, Mitsuyoshi; Suwa, Yusuke; Ishibe, Atsushi; Masui, Hidenobu; Nagahori, Kaoru

2017-02-01

The treatment of splenic flexural colon cancer is not standardized because the lymphatic drainage is variable. The aim of this study is to evaluate the lymph flow at the splenic flexure. From July 2013 to January 2016, consecutive patients of the splenic flexural colon cancer with a preoperative diagnosis of N0 who underwent laparoscopic surgery were enrolled. Primary outcome is frequency of the direction of lymph flow from splenic flexure. We injected indocyanine green (2.5 mg) into the submucosal layer around the tumor and observed lymph flow using the laparoscopic near-infrared camera system in 30 min after injection. Thirty-one patients were enrolled in this study. The lymph flow was visualized in 31 patients (100 %) without any complications. No case exhibited lymph flow in both the left colic artery (LCA) and left branch of the middle colic artery (lt-MCA) areas. There were 19 cases (61.3 %) with lymph flow directed to the area of the root of the inferior mesenteric vein (IMV), regardless of the presence of the left accessory aberrant colic artery. Lymph node metastases were observed in six cases (19.4 %), and all of the involved lymph nodes existed in lymph flow areas determined by real-time indocyanine green fluorescence imaging. The findings of the lymph flow pattern of splenic flexure suggest that lymph node dissection at the root of the IMV area is important, and it may be not necessary to ligate both the lt-MCA and LCA, at least in cases without widespread lymph node metastases.

Investigation on laser-assisted tissue repair with NIR millisecond-long light pulses and Indocyanine Green-biopolymeric patches

NASA Astrophysics Data System (ADS)

Matteini, Paolo; Banchelli, Martina; Cottat, Maximilien; Osticioli, Iacopo; de Angelis, Marella; Rossi, Francesca; Pini, Roberto

2016-03-01

In previous works a minimally invasive laser-assisted technique for vascular repair was presented. The technique rests on the photothermal adhesion of a biocompatible and bioresorbable patch containing Indocyanine Green that is brought into contact with the site to be repaired. Afterward the use of NIR millisecond-long light pulses generates a strong welding effect between the patch and the underlying tissue and in turn the repair of the wound. This technique was shown to be effective in animal model and provides several advantages over conventional suturing methods. Here we investigate and discuss the optical stability of the ICG-biopolymeric patches and the photothermal effects induced to the irradiated tissue.

Preferential tumor cellular uptake and retention of indocyanine green for in vivo tumor imaging.

PubMed

Onda, Nobuhiko; Kimura, Masayuki; Yoshida, Toshinori; Shibutani, Makoto

2016-08-01

Indocyanine green (ICG) is a fluorescent agent approved for clinical applications by the Food and Drug Administration and European Medicines Agency. This study examined the mechanism of tumor imaging using intravenously administered ICG. The in vivo kinetics of intravenously administered ICG were determined in tumor xenografts using microscopic approaches that enabled both spatio-temporal and high-magnification analyses. The mechanism of ICG-based tumor imaging was examined at the cellular level in six phenotypically different human colon cancer cell lines exhibiting different grades of epithelioid organization. ICG fluorescence imaging detected xenograft tumors, even those < 1 mm in size, based on their preferential cellular uptake and retention of the dye following its rapid tissue-non-specific delivery, in contrast to its rapid clearance by normal tissue. Live-cell imaging revealed that cellular ICG uptake is temperature-dependent and occurs after ICG binding to the cellular membrane, a pattern suggesting endocytic uptake as the mechanism. Cellular ICG uptake correlated inversely with the formation of tight junctions. Intracellular ICG was entrapped in the membrane traffic system, resulting in its slow turnover and prolonged retention by tumor cells. Our results suggest that tumor-specific imaging by ICG involves non-specific delivery of the dye to tissues followed by preferential tumor cellular uptake and retention. The tumor cell-preference of ICG is driven by passive tumor cell-targeting, the inherent ability of ICG to bind to cell membranes, and the high endocytic activity of tumor cells in association with the disruption of their tight junctions. © 2016 UICC.

Indocyanine green detects sentinel lymph nodes in early breast cancer.

PubMed

Liu, Jun; Huang, Linping; Wang, Ning; Chen, Ping

2017-04-01

Objective To explore the clinical value of indocyanine green (ICG) for the fluorescence-guided detection of sentinel lymph nodes (SLNs) during sentinel lymph node biopsy (SLNB) in patients with early breast cancer. Methods This retrospective study included female patients with breast cancer. Patients were administered methylene blue and ICG using standard techniques. All SLNs that were collected during surgery were submitted for pathological examination. SLNs were defined as those that were either fluorescent, blue, fluorescent and blue or palpably suspicious. Surgical complications, axillary recurrence, distant metastasis and overall survival rates were observed postoperatively. Results A total of 60 patients were enrolled in the study. The fluorescence detection rate of SLNs was 100% ( n = 177), with a mean of 2.95 SLNs per patient. The methylene blue staining rate was 88.3% ( n = 106), with a mean of 1.77 SLNs per patient. Pathological assessment of intraoperative frozen specimens revealed SLN metastases in 10 patients, who immediately underwent axillary lymph node dissection. No patient had axillary recurrence or distant metastases, with a survival rate of 100%. Patients who underwent SLNB showed good appearance in the axillary wound, with no limited shoulder joint abduction and upper limb oedema. Conclusion Fluorescence-guided SLNB has several advantages and is suitable for clinical application.

Clinical application of indocyanine green (ICG) fluorescent imaging of hepatoblastoma.

PubMed

Yamamichi, Taku; Oue, Takaharu; Yonekura, Takeo; Owari, Mitsugu; Nakahata, Kengo; Umeda, Satoshi; Nara, Keigo; Ueno, Takehisa; Uehara, Shuichiro; Usui, Noriaki

2015-05-01

Although the usefulness of intraoperative indocyanine green (ICG) fluorescent imaging for the resection of hepatocellular carcinoma has been reported, its usefulness for the resection of hepatoblastoma remains unclear. This study clarifies the feasibility of intraoperative ICG fluorescent imaging for the resection of hepatoblastoma. In three hepatoblastoma patients, a primary tumor, recurrent tumor, and lung metastatic lesions were intraoperatively examined using a near-infrared fluorescence imaging system after the preoperative administration of ICG. ICG fluorescent imaging was useful for the surgical navigation in hepatoblastoma patients. In the first case, the primary hepatoblastoma exhibited intense fluorescence during right hepatectomy, but no fluorescence was detected in the residual liver. In the second case, a recurrent tumor exhibited fluorescence between the residual liver and diaphragm. A complete resection of the residual liver, with a partial resection of the diaphragm, followed by liver transplantation was performed. In the third case with multiple lung metastases, each metastatic lesion showed positive fluorescence, and all were completely resected. These fluorescence-positive lesions were pathologically proven to be viable hepatoblastoma cells. Intraoperative ICG fluorescence imaging for patients with hepatoblastoma was feasible and useful for identifying small viable lesions and confirming that no remnant tumor remained after resection. Copyright © 2015 Elsevier Inc. All rights reserved.

Intraoperative indocyanine green videoangiography for spinal vascular lesions: case report.

PubMed

Murakami, Tomohiro; Koyanagi, Izumi; Kaneko, Takahisa; Iihoshi, Satoshi; Houkin, Kiyohiro

2011-03-01

In surgery of spinal vascular lesions such as spinal arteriovenous fistula or vascular tumors, assessment of feeding arteries and draining veins is important. Intraoperative digital subtraction angiography is useful but is invasive and sometimes technically demanding. Near-infrared indocyanine green (ICG) videoangiography is less invasive and has been reported as an intraoperative diagnosis of arterial patency during clipping surgery of cerebral aneurysms or bypass surgeries. We present our experience with intraoperative ICG videoangiography in 3 cases of spinal vascular lesions. Two patients had spinal arteriovenous fistula (perimedullary, n = 1; dural, n = 1), and 1 patient had spinal cord hemangioblastoma at the thoracic or thoracolumbar level. The surgical microscope was an OPMI Pentero (Carl Zeiss, Oberkochen, Germany). After laminectomy and opening of the dura, ICG (5 mg) was injected intravenously. The ICG angiography clearly demonstrated feeding and draining vessels. The ICG findings greatly helped successful interruption of arteriovenous fistula and total removal of the tumor. Intraoperative ICG videoangiography for spinal vascular lesions was useful by providing information on vascular dynamics directly. However, the diagnostic area is limited to the field of the surgical microscope. Although intraoperative digital subtraction angiography is still needed in cases of complex spinal vascular lesions, ICG videoangiography will be an important diagnostic modality in the field of spinal vascular surgeries.

Indocyanine green angiography in patients with human T cell-lymphotropic virus type 1 uveitis.

PubMed

Sakurai, Toshiya; Yukawa, Eiichi; Hara, Yoshiaki; Miyata, Norio; Mochizuki, Manabu

2002-02-01

To determine the indocyanine green (ICG) angiographic features and to evaluate the choroidal involvement of human T-cell lymphotropic virus type 1 (HTLV-1)-associated uveitis. We performed ICG angiography using scanning laser ophthalmoscopy in 54 eyes of 27 patients (8 men and 19 women) diagnosed with HTLV-1 uveitis. The patient's mean age was 51.5 years with a range of 24-65 years. The early phase of ICG angiography revealed ICG leakage from the choroidal vessels in the posterior pole, hyperfluorescent spots that which were not detected with fluorescein angiography, and small hypofluorescent lesions in the macula which most likely corresponded to microcirculatory disturbances in the choriocapillaris. We suggest that the ICG angiographic findings reflect choroidal lesions such as infiltration with leukocytes and edema. ICG angiography may provide useful information on choroidopathy in HTLV-1 uveitis.

Affinity of Indocyanine Green in the Detection of Colorectal Peritoneal Carcinomatosis.

PubMed

Filippello, Alexandre; Porcheron, Jack; Klein, Jean Philippe; Cottier, Michèle; Barabino, Gabriele

2017-04-01

Indocyanine green (ICG) is increasingly being used in digestive oncology. In colorectal cancer, ICG can be used to detect lymph node metastasis and hepatic metastasis on the surface of the liver. In peritoneal carcinomatosis, it was previously suspected that the diffusion of ICG in the tumor mass was due to the enhanced permeability and retention effect; however, this phenomenon has not been clearly demonstrated. Using bevacizumab, an antibody directed against vascular endothelial growth factor that consequently inhibits neoangiogenesis, we sought to confirm the mode of ICG diffusion. We compared the fluorescence of peritoneal carcinomatosis nodules from patients who had previously received bevacizumab during their oncologic treatment with those who did not receive this therapy. The sensitivity of the carcinomatosis nodule fluorescence was higher in the patients who did not receive bevacizumab compared with those who received the drug (76.3% and 65.0%, respectively). The rate of false-negative results was higher in the bevacizumab group than in the group that did not receive the drug (53.8% and 42.9%, respectively). Using bevacizumab, we demonstrate that the enhanced permeability and retention effect causes ICG accumulation in peritoneal carcinomatosis resulting from colorectal cancer.

Principal component analysis of indocyanine green fluorescence dynamics for diagnosis of vascular diseases

NASA Astrophysics Data System (ADS)

Seo, Jihye; An, Yuri; Lee, Jungsul; Choi, Chulhee

2015-03-01

Indocyanine green (ICG), a near-infrared fluorophore, has been used in visualization of vascular structure and non-invasive diagnosis of vascular disease. Although many imaging techniques have been developed, there are still limitations in diagnosis of vascular diseases. We have recently developed a minimally invasive diagnostics system based on ICG fluorescence imaging for sensitive detection of vascular insufficiency. In this study, we used principal component analysis (PCA) to examine ICG spatiotemporal profile and to obtain pathophysiological information from ICG dynamics. Here we demonstrated that principal components of ICG dynamics in both feet showed significant differences between normal control and diabetic patients with vascula complications. We extracted the PCA time courses of the first three components and found distinct pattern in diabetic patient. We propose that PCA of ICG dynamics reveal better classification performance compared to fluorescence intensity analysis. We anticipate that specific feature of spatiotemporal ICG dynamics can be useful in diagnosis of various vascular diseases.

Recent advances in near-infrared fluorescence-guided imaging surgery using indocyanine green.

PubMed

Namikawa, Tsutomu; Sato, Takayuki; Hanazaki, Kazuhiro

2015-12-01

Near-infrared (NIR) fluorescence imaging has better tissue penetration, allowing for the effective rejection of excitation light and detection deep inside organs. Indocyanine green (ICG) generates NIR fluorescence after illumination by an NIR ray, enabling real-time intraoperative visualization of superficial lymphatic channels and vessels transcutaneously. The HyperEye Medical System (HEMS) can simultaneously detect NIR rays under room light to provide color imaging, which enables visualization under bright light. Thus, NIR fluorescence imaging using ICG can provide for excellent diagnostic accuracy in detecting sentinel lymph nodes in cancer and microvascular circulation in various ischemic diseases, to assist us with intraoperative decision making. Including HEMS in this system could further improve the sentinel lymph node mapping and intraoperative identification of blood supply in reconstructive organs and ischemic diseases, making it more attractive than conventional imaging. Moreover, the development of new laparoscopic imaging systems equipped with NIR will allow fluorescence-guided surgery in a minimally invasive setting. Future directions, including the conjugation of NIR fluorophores to target specific cancer markers might be realistic technology with diagnostic and therapeutic benefits.

Near-infrared Fluorescence-guided Sentinel Node Mapping of the Ovary With Indocyanine Green in a Minimally Invasive Setting: A Feasible Study.

PubMed

Buda, Alessandro; Passoni, Paolo; Corrado, Giacomo; Bussi, Beatrice; Cutillo, Giuseppe; Magni, Sonia; Vizza, Enrico

2017-01-01

Sentinel lymph node (SLN) mapping has increased its feasibility in both early-stage cervical and endometrial cancer. There are few SLN studies regarding the ovary because of the risk of tumor dissemination and perhaps because the ovary represents an inconvenient site for injection. In this preliminary study, we have shown the feasibility of SLN mapping of the ovary with indocyanine green during laparoscopic retroperitoneal aortic surgical staging. The 10 women who were included in this study underwent aortic with pelvic laparoscopic staging, which included SLN biopsy, extrafascial total hysterectomy, and bilateral salpingo-oophorectomy in case of an ovarian tumor. The fluorescent dye was injected on the dorsal and ventral side of the proper ovarian ligament and the suspensory ligament, close to the ovary and just underneath the peritoneum. In all cases except 1, SLNs were detected soon after the injection in the aortic compartment and in 3 cases also in the common iliac region. Only 1 intraoperative complication occurred: a superficial lesion of the vena cava that was recovered with a laparoscopic suture. Laparoscopic ovarian SLN mapping performed by means of an injection of indocyanine green fluorescent tracer in the ovarian ligaments seems feasible and promising. Further investigation are encouraged and necessary to evaluate the possible applications of this new technique for staging patients with early-stage ovarian cancer. Copyright © 2016 AAGL. Published by Elsevier Inc. All rights reserved.

Relevance of intraoperative indocyanine green injection in breast reconstruction using DIEP procedure for abdominal scars.

PubMed

Louges, M A; Bellaiche, J; Correia, N; Chiriac, S; François, C

2016-06-01

The presence of midline sub-umbilical and/or suprapubic scar can sometimes hinder breast reconstruction using deep inferior epigastric perforator (DIEP) procedure. We report the use of indocyanine green injection in a 60-year-old woman in the context of deep inferior epigastric perforator (DIEP) procedure for unilateral breast reconstruction (bilateral breast cancer) with abdominal scar (midline sub-umbilical scar and Pfannenstiel incision scar). This technique underlines the importance of neoangiogenesis mechanisms and helped simplify the surgical gesture initially planned (in order to ensure volume in spite of the scars as a DIEP procedure with double anastomoses was initially planned). This intraoperative vascular imaging technique is a minimally invasive, simple and quick procedure allowing the precise visualization of vascularized territories. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

In Vitro and In Vivo Analysis of Indocyanine Green-Labeled Panitumumab for Optical Imaging—A Cautionary Tale

PubMed Central

2015-01-01

Indocyanine green (IC-Green), the only FDA approved near-infrared (NIR) fluorophore for clinical use, is attractive to researchers for the development of targeted optical imaging agents by modification of its structure and conjugation to monoclonal antibodies (mAbs) or their fragments. IC-Green derivative, ICG-sulfo-OSu (ICG-sOSu), is frequently used for antibody conjugation. However, ICG-sOSu is amphiphilic and readily facilitates aggregation of mAbs that is not easily separable from the desired immunoconjugates. Complications originating from this behavior are frequently overlooked by researchers. This study examined detailed chemical and biological characteristics of an ICG-sOSu-labeled mAb, panitumumab, and provided a clinically applicable strategy to deliver a pure conjugation product. Size-exclusion high-performance liquid chromatography (SE-HPLC) analysis of conjugation reactions, performed at molar reaction ratios of ICG-sOSu: mAb of 5, 10, or 20, resulted in isolable desired ICG-sOSu-panitumumab conjugation product in 72%, 53%, and 19% yields, respectively, with the remainder consisting of high molecular weight aggregates (>150 kDa) 14%, 30%, and 51%, respectively. The HPLC-purified ICG-sOSu-panitumumab products were analyzed by native and SDS polyacrylamide gel electrophoresis (PAGE) followed by optical imaging. Results indicated that the interaction between ICG-sOSu and panitumumab was due to both covalent and noncovalent binding of the ICG-sOSu to the protein. Noncovalently bound dye in the ICG-sOSu-panitumumab conjugate products was removed by extraction with ethyl acetate to further purify the HPLC-isolated conjugation products. With conserved immunoreactivity, excellent target-specific uptake of the doubly purified bioconjugates was observed with minimal liver retention in athymic nude mice bearing HER1-expressing tumor xenografts. In summary, the preparation of well-defined bioconjugate products labeled with commercial ICG-sOSu dye is not a simple

In vitro and in vivo analysis of indocyanine green-labeled panitumumab for optical imaging-a cautionary tale.

PubMed

Zhou, Yang; Kim, Young-Seung; Milenic, Diane E; Baidoo, Kwamena E; Brechbiel, Martin W

2014-10-15

Indocyanine green (IC-Green), the only FDA approved near-infrared (NIR) fluorophore for clinical use, is attractive to researchers for the development of targeted optical imaging agents by modification of its structure and conjugation to monoclonal antibodies (mAbs) or their fragments. IC-Green derivative, ICG-sulfo-OSu (ICG-sOSu), is frequently used for antibody conjugation. However, ICG-sOSu is amphiphilic and readily facilitates aggregation of mAbs that is not easily separable from the desired immunoconjugates. Complications originating from this behavior are frequently overlooked by researchers. This study examined detailed chemical and biological characteristics of an ICG-sOSu-labeled mAb, panitumumab, and provided a clinically applicable strategy to deliver a pure conjugation product. Size-exclusion high-performance liquid chromatography (SE-HPLC) analysis of conjugation reactions, performed at molar reaction ratios of ICG-sOSu: mAb of 5, 10, or 20, resulted in isolable desired ICG-sOSu-panitumumab conjugation product in 72%, 53%, and 19% yields, respectively, with the remainder consisting of high molecular weight aggregates (>150 kDa) 14%, 30%, and 51%, respectively. The HPLC-purified ICG-sOSu-panitumumab products were analyzed by native and SDS polyacrylamide gel electrophoresis (PAGE) followed by optical imaging. Results indicated that the interaction between ICG-sOSu and panitumumab was due to both covalent and noncovalent binding of the ICG-sOSu to the protein. Noncovalently bound dye in the ICG-sOSu-panitumumab conjugate products was removed by extraction with ethyl acetate to further purify the HPLC-isolated conjugation products. With conserved immunoreactivity, excellent target-specific uptake of the doubly purified bioconjugates was observed with minimal liver retention in athymic nude mice bearing HER1-expressing tumor xenografts. In summary, the preparation of well-defined bioconjugate products labeled with commercial ICG-sOSu dye is not a simple

Clinical application of indocyanine green-fluorescence imaging during hepatectomy

PubMed Central

Ishizawa, Takeaki; Saiura, Akio

2016-01-01

In hepatobiliary surgery, the fluorescence and bile excretion of indocyanine green (ICG) can be used for real-time visualization of biological structure. Fluorescence cholangiography is used to obtain fluorescence images of the bile ducts following intrabiliary injection of 0.025−0.5 mg/mL ICG or intravenous injection of 2.5 mg ICG. Recently, the latter technique has been used in laparoscopic/robotic cholecystectomy. Intraoperative fluorescence imaging can be used to identify subcapsular hepatic tumors. Primary and secondary hepatic malignancy can be identified by intraoperative fluorescence imaging using preoperative intravenous injection of ICG through biliary excretion disorders that exist in cancerous tissues of hepatocellular carcinoma (HCC) and in non-cancerous hepatic parenchyma around adenocarcinoma foci. Intraoperative fluorescence imaging may help detect tumors to be removed, especially during laparoscopic hepatectomy, in which visual inspection and palpation are limited, compared with open surgery. Fluorescence imaging can also be used to identify hepatic segments. Boundaries of hepatic segments can be visualized following injection of 0.25−2.5 mg/mL ICG into the portal veins or by intravenous injection of 2.5 mg ICG following closure of the proximal portal pedicle toward hepatic regions to be removed. These techniques enable identification of hepatic segments before hepatectomy and during parenchymal transection for anatomic resection. Advances in imaging systems will increase the use of fluorescence imaging as an intraoperative navigation tool that can enhance the safety and accuracy of open and laparoscopic/robotic hepatobiliary surgery. PMID:27500144

Lymphatic mapping with fluorescence navigation using indocyanine green and axillary surgery in patients with primary breast cancer.

PubMed

Takeuchi, Megumi; Sugie, Tomoharu; Abdelazeem, Kassim; Kato, Hironori; Shinkura, Nobuhiko; Takada, Masahiro; Yamashiro, Hiroyasu; Ueno, Takayuki; Toi, Masakazu

2012-01-01

The indocyanine green fluorescence (ICGf) navigation method provides real-time lymphatic mapping and sentinel lymph node (SLN) visualization, which enables the removal of SLNs and their associated lymphatic networks. In this study, we investigated the features of the drainage pathways detected with the ICGf navigation system and the order of metastasis in axillary nodes. From April 2008 to February 2010, 145 patients with clinically node-negative breast cancer underwent SLN surgery with ICGf navigation. The video-recorded data from 79 patients were used for lymphatic mapping analysis. We analyzed 145 patients with clinically node-negative breast cancer who underwent SLN surgery with the ICGf navigation system. Fluorescence-positive SLNs were identified in 144 (99%) of 145 patients. Both single and multiple routes to the axilla were identified in 47% of cases using video-recorded lymphatic mapping data. An internal mammary route was detected in 6% of the cases. Skip metastasis to the second or third SLNs was observed in 6 of the 28 node-positive patients. We also examined the strategy of axillary surgery using the ICGf navigation system. We found that, based on the features of nodal involvement, 4-node resection could provide precise information on the nodal status. The ICGf navigation system may provide a different lymphatic mapping result than computed tomography lymphography in clinically node-negative breast cancer patients. Furthermore, it enables the identification of lymph nodes that do not accumulate indocyanine green or dye adjacent to the SLNs in the sequence of drainage. Knowledge of the order of nodal metastasis as revealed by the ICGf system may help to personalize the surgical treatment of axilla in SLN-positive cases, although additional studies are required. © 2012 Wiley Periodicals, Inc.

Fluorescent Imaging With Indocyanine Green During Laparoscopic Cholecystectomy in Patients at Increased Risk of Bile Duct Injury

PubMed Central

Ankersmit, Marjolein; van Dam, Dieuwertje A.; van Rijswijk, Anne-Sophie; van den Heuvel, Baukje; Tuynman, Jurriaan B.; Meijerink, Wilhelmus J. H. J.

2017-01-01

Background. Although rare, injury to the common bile duct (CBD) during laparoscopic cholecystectomy (LC) can be reduced by better intraoperative visualization of the cystic duct (CD) and CBD. The aim of this study was to establish the efficacy of early visualization of the CD and the added value of CBD identification, using near-infrared (NIR) light and the fluorescent agent indocyanine green (ICG), in patients at increased risk of bile duct injury. Materials and Methods. Patients diagnosed with complicated cholecystitis and scheduled for LC were included. The CBD and CD were visualized with NIR light before and during dissection of the liver hilus and at critical view of safety (CVS). Results. Of the 20 patients originally included, 2 were later excluded due to conversion. In 6 of 18 patients, the CD was visualized early during dissection and prior to imaging with conventional white light. The CBD was additionally visualized with ICG-NIR in 7 of 18 patients. In 1 patient, conversion was prevented due to detection of the CD and CBD with ICG-NIR. Conclusions. Early visualization of the CD or additional identification of the CBD using ICG-NIR in patients with complicated cholecystolithiasis can be helpful in preventing CBD injury. Future studies should attempt to establish the optimal dosage and time frame for ICG administration and bile duct visualization with respect to different gallbladder pathologies. PMID:28178882

Sentinel lymph node biopsy in cutaneous melanoma of the head and neck using the indocyanine green SPY Elite system.

PubMed

Vahabzadeh-Hagh, Andrew M; Blackwell, Keith E; Abemayor, Elliot; St John, Maie A

2018-05-17

Lymph node status is the single most important prognostic factor for patients with early-stage cutaneous melanoma. Sentinel lymph node biopsy (SLNB) has become the standard of care for intermediate depth melanomas. Modern SLNB implementation includes technetium-99 lymphoscintigraphy combined with local administration of a vital blue dye. However, sentinel lymph nodes may fail to localize in some cases and false-negative rates range from 0 to 34%. Here we demonstrate the feasibility of a new sentinel lymph node biopsy technique using indocyanine green (ICG) and the SPY Elite near-infrared imaging system. Cases of primary cutaneous melanoma of the head and neck without locoregional metastasis, underwent SLNB at a single quaternary care institution between May 2016 and June 2017. Intraoperatively, 0.25 mL of ICG was injected intradermal in 4 quadrants around the primary lesion. 10-15 minute circulation time was permitted. SPY Elite identified the sentinel lymph node within the nodal basin marked by lymphoscintigraphy. Target first echelon lymph nodes were confirmed with a gamma probe and ICG fluorescence. 14 patients were included with T1a to T4b cutaneous melanomas. Success rates for sentinel lymph node identification using lymphoscintigraphy and the SPY Elite system were both 86%. Zero false negatives occurred. Median length of follow-up was 323 days. In this pilot study, Indocyanine green near-infrared fluorescence demonstrates a safe, and facile method of sentinel lymph node biopsy for cutaneous melanoma of the head and neck compared with lymphoscintigraphy and vital blue dyes. Copyright © 2018 Elsevier Inc. All rights reserved.

Diagnostic evaluation of sentinel lymph node biopsy using indocyanine green and infrared or fluorescent imaging in gastric cancer: a systematic review and meta-analysis.

PubMed

Skubleny, Daniel; Dang, Jerry T; Skulsky, Samuel; Switzer, Noah; Tian, Chunhong; Shi, Xinzhe; de Gara, Christopher; Birch, Daniel W; Karmali, Shahzeer

2018-06-01

Sentinel node navigation surgery (SNNS) for gastric cancer using infrared visualization of indocyanine green (ICG) is intriguing because it may limit operative morbidity. We are the first to systematically review and perform meta-analysis on the diagnostic utility of ICG and infrared electronic endoscopy (IREE) or near infrared fluorescent imaging (NIFI) for SNNS exclusively in gastric cancer. A search of electronic databases MEDLINE, EMBASE, SCOPUS, Web of Science, and the Cochrane Library using search terms "gastric/stomach" AND "tumor/carcinoma/cancer/neoplasm/adenocarcinoma/malignancy" AND "indocyanine green" was completed in May 2017. Articles were selected by two independent reviewers based on the following major inclusion criteria: (1) diagnostic accuracy study design; (2) indocyanine green was injected at tumor site; (3) IREE or NIFI was used for intraoperative visualization. 327 titles or abstracts were screened. The quality of included studies was assessed using the Quality Assessment of Diagnostic Accuracy Studies-2. Ten full text studies were selected. 643 patients were identified with the majority of patients possessing T1 tumors (79.8%). Pooled identification rate, diagnostic odds ratio, sensitivity, and specificity were 0.99 (0.97-1.0), 380.0 (68.71-2101), 0.87 (0.80-0.93), and 1.00 (0.99-1.00), respectively. The summary receiver operator characteristic for ICG + IREE/NIFI demonstrated a test accuracy of 98.3%. Subgroup analysis found improved test performance for studies with low-risk QUADAS-2 scores, studies published after 2010 and submucosal ICG injection. IREE had improved diagnostic odds ratio, sensitivity, and identification rate compared to NIFI. Heterogeneity among studies ranged from low (I 2  < 25%) to high (I 2  > 75%). We found encouraging results regarding the accuracy, diagnostic odds ratio, and specificity of the test. The sensitivity was not optimal but may be improved by a strict protocol to augment the technique. Given

Near-infrared-fluorescence imaging of lymph nodes by using liposomally formulated indocyanine green derivatives.

PubMed

Toyota, Taro; Fujito, Hiromichi; Suganami, Akiko; Ouchi, Tomoki; Ooishi, Aki; Aoki, Akira; Onoue, Kazutaka; Muraki, Yutaka; Madono, Tomoyuki; Fujinami, Masanori; Tamura, Yutaka; Hayashi, Hideki

2014-01-15

Liposomally formulated indocyanine green (LP-ICG) has drawn much attention as a highly sensitive near-infrared (NIR)-fluorescence probe for tumors or lymph nodes in vivo. We synthesized ICG derivatives tagged with alkyl chains (ICG-Cn), and we examined NIR-fluorescence imaging for lymph nodes in the lower extremities of mice by using liposomally formulated ICG-Cn (LP-ICG-Cn) as well as conventional liposomally formulated ICG (LP-ICG) and ICG. Analysis with a noninvasive preclinical NIR-fluorescence imaging system revealed that LP-ICG-Cn accumulates in only the popliteal lymph node 1h after injection into the footpad, whereas LP-ICG and ICG accumulate in the popliteal lymph node and other organs like the liver. This result indicates that LP-ICG-Cn is a useful NIR-fluorescence probe for noninvasive in vivo bioimaging, especially for the sentinel lymph node. Copyright © 2013 Elsevier Ltd. All rights reserved.

The utility of indocyanine green fluorescence imaging during robotic adrenalectomy.

PubMed

Colvin, Jennifer; Zaidi, Nisar; Berber, Eren

2016-08-01

Indocyanine green (ICG) has been used for medical imaging since 1950s, but has more recently become available for use in minimally invasive surgery owing to improvements in technology. This study investigates the use of ICG florescence to guide an accurate dissection by delineating the borders of adrenal tumors during robotic adrenalectomy (RA). This prospective study compared conventional robotic view with ICG fluorescence imaging in 40 consecutive patients undergoing RA. Independent, non-blinded observers assessed how accurately ICG fluorescence delineated the borders of adrenal tumors compared to conventional robotic view. A total of 40 patients underwent 43 adrenalectomies. ICG imaging was superior, equivalent, or inferior to conventional robotic view in 46.5% (n = 20), 25.6% (n = 11), and 27.9% (n = 12) of the procedures. On univariate analysis, the only parameter that predicted the superiority of ICG imaging over conventional robotic view was the tumor type, with adrenocortical tumors being delineated more accurately on ICG imaging compared to conventional robotic view. This study demonstrates the utility of ICG to guide the dissection and removal of adrenal tumors during RA. A simple reproducible method is reported, with a detailed description of the utility based on tumor type, approach and side. J. Surg. Oncol. 2016;114:153-156. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Targeting tumor hypoxia with 2-nitroimidazole-indocyanine green dye conjugates

PubMed Central

Xu, Yan; Zanganeh, Saeid; Mohammad, Innus; Aguirre, Andres; Wang, Tianheng; Yang, Yi; Kuhn, Liisa; Smith, Michael B.

2013-01-01

Abstract. Tumor hypoxia is a major indicator of treatment resistance to chemotherapeutic drugs, and fluorescence optical tomography has tremendous potential to provide clinically useful, functional information by identifying tumor hypoxia. The synthesis of a 2-nitroimidazole-indocyanine green conjugate using a piperazine linker (piperazine-2-nitroimidazole-ICG) capable of robust fluorescent imaging of tumor hypoxia is described. In vivo mouse tumor imaging studies were completed and demonstrate an improved imaging capability of the new dye relative to an earlier version of the dye that was synthesized with an ethanolamine linker (ethanolamine-2-nitroimidazole-ICG). Mouse tumors located at imaging depths of 1.5 and 2.0 cm in a turbid medium were imaged at various time points after intravenous injection of the dyes. On average, the reconstructed maximum fluorescence concentration of the tumors injected with piperazine-2-nitroimidazole-ICG was twofold higher than that injected with ethanolamine-2-nitroimidazole-ICG within 3 h postinjection period and 1.6 to 1.7 times higher beyond 3 h postinjection. The untargeted bis-carboxylic acid ICG completely washed out after 3 h postinjection. Thus, the optimal window to assess tumor hypoxia is beyond 3 h postinjection. These findings were supported with fluorescence images of histological sections of tumor samples and an immunohistochemistry technique for identifying tumor hypoxia. PMID:23764695

Photodynamic actions of indocyanine green and trypan blue on human lens epithelial cells in vitro.

PubMed

Melendez, Robert F; Kumar, Neeru; Maswadi, Saher M; Zaslow, Kenneth; Glickmank, Randolph D

2005-07-01

The purpose of this study was to evaluate the toxicity and photodynamic activity of indocyanine green (ICG) and trypan blue (TryB) on cultured human lensepithelial cells (LECs). Experimental study. Lens epithelial cell viability was assessed after treatment with ICG and TryB concentrations ranging from 0.025 to 5.0 mg/ml, and exposure to 806 nm diode laser. At ICG concentrations below 0.5 mg/ml, there was > or =75% cell viability; at higher ICG concentrations there was dose-dependent cytotoxicity in addition to loss of cellular viability due to ICG photosensitization. TryB had little cytotoxicity to the LECs: >80% cells were viable irrespective of the dye concentration or laser treatment. These data indicate that ICG may have application as a photosensitizer in the selective eradication of residual LECs after cataract surgery to reduce the incidence of posterior capsule opacification.

Symmetricity analysis of time to peak parameter of indocyanine green dynamics

NASA Astrophysics Data System (ADS)

An, Yuri; Lee, Jungsul; Choi, Chulhee

2013-03-01

We have previously discovered that near-infrared optical imaging of indocyanine green (ICG) signal and analyzing its dynamics can be applied for measurement of blood perfusion rate and detection of Raynaud's phenomenon (RP). Especially, RP is closely associated with abnormal vasomotor responses and can progress to tissue necrosis due to excessively sustained vasoconstriction. Therefore, early detecting of RP is one of important implication to prevent tissue damage from peripheral vascular disorders. In the present study, we propose new analysis and scoring method of symmetricity of Tmax value of left and right extremities. Moreover, this symmetricity analysis can give further information about microvascular insufficiency. For validation of the proposed method, we tested whether the segmental and paired analysis of Tmax value (time-to-peak) of ICG dynamics can be used for sensitive diagnosis of microvascular abnormalities which cannot be detected by conventional methods. From the near-infrared images of diabetes mellitus patients with vascular complications, the trend of asymmetry in Tmax value was observed. We assumed that decreasing local blood perfusion by autonomic nerve dysfunction causes the asymmetric Tmax value of right and left feet. These results collectively indicate that the proposed method can be used as a useful diagnostic tool for RP or other microvascular disorders.

Characterization of skin tissue soldering using diode laser and indocyanine green: in vitro studies.

PubMed

Khosroshahi, M E; Nourbakhsh, M S; Saremi, S; Tabatabaee, F

2010-03-01

Laser tissue soldering based on protein as biological glues and other compounds can provide greater bond strength and less collateral damage. Endogenous and exogenous materials such as indocyanine green (ICG) are often added to solders to enhance light absorption. The purpose of this in vitro study was to examine the impact of different parameters of laser soldering on the thermo-physical properties of the skin. A mixture of albumin solder and ICG was prepared, and then the coated samples were irradiated by an 810 nm diode laser under different conditions. The temperature rise, number of scans (N(s)), and scan velocity (V(s)) were investigated in this study. The results showed that, at each laser irradiance (I), the tensile strength (sigma) of incisions repaired in static mode was higher than in dynamic mode and that the sigma increased with both increasing N(s) and increasing I. It is therefore important to consider the trade off between scan velocity and surface temperature for achieving an optimum operating condition.

New technique for laryngotracheal mucosa transplantation. 'Stamp' welding using indocyanine green dye and albumin interaction with diode laser.

PubMed

Wang, Z; Pankratov, M M; Gleich, L L; Rebeiz, E E; Shapshay, S M

1995-07-01

To investigate (1) the possibility of survival of free mucosa "stamp" grafts fixed in the airway with a new technique using indocyanine green-dyed albumin solder activated with a diode laser and (2) the degree of improvement of wound healing in the airway by applying modified microskin transplantation techniques from burn surgery to cover a relatively large wound with a few small pieces of mucosa anchored in place with the previously mentioned technique. Three (one control and two experimental) rectangular (10 x 8 mm) wounds in tracheal mucosa were produced in four experimental animals (dogs) using a carbon dioxide laser. The control wound was left uncovered. In the first experimental wound, a mucosal flap was raised and then fixed in place by a trapdoor flap method. In the second experimental wound, two small (each 2 x 3 mm) autogenous mucosa grafts were anchored onto the surface with indocyanine green-dyed albumin activated with an 810-nm diode laser. Histomorphologically, the postoperative results from three wounds were compared. The experimental wounds were completely covered by regenerated squamous cells in 1 week and by ciliated epithelium in 2 weeks after the operation despite the discrepancy in size of the graft to wound area (1:6.7) covered with the stamp mucosa. No thermal damage from the diode laser was noted in the second experimental wounds. In the control wounds, no coverage was observed at 1 week, and only squamous cells were noted 2 weeks postoperatively. All the wounds had normal ciliated epithelium coverage at 4 weeks. Transplanted stamp grafts provided similar or better healing than trapdoor flap transplants. This new technique made endoscopic mucosal grafting possible and offers a potential breakthrough in the management of laryngotracheal stenosis.

Prognostic Impact of Indocyanine Green Plasma Disappearance Rate in Hepatocellular Carcinoma Patients after Radiofrequency Ablation: A Prognostic Nomogram Study

PubMed Central

Azumi, Motoi; Suda, Takeshi; Terai, Shuji; Akazawa, Kouhei

2017-01-01

Objective Radiofrequency ablation has been used widely for the local ablation of hepatocellular carcinoma, particularly in its early stages. The study aim was to identify significant prognostic factors and develop a predictive nomogram for patients with hepatocellular carcinoma who have undergone radiofrequency ablation. We also developed the formula to predict the probability of 3- and 5-year overall survival based on clinical variables. Methods We retrospectively studied 96 consecutive patients with hepatocellular carcinoma who had undergone radiofrequency ablation as a first-line treatment. Independent and significant factors affecting the overall survival were selected using a Cox proportional hazards model, and a prognostic nomogram was developed based on these factors. The predictive accuracy of the nomogram was determined by Harrell's concordance index and compared with the Cancer of the Liver Italian Program score and Japan Integrated Staging score. Results A multivariate analysis revealed that age, indocyanine green plasma disappearance rate, and log(des-gamma-carboxy prothrombin) level were independent and significant factors influencing the overall survival. The nomogram was based on these three factors. The mean concordance index of the nomogram was 0.74±0.08, which was significantly better than that of conventional staging systems using the Cancer of the Liver Italian Program score (0.54±0.03) and Japan Integrated Staging score (0.59±0.07). Conclusion This study suggested that the indocyanine green plasma disappearance rate and age at radiofrequency ablation (RFA) and des-gamma-carboxy-prothrombin (DCP) are good predictors of the prognosis in hepatocellular carcinoma patients after radiofrequency ablation. We successfully developed a nomogram using obtainable variables before treatment. PMID:28458303

Prognostic Impact of Indocyanine Green Plasma Disappearance Rate in Hepatocellular Carcinoma Patients after Radiofrequency Ablation: A Prognostic Nomogram Study.

PubMed

Azumi, Motoi; Suda, Takeshi; Terai, Shuji; Akazawa, Kouhei

2017-01-01

Objective Radiofrequency ablation has been used widely for the local ablation of hepatocellular carcinoma, particularly in its early stages. The study aim was to identify significant prognostic factors and develop a predictive nomogram for patients with hepatocellular carcinoma who have undergone radiofrequency ablation. We also developed the formula to predict the probability of 3- and 5-year overall survival based on clinical variables. Methods We retrospectively studied 96 consecutive patients with hepatocellular carcinoma who had undergone radiofrequency ablation as a first-line treatment. Independent and significant factors affecting the overall survival were selected using a Cox proportional hazards model, and a prognostic nomogram was developed based on these factors. The predictive accuracy of the nomogram was determined by Harrell's concordance index and compared with the Cancer of the Liver Italian Program score and Japan Integrated Staging score. Results A multivariate analysis revealed that age, indocyanine green plasma disappearance rate, and log (des-gamma-carboxy prothrombin) level were independent and significant factors influencing the overall survival. The nomogram was based on these three factors. The mean concordance index of the nomogram was 0.74±0.08, which was significantly better than that of conventional staging systems using the Cancer of the Liver Italian Program score (0.54±0.03) and Japan Integrated Staging score (0.59±0.07). Conclusion This study suggested that the indocyanine green plasma disappearance rate and age at radiofrequency ablation (RFA) and des-gamma-carboxy-prothrombin (DCP) are good predictors of the prognosis in hepatocellular carcinoma patients after radiofrequency ablation. We successfully developed a nomogram using obtainable variables before treatment.

Axillary reverse mapping with indocyanine green or isosulfan blue demonstrate similar crossover rates to radiotracer identified sentinel nodes.

PubMed

Foster, Deshka; Choy, Nicole; Porter, Catherine; Ahmed, Shushmita; Wapnir, Irene

2018-03-01

Sentinel lymph node (SLN) resection is imperative for breast cancer staging. Axillary reverse mapping (ARM) can preserve arm draining nodes and lymphatics during surgery. ARM is generally performed with isosulfan blue (ISB), restricting its use for concurrent SLN biopsy. Indocyanine green (ICG) could serve as an alternative to ISB for ARM procedures. SLN mapping and biopsy was performed via periareolar injection of 99 technetium-sulfur colloid ( 99m TcSc, TSC). ISB and ICG were injected in the upper arm. Blue-stained lymphatics or nodes were visualized in the axilla; ICG was identified using the SPY Elite® system. Twenty-three patients underwent SLN biopsy with or without axillary node dissection and ARM procedures. Twenty of these patients had at least one hot node; 12 patients had SLNs that were only hot, 6 hot/blue/fluorescent, and 2 hot/fluorescent. Overall, crossover of ARM agents with SLNs occurred in 8 cases. Inspection of the axillary cavity after SLN biopsy revealed fluorescent lymphatics and nodes remaining in 14 and 7 patients, respectively. Blue lymphatics and blue nodes were detected in fewer cases. Nearly one-third of patients showed crossover between breast and arm draining nodes, which provides insight as to why some patients develop lymphedema symptoms after SLN biopsy. ICG and ISB identify similar numbers of SLNs. As such ICG could substitute for ISB in ARM procedures. © 2017 Wiley Periodicals, Inc.

Liver tumor boundaries identified intraoperatively using real-time indocyanine green fluorescence imaging.

PubMed

Zhang, Ya-Min; Shi, Rui; Hou, Jian-Cun; Liu, Zi-Rong; Cui, Zi-Lin; Li, Yang; Wu, Di; Shi, Yuan; Shen, Zhong-Yang

2017-01-01

Clear delineation between tumors and normal tissues is ideal for real-time surgical navigation imaging. We investigated applying indocyanine green (ICG) fluorescence imaging navigation using an intraoperative administration method in liver resection. Fifty patients who underwent liver resection were divided into two groups based on clinical situation and operative purpose. In group I, sizes of superficial liver tumors were determined; tiny tumors were identified. In group II, the liver resection margin was determined; real-time navigation was performed. ICG was injected intravenously at the beginning of the operation; the liver surface was observed with a photodynamic eye (PDE). Liver resection margins were determined using PDE. Fluorescence contrast between normal liver and tumor tissues was obvious in 32 of 35 patients. A boundary for half the liver or specific liver segments was determined in nine patients by examining the portal vein anatomy after ICG injection. Eight small tumors not observed preoperatively were detected; the smallest was 2 mm. ICG fluorescence imaging navigation is a promising, simple, and safe tool for routine real-time intraoperative imaging during hepatic resection and clinical exploration in hepatocellular carcinoma, enabling high sensibility for identifying liver resection margins and detecting tiny superficial tumors.

Indocyanine green angiography findings of cystoid macular edema secondary to paclitaxel therapy.

PubMed

Nomi, Nanami; Ota, Manami; Fukumura, Miho; Nuno, Yoshihisa; Hatano, Makoto; Wakuta, Makiko; Yanai, Ryoji; Kimura, Kazuhiro

2018-03-01

To report 2 cases of paclitaxel-related maculopathy manifesting as cystoid macular edema (CME) with late petaloid hyperfluorescence on indocyanine green angiography (IA). A 74-year-old man (patient 1) undergoing paclitaxel chemotherapy for gastric and metastatic liver cancer and a 69-year-old man (patient 2) receiving paclitaxel for hypopharyngeal cancer presented with anorthopia in both eyes. Spectral domain-optical coherence tomography (SD-OCT) revealed macular edema in both eyes of each patient. Fluorescein angiography showed weak petaloid pooling around the fovea in the late phase. IA revealed CME with petaloid hyperfluorescence that matched the region of macular edema detected by SD-OCT. The CME was attenuated in the right eye but not in the left eye of patient 1 at 2 weeks after discontinuation of paclitaxel treatment, whereas it was no longer apparent in either eye at 3 months. The CME was no longer detected in either eye of patient 2 at 3 months after discontinuation of paclitaxel. These cases suggest that paclitaxel-induced CME may result from intraretinal accumulation of intracellular fluid and minimal impairment of the blood retinal barrier.

Indocyanine green plasma disappearance rate during the anhepatic phase of orthotopic liver transplantation.

PubMed

Bruegger, Lukas; Studer, Peter; Schmid, Stefan W; Pestel, Gunther; Reichen, Juerg; Seiler, Christian; Candinas, Daniel; Inderbitzin, Daniel

2008-01-01

Non-invasive pulse spectrophotometry to measure indocyanine green (ICG) elimination correlates well with the conventional invasive ICG clearance test. Nevertheless, the precision of this method remains unclear for any application, including small-for-size liver remnants. We therefore measured ICG plasma disappearance rate (PDR) during the anhepatic phase of orthotopic liver transplantation using pulse spectrophotometry. Measurements were done in 24 patients. The median PDR after exclusion of two outliers and two patients with inconstant signal was 1.55%/min (95% confidence interval [CI]=0.8-2.2). No correlation with patient age, gender, body mass, blood loss, administration of fresh frozen plasma, norepinephrine dose, postoperative albumin (serum), or difference in pre and post transplant body weight was detected. In conclusion, we found an ICG-PDR different from zero in the anhepatic phase, an overestimation that may arise in particular from a redistribution into the interstitial space. If ICG pulse spectrophotometry is used to measure functional hepatic reserve, the verified average difference from zero (1.55%/min) determined in our study needs to be taken into account.

Indocyanine green kinetics to assess liver function: Ready for a clinical dynamic assessment in major liver surgery?

PubMed Central

De Gasperi, Andrea; Mazza, Ernestina; Prosperi, Manlio

2016-01-01

Indocyanine green (ICG) kinetics (PDR/R15) used to quantitatively assess hepatic function in the perioperative period of major resective surgery and liver transplantation have been the object of an extensive, updated and critical review. New, non invasive bedside monitors (pulse dye densitometry technology) make this opportunity widely available in clinical practice. After having reviewed basic concepts of hepatic clearance, we analysed the most common indications ICG kinetic parameters have nowadays in clinical practice, focusing in particular on the diagnostic and prognostic role of PDR and R15 in the perioperative period of major liver surgery and liver transplantation. As recently pointed out, even if of extreme interest, ICG clearance parameters have still some limitations, to be considered when using these tests. PMID:26981173

Indocyanine green video-angiography as an aid to surgical treatment of spinal dural arteriovenous fistulae.

PubMed

Hettige, Samantha; Walsh, Daniel

2010-03-01

To illustrate the use of indocyanine green (ICG) video-angiography to confirm abolition of spinal dural arteriovenous fistula (SDAVF) and preserve the normal vascular anatomy intraoperatively. A 73-year-old woman presenting with progressive myelopathy was diagnosed with an SDAVF, where the origin of the fistula was in close proximity to the origin of the posterior spinal artery. ICG was injected intravenously. Using a filter on the microscope, dynamic filling of the abnormal vasculature was visualised. After applying a clip to the fistulous connection, we were able to see the successful interruption of the dural fistula, on-table in real time. ICG video angiography confirmed interruption of the fistula and preservation of the associated posterior spinal artery. We find the application of this relatively new technology has the potential to shorten operating times, gives additional reassurance of completeness of surgical treatment and preservation of normal spinal vasculature.

Molecular imaging-guided photothermal/photodynamic therapy against tumor by iRGD-modified indocyanine green nanoparticles.

PubMed

Yan, Fei; Wu, Hao; Liu, Hongmei; Deng, Zhiting; Liu, Hong; Duan, Wanlu; Liu, Xin; Zheng, Hairong

2016-02-28

Multifunctional near-infrared (NIR) nanoparticles demonstrate great potential in tumor theranostic applications. To achieve the sensitive detection and effective phototherapy in the early stage of tumor genesis, it is highly desirable to improve the targeting of NIR theranostic agents to biomarkers and to enhance their accumulation in tumor. Here we report a novel targeted multifunctional theranostic nanoparticle, internalized RGD (iRGD)-modified indocyanine green (ICG) liposomes (iRGD-ICG-LPs), for molecular imaging-guided photothermal therapy (PTT) and photodynamic therapy (PDT) therapy against breast tumor. The iRGD peptides with high affinity to αvβ3 integrin and effective tumor-internalized property were firstly used to synthesize iRGD-PEG2000-DSPE lipopeptides, which were further utilized to fabricate the targeted ICG liposomes. The results indicated that iRGD-ICG-LPs exhibited excellent stability and could provide an accurate and sensitive detection of breast tumor through NIR fluorescence molecular imaging. We further employed this nanoparticle for tumor theranostic application, demonstrating significantly higher tumor accumulation and tumor inhibition efficacy through PTT/PDT effects. Histological analysis further revealed much more apoptotic cells, confirming the advantageous anti-tumor effect of iRGD-ICG-LPs over non-targeted ICG-LPs. Notably, the targeting therapy mediated by iRGD provides almost equivalent anti-tumor efficacy at a 12.5-fold lower drug dose than that by monoclonal antibody, and no tumor recurrence and obvious treatment-induced toxicity were observed in our study. Our study provides a promising strategy to realize the sensitive detection and effective treatment of tumors by integrating molecular imaging into PTT/PDT therapy. Copyright © 2015. Published by Elsevier B.V.

Comparison of the photothermal effects of 808nm gold nanorod and indocyanine green solutions using an 805nm diode laser

NASA Astrophysics Data System (ADS)

Hasanjee, Aamr M.; Zhou, Feifan; West, Connor; Silk, Kegan; Doughty, Austin; Bahavar, Cody F.; Chen, Wei R.

2016-03-01

Non-invasive laser immunotherapy (NLIT) is a treatment method for metastatic cancer which combines noninvasive laser irradiation with immunologically modified nanostructures to ablate a primary tumor and induce a systemic anti-tumor response. To further expand the development of NLIT, two different photosensitizing agents were compared: gold nanorods (GNR) with an optical absorption peak of 808 nm and indocyanine green (ICG) with an optical absorption peak of ~800 nm. Various concentrations of GNR and ICG solutions were irradiated at different power densities using an 805 nm diode laser, and the temperature of the solutions was monitored during irradiation using a thermal camera. For comparison, dye balls made up of a 1:1 volume ratio of gel solution to GNR or ICG solution were placed in phantom gels and were then irradiated using the 805 nm diode laser to imitate the effect of laser irradiation on in vivo tumors. Non-invasive laser irradiation of GNR solution for 2 minutes resulted in a maximum increase in temperature by 31.8 °C. Additionally, similar irradiation of GNR solution dye ball within phantom gel for 10 minutes resulted in a maximum temperature increase of 8.2 °C. Comparatively, non-invasive laser irradiation of ICG solution for 2 minutes resulted in a maximum increase in temperature by 28.0 °C. Similar irradiation of ICG solution dye ball within phantom gel for 10 minutes yielded a maximum temperature increase of only 3.4 °C. Qualitatively, these studies showed that GNR solutions are more effective photosensitizing agents than ICG solution.

Voltage-Sensitive Fluorescence of Indocyanine Green in the Heart

PubMed Central

Martišienė, Irma; Mačianskienė, Regina; Treinys, Rimantas; Navalinskas, Antanas; Almanaitytė, Mantė; Karčiauskas, Dainius; Kučinskas, Audrius; Grigalevičiūtė, Ramunė; Zigmantaitė, Vilma; Benetis, Rimantas; Jurevičius, Jonas

2016-01-01

So far, the optical mapping of cardiac electrical signals using voltage-sensitive fluorescent dyes has only been performed in experimental studies because these dyes are not yet approved for clinical use. It was recently reported that the well-known and widely used fluorescent dye indocyanine green (ICG), which has FDA approval, exhibits voltage sensitivity in various tissues, thus raising hopes that electrical activity could be optically mapped in the clinic. The aim of this study was to explore the possibility of using ICG to monitor cardiac electrical activity. Optical mapping experiments were performed on Langendorff rabbit hearts stained with ICG and perfused with electromechanical uncouplers. The residual contraction force and electrical action potentials were recorded simultaneously. Our research confirms that ICG is a voltage-sensitive dye with a dual-component (fast and slow) response to membrane potential changes. The fast component of the optical signal (OS) can have opposite polarities in different parts of the fluorescence spectrum. In contrast, the polarity of the slow component remains the same throughout the entire spectrum. Separating the OS into these components revealed two different voltage-sensitivity mechanisms for ICG. The fast component of the OS appears to be electrochromic in nature, whereas the slow component may arise from the redistribution of the dye molecules within or around the membrane. Both components quite accurately track the time of electrical signal propagation, but only the fast component is suitable for estimating the shape and duration of action potentials. Because ICG has voltage-sensitive properties in the entire heart, we suggest that it can be used to monitor cardiac electrical behavior in the clinic. PMID:26840736

A new NIR-triggered doxorubicin and photosensitizer indocyanine green co-delivery system for enhanced multidrug resistant cancer treatment through simultaneous chemo/photothermal/photodynamic therapy.

PubMed

Yu, Yanna; Zhang, Zhipeng; Wang, Yun; Zhu, Hao; Li, Fangzhou; Shen, Yuanyuan; Guo, Shengrong

2017-09-01

It is a great challenge to combat multidrug resistant (MDR) cancer effectively. To address this issue, we developed a new near-infrared (NIR) triggered chemotherapeutic agent doxorubicin (DOX) and photosensitizer indocyanine green (ICG) co-release system by aid of NIR induced photothermal effect of gold nanocages (AuNCs) and temperature sensitive phase-change property of 1-tetradecanol at its melting point of 39°C, which could simultaneously exerted chemo/photothermal/photodynamic treatment on MDR human breast cancer MCF-7/ADR cells. This nano-sized system was constructed by filling the interior of AuNCs with DOX, ICG and 1-tetradecanol, and modifying the surface with biotinylated poly (ethylene glycol) via Au-S bonds, termed as DOX/ICG@biotin-PEG-AuNC-PCM. The DOX and ICG co-release from DOX/ICG@biotin-PEG-AuNC-PCM was much faster in PBS at 40°C or under 808nm NIR irradiation at 2.5W/cm 2 than at 37°C (e.g. 67.27% or 80.31% vs. 5.57% of DOX, 76.08% vs. 3.83% of ICG for 20min). The flow cytometry and confocal laser scanning microscopy (CLSM) results showed, the AuNCs were taken up by MCF-7/ADR cells via endocytosis, thus enhancing DOX uptake; the biotin on AuNCs facilitated this endocytosis; NIR irradiation caused the heating of the AuNCs, triggering the DOX and ICG co-release and enhancing the distribution of DOX in nuclei, the released ICG generated ROS to take photodynamic therapy. Due to the above unique properties, DOX/ICG@biotin-PEG-AuNC-PCM exerted excellent anti-tumor effects under NIR irradiation, its IC 50 against MCF-7/ADR cells was very low, only 0.48µg/mL, much smaller than that of free DOX (74.51μg/mL). A new near-infrared (NIR) triggered chemotherapeutic agent doxorubicin (DOX) and photosensitizer indocyanine green (ICG) co-release system by aid of NIR induced photothermal effect of gold nanocages (AuNCs) and temperature sensitive phase-change property of 1-tetradecanol at its melting point of 39°C, was prepared, termed as DOX

New Irradiation Method with Indocyanine Green-Loaded Nanospheres for Inactivating Periodontal Pathogens

PubMed Central

Sasaki, Yasuyuki; Hayashi, Jun-ichiro; Fujimura, Takeki; Iwamura, Yuki; Yamamoto, Genta; Nishida, Eisaku; Ohno, Tasuku; Okada, Kosuke; Yamamoto, Hiromitsu; Kikuchi, Takeshi; Mitani, Akio; Fukuda, Mitsuo

2017-01-01

Antimicrobial photodynamic therapy (aPDT) has been proposed as an adjunctive strategy for periodontitis treatments. However, use of aPDT for periodontal treatment is complicated by the difficulty in accessing morphologically complex lesions such as furcation involvement, which the irradiation beam (which is targeted parallel to the tooth axis into the periodontal pocket) cannot access directly. The aim of this study was to validate a modified aPDT method that photosensitizes indocyanine green-loaded nanospheres through the gingivae from outside the pocket using a diode laser. To establish this trans-gingival irradiation method, we built an in vitro aPDT model using a substitution for gingivae. Irradiation conditions and the cooling method were optimized before the bactericidal effects on Porphyromonas gingivalis were investigated. The permeable energy through the gingival model at irradiation conditions of 2 W output power in a 50% duty cycle was comparable with the transmitted energy of conventional irradiation. Intermittent irradiation with air cooling limited the temperature increase in the gingival model to 2.75 °C. The aPDT group showed significant bactericidal effects, with reductions in colony-forming units of 99.99% after 5 min of irradiation. This effect of aPDT against a periodontal pathogen demonstrates the validity of trans-gingival irradiation for periodontal treatment. PMID:28098777

New Irradiation Method with Indocyanine Green-Loaded Nanospheres for Inactivating Periodontal Pathogens.

PubMed

Sasaki, Yasuyuki; Hayashi, Jun-Ichiro; Fujimura, Takeki; Iwamura, Yuki; Yamamoto, Genta; Nishida, Eisaku; Ohno, Tasuku; Okada, Kosuke; Yamamoto, Hiromitsu; Kikuchi, Takeshi; Mitani, Akio; Fukuda, Mitsuo

2017-01-13

Antimicrobial photodynamic therapy (aPDT) has been proposed as an adjunctive strategy for periodontitis treatments. However, use of aPDT for periodontal treatment is complicated by the difficulty in accessing morphologically complex lesions such as furcation involvement, which the irradiation beam (which is targeted parallel to the tooth axis into the periodontal pocket) cannot access directly. The aim of this study was to validate a modified aPDT method that photosensitizes indocyanine green-loaded nanospheres through the gingivae from outside the pocket using a diode laser. To establish this trans-gingival irradiation method, we built an in vitro aPDT model using a substitution for gingivae. Irradiation conditions and the cooling method were optimized before the bactericidal effects on Porphyromonas gingivalis were investigated. The permeable energy through the gingival model at irradiation conditions of 2 W output power in a 50% duty cycle was comparable with the transmitted energy of conventional irradiation. Intermittent irradiation with air cooling limited the temperature increase in the gingival model to 2.75 °C. The aPDT group showed significant bactericidal effects, with reductions in colony-forming units of 99.99% after 5 min of irradiation. This effect of aPDT against a periodontal pathogen demonstrates the validity of trans-gingival irradiation for periodontal treatment.

Highly enhanced optical properties of indocyanine green/perfluorocarbon nanoemulsions for efficient lymph node mapping using near-infrared and magnetic resonance imaging

NASA Astrophysics Data System (ADS)

Bae, Pan Kee; Jung, Juyeon; Chung, Bong Hyun

2014-03-01

The near-infrared (NIR) fluorescence probe has better tissue penetration and lower autofluorescence. Indocyanine green (ICG) is an NIR organic dye for extensive biological application, and it has been clinically approved for human medical imaging and diagnosis. However, application of this dye is limited by its numerous disadvantageous properties in aqueous solution, including its concentration-dependent aggregation, poor aqueous stability in vitro, and low quantum yield. Its use in molecular imaging probes is limited because it loses fluorescence after binding to nonspecific plasma proteins, leading to rapid elimination from the body with a half-life of 2 - 4 min. In this study, the multifunctional perfluorocarbon (PFC)/ICG nanoemulsions were investigated with the aim of overcoming these limitations. The PFC/ICG nanoemulsions as a new type of delivery vehicle for contrast agents have both NIR optical imaging and 19 F-MR imaging moieties. These nanoemulsions exhibited less aggregation, increased fluorescence intensity, long-term stability, and physicochemical stability against external light and temperature compared to free aqueous ICG. Also, the PFC/ICG bimodal nanoemulsions allow excellent detection of lymph nodes in vivo through NIR optical imaging and 19 F-MR imaging. This result showed the suitability of the proposed nanoemulsions for non-invasive lymph node mapping as they enable long-time detection of lymph nodes.

Clinical values of intraoperative indocyanine green fluorescence video angiography with Flow 800 software in cerebrovascular surgery.

PubMed

Ye, Xun; Liu, Xing-Ju; Ma, Li; Liu, Ling-Tong; Wang, Wen-Lei; Wang, Shuo; Cao, Yong; Zhang, Dong; Wang, Rong; Zhao, Ji-Zong; Zhao, Yuan-Li

2013-11-01

Microscope-integrated near-infrared indocyanine green video angiography (ICG-VA) has been used in neurosurgery for a decade. This study aimed to assess the value of intraoperative indocyanine green (ICG) video angiography with Flow 800 software in cerebrovascular surgery and to discover its hemodynamic features and changes of cerebrovascular diseases during surgery. A total of 87 patients who received ICG-VA during various surgical procedures were enrolled in this study. Among them, 45 cases were cerebral aneurysms, 25 were cerebral arteriovenous malformations (AVMs), and 17 were moyamoya disease (MMD). A surgical microscope integrating an infrared fluorescence module was used to confirm the residual aneurysms and blocking of perforating arteries in aneurysms. Feeder arteries, draining veins, and normal cortical vessels were identified by the time delay color mode of Flow 800 software. Hemodynamic parameters were recorded. All data were analyzed by SPSS version 18.0 (SPSS Inc., USA). T-test was used to analyze the hemodynamic features of AVMs and MMDs, the influence on peripheral cortex after resection in AVMs, and superficial temporal artery to middle cerebral artery (STA-MCA) bypass in MMDs. The visual delay map obtained by Flow 800 software had more advantages than the traditional playback mode in identifying the feeder arteries, draining veins, and their relations to normal cortex vessels. The maximum fluorescence intensity (MFI) and the slope of ICG fluorescence curve of feeder arteries and draining veins were higher than normal peripheral vessels (MFI: 584.24±85.86 vs. 382.94 ± 91.50, slope: 144.95 ± 38.08 vs. 69.20 ± 13.08, P < 0.05). The arteriovenous transit time in AVM was significantly shorter than in normal cortical vessels ((0.60 ± 0.27) vs. (2.08 ± 1.42) seconds, P < 0.05). After resection of AVM, the slope of artery in the cortex increased, which reflected the increased cerebral flow. In patients with MMD, after STA-MCA bypass, cortex perfusion

Indocyanine green videoangiography "in negative": definition and usefulness in intracranial dural arteriovenous fistulae.

PubMed

Simal Julián, Juan Antonio; Miranda Lloret, Pablo; Aparici Robles, Fernando; Beltrán Giner, Andrés; Botella Asunción, Carlos

2013-09-01

Indocyanine green videoangiography (IGV) raises important limitations when we use it in vascular pathology, especially in cases with arterialization of the venous system such as arteriovenous malformations and fistulae. Our objective was to provide a simple procedure that overcomes the limitations of conventional IGV. We define IGV in negative (IGV-IN), so-called because, in its first phase, the vessel to analyze is clipped, and we report 3 cases of intracranial dural arteriovenous fistulae treated with this procedure. In 2011, we applied IGV-IN to 3 patients at our center with Borden type III intracranial arteriovenous fistulae. In all 3 cases, IGV-IN enabled both diagnosis and post-dural arteriovenous fistula exclusion control in 1 integrated procedure no longer than 1 minute, requiring only 1 visualization. IGV-IN is an improvement over the conventional IGV method and is able to provide more information in a shorter period of time. It is an intuitive and highly visual procedure, and, more importantly, it is reversible. Studies with larger samples are necessary to determine whether IGV-IN can further reduce the need for postoperative digital subtraction angiography.

Indocyanine Green Loaded Reduced Graphene Oxide for In Vivo Photoacoustic/Fluorescence Dual-Modality Tumor Imaging

NASA Astrophysics Data System (ADS)

Chen, Jingqin; Liu, Chengbo; Zeng, Guang; You, Yujia; Wang, Huina; Gong, Xiaojing; Zheng, Rongqin; Kim, Jeesu; Kim, Chulhong; Song, Liang

2016-02-01

Multimodality imaging based on multifunctional nanocomposites holds great promise to fundamentally augment the capability of biomedical imaging. Specifically, photoacoustic and fluorescence dual-modality imaging is gaining much interest because of their non-invasiveness and the complementary nature of the two modalities in terms of imaging resolution, depth, sensitivity, and speed. Herein, using a green and facile method, we synthesize indocyanine green (ICG) loaded, polyethylene glycol (PEG)ylated, reduced nano-graphene oxide nanocomposite (rNGO-PEG/ICG) as a new type of fluorescence and photoacoustic dual-modality imaging contrast. The nanocomposite is shown to have minimal toxicity and excellent photoacoustic/fluorescence signals both in vitro and in vivo. Compared with free ICG, the nanocomposite is demonstrated to possess greater stability, longer blood circulation time, and superior passive tumor targeting capability. In vivo study shows that the circulation time of rNGO-PEG/ICG in the mouse body can sustain up to 6 h upon intravenous injection; while after 1 day, no obvious accumulation of rNGO-PEG/ICG is found in any major organs except the tumor regions. The demonstrated high fluorescence/photoacoustic dual contrasts, together with its low toxicity and excellent circulation life time, suggest that the synthesized rNGO-PEG/ICG can be a promising candidate for further translational studies on both the early diagnosis and image-guided therapy/surgery of cancer.

The synergistic effect of photodynamic therapy and photothermal therapy in the presence of gold-gold sulfide nanoshells conjugated Indocyanine green on HeLa cells.

PubMed

Ghorbani, Farzaneh; Attaran-Kakhki, Neda; Sazgarnia, Ameneh

2017-03-01

Photodynamic therapy (PDT) and photothermal therapy (PTT) are two known optical remedies of cancer. PTT can be combined with other therapies. One of the limitations of optical therapies is the penetration of light into biological tissues, which reduces its effectiveness due to usage of photosensitizers and PTT agents, which are absorbed in the NIR region that provides the maximum penetration. For instance, Indocyanine green (ICG) serves as a photosensitizer and Gold nanostructures as agents for PTT. GGS is a gold nanoshell with two absorption peaks in the NIR and visible regions. The aim of this study is to evaluate the synergistic effect of PDT and PTT in the presence of GGS conjugated with ICG. After synthesizing GGS, ICG was conjugated with GGS. The specifications and cytotoxicity of agents were identified. Cells were irradiated by an 808nm laser with or without the agents and three laser outputs were achieved, with each having four different exposure times. The viability of treated cells was determined via MTT assay. The irradiation of the laser did not produce any significant effect by itself or in the presence of GGS. The maximum cell death recorded for GGS, ICG and GGS-ICG were 15±7%, 50±3% and 31±3% respectively. ICG and GGS-ICG differs significantly for exposures higher than 2250J/cm 2 . The conjugate was provided through a simple process and a greater chemical stability compared to GGS was achieved. Moreover, it induced a stronger photodynamic and photothermal effect on the cells. This is a promising result which can help enhance the effectiveness of a minimally invasive treatment. Copyright © 2016 Elsevier B.V. All rights reserved.

A pilot study to assess near infrared laparoscopy with indocyanine green (ICG) for intraoperative sentinel lymph node mapping in early colon cancer.

PubMed

Currie, A C; Brigic, A; Thomas-Gibson, S; Suzuki, N; Moorghen, M; Jenkins, J T; Faiz, O D; Kennedy, R H

2017-11-01

Previous attempts at sentinel lymph node (SLN) mapping in colon cancer have been compromised by ineffective tracers and the inclusion of advanced disease. This study evaluated the feasibility of fluorescence detection of SLNs with indocyanine green (ICG) for lymphatic mapping in T1/T2 clinically staged colonic malignancy. Consecutive patients with clinical T1/T2 stage colon cancer underwent endoscopic peritumoral submucosal injection of indocyanine green (ICG) for fluorescence detection of SLN using a near-infrared (NIR) camera. All patients underwent laparoscopic complete mesocolic excision surgery. Detection rate and sensitivity of the NIR-ICG technique were the study endpoints. Thirty patients mean age = 68 years [range = 38-80], mean BMI = 26.2 (IQR = 24.7-28.6) were studied. Mesocolic sentinel nodes (median = 3/patient) were detected by fluorescence within the standard resection field in 27/30 patients. Overall, ten patients had lymph node metastases, with one of these patients having a failed SLN procedure. Of the 27 patients with completed SLN mapping, nine patients had histologically positive lymph nodes containing malignancy. 3/9 had positive SLNs with 6 false negatives. In five of these false negative patients, tumours were larger than 35 mm with four also being T3/T4. ICG mapping with NIR fluorescence allowed mesenteric detection of SLNs in clinical T1/T2 stage colonic cancer. CLINICALTRIALS.GOV: ID: NCT01662752. Copyright © 2017 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.

Intraoperative Detection of Superficial Liver Tumors by Fluorescence Imaging Using Indocyanine Green and 5-aminolevulinic Acid.

PubMed

Kaibori, Masaki; Matsui, Kosuke; Ishizaki, Morihiko; Iida, Hiroya; Okumura, Tadayoshi; Sakaguchi, Tatsuma; Inoue, Kentaro; Ikeura, Tsukasa; Asano, Hiroaki; Kon, Masanori

2016-04-01

Indocyanine green (ICG) and the porphyrin precursor 5-aminolevulinic acid (5-ALA) have been approved as fluorescence imaging agents in the clinical setting. This study evaluated the usefulness of fluorescence imaging with both ICG and 5-ALA for intraoperative identification of latent small liver tumors. There were 48 patients who had main tumors within 5 mm of the liver surface. 5-ALA hydrochloride was orally administered to patients 3 h before surgery. ICG had been intravenously injected within 14 days prior to surgery. Intraoperatively, after visual inspection, manual palpation and ultrasonography fluorescence images of the liver surface were obtained with ICG and 5-ALA prior to resection. With ICG, the sensitivity, specificity and accuracy for detecting the preoperatively identified main tumors were 96%, 50% and 94%, respectively. Twelve latent small tumors were newly detected on the liver surface using ICG, five of which proved to be carcinomas. With 5-ALA, the sensitivity, specificity and accuracy for detecting the main tumors were 57%, 100% and 58%, respectively. Five latent small tumors were newly detected using 5-ALA; all were carcinomas. Overall, five new tumors were detected by both ICG and 5-ALA fluorescence imaging; two were hepatocellular carcinomas (HCCs) and three were metastases of colorectal cancer. The sensitivity and specificity of ICG fluorescence imaging for main tumor detection were relatively high and low, respectively, but the opposite was true of 5-ALA imaging. Fluorescence imaging using 5-ALA may provide greater specificity in the detection of surface-invisible malignant liver tumors than using ICG fluorescence imaging alone. Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Sensitivity and specificity of indocyanine green near-infrared fluorescence imaging in detection of metastatic lymph nodes in colorectal cancer: Systematic review and meta-analysis.

PubMed

Emile, Sameh H; Elfeki, Hossam; Shalaby, Mostafa; Sakr, Ahmad; Sileri, Pierpaolo; Laurberg, Søren; Wexner, Steven D

2017-11-01

This review aimed to determine the overall sensitivity and specificity of indocyanine green (ICG) near-infrared (NIR) fluorescence in sentinel lymph node (SLN) detection in Colorectal cancer (CRC). A systematic search in electronic databases was conducted. Twelve studies including 248 patients were reviewed. The median sensitivity, specificity, and accuracy rates were 73.7, 100, and 75.7. The pooled sensitivity and specificity rates were 71% and 84.6%. In conclusion, ICG-NIR fluorescence is a promising technique for detecting SLNs in CRC. © 2017 Wiley Periodicals, Inc.

Interactions of Indocyanine Green and Lipid in Enhancing Near-Infrared Fluorescence Properties: The Basis for Near-Infrared Imaging in Vivo

PubMed Central

2015-01-01

Indocyanine green (ICG) is a near-infrared (NIR) contrast agent commonly used for in vivo cardiovascular and eye imaging. For medical diagnosis, ICG is limited by its aqueous instability, concentration-dependent aggregation, and rapid degradation. To overcome these limitations, scientists have formulated ICG in various liposomes, which are spherical lipid membrane vesicles with an aqueous core. Some encapsulate ICG, while others mix it with liposomes. There is no clear understanding of lipid–ICG interactions. Therefore, we investigated lipid–ICG interactions by fluorescence and photon correlation spectroscopy. These data were used to design stable and maximally fluorescent liposomal ICG nanoparticles for NIR optical imaging of the lymphatic system. We found that ICG binds to and is incorporated completely and stably into the lipid membrane. At a lipid:ICG molar ratio of 250:1, the maximal fluorescence intensity was detected. ICG incorporated into liposomes enhanced the fluorescence intensity that could be detected across 1.5 cm of muscle tissue, while free ICG only allowed 0.5 cm detection. When administered subcutaneously in mice, lipid-bound ICG in liposomes exhibited a higher intensity, NIR image resolution, and enhanced lymph node and lymphatic vessel visualization. It also reduced the level of fluorescence quenching due to light exposure and degradation in storage. Lipid-bound ICG could provide additional medical diagnostic value with NIR optical imaging for early intervention in cases of lymphatic abnormalities. PMID:24512123

Leveraging Engineering of Indocyanine Green-Encapsulated Polymeric Nanocomposites for Biomedical Applications.

PubMed

Han, Ya-Hui; Kankala, Ranjith Kumar; Wang, Shi-Bin; Chen, Ai-Zheng

2018-05-24

In recent times, photo-induced therapeutics have attracted enormous interest from researchers due to such attractive properties as preferential localization, excellent tissue penetration, high therapeutic efficacy, and minimal invasiveness, among others. Numerous photosensitizers have been considered in combination with light to realize significant progress in therapeutics. Along this line, indocyanine green (ICG), a Food and Drug Administration (FDA)-approved near-infrared (NIR, >750 nm) fluorescent dye, has been utilized in various biomedical applications such as drug delivery, imaging, and diagnosis, due to its attractive physicochemical properties, high sensitivity, and better imaging view field. However, ICG still suffers from certain limitations for its utilization as a molecular imaging probe in vivo, such as concentration-dependent aggregation, poor in vitro aqueous stability and photodegradation due to various physicochemical attributes. To overcome these limitations, much research has been dedicated to engineering numerous multifunctional polymeric composites for potential biomedical applications. In this review, we aim to discuss ICG-encapsulated polymeric nanoconstructs, which are of particular interest in various biomedical applications. First, we emphasize some attractive properties of ICG (including physicochemical characteristics, optical properties, metabolic features, and other aspects) and some of its current limitations. Next, we aim to provide a comprehensive overview highlighting recent reports on various polymeric nanoparticles that carry ICG for light-induced therapeutics with a set of examples. Finally, we summarize with perspectives highlighting the significant outcome, and current challenges of these nanocomposites.

Effects of repetitive photodynamic therapy using indocyanine green for acne vulgaris.

PubMed

Seo, Hyun-Min; Min, Hyung-Geun; Kim, Hee-Joong; Shin, Jong-Hun; Nam, Sang-Ho; Han, Kwang-Soo; Ryu, Joung-Ho; Oh, Jeong-Joon; Kim, Ji Young; Lee, Kwang-Joon; Lee, Seung Jae; Kim, Han-Saem; Kim, Jung-In; Song, Min-Kyu; Kim, Won-Serk

2016-10-01

Indocyanine green (ICG) is a photosensitizer recently introduced for the treatment of acne. To evaluate the efficacy and safety of photodynamic therapy (PDT) using ICG in subjects with acne vulgaris and to evaluate whether there was a difference in the efficacy of ICG-PDT between different numbers of treatment. Subjects with acne on the face were included. ICG lotion (0.1%) was applied for 30 minutes, and a long pulse diode laser was used. Three or five treatments per subject were performed over 2 weeks. Acne lesion counts and Leeds revised acne grades were evaluated at baseline and 2 weeks after the last treatment. In total, 47 subjects completed the study. After both three and five ICG-PDT sessions, a significant reduction in acne lesions and significant improvement in Leeds revised acne grades were found in all treated subjects compared to baseline. In the subjects receiving five ICG-PDT sessions, the reduction of papules/pustules was greater than in the subjects receiving three ICG-PDT sessions (P < 0.01, respectively). However, there was no significant change in the count of nodules/cysts, although it is a negative trend (P = 0.066). Adverse effects were minimal. ICG-PDT using long-pulsed diode laser can be a safe and effective tool for acne vulgaris. Moreover, repetitive treatments of five can cause further improvement of inflammatory acne lesions. © 2016 The International Society of Dermatology.

Thermal injury decreases hepatic blood flow and the intrinsic clearance of indocyanine green in the rat.

PubMed

Pollack, G M; Brouwer, K L

1991-01-01

The influence of severe thermal injury (full-thickness burns involving 50% of the body surface area) on hepatic blood flow in the rat was assessed using the tricarbocyanine dye indocyanine green (ICG). In a randomized crossover fashion, rats received sequential infusions of ICG through both the femoral vein and the portal vein, allowing the estimation of total hepatic plasma clearance and transhepatic extraction of the dye. These two parameters, along with the hematocrit, were used to calculate intrinsic hepatic clearance of ICG and hepatic blood flow. Animals were examined at 0 (control), 0.5, 12, or 24 hr following infliction of scald burns. Hepatic blood flow was decreased significantly by 0.5 hr postburn and remained approximately 20% below normal throughout the remainder of the study. The intrinsic efficiency of the liver in removing ICG from the systemic circulation was also decreased by thermal injury. The potential mechanisms involved in these two physiologic perturbations are discussed.

Indocyanine Green Fluorescence Endoscopy at Endonasal Transsphenoidal Surgery for an Intracavernous Sinus Dermoid Cyst: Case Report

PubMed Central

HIDE, Takuichiro; YANO, Shigetoshi; KURATSU, Jun-ichi

2014-01-01

The complete resection of intracavernous sinus dermoid cysts is very difficult due to tumor tissue adherence to important anatomical structures such as the internal carotid artery (ICA), cavernous sinus, and cranial nerves. As residual dermoid cyst tissue sometimes induces symptoms and repeat surgery may be required after cyst recurrence, minimal invasiveness is an important consideration when selecting the surgical approach to the lesion. We addressed a recurrent intracavernous sinus dermoid cyst by the endoscopic endonasal transsphenoidal approach assisted by neuronavigation and indocyanine green (ICG) endoscopy to confirm the ICA and patency of the cavernous sinus. The ICG endoscope detected the fluorescence signal from the ICA and cavernous sinus; its intensity changed with the passage of time. The ICG endoscope was very useful for real-time imaging, and its high spatial resolution facilitated the detection of the ICA and the patent cavernous sinus. We found it to be of great value for successful endonasal transsphenoidal surgery. PMID:25446381

Multipixel frequency-domain imaging of spontaneous canine breast disease using fluorescent contrast agents

NASA Astrophysics Data System (ADS)

Reynolds, Jeffery S.; Thompson, Alan B.; Troy, Tamara L.; Mayer, Ralf H.; Waters, David J.; Sevick-Muraca, Eva M.

1999-07-01

In this paper we demonstrate the ability to detect the frequency-domain fluorescent signal from the contrast agent indocyanine green within the mammary chain of dogs with spontaneous mammary tumors. We use a gain-modulated image intensifier to rapidly capture multi-pixel images of the fluorescent modulation amplitude, modulation phase, and average intensity signals. Excitation is provided by a 100 MHz amplitude-modulated, 780 nm laser diode. Time series images of the uptake and clearance of the contrast agent in the diseased tissue are also presented.

Illuminating necrosis: From mechanistic exploration to preclinical application using fluorescence molecular imaging with indocyanine green

PubMed Central

Fang, Cheng; Wang, Kun; Zeng, Chaoting; Chi, Chongwei; Shang, Wenting; Ye, Jinzuo; Mao, Yamin; Fan, Yingfang; Yang, Jian; Xiang, Nan; Zeng, Ning; Zhu, Wen; Fang, Chihua; Tian, Jie

2016-01-01

Tissue necrosis commonly accompanies the development of a wide range of serious diseases. Therefore, highly sensitive detection and precise boundary delineation of necrotic tissue via effective imaging techniques are crucial for clinical treatments; however, no imaging modalities have achieved satisfactory results to date. Although fluorescence molecular imaging (FMI) shows potential in this regard, no effective necrosis-avid fluorescent probe has been developed for clinical applications. Here, we demonstrate that indocyanine green (ICG) can achieve high avidity of necrotic tissue owing to its interaction with lipoprotein (LP) and phospholipids. The mechanism was explored at the cellular and molecular levels through a series of in vitro studies. Detection of necrotic tissue and real-time image-guided surgery were successfully achieved in different organs of different animal models with the help of FMI using in house-designed imaging devices. The results indicated that necrotic tissue with a 0.6 mm diameter could be effectively detected with precise boundary definition. We believe that the new discovery and the associated imaging techniques will improve personalized and precise surgery in the near future. PMID:26864116

Fluorescence assessment of the delivery and distribution of nebulized indocyanine green in a murine model

NASA Astrophysics Data System (ADS)

Kassab, Giulia; C. Geralde, Mariana; M. Inada, Natalia; Bagnato, Vanderlei S.

2018-02-01

Photodynamic inactivation (PDI) is a promising alternative for the treatment of infectious diseases, and the combination of indocyanine green (ICG) and extracorporeal infrared light has shown optimistic results against pneumonia in vitro and in vivo. However, the pharmacokinetics and the possible side effects of the pulmonary delivery via nebulization have not been fully investigated. This study assessed the distribution of the photosensitizer within the lungs and to other organs of mice, and monitored the fluorescence of ICG in the thorax in the presence and absence of the activating light. The excitation wavelength was 780 nm and detection focused on the emission between 795 and 890 nm. Experiments demonstrated that the amount of fluorescence detected from outside the body was significantly higher after the nebulization of ICG, and reduced after the illumination, allowing for the monitoring of the PDI in real time. The fluorescence remained detectable in the mice for at least 24 hours, and was present in the lungs, stomach, liver, small and large intestines, bladder, spleen and heart after this time.

Development and validation of a custom made indocyanine green fluorescence lymphatic vessel imager

NASA Astrophysics Data System (ADS)

Pallotta, Olivia J.; van Zanten, Malou; McEwen, Mark; Burrow, Lynne; Beesley, Jack; Piller, Neil

2015-06-01

Lymphoedema is a chronic progressive condition often producing significant morbidity. An in-depth understanding of an individual's lymphatic architecture is valuable both in the understanding of underlying pathology and for targeting and tailoring treatment. Severe lower limb injuries resulting in extensive loss of soft tissue require transposition of a flap consisting of muscle and/or soft tissue to close the defect. These patients are at risk of lymphoedema and little is known about lymphatic regeneration within the flap. Indocyanine green (ICG), a water-soluble dye, has proven useful for the imaging of lymphatic vessels. When injected into superficial tissues it binds to plasma proteins in lymph. By exposing the dye to specific wavelengths of light, ICG fluoresces with near-infrared light. Skin is relatively transparent to ICG fluorescence, enabling the visualization and characterization of superficial lymphatic vessels. An ICG fluorescence lymphatic vessel imager was manufactured to excite ICG and visualize real-time fluorescence as it travels through the lymphatic vessels. Animal studies showed successful ICG excitation and detection using this imager. Clinically, the imager has assisted researchers to visualize otherwise hidden superficial lymphatic pathways in patients postflap surgery. Preliminary results suggest superficial lymphatic vessels do not redevelop in muscle flaps.

Tracheal anastomosis using indocyanine green dye enhanced fibrinogen with a near-infrared diode laser

NASA Astrophysics Data System (ADS)

Auteri, Joseph S.; Jeevanandam, Valluvan; Oz, Mehmet C.; Libutti, Steven K.; Kirby, Thomas J.; Smith, Craig R.; Treat, Michael R.

1990-06-01

A major obstacle to lung transplantation and combined heart- lung transplantation is dehiscence of the tracheobronchial anastomosis. We explored the possibility of laser welded anastomoses in canine tracheas in vivo. Laser anastomoses were performed on three-quarter circumferential anterior tracheotomies. A continous wave diode laser (808 +1 nm) at a power density of 9.6 watts/cm was used. Human fibrinogen was mixed with indocyanine green dye (ICG, max absorbance 805 nm) and applied to the anastomosis site prior to laser exposure. Animals were sacrificed at 0, 21 and 28 days post-operatively. At sacrifice weld bursting pressures were measured by raising intratracheal pressure using forced ventilation via an endotracheal tube. Sutured and laser welded anastomoses had similar bursting pressures, and exhibited satisfactory histologic evidence of healing. However, compared to polypropylene sutured controls, the laser welded anastomoses exhibited less peritracheal inflammatory reaction and showed visibly smoother luminal surfaces at 21 and 28 days post- operatively. Tracheal anastomosis using ICG dye enhanced fibrinogen combined with the near-infrared diode laser is a promising extension of the technology of laser tissue fusion and deserves further study.

Usefulness of tumor blood flow imaging by intraoperative indocyanine green videoangiography in hemangioblastoma surgery.

PubMed

Hojo, Masato; Arakawa, Yoshiki; Funaki, Takeshi; Yoshida, Kazumichi; Kikuchi, Takayuki; Takagi, Yasushi; Araki, Yoshio; Ishii, Akira; Kunieda, Takeharu; Takahashi, Jun C; Miyamoto, Susumu

2014-01-01

Hemangioblastomas remain a surgical challenge because of their arteriovenous malformation-like character. Recently, indocyanine green (ICG) videoangiography has been applied to neurosurgical vascular surgery. The aim of this study was to evaluate the usefulness of tumor blood flow imaging by intraoperative ICG videoangiography in surgery for hemangioblastomas. Twenty intraoperative ICG videoangiography procedures were performed in 12 patients with hemangioblastomas. Seven lesions were located in the cerebellum, two lesions were in the medulla oblongata, and three lesions were in the spinal cord. Ten procedures were performed before or during dissection, and 10 procedures were performed after tumor resection. ICG videoangiography could provide dynamic images of blood flow in the tumor and its related vessels under surgical view. Interpretation of these dynamic images of tumor blood flow was useful for discrimination of transit feeders (feeders en passage) and also for estimation of unexposed feeders covered with brain parenchyma. Postresection ICG videoangiography could confirm complete tumor resection and normalized blood flow in surrounding vessels. In surgery for hemangioblastomas, careful interpretation of dynamic ICG images can provide useful information on transit feeders and unexposed hidden vessels that cannot be directly visualized by ICG. Copyright © 2014 Elsevier Inc. All rights reserved.

Selective protection of normal hepatocytes by indocyanine green in photodynamic therapy for the hepatoma of rat

NASA Astrophysics Data System (ADS)

Gu, Ying; Li, Junheng; Guo, Zhong-He

1993-03-01

Using hepatocarcinoma transplanted rats, the present study made consecutive observation for the color change and indocyanine green (ICG) absorption peak of the normal liver and tumor tissues after intravenous injection of ICG. The normal liver tissue of the rat was found to turn violet-green soon after ICG injection and the optic density (OD) of ICG-characteristic spectral peak of the tissue homogenate reached its maximum value at 35 minutes post-injection, while neither color change nor OD value increase was noticed in the tissue of transplanted hepatocarcinoma, suggesting that there is a specific absorption of ICG by the normal liver tissue. Chemiluminescentoassay revealed inhibited luminal chemiluminescence by ICG, indicating the depression of singlet oxygen and reactive oxygen species (ROS) oxidation during HPD photosensitization by ICG. In PDT of the hepatocarcinoma, the irradiated area was examined under microscope and auto-microimage analysis system after ICG administration. For tumor-free tissue, the photosensitization induced necrotic area was found smaller in those with than those without ICG administration, whereas the tumor killing effect was almost the same of the two. It is suggested that ICG may offer selective protection for healthy hepatocytes without diminishing the destruction of tumor cells. The protection of healthy hepatocytes by ICG is thought to be in accordance with the amount of ICG in the cell and the distribution of light energy.

Silibinin and indocyanine green-loaded nanoparticles inhibit the growth and metastasis of mammalian breast cancer cells in vitro.

PubMed

Sun, Hui-Ping; Su, Jing-Han; Meng, Qing-Shuo; Yin, Qi; Zhang, Zhi-Wen; Yu, Hai-Jun; Zhang, Peng-Cheng; Wang, Si-Ling; Li, Ya-Ping

2016-07-01

To improve the therapeutic efficacy of cancer treatments, combinational therapies based on nanosized drug delivery system (NDDS) has been developed recently. In this study we designed a new NDDS loaded with an anti-metastatic drug silibinin and a photothermal agent indocyanine green (ICG), and investigated its effects on the growth and metastasis of breast cancer cells in vitro. Silibinin and ICG were self-assembled into PCL lipid nanoparticles (SIPNs). Their physical characteristics including the particle size, zeta potential, morphology and in vitro drug release were examined. 4T1 mammalian breast cancer cells were used to evaluate their cellular internalization, cytotoxicity, and their influences on wound healing, in vitro cell migration and invasion. SIPNs showed a well-defined spherical shape with averaged size of 126.3±0.4 nm and zeta potential of -10.3±0.2 mV. NIR laser irradiation substantially increased the in vitro release of silibinin from the SIPNs (58.3% at the first 8 h, and 97.8% for the total release). Furthermore, NIR laser irradiation markedly increased the uptake of SIPNs into 4T1 cells. Under the NIR laser irradiation, both SIPNs and IPNs (PCL lipid nanoparticles loaded with ICG alone) caused dose-dependent ablation of 4T1 cells. The wound healing, migration and invasion experiments showed that SIPNs exposed to NIR laser irradiation exhibited dramatic in vitro anti-metastasis effects. SIPNs show temperature-sensitive drug release following NIR laser irradiation, which can inhibit the growth and metastasis of breast cancer cells in vitro.

Choroidal circulation impairment during the anterior recurrence of Vogt-Koyanagi-Harada disease confirmed with indocyanine green angiography and laser speckle flowgraphy.

PubMed

Takemoto, Yuko; Namba, Kenichi; Mizuuchi, Kazuomi; Iwata, Daiju; Uno, Tomoe; Ohno, Shigeaki; Hirooka, Kiriko; Hashimoto, Yuki; Saito, Wataru; Sugiyama, Kazuhisa; Ishida, Susumu

2016-11-01

To assess choroidal inflammation-related circulatory changes associated with the anterior recurrence of Vogt-Koyanagi-Harada (VKH) disease, using indocyanine green angiography (ICGA) and laser speckle flowgraphy (LSFG). This retrospective case series included 17 eyes of 11 patients with VKH disease showing recurrent inflammatory findings in the anterior, but not posterior, segment (i.e. anterior recurrence). Indocyanine green angiography (ICGA) and LSFG were performed at the time of recurrence and one month after the initiation of corticosteroid therapy. The number and total area of hypofluorescent dark dots (HDDs) on ICGA were independently counted by three physicians and measured with ImageJ, respectively. Mean blur rate (MBR), a quantitative index of relative blood flow velocity, was calculated via the LSFG Analyzer software. Hypofluorescent dark dots (HDDs) were identified on ICGA in 13 of 17 eyes (76%) with the anterior recurrence of VKH disease. The number and total area of HDDs significantly decreased from 203 ± 101 dots to 59 ± 51 dots and from 48 789 ± 24 251 pixels to 15 664 ± 13 254 pixels, respectively. The change ratio of MBR significantly increased by 17.9 ± 16.3% after the treatment. Importantly, there was no significant association between the change ratios of HDDs and MBR. These findings on LSFG and ICGA clearly demonstrated subclinical involvement as well as post-treatment improvement of choroidal circulation impairment due to granulomatous inflammation in eyes with the anterior recurrence of VKH disease. The present data suggest the validity of using these two examinations, capable of detecting different circulatory changes, in the management of recurrent VKH disease. © 2016 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

Intraoperative indocyanine green fluorescent angiography-assisted modified superior gluteal artery perforator flap for reconstruction of sacral pressure sores.

PubMed

Chang, Chun-Kai; Wu, Chien-Ju; Chen, Chun-Yu; Wang, Chi-Yu; Chu, Tzi-Shiang; Hsu, Kuo-Feng; Chiu, Han-Ting; Liu, Hung-Hui; Chou, Chang-Yi; Wang, Chih-Hsin; Lin, Chin-Ta; Dai, Niann-Tzyy; Tzeng, Yuan-Sheng

2017-12-01

Pressure sores are often observed in patients who are bedridden. They can be a severe problem not only for patients and their caregivers but also for plastic surgeons. Here, we describe a new method of superior gluteal artery perforator flap harvesting and anchoring with the assistance of intraoperative indocyanine green fluorescent angiography. In this report, we describe the procedure and outcomes for 19 patients with grades III and IV sacral pressure sores who underwent the operation between September 2015 and November 2016. All flaps survived, and two experienced wound-edge partial dehiscence. With the assistance of this imaging device, we were able to acquire a reliable superior gluteal artery perforator flap and perform modified operations with it that are safe, easy to learn and associated with fewer complications than are traditional. © 2017 Medicalhelplines.com Inc and John Wiley & Sons Ltd.

In silico identification of a therapeutic target for photo-activated disinfection with indocyanine green: Modeling and virtual screening analysis of Arg-gingipain from Porphyromonas gingivalis.

PubMed

Pourhajibagher, Maryam; Bahador, Abbas

2017-06-01

Porphyromonas gingivalis is a momentous bacterial etiological agent associated with periodontitis, peri-implantitis as well as endodontic infections. The potential advantage of Photo-activated disinfection (PAD) as a promising novel approach is the choice of a suitable target site, specific photosensitizer, and wavelength of light for delivery of the light from source to target. Since Arg-gingipain is a cysteine proteinase that is involved in the virulence of P. gingivalis, it was evaluated as a target site for PAD with indocyanine green (ICG) as a photosensitizer. In this study, we used a range of in silico strategies, bioinformatics tools, biological databases, and computer simulation molecular modeling to evaluate the capacity of Arg-gingipain. The predicted structure of Arg-gingipain indicated that it is located outside the cell and has nine domains and 17 ligands, including two calcium ions and three sodium ions with positive charges which can be a site of interaction for anionic ICG. Based on the results of this study, anionic ICG desires to bind and interact with residues of Arg-gingipain during PAD as a main site to enhance the yield of treatment of endo-periodontal lesions. Copyright © 2017 Elsevier B.V. All rights reserved.

Excitation-resolved wide-field fluorescence imaging of indocyanine green visualizes the microenvironment properties in vivo via solvatochromic shift (Conference Presentation)

NASA Astrophysics Data System (ADS)

Cho, Jaedu; Kim, Chang-Seok; Gulsen, Gultekin

2016-03-01

Near-infrared fluorescence imaging (NIRF) is a powerful wide-field optical imaging tool that has a potential to visualize molecular-specific exogenous fluorescence agents, such as FDA approved Indocyanine Green (ICG), in thick tissue. Indeed, ICG is sensitive to biochemical environment such that it can be used to detect micro- or macroscopic environmental changes in tissue by solvatochromic shift that is defined by the dependence of absorption and emission spectra with the solvent polarity. For example, dimethyl sulfoxide (DMSO) is a very powerful drug carrier that can penetrate biological barriers such as the skin, the membranes, and the blood-brain-barrier. In presence of DMSO, ICG in tissue shows the excitation blue shift. However, NIRF imaging of microenvironment dependent changes of ICG has been challenging for the following reasons. First, the Stoke's shift of ICG is too small to separate the excitation and emission spectra easily. Second, the solvatochromic shift of ICG is too small to be detected by conventional NIRF techniques. Last but not least, the multiple scattering in tissue degrades not only the spatial information but also the spectral contents by the red-shift. We developed a wavelength-swept laser-based NIRF system that can resolve the excitation shift of ICG in tissue such that DMSO can be indirectly visualized. We plan to conduct an in-vivo lymph-node drug-delivery study in a mouse model to show feasibility of the indirect imaging of the drug-carrier with the wavelength-swept-laser based NIRF system.

Multiparametric evaluation of hindlimb ischemia using time-series indocyanine green fluorescence imaging.

PubMed

Guang, Huizhi; Cai, Chuangjian; Zuo, Simin; Cai, Wenjuan; Zhang, Jiulou; Luo, Jianwen

2017-03-01

Peripheral arterial disease (PAD) can further cause lower limb ischemia. Quantitative evaluation of the vascular perfusion in the ischemic limb contributes to diagnosis of PAD and preclinical development of new drug. In vivo time-series indocyanine green (ICG) fluorescence imaging can noninvasively monitor blood flow and has a deep tissue penetration. The perfusion rate estimated from the time-series ICG images is not enough for the evaluation of hindlimb ischemia. The information relevant to the vascular density is also important, because angiogenesis is an essential mechanism for post-ischemic recovery. In this paper, a multiparametric evaluation method is proposed for simultaneous estimation of multiple vascular perfusion parameters, including not only the perfusion rate but also the vascular perfusion density and the time-varying ICG concentration in veins. The target method is based on a mathematical model of ICG pharmacokinetics in the mouse hindlimb. The regression analysis performed on the time-series ICG images obtained from a dynamic reflectance fluorescence imaging system. The results demonstrate that the estimated multiple parameters are effective to quantitatively evaluate the vascular perfusion and distinguish hypo-perfused tissues from well-perfused tissues in the mouse hindlimb. The proposed multiparametric evaluation method could be useful for PAD diagnosis. The estimated perfusion rate and vascular perfusion density maps (left) and the time-varying ICG concentration in veins of the ankle region (right) of the normal and ischemic hindlimbs. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Enhanced laser tissue soldering using indocyanine green chromophore and gold nanoshells combination.

PubMed

Khosroshahi, Mohammad E; Nourbakhsh, Mohammad S

2011-08-01

Gold nanoshells (GNs) are new materials that have an optical response dictated by the plasmon resonance. The wavelength at which the resonance occurs depends on the core and shell sizes. The purposes of this study were to use the combination of indocyanine green (ICG) and different concentration of gold nanoshells for skin tissue soldering and also to examine the effect of laser soldering parameters on the properties of repaired skin. Two mixtures of albumin solder and different combinations of ICG and gold nanoshells were prepared. A full thickness incision of 2 × 20 mm(2) was made on the surface and after addition of mixtures it was irradiated by an 810 nm diode laser at different power densities. The changes of tensile strength (σ(t)) due to temperature rise, number of scan (Ns), and scan velocity (Vs) were investigated. The results showed at constant laser power density (I), σ(t) of repaired incisions increases by increasing the concentration of gold nanoshells in solder, Ns, and decreasing Vs. It was demonstrated that laser soldering using combination of ICG + GNs could be practical provided the optothermal properties of the tissue are carefully optimized. Also, the tensile strength of soldered skin is higher than skins that soldered with only ICG or GNs. In our case, this corresponds to σ(t) = 1800 g cm(-2) at I ∼ 47 Wcm(-2), T ∼ 85 [ordinal indicator, masculine]C, Ns = 10, and Vs = 0.3 mms(-1).

Fully integrated optical coherence tomography, ultrasound, and indocyanine green based fluorescence tri-modality system for intravascular imaging (Conference Presentation)

NASA Astrophysics Data System (ADS)

Li, Yan; Jing, Joseph C.; Qu, Yueqiao; Miao, Yusi; Ma, Teng; Yu, Mingyue; Zhou, Qifa; Chen, Zhongping

2017-02-01

The rupture of atherosclerotic plaques is the leading cause of acute coronary events, so accurate assessment of plaque is critical. A large lipid pool, thin fibrous cap, and inflammatory reaction are the crucial characteristics for identifying vulnerable plaques. In our study, a tri-modality imaging system for intravascular imaging was designed and implemented. The tri-modality imaging system with a 1-mm probe diameter is able to simultaneously acquire optical coherence tomography (OCT), intravascular ultrasound (IVUS), and fluorescence imaging. Moreover, for fluorescence imaging, we used the FDA-approved indocyanine green (ICG) dye as the contrast agent to target lipid-loaded macrophages. Firstly, IVUS is used as the first step for identifying plaque since IVUS enables the visualization of the layered structures of the artery wall. Due to low soft-tissue contrast, IVUS only provides initial identification of the lipid plaque. Then OCT is used for differentiating fibrosis and lipid pool based on its relatively higher soft tissue contrast and high sensitivity/specificity. Last, fluorescence imaging is used for identifying inflammatory reaction to further confirm whether the plaque is vulnerable or not. Ex vivo experiment of a male New Zealand white rabbit aorta was performed to validate the performance of our tri-modality system. H and E histology results of the rabbit aorta were also presented to check assessment accuracy. The miniature tri-modality probe, together with the use of ICG dye suggest that the system is of great potential for providing a more accurate assessment of vulnerable plaques in clinical applications.

Fluorescence contrast-enhanced proliferative lesion imaging by enema administration of indocyanine green in a rat model of colon carcinogenesis

PubMed Central

Onda, Nobuhiko; Mizutani-Morita, Reiko; Yamashita, Susumu; Nagahara, Rei; Matsumoto, Shinya; Yoshida, Toshinori; Shibutani, Makoto

2017-01-01

The fluorescent contrast agent indocyanine green (ICG) is approved by the Food and Drug Administration for clinical applications. We previously reported that cultured human colon tumor cells preferentially take up ICG by endocytic activity in association with disruption of their tight junctions. The present study explored ICG availability in fluorescence imaging of the colon to identify proliferative lesions during colonoscopy. The cellular uptake of ICG in cultured rat colon tumor cells was examined using live-cell imaging. Colon lesions in rats administered an ICG-containing enema were further assessed in rats with azoxymethane-induced colon carcinogenesis, using in vivo endoscopy, ex vivo microscopy, and immunofluorescence microscopy. The uptake of ICG by the cultured cells was temperature-dependent. The intracellular retention of the dye in the membrane trafficking system suggested endocytosis as the uptake mechanism. ICG administered via enema accumulated in colon proliferative lesions ranging from tiny aberrant crypt foci to adenomas and localized in proliferating cells. Fluorescence endoscopy detected these ICG-positive colonic proliferative lesions in vivo. The immunoreactivity of the tight-junction molecule occludin was altered in the proliferative lesions, suggesting the disruption of the integrity of tight junctions. These results suggest that fluorescence contrast-enhanced imaging following the administration of an ICG-containing enema can enhance the detection of mucosal proliferative lesions of the colon during colonoscopy. The tissue preference of ICG in the rat model evaluated in this study can be attributed to the disruption of tight junctions, which in turn promotes endocytosis by proliferative cells and the cellular uptake of ICG. PMID:29163827

Analysis of the optical characteristics of adipose tissue in vitro sensitized by indocyanine green and exposed to IR-laser irradiation

NASA Astrophysics Data System (ADS)

Yanina, I. Yu.; Doubrovski, V. A.; Tuchin, V. V.

2015-03-01

The effect of IR-laser irradiation on adipose tissue sensitized by indocyanine green is studied in vitro. Experiments and statistical analysis are used to show that wavelength-selective irradiation leads to an increase in the homogeneity of optical images of adipose cells with time. The transmission coefficient that is averaged over the image area weakly depends on the observation time. An increase in the homogeneity of images is interpreted as a result of immersion of optical inhomogeneities of tissue owing to the intracellular liquid that is released through the photochemically induced pores in cellular membranes. An increase in the optical homogeneity of the medium is compensated for by a decrease in the transmission coefficient of the sensitizer, which is manifested as a weak time dependence of the image-averaged transmittance of tissue.

Imaging of pharmacokinetic rates of indocyanine green in mouse liver with a hybrid fluorescence molecular tomography/x-ray computed tomography system.

PubMed

Zhang, Guanglei; Liu, Fei; Zhang, Bin; He, Yun; Luo, Jianwen; Bai, Jing

2013-04-01

Pharmacokinetic rates have the potential to provide quantitative physiological and pathological information for biological studies and drug development. Fluorescence molecular tomography (FMT) is an attractive imaging tool for three-dimensionally resolving fluorophore distribution in small animals. In this letter, pharmacokinetic rates of indocyanine green (ICG) in mouse liver are imaged with a hybrid FMT and x-ray computed tomography (XCT) system. A recently developed FMT method using structural priors from an XCT system is adopted to improve the quality of FMT reconstruction. In the in vivo experiments, images of uptake and excretion rates of ICG in mouse liver are obtained, which can be used to quantitatively evaluate liver function. The accuracy of the results is validated by a fiber-based fluorescence measurement system.

Self-assembly synthesis, tumor cell targeting, and photothermal capabilities of antibody-coated indocyanine green nanocapsules

PubMed Central

Yu, Jie; Javier, David; Yaseen, Mohammad A.; Nitin, Nitin; Richards-Kortum, Rebecca; Anvari, Bahman; Wong, Michael S.

2010-01-01

New colloidal materials that can generate heat upon irradiation are being explored for photothermal therapy as a minimally invasive approach to cancer treatment. The near-infrared dye indocyanine green (ICG) could serve as a basis for such a material, but its encapsulation and subsequent use is very difficult to carry out. We report the three-step room-temperature synthesis of ~120-nm capsules loaded with ICG within salt-crosslinked polyallylamine aggregates, and coated with anti-epidermal growth factor receptor (anti-EGFR) antibodies for tumor cell targeting capability. We studied the synthesis conditions such as temperature and water dilution to control the capsule size and characterized the size distribution via dynamic light scattering and scanning electron microscopy. We further studied the specificity of tumor cell targeting using three carcinoma cell lines with different levels of EGFR expression, and investigated the photothermal effects of ICG containing nanocapsules on EGFR-rich tumor cells. Significant thermal toxicity was observed for encapsulated ICG as compared to free ICG at 808 nm laser irradiation with radiant exposure of 6 W/cm2. These results illustrate the ability to design a colloidal material with cell targeting and heat generating capabilities using non-covalent chemistry. PMID:20092330

Laser-initiated decomposition products of indocyanine green (ICG) and carbon black sensitized biological tissues

NASA Astrophysics Data System (ADS)

Kokosa, John M.; Przyjazny, Andrzej; Bartels, Kenneth E.; Motamedi, Massoud; Hayes, Donald J.; Wallace, David B.; Frederickson, Christopher J.

1997-05-01

Organic dyes have found increasing use a s sensitizers in laser surgical procedures, due to their high optical absorbances. Little is known, however, about the nature of the degradation products formed when these dyes are irradiated with a laser. Previous work in our laboratories has shown that irradiation of polymeric and biological tissues with CO2 and Nd:YAG lasers produces a host of volatile and semivolatile by-products, some of which are known to be potential carcinogens. This work focuses on the identification of the chemical by-products formed by diode laser and Nd:YAG laser irradiation of indocyanine green (ICG) and carbon black based ink sensitized tissues, including bone, tendon and sheep's teeth. Samples were mounted in a 0.5-L Pyrex sample chamber equipped with quartz optical windows, charcoal filtered air inlet and an outlet attached to an appropriate sample trap and a constant flow pump. By-products were analyzed by GC/MS and HPLC. Volatiles identified included benzene and formaldehyde. Semi-volatiles included traces of polycyclic aromatics, arising from the biological matrix and inks, as well as fragments of ICG and the carbon ink components. The significance of these results will be discussed, including the necessity of using appropriate evacuation devices when utilizing lasers for surgical procedures.

Indocyanine Green Fluorescence to Evaluate Nasoseptal Flap Viability in Endoscopic Endonasal Cranial Base Surgery.

PubMed

Kerr, Edward E; Jamshidi, Ali; Carrau, Ricardo L; Campbell, Raewyn G; Filho, Leo F Ditzel; Otto, Bradley A; Prevedello, Daniel M

2017-10-01

Objectives  The pedicled nasoseptal flap (NSF) has dramatically reduced postoperative cerebrospinal fluid leakage following endoscopic endonasal approach (EEA) surgery. Although rare, its arterial supply may be damaged during harvest or may be preoperatively damaged for numerous reasons. Early recognition permits harvesting a contralateral flap before sacrificing its pedicle as part of the surgical exposure or use of an alternative flap. Design  Technical feasibility study and case series. Setting  Tertiary care university-associated medical center. Participants  Five patients requiring an EEA with NSF reconstruction. Main Outcome Measures  During NSF harvest, intravenous indocyanine green (IVICG) was administered, and a customized endoscopic system was used to visualize the emerging fluorescence. At the end of each case, just before final positioning of the NSF, additional IVICG was administered, and the custom endoscope was again introduced to evaluate fluorescence. Results  In four patients, the entire NSF fluoresced brightly with IVICG on initial harvest and before final positioning. One patient showed heterogeneous fluorescence of the pedicle and distal parts of the NSF at both stages. All NSFs healed well without complication. Conclusion  IVICG facilitates real-time evaluation NSF's arterial supply. This may provide early recognition of arterial compromise, allowing the harvest of alternate flaps or modification of surgery.

Biomimetic HDL nanoparticle mediated tumor targeted delivery of indocyanine green for enhanced photodynamic therapy.

PubMed

Wang, Yazhe; Wang, Cheng; Ding, Yang; Li, Jing; Li, Min; Liang, Xiao; Zhou, Jianping; Wang, Wei

2016-12-01

Photodynamic therapy has emerged as a promising strategy for cancer treatment. To ensure the efficient delivery of a photosensitizer to tumor for anticancer effect, a safe and tumor-specific delivery system is highly desirable. Herein, we introduce a novel biomimetic nanoparticle named rHDL/ICG (rHDL/I), by loading amphiphilic near-infrared (NIR) fluorescent dye indocyanine green (ICG) into reconstituted high density lipoproteins (rHDL). In this system, rHDL can mediate photoprotection effect and receptor-guided tumor-targeting transportation of cargos into cells. Upon NIR irradiation, ICG can generate fluorescent imaging signals for diagnosis and monitoring therapeutic activity, and produce singlet oxygen to trigger photodynamic therapy (PDT). Our studies demonstrated that rHDL/I exhibited excellent size and fluorescence stability, light-triggered controlled release feature, and neglectable hemolytic activity. It also showed equivalent NIR response compared to free ICG under laser irradiation. Importantly, the fluorescent signal of ICG loaded in rHDL/I could be visualized subcellularly in vitro and exhibited metabolic distribution in vivo, presenting superior tumor targeting and internalization. This NIR-triggered image-guided nanoparticle produced outstanding therapeutic outcomes against cancer cells, demonstrating great potential of biomimetic delivery vehicles in future clinical practice. Copyright © 2016 Elsevier B.V. All rights reserved.

[Indocyanine green infrared fluorescence angiography and vascular cast--preparation in experimental choroidal circulatory disturbance].

PubMed

Matsunaga, H; Andoh, A; Matsubara, T; Fukushima, I; Takahashi, K; Ohkuma, H; Uyama, M

1996-03-01

We performed experiments in 20 monkey eyes in order to clarify basic problems about interpretation of indocyanine green fluorescence angiography (ICG angiography). We severed the temporal group of posterior ciliary arteries to produce choroidal circulatory disturbance. ICG angiography was performed immediately, and 2 days, 4 days, and 2 weeks later. Following each ICG angiography, the eye was studied by plastic vascular cast technique with scanning electron microscopy. Immediately after occlusion, ICG angiography showed filling defect in the temporal choroidal hemisphere during the early phase. In the later phase, this area was gradually filled by the dye from choroidal arteries in the nasal hemisphere and the anterior ciliary arteries. Vascular cast preparations showed filling defect in the temporal choroidal hemisphere, corresponding with the early ICG angiogaphic findings. Both filling delay in ICG angiography and filling defect in vascular casts improved daily after occlusion. Two weeks after occlusion, The area of choroidal infarct temporal to the macula turned into chorioretinal atrophy. This area showed hypofluorescence in the early-phase ICG angiography and filling defect of the choriocapillaris in plastic casts. The early-phase ICG angiographic findings thus corresponded well with observations of vascular casts. We conclude that ICG angiography correctly reflects the actual circulatory disturbances in the choroid.

Photodynamic hyperthermal chemotherapy with indocyanine green: a novel cancer therapy for 16 cases of malignant soft tissue sarcoma

PubMed Central

Onoyama, Masaki; Tsuka, Takeshi; Imagawa, Tomohiro; Osaki, Tomohiro; Minami, Saburo; Azuma, Kazuo; Kawashima, Kazuhiko; Ishi, Hiroshi; Takayama, Takahiro; Ogawa, Nobuhiko

2014-01-01

Sixteen cases of malignant soft tissue sarcoma (STS; 10 canines and six felines) were treated with a novel triple therapy that combined photodynamic therapy, hyperthermia using indocyanine green with a broadband light source, and local chemotherapy after surgical tumor resection. This triple therapy was called photodynamic hyperthermal chemotherapy (PHCT). In all cases, the surgical margin was insufficient. In one feline case, PHCT was performed without surgical resection. PHCT was performed over an interval of 1 to 2 weeks and was repeated three to 21 times. No severe side effects, including severe skin burns, necrosis, or skin suture rupture, were observed in any of the animals. No disease recurrence was observed in seven out of 10 (70.0%) dogs and three out of six (50.0%) cats over the follow-up periods ranging from 238 to 1901 days. These results suggest that PHCT decreases the risk of STS recurrence. PHCT should therefore be considered an adjuvant therapy for treating companion animals with STS in veterinary medicine. PMID:24136207

Safety, efficacy, and cost of intraoperative indocyanine green angiography compared to intraoperative catheter angiography in cerebral aneurysm surgery.

PubMed

Hardesty, Douglas A; Thind, Harjot; Zabramski, Joseph M; Spetzler, Robert F; Nakaji, Peter

2014-08-01

Intraoperative angiography in cerebrovascular neurosurgery can drive the repositioning or addition of aneurysm clips. Our institution has switched from a strategy of intraoperative digital subtraction angiography (DSA) universally, to a strategy of indocyanine green (ICG) videoangiography with DSA on an as-needed basis. We retrospectively evaluated whether the rates of perioperative stroke, unexpected postoperative aneurysm residual, or parent vessel stenosis differed in 100 patients from each era (2002, "DSA era"; 2007, "ICG era"). The clip repositioning rate for neck residual or parent vessel stenosis did not differ significantly between the two eras. There were no differences in the rate of perioperative stroke or rate of false-negative studies. The per-patient cost of intraoperative imaging within the DSA era was significantly higher than in the ICG era. The replacement of routine intraoperative DSA with ICG videoangiography and selective intraoperative DSA in cerebrovascular aneurysm surgery is safe and effective. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

Wall-to-lumen ratio of intracranial arteries measured by indocyanine green angiography

PubMed Central

Nakagawa, Daichi; Shojima, Masaaki; Yoshino, Masanori; Kin, Taichi; Imai, Hideaki; Nomura, Seiji; Saito, Toki; Nakatomi, Hirofumi; Oyama, Hiroshi; Saito, Nobuhito

2016-01-01

Background: The wall-to-lumen ratio (WLR) is an important parameter in vascular medicine because it indicates the character of vascular wall as well as the degree of stenosis. Despite the advances in medical imaging technologies, it is still difficult to measure the thin-walled normal intracranial arteries, and the reports on the WLR of normal intracranial artery are limited. It might be possible to calculate the WLR using the indocyanine green (ICG) angiography, which is used to observe intracranial vessels during microsurgery. Purpose: To evaluate the WLR of normal intracranial arteries using ICG angiography. Materials and Methods: From the three cases in which ICG angiography was recorded with a ruler during microsurgery, 20 measurement points were chosen for the analysis. The ICG was injected intravenously with a dose of 0.2 mg/kg, and the vessels were inspected at high magnification using an operating microscope equipped with near-infrared illumination system. The vessel outer diameter and the luminal diameter were measured using the images before and after the ICG arrival based on the pixel ratio method using a ruler as reference, respectively. The WLR was calculated as 0.5 × (vessel outer diameter − vessel luminal diameter). Results: The WLR (mean ± standard deviation) of normal intracranial arteries was 0.086 ± 0.022. The WLR tended to be high in small arteries. Conclusion: The WLR of normal intracranial arteries calculated using ICG angiography was consistent with the WLR reported in the previous reports based on human autopsy. PMID:27695538

Value of Indocyanine Green Videoangiography in Deciding the Completeness of Cerebrovascular Surgery

PubMed Central

Moon, Hyung-Sik; Joo, Sung-Pil; Seo, Bo-Ra; Jang, Jae-Won; Kim, Jae-Hyoo

2013-01-01

Objective Recently, microscope-integrated near infrared indocyanine green videoangiography (ICG-VA) has been widely used in cerebrovascular surgery because it provides real-time high resolution images. In our study, we evaluate the efficacy of intraoperative ICG-VA during cerebrovascular surgery. Methods Between August 2011 and April 2012, 188 patients with cerebrovascular disease were surgically treated in our institution. We used ICG-VA in that operations with half of recommended dose (0.2 to 0.3 mg/kg). Postoperative digital subtraction angiography and computed tomography angiography was used to confirm anatomical results. Results Intraoperative ICG-VA demonstrated fully occluded aneurysm sack, no neck remnant, and without vessel compromise in 119 cases (93.7%) of 127 aneurysms. Eight clipping (6.3%) of 127 operations were identified as an incomplete aneurysm occlusion or compromising vessel after ICG-VA. In 41 (97.6%) of 42 patients after carotid endarterectomy, the results were the same as that of postoperative angiography with good patency. One case (5.9%) of 17 bypass surgeries was identified as a nonfunctioning anastomosis after ICG-VA, which could be revised successfully. In the two patients of arteriovenous malformation, ICG-VA was useful for find the superficial nature of the feeding arteries and draining veins. Conclusion ICG-VA is simple and provides real-time information of the patency of vessels including very small perforators within the field of the microscope and has a lower rate of adverse reactions. However, ICG-VA is not a perfect method, and so a combination of monitoring tools assures the quality of cerebrovascular surgery. PMID:24003369

Blood flow speed of the gastric conduit assessed by indocyanine green fluorescence

PubMed Central

Koyanagi, Kazuo; Ozawa, Soji; Oguma, Junya; Kazuno, Akihito; Yamazaki, Yasushi; Ninomiya, Yamato; Ochiai, Hiroki; Tachimori, Yuji

2016-01-01

Abstract Anastomotic leakage is considered as an independent risk factor for postoperative mortality after esophagectomy, and an insufficient blood flow in the reconstructed conduit may be a risk factor of anastomotic leakage. We investigated the clinical significance of blood flow visualization by indocyanine green (ICG) fluorescence in the gastric conduit as a means of predicting the leakage of esophagogastric anastomosis after esophagectomy. Forty patients who underwent an esophagectomy with gastric conduit reconstruction were prospectively investigated. ICG fluorescence imaging of the gastric conduit was detected by a near-infrared camera system during esophagectomy and correlated with clinical parameters or surgical outcomes. In 25 patients, the flow speed of ICG fluorescence in the gastric conduit wall was simultaneous with that of the greater curvature vessels (simultaneous group), whereas in 15 patients this was slower than that of the greater curvature vessels (delayed group). The reduced speed of ICG fluorescence stream in the gastric conduit wall was associated with intraoperative blood loss (P = 0.008). Although anastomotic leakage was not found in the simultaneous group, it occurred in 7 patients of the delayed group (P < 0.001). A flow speed of ICG fluorescence in the gastric conduit wall of 1.76 cm/s or less was determined by a receiver operating characteristic (ROC) curve, identified as a significant independent predictor of anastomotic leakage after esophagectomy (P = 0.004). This preliminary study demonstrates that intraoperative evaluation of blood flow speed by ICG fluorescence in the gastric conduit wall is a useful means to predict the risk of anastomotic leakage after esophagectomy. PMID:27472732

Indocyanine Green-Loaded Polydopamine-Reduced Graphene Oxide Nanocomposites with Amplifying Photoacoustic and Photothermal Effects for Cancer Theranostics.

PubMed

Hu, Dehong; Zhang, Jingnan; Gao, Guanhui; Sheng, Zonghai; Cui, Haodong; Cai, Lintao

2016-01-01

Photoacoustic (PA) imaging and photothermal therapy (PTT) as light-induced theranostic platforms have been attracted much attention in recent years. However, the development of highly efficient and integrated phototheranostic nanoagents for amplifying PA imaging and PTT treatments poses great challenges. Here, we report a novel phototheranostic nanoagent using indocyanine green-loaded polydopamine-reduced graphene oxide nanocomposites (ICG-PDA-rGO) with amplifying PA and PTT effects for cancer theranostics. The results demonstrate that the PDA layer coating on the surface of rGO could effectively absorb a large number of ICG molecules, quench ICG's fluorescence, and enhance the PDA-rGO's optical absorption at 780 nm. The obtained ICG-PDA-rGO exhibits stronger PTT effect and higher PA contrast than that of pure GO and PDA-rGO. After PA imaging-guided PTT treatments, the tumors in 4T1 breast subcutaneous and orthotopic mice models are suppressed completely and no treatment-induced toxicity being observed. It illustrates that the ICG-PDA-rGO nanocomposites constitute a new class of theranostic nanomedicine for amplifying PA imaging and PTT treatments.

Visualization of subcapsular hepatic malignancy by indocyanine-green fluorescence imaging during laparoscopic hepatectomy.

PubMed

Kudo, Hiroki; Ishizawa, Takeaki; Tani, Keigo; Harada, Nobuhiro; Ichida, Akihiko; Shimizu, Atsushi; Kaneko, Junichi; Aoki, Taku; Sakamoto, Yoshihiro; Sugawara, Yasuhiko; Hasegawa, Kiyoshi; Kokudo, Norihiro

2014-08-01

Although laparoscopic hepatectomy has increasingly been used to treat cancers in the liver, the accuracy of intraoperative diagnosis may be inferior to that of open surgery because the ability to visualize and palpate the liver surface during laparoscopy is relatively limited. Fluorescence imaging has the potential to provide a simple compensatory diagnostic tool for identification of cancers in the liver during laparoscopic hepatectomy. In 17 patients who were to undergo laparoscopic hepatectomy, 0.5 mg/kg body weight of indocyanine green (ICG) was administered intravenously within the 2 weeks prior to surgery. Intraoperatively, a laparoscopic fluorescence imaging system obtained fluorescence images of its surfaces during mobilization of the liver. In all, 16 hepatocellular carcinomas (HCCs) and 16 liver metastases (LMs) were resected. Of these, laparoscopic ICG fluorescence imaging identified 12 HCCs (75%) and 11 LMs (69%) on the liver surfaces distributed over Couinaud's segments 1-8, including the 17 tumors that had not been identified by visual inspections of normal color images. The 23 tumors that were identified by fluorescence imaging were located closer to the liver surfaces than another nine tumors that were not identified by fluorescence imaging (median [range] depth 1 [0-5] vs. 11 [8-30] mm; p < 0.001). Like palpation during open hepatectomy, laparoscopic ICG fluorescence imaging enables real-time identification of subcapsular liver cancers, thus facilitating estimation of the required extent of hepatic mobilization and determination of the location of an appropriate hepatic transection line.

Multiwavelength time-resolved detection of fluorescence during the inflow of indocyanine green into the adult's brain

NASA Astrophysics Data System (ADS)

Gerega, Anna; Milej, Daniel; Weigl, Wojciech; Botwicz, Marcin; Zolek, Norbert; Kacprzak, Michal; Wierzejski, Wojciech; Toczylowska, Beata; Mayzner-Zawadzka, Ewa; Maniewski, Roman; Liebert, Adam

2012-08-01

Optical technique based on diffuse reflectance measurement combined with indocyanine green (ICG) bolus tracking is extensively tested as a method for clinical assessment of brain perfusion in adults at the bedside. Methodology of multiwavelength and time-resolved detection of fluorescence light excited in the ICG is presented and advantages of measurements at multiple wavelengths are discussed. Measurements were carried out: 1. on a physical homogeneous phantom to study the concentration dependence of the fluorescence signal, 2. on the phantom to simulate the dynamic inflow of ICG at different depths, and 3. in vivo on surface of the human head. Pattern of inflow and washout of ICG in the head of healthy volunteers after intravenous injection of the dye was observed for the first time with time-resolved instrumentation at multiple emission wavelengths. The multiwavelength detection of fluorescence signal confirms that at longer emission wavelengths, probability of reabsorption of the fluorescence light by the dye itself is reduced. Considering different light penetration depths at different wavelengths, and the pronounced reabsorption at longer wavelengths, the time-resolved multiwavelength technique may be useful in signal decomposition, leading to evaluation of extra- and intracerebral components of the measured signals.

Antibacterial photodynamic therapy with 808-nm laser and indocyanine green on abrasion wound models

NASA Astrophysics Data System (ADS)

Topaloglu, Nermin; Güney, Melike; Yuksel, Sahru; Gülsoy, Murat

2015-02-01

Infections with pathogens could cause serious health problems, such as septicemia and subsequent death. Some of these deaths are caused by nosocomial, chronic, or burn-related wound infections. Photodynamic therapy (PDT) can be useful for the treatment of these infections. Our aim was to investigate the antibacterial effect of indocyanine green (ICG) and 808-nm laser on a rat abrasion wound model infected with the multidrug resistant Staphylococcus aureus strain. Abrasion wounds were infected with a multidrug resistant clinical isolate of S. aureus. ICG concentrations of 500, 1000, and 2000 μg/ml were applied with a 450 J/cm2 energy dose. Temperature change was monitored by a thermocouple system. The remaining bacterial burden was determined by the serial dilution method after each application. Wounds were observed for 11 days posttreatment. The recovery process was assessed macroscopically. Tissue samples were also examined histologically by hematoxylin-eosin staining. Around a 90% reduction in bacterial burden was observed after PDT applications. In positive control groups (ICG-only and laser-only groups), there was no significant reduction. The applied energy dose did not cause any thermal damage to the target tissue or host environment. Results showed that ICG together with a 808-nm laser might be a promising antibacterial method to eliminate infections in animals and accelerate the wound-healing process.

[Place of indocyanine green coupled with fluorescence imaging in research of breast cancer sentinel node].

PubMed

Vermersch, Charlotte; Raia Barjat, Tiphaine; Perrot, Marianne; Lima, Suzanne; Chauleur, Céline

2016-04-01

The sentinel node has a fundamental role in the management of early breast cancer. Currently, the double detection of blue and radioisotope is recommended. But in common practice, many centers use a single method. However, with a single detection, the risk of false negatives and the identification failure rate increase to a significant extent and the number of sentinel lymph node detected and removed is not enough. Furthermore, the tracers used until now show inconveniences. The purpose of this work is to present a new method of detection, using the green of indocyanine coupled with fluorescence imaging, and to compare it with the already existing methods. The method combined by fluorescence and isotopic is reliable, sure, of fast learning and could constitute a good strategy of detection. The major interest is to obtain a satisfactory number of sentinel nodes. The profit could be even more important for overweight patients. The fluorescence used alone is at the moment not possible. Wide ranging studies are necessary. The FLUOTECH, randomized study of 100 patients, comparing the isotopic method of double isotope technique and fluorescence, is underway to confirm these data. Copyright © 2016 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.

In vivo fluorescence confocal microscopy: indocyanine green enhances the contrast of epidermal and dermal structures

NASA Astrophysics Data System (ADS)

Skvara, Hans; Kittler, Harald; Schmid, Johannes A.; Plut, Ulrike; Jonak, Constanze

2011-09-01

In recent years, in vivo skin imaging devices have been successfully implemented in skin research as well as in clinical routine. Of particular importance is the use of reflectance confocal microscopy (RCM) and fluorescence confocal microscopy (FCM) that enable visualization of the tissue with a resolution comparable to histology. A newly developed commercially available multi-laser device in which both technologies are integrated now offers the possibility to directly compare RCM with FCM. The fluorophore indocyanine green (ICG) was intradermally injected into healthy forearm skin of 10 volunteers followed by in vivo imaging at various time points. In the epidermis, accurate assessment of cell morphology with FCM was supplemented by identification of pigmented cells and structures with RCM. In dermal layers, only with FCM connective tissue fibers were clearly contoured down to a depth of more than 100 μm. The fluorescent signal still provided a favorable image contrast 24 and 48 hours after injection. Subsequently, ICG was applied to different types of skin diseases (basal cell carcinoma, actinic keratosis, seborrhoeic keratosis, and psoriasis) in order to demonstrate the diagnostic benefit of FCM when directly compared with RCM. Our data suggest a great impact of FCM in combination with ICG on clinical and experimental dermatology in the future.

Comparison of Intraoperative Indocyanine Green Angiography and Digital Subtraction Angiography for Clipping of Intracranial Aneurysms

PubMed Central

Doss, Vinodh T.; Goyal, Nitin; Humphries, William; Hoit, Dan; Arthur, Adam; Elijovich, Lucas

2015-01-01

Background Residual aneurysm after microsurgical clipping carries a risk of aneurysm growth and rupture. Digital subtraction angiography (DSA) remains the standard to determine the adequacy of clipping. Intraoperative indocyanine green (ICG) angiography is increasingly utilized to confirm optimal clip positioning across the neck and to evaluate the adjacent vasculature. Objective We evaluated the correlation between ICG and DSA in clipped intracranial aneurysms. Methods A retrospective study of patients who underwent craniotomy and microsurgical clipping of intracranial aneurysms with ICG for 2 years. Patient characteristics, presentation details, operative reports, and pre- and postclipping angiographic images were reviewed to determine the adequacy of the clipping. Results Forty-seven patients underwent clipping with ICG and postoperative DSA: 57 aneurysms were clipped; 23 patients (48.9%) presented with subarachnoid hemorrhage. Nine aneurysms demonstrated a residual on DSA not identified on ICG (residual sizes ranged from 0.5 to 4.3 mm; average size: 1.8 mm). Postoperative DSA demonstrated no branch occlusions. Conclusion Intraoperative ICG is useful in the clipping of intracranial aneurysms to ensure a gross patency of branch vessels; however, the presence of residual aneurysms and subtle changes in flow in branch vessels is best seen by DSA. This has important clinical implications with regard to follow-up imaging and surgical/endovascular management. PMID:26279659

Morphology alterations of skin and subcutaneous fat at NIR laser irradiation combined with delivery of encapsulated indocyanine green

NASA Astrophysics Data System (ADS)

Yanina, Irina Yu.; Navolokin, Nikita A.; Svenskaya, Yulia I.; Bucharskaya, Alla B.; Maslyakova, Galina N.; Gorin, Dmitry A.; Sukhorukov, Gleb B.; Tuchin, Valery V.

2017-05-01

The goal of this study is to quantify the impact of the in vivo photochemical treatment of rats with obesity using indocyanine green (ICG) dissolved in saline or dispersed in an encapsulated form at NIR laser irradiation, which was monitored by tissue sampling and histochemistry. The subcutaneous injection of the ICG solution or ICG encapsulated into polyelectrolyte microcapsules, followed by diode laser irradiation (808 nm, 8 W/cm2, 1 min), resulted in substantial differences in lipolysis of subcutaneous fat. Most of the morphology alterations occurred in response to the laser irradiation if a free-ICG solution had been injected. In such conditions, membrane disruption, stretching, and even delamination in some cases were observed for a number of cells. The encapsulated ICG aroused similar morphology changes but with weakly expressed adipocyte destruction under the laser irradiation. The Cochran Q test rendered the difference between the treatment alternatives statistically significant. By this means, laser treatment using the encapsulated form of ICG seems more promising and could be used for safe layerwise laser treatment of obesity and cellulite.

Morphology alterations of skin and subcutaneous fat at NIR laser irradiation combined with delivery of encapsulated indocyanine green.

PubMed

Yanina, Irina Yu; Navolokin, Nikita A; Svenskaya, Yulia I; Bucharskaya, Alla B; Maslyakova, Galina N; Gorin, Dmitry A; Sukhorukov, Gleb B; Tuchin, Valery V

2017-05-01

The goal of this study is to quantify the impact of the in vivo photochemical treatment of rats with obesity using indocyanine green (ICG) dissolved in saline or dispersed in an encapsulated form at NIR laser irradiation, which was monitored by tissue sampling and histochemistry. The subcutaneous injection of the ICG solution or ICG encapsulated into polyelectrolyte microcapsules, followed by diode laser irradiation (808 nm, 8 ?? W / cm 2 , 1 min), resulted in substantial differences in lipolysis of subcutaneous fat. Most of the morphology alterations occurred in response to the laser irradiation if a free-ICG solution had been injected. In such conditions, membrane disruption, stretching, and even delamination in some cases were observed for a number of cells. The encapsulated ICG aroused similar morphology changes but with weakly expressed adipocyte destruction under the laser irradiation. The Cochran Q test rendered the difference between the treatment alternatives statistically significant. By this means, laser treatment using the encapsulated form of ICG seems more promising and could be used for safe layerwise laser treatment of obesity and cellulite.

Patent blue V and indocyanine green for fluorescence microimaging of human peritoneal carcinomatosis using probe-based confocal laser endomicroscopy.

PubMed

Abbaci, Muriel; Dartigues, Peggy; De Leeuw, Frederic; Soufan, Ranya; Fabre, Monique; Laplace-Builhé, Corinne

2016-12-01

Peritoneal carcinomatosis is a metastatic stage aggravating abdominal and pelvic cancer dissemination. The preoperative evaluation of lesions remains difficult today. Probe-based confocal laser endomicroscopy (pCLE) provides dynamic images of tissue architecture and cellular details. This technology allows in vivo histological interpretation of tissue. The main limitation of pCLE for adoption in the clinic is the unavailability of fluorescent contrast agents. The aim of our study was to evaluate the staining performance of indocyanine green and patent blue V for histological diagnosis of pCLE images of pathological and non-pathological peritoneal tissue. We performed a correlative study with the histological gold standard on ex vivo human specimens from 25 patients operated for peritoneal carcinomatosis; 70 specimens were stained by topical application with ICG or patent blue V and then imaged with a probe-based confocal laser endomicroscope. A total of 350 pCLE images and 70 corresponding histological sections were randomly and blindly interpreted by two pathologists (PT1 and PT2). The images were first classified into two categories, tumoral versus non-tumoral, and a refined histological diagnosis was then given. All presented images were interpreted by PT1 (who received prior training on PCLE image reading) and PT2 (no training). 100 % sensitivity for PT1 and PT2 was noticed with tissues stained with ICG to differentiate tumoral and non-tumoral tissue. Global scores were always better for PT1 (major concordance between 86 and 94 %) than for PT2 (major concordance between 77 and 89 %) independently of the fluorescent dye when histological diagnosis was done on pCLE images. In conclusion, the pair ICG-pCLE offers the best combination for a non-trained pathologist for the interpretation of pCLE images from peritoneum.

Use of Indocyanine Green for Sentinel Lymph Node Biopsy: Case Series and Methods Comparison.

PubMed

McGregor, Andrew; Pavri, Sabrina N; Tsay, Cynthia; Kim, Samuel; Narayan, Deepak

2017-11-01

Sentinel lymph node biopsy is indicated for patients with biopsy-proven thickness melanoma greater than 1.0 mm. Use of lymphoscintigraphy along with vital blue dyes is the gold standard for identifying sentinel lymph nodes intraoperatively. Indocyanine green (ICG) has recently been used as a method of identifying sentinel lymph nodes. We herein describe a case series of patients who have successfully undergone ICG-assisted sentinel lymph node biopsy for melanoma. We compare 2 imaging systems that are used for ICG-assisted sentinel lymph node biopsy. Fourteen patients underwent ICG-assisted sentinel lymph node biopsy for melanoma using the SPY Elite system (Novadaq, Mississigua, Canada) and the Hamamatsu PDE-Neo probe system (Mitaka USA, Park City, Utah). We analyzed costs for 2 systems that utilize ICG for sentinel lymph node biopsies. Intraoperative use of ICG for sentinel lymph node biopsies was successful in correctly identifying sentinel lymph nodes. There was no difference between the Hamamatsu PDE-Neo probe and SPY Elite systems in the ability to detect sentinel lymph nodes; however, the former was associated with a lower operating cost and ease of use compared with the latter. ICG-assisted sentinel lymph biopsy using the SPY Elite or the Hamamatsu PDE-Neo probe systems for melanoma are comparable in terms of sentinel node detection. The Neo probe system delivers pertinent clinical data with the advantages of lower cost and ease of operation.

Parathyroid gland angiography with indocyanine green fluorescence to predict parathyroid function after thyroid surgery

PubMed Central

Vidal Fortuny, J.; Belfontali, V.; Sadowski, S. M.; Karenovics, W.; Guigard, S.

2016-01-01

Background Postoperative hypoparathyroidism remains the most common complication following thyroidectomy. The aim of this pilot study was to evaluate the use of intraoperative parathyroid gland angiography in predicting normal parathyroid gland function after thyroid surgery. Methods Angiography with the fluorescent dye indocyanine green (ICG) was performed in patients undergoing total thyroidectomy, to visualize vascularization of identified parathyroid glands. Results Some 36 patients underwent ICG angiography during thyroidectomy. All patients received standard calcium and vitamin D supplementation. At least one well vascularized parathyroid gland was demonstrated by ICG angiography in 30 patients. All 30 patients had parathyroid hormone (PTH) levels in the normal range on postoperative day (POD) 1 and 10, and only one patient exhibited asymptomatic hypocalcaemia on POD 1. Mean(s.d.) PTH and calcium levels in these patients were 3·3(1·4) pmol/l and 2·27(0·10) mmol/l respectively on POD 1, and 4·0(1.6) pmol/l and 2·32(0·08) mmol/l on POD 10. Two of the six patients in whom no well vascularized parathyroid gland could be demonstrated developed transient hypoparathyroidism. None of the 36 patients presented symptomatic hypocalcaemia, and none received treatment for hypoparathyroidism. Conclusion PTH levels on POD 1 were normal in all patients who had at least one well vascularized parathyroid gland demonstrated during surgery by ICG angiography, and none required treatment for hypoparathyroidism. PMID:26864909

Biodistribution of indocyanine green-loaded nanoparticles with surface modifications of PEG and folic acid.

PubMed

Ma, Ying; Sadoqi, Mostafa; Shao, Jun

2012-10-15

To establish the biodistribution profile of the PLGA nanoparticles with dual surface modifications of PEG and folic acid (FA) in mice xenografted with MDA-MB-231 human breast cancer cells with high expression of folate receptor (FR); and to illustrate that the modified nanoparticles can target the loaded indocyanine green (ICG) to the tumor with high FR expression. ICG-loaded nanoparticles were prepared with PLGA (non-modified nanoparticles, NM-NP) or mPEG-PLGA and FA-PLGA (dual modified nanoparticles, DM-NP). Biodistribution of the ICG-loaded nanoparticles (1.25 mg/kg) after i.v. injection was investigated on athymic mice transplanted with MDA-MB-231 tumor. ICG concentration in plasma from the DM-NP group was significantly (p<0.05) higher than the NM-NP group from 90 min to the end of the study (12 h). After 4 h, the drug concentration in the tumor tissue from the DM-NP started to be significantly (p<0.05) higher than the NM-NP until 12 h. Compared to the NM-NP, the DM-NP increased the AUC(0-12 h) in plasma by 245% and the AUC(0-12 h) in tumor by 194%, while decreased the AUC(0-12 h) in liver by 13%. The accumulation of DM-NP into the tumor was significantly higher than NM-NP due to the long circulation and FR-mediated uptake. Copyright © 2012 Elsevier B.V. All rights reserved.

Photo-activated disinfection based on indocyanine green against cell viability and biofilm formation of Porphyromonas gingivalis.

PubMed

Pourhajibagher, Maryam; Chiniforush, Nasim; Ghorbanzadeh, Roghayeh; Bahador, Abbas

2017-03-01

Photo-activated disinfection (PAD) is a novel treatment approach, in which bacteria in the root canal system may be exposed to sub-lethal doses of PAD. Such exposure can affect bacterial survival and virulence features, such as biofilm formation ability. The aim of this study was to evaluate the effects of sub-lethal doses of PAD (sPAD) using indocyanine green (ICG) on load and biofilm formation ability of Porphyromonas gingivalis as an anaerobic bacterium associated with endodontic infection. The anti-bacterial and anti-biofilm potential of sPAD against P. gingivalis at sub-lethal doses of ICG as a photosensitizer and using 810nm wavelength of diode laser light via colony forming unit and crystal violet assays, respectively, was determined. High concentrations of ICG and light irradiation time significantly reduced bacteria. High doses of sPAD markedly reduced the number of bacteria and the formation of biofilm, up to 30.4% and 25.1%, respectively. High doses of sPAD affected cell viability and the biofilm formation ability of P. gingivalis; lower doses did not. Thus, selection of appropriate PAD dosage should be considered for the successful treatment of endodontic in vivo. Copyright © 2016 Elsevier B.V. All rights reserved.

Indocyanine green videoangiography (ICGV)-guided surgery of parasagittal meningiomas occluding the superior sagittal sinus (SSS).

PubMed

d'Avella, Elena; Volpin, Francesco; Manara, Renzo; Scienza, Renato; Della Puppa, Alessandro

2013-03-01

Maximal safe resection is the goal of correct surgical treatment of parasagittal meningiomas, and it is intimately related to the venous anatomy both near and directly involved by the tumor. Indocyanine green videoangiography (ICGV) has already been advocated as an intra-operative resourceful technique in brain tumor surgery for the identification of vessels. The aim of this study was to investigate the role of ICGV in surgery of parasagittal meningiomas occluding the superior sagittal sinus (SSS). In this study, we prospectively analyzed clinical, radiological and intra-operative findings of patients affected by parasagittal meningioma occluding the SSS, who underwent ICGV assisted-surgery. Radiological diagnosis of complete SSS occlusion was pre-operatively established in all cases. ICGV was performed before dural opening, before and during tumor resection, at the end of the procedure. Five patients were included in our study. In all cases, ICGV guided dural opening, tumor resection, and venous management. The venous collateral pathway was easily identified and preserved in all cases. Radical resection was achieved in four cases. Surgery was uneventful in all cases. Despite the small number of patients, our study shows that ICG videoangiography could play a crucial role in guiding surgery of parasagittal meningioma occluding the SSS. Further studies are needed to define the role of this technique on functional and oncological outcome of these patients.

Portal vein territory identification using indocyanine green fluorescence imaging: Technical details and short-term outcomes.

PubMed

Kobayashi, Yuta; Kawaguchi, Yoshikuni; Kobayashi, Kosuke; Mori, Kazuhiro; Arita, Junichi; Sakamoto, Yoshihiro; Hasegawa, Kiyoshi; Kokudo, Norihiro

2017-12-01

Portal vein (PV) territory identification during liver resection may be performed using indocyanine green (ICG) fluorescence imaging technique. However, the technical details of the fluorescence staining technique have not been fully elucidated. This study was performed to demonstrate the technical details of PV territory identification using fluorescence imaging and evaluates the short-term outcomes. From 2011 to 2015, 105 underwent liver resection at the University of Tokyo Hospital with one of the following fluorescence staining techniques by transhepatic PV injection or intravenous injection of ICG: single staining (n = 36), multiple staining (n = 31), counterstaining (n = 22), negative staining (n = 13), or paradoxical negative staining (n = 3). The PV territory was identified as a region with fluorescence or a defect of fluorescence using one of the five staining techniques. ICG was administered by transhepatic PV injection in all but the negative staining technique, which employed intravenous injection. No adverse events associated with the ICG administration occurred. The mortality, postoperative total morbidity, and the major complication (Clavien-Dindo grade ≥III) rates were 0.0%, 14.3%, and 7.6%. We have demonstrated the technical details of five types of fluorescence staining techniques. These techniques are safe to perform and facilitate clear visualization of the PV territory in real time, enhancing the efficacy of anatomical removal of such territories. © 2017 Wiley Periodicals, Inc.

Application of intraoperative indocyanine green angiography for CNS tumors: results on the first 100 cases.

PubMed

Ferroli, P; Acerbi, F; Albanese, E; Tringali, G; Broggi, M; Franzini, A; Broggi, G

2011-01-01

To investigate the application of indocyanine green (ICG) videoangiography during microsurgery for central nervous system (CNS) tumors. One hundred patients with CNS tumors who underwent microsurgical resection from December 2006 to December 2008 were retrospectively analyzed. The diagnosis was high grade glioma in 54 cases, low grade in 17 cases, meningioma in 14 cases, metastasis in 12 cases and hemangioblastoma in 3 cases. Overall, ICG was injected intraoperatively 194 times. The standard dose of 25mg of dye was injected intravenously and intravascular fluorescence from within the blood vessels was imaged through an ad hoc microscope with dedicated software (Pentero, Carl Zeiss Co., Oberkochen, Germany). Pre-resection and post-resection arterial, capillary and venous ICG videoangiographic phases were intraoperatively observed and recorded. ICG videangiography allowed for a good evaluation of blood flow in the tumoral and peritumoral exposed vessels in all cases. No side effects due to ICG were observed. ICG video-angiography is a significant method for monitoring blood flow in the exposed vessels during microsurgical removal of CNS tumors. Pre-resection videoangiography provides useful information on the tumoral circulation and the pathology-induced alteration in surrounding brain circulation. Post-resection examination allows for an immediate check of patency of those vessels that are closely related to the tumor mass and that the surgeon does not want to damage.

Donor Indocyanine Green Clearance Test Predicts Graft Quality and Early Graft Prognosis After Liver Transplantation.

PubMed

Tang, Yunhua; Han, Ming; Chen, Maogen; Wang, Xiaoping; Ji, Fei; Zhao, Qiang; Zhang, Zhiheng; Ju, Weiqiang; Wang, Dongping; Guo, Zhiyong; He, Xiaoshun

2017-11-01

Transplantation centers have given much attention to donor availability. However, no reliable quantitative methods have been employed to accurately assess graft quality before transplantation. Here, we report that the indocyanine green (ICG) clearance test is a valuable index for liver grafts. We performed the ICG clearance test on 90 brain-dead donors within 6 h before organ procurement between March 2015 and November 2016. We also analyzed the relationship between graft liver function and early graft survival after liver transplantation (LT). Our results suggest that the ICG retention rate at 15 min (ICGR15) of donors before procurement was independently associated with 3-month graft survival after LT. The best donor ICGR15 cutoff value was 11.0%/min, and we observed a significant increase in 3-month graft failure among patients with a donor ICGR15 above this value. On the other hand, a donor ICGR15 value of ≤ 11.0%/min could be used as an early assessment index of graft quality because it provides additional information to the transplant surgeon or organ procurement organization members who must maintain or improve organ function to adapt the LT. An ICG clearance test before liver procurement might be an effective quantitative method to predict graft availability and improve early graft prognosis after LT.

Thermal and infrared-diode laser effects on indocyanine-green-treated corneal collagen

NASA Astrophysics Data System (ADS)

Timberlake, George T.; Patmore, Ann; Shallal, Assaad; McHugh, Dominic; Marshall, John

1993-07-01

It has been suggested that laser welds of collagenous tissues form by interdigitation and chemical bonding of thermally 'unraveled' collagen fibrils. We investigated this proposal by attempting to weld highly collagenous, avascular corneal tissue with an infrared (IR) diode laser as follows. First, the temperature at which corneal collagen shrinks and collagen fibrils 'split' into subfibrillary components was determined. Second, since use of a near-IR laser wavelength necessitated addition of an absorbing dye (indocyanine green (ICG) to the cornea, we measured absorption spectra of ICG-treated tissue to ensure that peak ICG absorbance did not change markedly when ICG was present in the cornea. Third, using gel electrophoresis of thermally altered corneal collagen, we searched for covalently crosslinked compounds predicted by the proposed welding mechanism. Finally, we attempted to weld partial thickness corneal incisions infused with ICG. Principal experimental findings were as follows: (1) Human corneal (type I) collagen splits into subfibrillary components at approximately 63 degree(s)C, the same temperature that produces collagen shrinkage. (2) Peak ICG absorption does not change significantly in corneal stroma or with laser heating. (3) No evidence was found for the formation of novel compounds or the loss of proteins as a result of tissue heating. All tissue treated with ICG, however, exhibited a novel 244 kD protein band indicating chemical activity between collagen and corneal stromal components. (4) Laser welding corneal incisions was unsuccessful possibly due to shrinkage of the sides of the incision, lack of incision compression during heating, or a less than optimal combination of ICG concentration and radiant exposure. In summary, these experiments demonstrate the biochemical and morphological complexity of ICG-enhanced IR laser-tissue welding and the need for further investigation of laser welding mechanisms.

Near-Infrared Fluorescence Imaging of Liver Metastases in Rats using Indocyanine Green

PubMed Central

van der Vorst, Joost R.; Hutteman, Merlijn; Mieog, Sven D.; de Rooij, Karien E.; Kaijzel, Eric L.; Löwik, Clemens W.G.M.; Putter, Hein; Kuppen, Peter J.K.; Frangioni, John V.; van de Velde, Cornelis J.H.; Vahrmeijer, Alexander L.

2011-01-01

Background Near-infrared (NIR) fluorescence imaging using indocyanine green (ICG) is a promising technique to obtain real-time assessment of the extent and number of colorectal liver metastases during surgery. The current study aims to optimize dosage and timing of ICG administration. Materials and methods Liver tumors were induced in 18 male WAG/Rij rats by subcapsular inoculation of CC531 rat colorectal cancer cells into three distinct liver lobes. Rats were divided in 2 groups: imaging after 24 and 48 hours or 72 and 96 hours after intravenous ICG administration. In each time group, rats were allocated to three dose groups: 0.04, 0.08, or 0.16 mg ICG. Intraoperative imaging and ex vivo measurements were performed using Mini-FLARE™ and confirmed by fluorescence microscopy. Fluorescence intensity was quantified using the Mini-FLARE software and the difference between tumor signal and liver signal (tumor-to-liver ratio; TLR) was calculated. Results In all 18 rats, all colorectal liver metastases (N = 34), some as small as 1.2 mm, were identified using ICG and the Mini-FLARE™ imaging system. Average tumor-to-liver ratio (TLR) over all groups was 3.0 ± 1.2. TLR was significantly higher in the 72 h time group compared to other time points. ICG dose did not significantly influence TLR, but a trend was found favoring the 0.08 mg dose group. Fluorescence microscopy demonstrated a clear fluorescent rim around the tumor. Conclusions This study demonstrates that colorectal cancer liver metastases can be clearly identified during surgery using ICG and the Mini-FLARE™ imaging system, with optimal timing of 72 h post-injection and an optimal dose of 0.08 mg (0.25 mg/kg) ICG. NIR fluorescence imaging has the potential to improve intraoperative detection of micrometastases and thus the completeness of resection. PMID:21396660

Photothermal and photochemical effects of laser light absorption by indocyanine green (ICG)

NASA Astrophysics Data System (ADS)

Yaseen, Mohammad A.; Diagaradjane, Parmeswaran; Pikkula, Brian M.; Yu, Jie; Wong, Michael S.; Anvari, Bahman

2005-04-01

Indocyanine Green (ICG) is clinically used as a fluorescent dye for imaging purposes. Its rapid circulation kinetics and minimal toxicity has prompted investigation into ICG's utility as a photosentitizer for therapeutic applications. Traditionally, optically mediated tumor therapy has focused on photodynamic therapy, which employs a photochemical mechanism resulting from the absorption of low intensity CW laser light by localized photosensitizers such as Photofrin II, Benzoporphyrin Derivative (BPD), ICG. Treatment of cutaneous vascular malformations such as port-wine stains, on the other hand, is based on a photothermal mechanism resulting from the absorption of high intensity pulsed laser light by hemoglobin. In this study, we compared the effectiveness of combining photochemical and photothermal mechanisms during application of ICG in conjunction with laser irradiation with the intention that the combined approach may lead to a reduction in the threshold dose of pulsed laser light required to treat hypervascular malformations. The blood vessels in rabbit ears were used as an in vivo model for targeted vasculature. Irradiation of the ears with IR light (λ=785 nm, Δτ = 3 min, Io = 120 mW) was used to elicit photochemical damage, while photothermal damage was brought about using pulses from a ruby laser (λ=694 nm, τ = 3 ms) with different fluences. For the combined modality, photochemical damage was induced first and followed by photothermal irradiation. This modality was compared with photothermal irradiation alone. The effectiveness of each irradiation scheme was assessed using histopathological analysis. We present preliminary data that suggests that pretreatment with photodynamic therapy before photothermal coagulation results in more severe vascular damage with lower photothermal fluence levels. The results of this study provide the foundation work for further exploration of the therapeutic potentials of photochemical and photothermal effects during

Feasibility of real‐time near‐infrared indocyanine green fluorescence endoscopy for the evaluation of mucosal head and neck lesions

PubMed Central

Schmidt, Florian; Dittberner, Andreas; Koscielny, Sven; Petersen, Iver

2016-01-01

Abstract Background The purpose of this study was to explore the feasibility and potential drawbacks of near‐infrared (NIR) endoscopy with indocyanine green (ICG) to examine mucosal head and neck lesions. Methods NIR ICG endoscopy was applied to image head and neck cancer epithelium in vivo. The evaluation of the ICG videos was performed off‐line independently by 2 evaluators and blinded with respect to final histopathological results from biopsies taken as the gold standard. Results Forty percent of the lesions from 55 patients were histologically malignant. ICG positivity showed a sensitivity, specificity, and accuracy to be related to a malignant tumor of 90.5%, 90.9%, and 89.1%, respectively. The kappa index for the interobserver assessment showed a 94.4% agreement for the assessment of the ICG positivity. Side effects of the NIR ICG endoscopy did not arise. Conclusion NIR ICG endoscopy in patients with mucosal head and neck lesions was feasible and safe. It might help intraoperatively to differentiate benign from malignant lesions. © 2016 Wiley Periodicals, Inc. Head Neck 39: 234–240, 2017 PMID:27590351

Ultra-widefield imaging with autofluorescence and indocyanine green angiography in central serous chorioretinopathy.

PubMed

Pang, Claudine E; Shah, Vinnie P; Sarraf, David; Freund, K Bailey

2014-08-01

To describe the spectrum of ultra-widefield autofluorescence (AF) and indocyanine green (ICG) angiographic findings in central serous chorioretinopathy (CSC). Retrospective observational case series. In 37 patients, 65 eyes with CSC from 2 vitreoretinal clinical practices were imaged using ultra-widefield AF and 24 of these eyes with ultra-widefield ICG angiography. Images were correlated with clinical findings and spectral-domain optical coherence tomography (OCT). In 37 (57%) eyes, a variety of altered AF patterns, including gravitational tracts, extended beyond the posterior 50 degrees of retina. Hyper-AF corresponded to areas of subretinal fluid (SRF) on spectral-domain OCT and was found to persist in 44 (70%) eyes for up to 8 years despite resolution of SRF. These areas corresponded to outer retinal atrophy with viable retinal pigment epithelium (RPE) on spectral-domain OCT and may be explained by the unmasking of normal background RPE AF. Ultra-widefield ICG angiography revealed dilated choroidal vessels and choroidal hyperpermeability in areas corresponding to altered AF on ultra-widefield AF in all 24 eyes. In 20 (83.3%) eyes, dilated vessels were observed in association with 1 or more congested vortex veins ampullas, suggesting that outflow congestion may be a contributing factor to the pathogenesis of CSC. Ultra-widefield AF and ICG angiography in CSC revealed more widespread disease in a single image than with standard field imaging and may be useful for identifying peripheral areas of previous or ongoing SRF and choroidal hyperpermeability that can assist in the diagnosis of CSC, surveillance of recurrent disease and treatment of active disease. Copyright © 2014 Elsevier Inc. All rights reserved.

Mechanistic background and clinical applications of indocyanine green fluorescence imaging of hepatocellular carcinoma.

PubMed

Ishizawa, Takeaki; Masuda, Koichi; Urano, Yasuteru; Kawaguchi, Yoshikuni; Satou, Shouichi; Kaneko, Junichi; Hasegawa, Kiyoshi; Shibahara, Junji; Fukayama, Masashi; Tsuji, Shingo; Midorikawa, Yutaka; Aburatani, Hiroyuki; Kokudo, Norihiro

2014-02-01

Although clinical applications of intraoperative fluorescence imaging of liver cancer using indocyanine green (ICG) have begun, the mechanistic background of ICG accumulation in the cancerous tissues remains unclear. In 170 patients with hepatocellular carcinoma cells (HCC), the liver surfaces and resected specimens were intraoperatively examined by using a near-infrared fluorescence imaging system after preoperative administration of ICG (0.5 mg/kg i.v.). Microscopic examinations, gene expression profile analysis, and immunohistochemical staining were performed for HCCs, which showed ICG fluorescence in the cancerous tissues (cancerous-type fluorescence), and HCCs showed fluorescence only in the surrounding non-cancerous liver parenchyma (rim-type fluorescence). ICG fluorescence imaging enabled identification of 273 of 276 (99%) HCCs in the resected specimens. HCCs showed that cancerous-type fluorescence was associated with higher cancer cell differentiation as compared with rim-type HCCs (P < 0.001). Fluorescence microscopy identified the presence of ICG in the canalicular side of the cancer cell cytoplasm, and pseudoglands of the HCCs showed a cancerous-type fluorescence pattern. The ratio of the gene and protein expression levels in the cancerous to non-cancerous tissues for Na(+)/taurocholate cotransporting polypeptide (NTCP) and organic anion-transporting polypeptide 8 (OATP8), which are associated with portal uptake of ICG by hepatocytes that tended to be higher in the HCCs that showed cancerous-type fluorescence than in those that showed rim-type fluorescence. Preserved portal uptake of ICG in differentiated HCC cells by NTCP and OATP8 with concomitant biliary excretion disorders causes accumulation of ICG in the cancerous tissues after preoperative intravenous administration. This enables highly sensitive identification of HCC by intraoperative ICG fluorescence imaging.

Intraoperative Identification of a Normal Pituitary Gland and an Adenoma Using Near-Infrared Fluorescence Imaging and Low-Dose Indocyanine Green.

PubMed

Verstegen, Marco J T; Tummers, Quirijn R J G; Schutte, Pieter J; Pereira, Alberto M; van Furth, Wouter R; van de Velde, Cornelis J H; Malessy, Martijn J A; Vahrmeijer, Alexander L

2016-09-01

The intraoperative distinction between normal and abnormal pituitary tissue is crucial during pituitary adenoma surgery to obtain a complete tumor resection while preserving endocrine function. Near-infrared (NIR) fluorescence imaging is a technique to intraoperatively visualize tumors by using indocyanine green (ICG), a contrast agent allowing visualization of differences in tissue vascularization. Although NIR fluorescence imaging has been described in pituitary surgery, it has, in contrast to other surgical areas, never become widely used. To evaluate NIR fluorescence imaging in pituitary surgery, both qualitatively and quantitatively, and to assess the additional value of resecting adenoma tissue under NIR fluorescence guidance. We included 10 patients planned to undergo transnasal transsphenoidal selective adenomectomy. Patients received multiple intravenous administrations of 5 mg ICG, up to a maximum of 15 mg per patient. Endoscopic NIR fluorescence imaging was performed at multiple points in time. The NIR fluorescent signal in both the adenoma and pituitary gland was obtained, and the fluorescence contrast ratio was assessed. Four patients had Cushing disease, 1 had acromegaly, and 1 had a prolactinoma. Four patients had a nonfunctioning macroadenoma. In 9 of 10 patients with a histologically proven pituitary adenoma, the normal pituitary gland showed a stronger fluorescent signal than the adenoma. A fluorescence contrast ratio of normal pituitary gland to adenoma of 1.5 ± 0.2 was obtained. In 2 patients; adenoma resection was actually performed under NIR fluorescence guidance instead of under white light. NIR fluorescence imaging can easily and safely be implemented in pituitary surgery. The timing of ICG administration is important for optimal results and warrants further study. It appears that injection of ICG can best be postponed until some part of the normal pituitary gland is identified. Subsequent repeated low-dose ICG administrations improved the

Intraoperative indocyanine green videoangiography for identification of pituitary adenomas using a microscopic transsphenoidal approach.

PubMed

Sandow, N; Klene, W; Elbelt, U; Strasburger, C J; Vajkoczy, P

2015-10-01

Initial successful surgical treatment of pituitary adenomas is crucial to reach long-term remission. Indocyanine green (ICG) videoangiography (VA) is well established in vascular neurosurgery nowadays and several reports described ICG application in brain tumor surgery. We designed this study to evaluate the feasibility of intravenous application of ICG and visualisation of a pituitary lesion via the fluorescence mode of the operation microscope. 22 patients with pituitary adenomas were treated with transsphenoidal microsurgery and were included in this study. Intraoperatively 25 mg ICG was administered intravenously and visualized via the fluorescence mode of the operation microscope (Pentero/Zeiss). 22 patients qualified for transsphenoidal surgery presenting with different clinical symptoms (13 patients with acromegaly, 6 with M. Cushing and 3 with other symptoms like vision disorder or dizziness) and identification of a pituitary lesion (21 of 22 patients) in preoperative MR-imaging (mean diameter: 9 mm; SD 3.6; 6 macroadenomas, 15 microadenomas, 1 MR-negative). In all 22 patients ICG VA was performed during surgery. No technical failures or adverse events after drug administration occurred. Visualization was optimal approximately 2.4 min after intravenous application. In all patients the adenoma could be detected via two different types of visualization: direct visualization by fluorophore emission versus indirect detection of the adenoma by a lower ICG fluorescence compared to the surrounding tissue. Our data show that intraoperative ICG VA can be a useful and easily applicable additional diagnostic tool for visualization of pituitary lesions using the microscopic approach.

Transdural Indocyanine Green Videography for Superficial Temporal Artery-to-Middle Cerebral Artery Bypass-Technical Note.

PubMed

Yokota, Hiroshi; Yonezawa, Taiji; Yamada, Tomonori; Miyamae, Seisuke; Kim, Taekyun; Takamura, Yoshiaki; Masui, Katsuya; Aketa, Shuta

2017-10-01

Neurosurgical application of indocyanine green (ICG) videography before performing a dural opening, known as transdural ICG videography, has been used during surgery of meningiomas associated with venous sinuses as well as cranial and spinal arteriovenous malformations. However, its use for a superficial temporal artery (STA)-to-middle cerebral artery (MCA) bypass has not been reported. We performed a retrospective analysis of medical records of patients who underwent transdural ICG videography during STA-MCA bypass performed between January 2012 and March 2015. The primary outcome was visualization of recipient cortical arteries; secondary outcomes were surgical modifications and complications as well as any adverse events associated with transdural ICG videography. We analyzed 29 STA-MCA bypass procedures performed in 30 hemispheres with atherosclerotic steno-occlusive disease and found that the proper recipient was identified in 28 hemispheres. Subsequently modified procedures for those were a tailored dural incision and craniotomy correction. No complications associated with ICG administration were encountered; during the postoperative course, transient aphasia was noted in 1 case, chronic subdural hematoma was noted in 1 case, and subdural effusion was noted in 2 cases. Transdural ICG videography for atherosclerotic steno-occlusive disease facilitates modifications during STA-MCA bypass procedures. Recognition of the proper recipient cortical arteries before a dural incision allows the neurosurgeon to perform a tailored dural incision and extension of the bone window, although the contribution to surgical outcome has yet to be determined. Copyright © 2017 Elsevier Inc. All rights reserved.

The use of intraoperative near-infrared indocyanine green videoangiography in the microscopic resection of hemangioblastomas.

PubMed

Tamura, Yoji; Hirota, Yuki; Miyata, Shiro; Yamada, Yoshitaka; Tucker, Adam; Kuroiwa, Toshihiko

2012-08-01

The authors assessed the usefulness of intraoperative near-infrared indocyanine green videoangiography (ICG-VA) in the microscopic resection of hemangioblastomas. From January 2009 to February 2012, nine consecutive patients (seven men, two women) who underwent surgery for hemangioblastomas using intraoperative ICG-VA were included in this study. Surgery was performed on four cystic cerebellar lesions with mural nodules, two solid tumors (one in the cerebellar hemisphere and one in the medulla oblongata), one spinal tumor and multiple tumors in two patients with von Hippel-Lindau disease. Of the nine patients, three were treated for recurrent tumor. The ICG-induced fluorescence images of hemangioblastomas with variable presentation were evaluated. All tumors could be completely removed en bloc. Blood flow in the tumor and tumor-related vessels at the brain surface were clearly detected by ICG-VA in all cases, except one recurrent tumor where postoperative adhesive scar tissue obstructed ICG-induced fluorescence resulting in poor delineation of the blood flow patterns and tumor margins. ICG-VA was also helpful for detecting the multiple small mural nodules within the cyst or the tumors buried under thin gliotic neural tissue despite reduced fluorescence. Intraoperative ICG-VA is a safe and easy modality for confirming the vascular flow patterns in hemangioblastomas. In addition, ICG-VA provided useful information for intracystic small lesions or lesions concealed under thin brain tissue in order to accomplish total resection of these tumors.

Observation of chest tumor using diffuse optical spectroscopy: time-varying Indocyanine green concentration in rabbit model

NASA Astrophysics Data System (ADS)

Kim, Yikeun; Kim, Sehun; Kim, Sungwon; Lee, Haeyoung; Oak, Chulho; Ahn, Yeh-Chan

2017-02-01

This experiment was conducted by using the diffuse optical spectroscopy based on near-infrared light. The near-infrared light in the water window was used to see the change of molecular concentration in the living tissue. The experiment subject was New Zealand rabbits weighing 3 +/- 0.3 kg. VX2 tumor cells were injected into the inside of the chest wall of rabbits. The concentration of indocyanine green (ICG) has been observed once every three days, after the size of the pleural tumor grew up over 1cm. We used five different wavelengths (732, 758, 805, 840, and 880 nm) with known ICG spectrum. The distance between light source and detector probes was fixed by 1 cm. The probes were placed on the skin right above the tumor with an aid of laparoscope. ICG was injected into rabbits via ear vein. The diffused light was measured through the tumor with time course using a spectrometer. These measured data enabled us to observe the change of ICG concentration in real time with respect to the baseline without ICG. ICG was present longer in tumor compared to normal tissue. This phenomenon is thought to be due to the excessive angiogenesis in the tumor tissue. Since this method can be applied to other cases easily, it is thought that there is a possibility of cancer screening with less cost and simple equipment.

Detection of posterior vortex veins in eyes with pathologic myopia by ultra-widefield indocyanine green angiography.

PubMed

Moriyama, Muka; Cao, Kejia; Ogata, Satoko; Ohno-Matsui, Kyoko

2017-09-01

To analyse the characteristics of posterior vortex veins detected in highly myopic eyes by wide-field indocyanine green angiography (ICGA). One hundred and fifty-eight consecutive patients (302 eyes) with high myopia (myopic refractive error >8.0 dioptres (D) or axial length ≥26.5 mm) were studied. Wide-field ICGA was performed with the Spectralis HRA module. Posterior vortex veins were found in 80 eyes (26%). The prevalence of posterior staphyloma was significantly higher in eyes in which posterior vortex vein was detected than in eyes without posterior vortex vein. The posterior vortex veins were classified into five types according to the site of exit from the eye; around the optic nerve in 28%, in the macular area in 17%, along the border of staphyloma in 6%, along the margin of macular atrophy or large peripapillary conus in 21%, and elsewhere in 28%. In one eye, two posterior vortex veins collected the choroidal venous blood from the entire fundus. Wide-field ICGA can analyse the characteristic features of choroidal blood outflow system through posterior vortex veins in highly myopic eyes. They may play an important role as routes of choroidal outflow in highly myopic eyes. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Establishment of novel detection system for embryonic stem cell-derived hepatocyte-like cells based on nongenetic manipulation with indocyanine green.

PubMed

Yoshie, Susumu; Ito, Jun; Shirasawa, Sakiko; Yokoyama, Tadayuki; Fujimura, Yuu; Takeda, Kazuo; Mizuguchi, Masahiro; Matsumoto, Ken; Tomotsune, Daihachiro; Sasaki, Katsunori

2012-01-01

Hepatocytes derived from embryonic stem cells (ESCs) are expected to be useful for basic research and clinical applications. However, in several studies, genetic methods used to detect and obtain them are difficult and pose major safety problems. Therefore, in this study, we established a novel detection system for hepatocytes by using indocyanine green (ICG), which is selectively taken up by hepatocytes, based on nongenetic manipulation. ICG has maximum light absorption near 780 nm, and it fluoresces between 800 and 900 nm. Making use of these properties, we developed flow cytometry equipped with an excitation lazer of 785 nm and specific bandpass filters and successfully detected ESC-derived ICG-positive cells that were periodic acid-Schiff positive and expressed hepatocyte phenotypic mRNAs. These results demonstrate that this detection system based on nongenetic manipulation with ICG will lead to isolate hepatocytes generated from ESCs and provide the appropriate levels of stability, quality, and safety required for cell source for cell-based therapy and pharmaceutical studies such as toxicology.

Effects of nanoencapsulation and PEGylation on biodistribution of indocyanine green in healthy mice: quantitative fluorescence imaging and analysis of organs

PubMed Central

Bahmani, Baharak; Lytle, Christian Y; Walker, Ameae M; Gupta, Sharad; Vullev, Valentine I; Anvari, Bahman

2013-01-01

Near-infrared nanoconstructs present a potentially effective platform for site-specific and deep tissue optical imaging and phototherapy. We have engineered a polymeric nanocapsule composed of polyallylamine hydrochloride (PAH) chains cross-linked with sodium phosphate and doped with indocyanine green (ICG) toward such endeavors. The ICG-doped nanocapsules were coated covalently with polyethylene glycol (5000 daltons) through reductive amination. We administrated the constructs by tail vein injection to healthy mice. To characterize the biodistribution of the constructs, we performed in vivo quantitative fluorescence imaging and subsequently analyzed the various extracted organs. Our results suggest that encapsulation of ICG in these PEGylated constructs is an effective approach to prolong the circulation time of ICG and delay its hepatic accumulation. Increased bioavailability of ICG, due to encapsulation, offers the potential of extending the clinical applications of ICG, which are currently limited due to rapid elimination of ICG from the vasculature. Our results also indicate that PAH and ICG-doped nanocapsules (ICG-NCs) are not cytotoxic at the levels used in this study. PMID:23637530

Laparoscopic Sentinel Node Mapping in Endometrial Cancer After Hysteroscopic Injection of Indocyanine Green.

PubMed

Martinelli, Fabio; Ditto, Antonino; Bogani, Giorgio; Signorelli, Mauro; Chiappa, Valentina; Lorusso, Domenica; Haeusler, Edward; Raspagliesi, Francesco

2017-01-01

To report the detection rate (DR) of sentinel lymph nodes (SLNs) in endometrial cancer (EC) patients after hysteroscopic injection of indocyanine green (ICG) and laparoscopic near-infrared (L-NIR) fluorescence mapping. Prospectively collected data (Canadian Task Force classification II-2). Gynecologic oncology referral center. Consecutive patients with apparent early-stage endometrioid EC scheduled for surgical treatment: total laparoscopic hysterectomy, bilateral salpingo-oophorectomy, SLN mapping. The mapping technique consisted in an intraoperative hysteroscopic peritumoral injection of 5 mg ICG followed by L-NIR fluorescence mapping. Evaluations of the SLN DR and sites of mapping were performed. A total of 57 procedures was performed. Patient mean age was 60 years (range, 28-80) and mean body mass index was 28.2 kg/m 2 (range, 19-43). At least 1 SLN was detected in 89.5% of the whole population (51/57). After the first 16 cases, L-NIR camera technical improvement led to a 95% DR (39/41). The mean number of harvested SLNs was 4.1 (range. 1-8), and in 47% of cases SLNs mapped to aortic nodes (24/51). Bilateral pelvic mapping was found in 74.5% of cases (38/51). Three patients had SLN metastases: 1 in the pelvic area only, 1 both in the pelvic and aortic area, and 1 presented with 2 metastatic aortic SLNs with negative pelvic SLNs. Overall, 2 of 3 node-positive patients (67%) had aortic SLN involvement. No adverse events were reported. Laparoscopic SLN mapping after the hysteroscopic injection of ICG has comparable DRs with both radioactive tracer series and ICG series with cervical injection, overcoming the need for radioactive substances. Hysteroscopic injection leads to a higher mapping in the aortic area compared with cervical injection. Further investigation is warranted on this topic. Copyright © 2016 AAGL. Published by Elsevier Inc. All rights reserved.

Novel use of indocyanine green for intraoperative, real-time localization of ureteral stenosis during robot-assisted ureteroureterostomy.

PubMed

Lee, Ziho; Simhan, Jay; Parker, Daniel C; Reilly, Christopher; Llukani, Elton; Lee, David I; Mydlo, Jack H; Eun, Daniel D

2013-09-01

To present a novel method to intraoperatively localize ureteral strictures during robot-assisted ureteroureterostomy via indocyanine green (ICG) visualization under near-infrared (NIR) light. Seven patients underwent robot-assisted ureteroureterostomy for ureteral stricture by a single surgeon (D.D.E.). Intraoperative localization of ureteral stricture involved instilling ICG (25 mg in 10 mL distilled water) above and below the level of stenosis through a ureteral catheter or a percutaneous nephrostomy tube, or both. The fluorescent tracer was detected as a green color using the NIR modality on the da Vinci Si (Intuitive Surgical, Sunnyvale, CA). All patients consented to off-label use of ICG after full disclosure. Intraoperative ICG injection and visualization under NIR light assisted in the performance of a tension-free anastomosis in all patients. At the time of surgery, mean age was 55.7 ± 12.4 years and mean body mass index was 30.3 ± 5.8 kg/m(2). Mean operative time was 171.3 ± 52.4 minutes, mean estimated blood loss was 175.0 ± 146.5 mL, and mean length of ureteral excision on pathologic analysis was 1.6 ± 0.7 cm. There were no immediate or delayed adverse effects attributable to intraureteral ICG administration. Mean hospital length of stay was 1.6 ± 1.5 days, with no postoperative complications. Mean follow-up was 5.9 ± 1.5 months, and all cases were clinically and radiographically successful at last follow-up. Intraureteral injection of ICG with visualization under NIR light allows for real-time delineation of the ureter. Additionally, ICG administration aids in discerning healthy ureter from diseased tissue, further assisting successful robotic ureteral repair. Copyright © 2013 Elsevier Inc. All rights reserved.

Efficiency of photodynamic therapy using indocyanine green and infrared light on MCF-7 breast cancer cells in vitro

NASA Astrophysics Data System (ADS)

Ruhi, Mustafa K.; Ak, Ayşe.; Gülsoy, Murat

2016-03-01

Cancer is one of the main reasons of death in all around the world. The main treatments of cancer include surgical intervention, radiation therapy and chemotherapy. These treatments can be applied separately or in a combined manner. Another therapeutic method that is still being researched and recently has started to be used in clinical applications is Photodynamic Therapy (PDT). Most photosensitizers currently being investigated are sensitive to red light. However, it is known that infrared light has a better penetration into the skin or tissue. Indocyanine Green (ICG), which is used in this study, is sensitive to infrared light. The aim of this in vitro study is to investigate the effect of PDT on breast cancer cells by using different doses of ICG and infrared light irradiation. 25, 50 and 100 μM ICG concentrations and 25 and 50 J/cm2 laser energy doses were applied to MCF-7 cell lines. MTT analyses were performed on 24, 48 and 72 hours following the treatments. As a result, inhibition of cell viability was observed in a time and dose dependent manner. It can be concluded that ICG-PDT application is a good alternative to conventional radiation therapy and chemotherapy for breast cancer treatment.

Indocyanine Green Videoangiography Transoptic Visualization and Clipping Confirmation of an Optic Splitting Ophthalmic Artery Aneurysm.

PubMed

Rustemi, Oriela; Cester, Giacomo; Causin, Francesco; Scienza, Renato; Della Puppa, Alessandro

2016-06-01

Ophthalmic artery aneurysms with medial and superior projection in exceptionally rare cases can split the optic nerve. Treatment of these aneurysms is challenging, because the aneurysm dome is hidden from the optic nerve, rendering its visualization and clipping confirmation difficult. In addition, optic nerve function should be preserved during surgical maneuvers. Preoperative detection of this growing feature is usually missing. We illustrate the first case of indocyanine green videoangiography (ICG-VA) application in an optic penetrating ophthalmic artery aneurysm treatment. A 57-year-old woman presented with temporal hemianopsia, slight right visual acuity deficit, and new onset of headache. The cerebral angiography detected a right ophthalmic artery aneurysm medially and superiorly projecting. The A1 tract of the ipsilateral anterior cerebral artery was elevated and curved, being suspicious for an under optic aneurysm growth. Surgery was performed. Initially the aneurysm was not visible. ICG-VA permitted the transoptic aneurysm visualization. After optic canal opening, the aneurysm was clipped and transoptic ICG-VA confirmed the aneurysm occlusion. ICG-VA showed also the slight improvement of the optic nerve pial vascularization. Postoperatively, the visual acuity was 10/10 and the hemianopsia did not worsen. The elevation and curve of the A1 tract in medially and superiorly projecting ophthalmic aneurysms may be an indirect sign of under optic growth, or optic splitting aneurysms. ICG-VA transoptic aneurysm detection and occlusion confirmation reduces the surgical maneuvers on the optic nerve, contributing to function preservation. Copyright © 2016 Elsevier Inc. All rights reserved.

Use of invisible near infrared light fluorescence with indocyanine green and methylene blue in urology. Part 2.

PubMed

Polom, Wojciech; Markuszewski, Marcin; Rho, Young Soo; Matuszewski, Marcin

2014-01-01

In the second part of this paper, concerning the use of invisible near infrared light (NIR) fluorescence with indocyanine green (ICG) and methylene blue (MB) in urology, other possible uses of this new technique will be presented. In kidney transplantation, this concerns allograft perfusion and real time NIR-guided angiography; moreover, perfusion angiography of tissue flaps, NIRF visualization of ureters, NIR-guided visualization of urinary calcifications, NIRF in male infertility and semen quality assessment. In this part, we have also analysed cancer targeting and imaging fluorophores as well as cost benefits associated with the use of these new techniques. PubMed and Medline databases were searched for ICG and MB use in urological settings, along with data published in abstracts of urological conferences. Although NIR-guided ICG and MB are still in their initial phases, there have been significant developments in a few more major domains of urology, including 1) kidney transplantation: kidney allograft perfusion and vessel reconstruction; 2) angiography perfusion of tissue flaps; 3) visualization of ureters; 4) visualization of urinary calcifications; and 5) NIRF in male infertility and semen quality assessment. Near infrared technology in urology is at its early stages. More studies are needed to assess the true potential and limitations of the technology. Initial studies show that this pioneering tool may influence various aspects of urology.

Early ovarian cancer surgery with indocyanine-green-guided targeted compartmental lymphadenectomy (TCL, pelvic part).

PubMed

Kimmig, Rainer; Buderath, Paul; Rusch, Peter; Mach, Pawel; Aktas, Bahriye

2017-09-01

Para-aortic indocyanine-green (ICG)-guided targeted compartmental lymphadenectomy is feasible in early ovarian cancer; systematic pelvic and para-aortic lymphadenectomy could potentially be avoided if thoroughly investigated sentinel nodes could predict whether residual nodes will be involved or free of disease. In contrast to advanced ovarian cancer, where the therapeutic potential of lymphadenectomy will soon be clarified by the results of the Arbeitsgemeinschaft Gynäkologische Onkologie lymphadenectomy in ovarian neoplasms (AGO LION) trial, systematic lymphadenectomy seems to be mandatory for diagnostic and also therapeutic purposes in early ovarian cancer. Sentinel node biopsy or resection of the regional lymphatic network may reduce morbidity compared to systematic lymphadenectomy as shown already for other entities. Apart from the ovarian mesonephric pathway, a second Müllerian uterine pathway exists for lymphatic drainage of the ovary. Lymphatic valves apparently do not exist at this level of the utero-ovarian network since injection of radioactivity into the ovarian ligaments also labelled pelvic nodes. We applied ICG using 4×0.5 mL of a 1.66 mg/mL ICG solution for transcervical injection into the fundal and midcorporal myometrium at each side [10] instead of injection into the infundibulopelvic ligament, since the utero-ovarian drainage was intact. In this case a 1.8 cm cancer of the right ovary was removed in continuity with its draining lymphatic vessels and at least the first 2 sentinel nodes in each channel "en bloc" as shown in this video for the pelvic part, consistent with the loco-regional ontogenetic approach. This could potentially avoid most of systematic lymphadenectomies in early ovarian cancer. Copyright © 2017. Asian Society of Gynecologic Oncology, Korean Society of Gynecologic Oncology

Perioperative Non-Invasive Indocyanine Green-Clearance Testing to Predict Postoperative Outcome after Liver Resection

PubMed Central

Haegele, Stefanie; Reiter, Silvia; Wanek, David; Offensperger, Florian; Pereyra, David; Stremitzer, Stefan; Fleischmann, Edith; Brostjan, Christine; Gruenberger, Thomas; Starlinger, Patrick

2016-01-01

Background Postoperative liver dysfunction may lead to morbidity and mortality after liver resection. Preoperative liver function assessment is critical to identify preexisting liver dysfunction in patients prior to resection. The aim of this study was to evaluate the predictive potential of perioperative indocyanine green (ICG)-clearance testing to prevent postoperative liver dysfunction and morbidity using standardized outcome parameters in a routine Western-clinical-setting. Study Design 137 patients undergoing partial hepatectomy between 2011 and 2013, at the general hospital of Vienna, were included. ICG-clearance was recorded one day prior to surgery as well as on the first and fifth postoperative day. Postoperative liver dysfunction was defined according to the International Study Group of Liver Surgery and evaluation of morbidity was based on the Dindo-Clavien classification. Statistical analyses were based on non-parametric tests. Results Preoperative reduced ICG—plasma disappearance rate (PDR) as well as increased ICG—retention rate at 15 min (R15) were able to significantly predict postoperative liver dysfunction (Area under the curve = PDR: 0.716, P = 0.018; R15: 0.719, P = 0.016). Furthermore, PDR <17%/min. or R15 >8%, were able to accurately predict postoperative complications prior to surgery. In addition to this, ICG-clearance on postoperative day 1 comparably predicted postoperative liver dysfunction (Area under the curve = PDR: 0.895; R15: 0.893; both P <0.001), specifically, PDR <10%/min or R15 >20% on postoperative day 1 predicted poor postoperative outcome. Conclusion PDR and R15 may represent useful parameters to distinguish preoperative high and low risk patients in a Western collective as well as on postoperative day 1, to identify patients who require closer monitoring for potential complications. PMID:27812143

Overcoming photodynamic resistance and tumor targeting dual-therapy mediated by indocyanine green conjugated gold nanospheres.

PubMed

Li, Wei; Guo, Xiaomeng; Kong, Fenfen; Zhang, Hanbo; Luo, Lihua; Li, Qingpo; Zhu, Chunqi; Yang, Jie; Du, Yongzhong; You, Jian

2017-07-28

Photodynamic therapy (PDT) and photothermal therapy (PTT) have captured much attention due to the great potential to cure malignant tumor. Nevertheless, photodynamic resistance of cancer cells has limited the further efficacy of PDT. Unfortunately, the resistance mechanism and efforts to overcome the resistance still have been rarely reported so far. Here, we report a nanosystem with specific tumor targeting for combined PDT and PTT mediated by near-infrared (NIR) light, which was established by covalently conjugating indocyanine green (ICG) and TNYL peptide onto the surface of hollow gold nanospheres (HAuNS). Our nanosystem (TNYL-ICG-HAuNS) was proved to possess significantly increased light stability, reactive oxygen species (ROS) production and photothermal effect under NIR light irradiation, thus presenting a remarkably enhanced antitumor efficacy. The up-regulation of nuclear factor erythroid 2-related factor 2 (NFE2L2, Nrf2) in cancer cells during PDT induced a significant increase of ABCG2, NQO-1 and HIF-1α expression, causing PDT resistance of the cells. Interestingly, ABCG2 expression could almost keep a normal level in the whole PDT process mediated by TNYL-ICG-HAuNS. After repeated irradiations, TNYL-ICG-HAuNS could still produce almost constant ROS in cells while the Nrf2 expression reduced significantly. Furthermore, PDT resistance induced an obvious decrease of the internalization of free ICG, but didn't influence the cell uptake of TNYL-ICG-HAuNS. Our data explained that TNYL-ICG-HAuNS could overcome the photodynamic resistance of cancer cells, acting as a promising modality for simultaneous photothermal and photodynamic cancer therapy. Copyright © 2017 Elsevier B.V. All rights reserved.

An initial report on the intraoperative use of indocyanine green fluorescence imaging in the surgical management of liver tumorss.

PubMed

Takahashi, Hideo; Zaidi, Nisar; Berber, Eren

2016-10-01

There has been a recent interest in the use of Indocyanine green (ICG) imaging. The aim of this study is to review our initial experience in liver surgery. ICG fluorescent imaging was used in 15 patients undergoing surgical treatment of their liver tumors between 2015 and 2016. ICG imaging was initially performed, followed by intraoperative ultrasound (IOUS). Findings on fluorescence were compared with preoperative cross-sectional imaging and IOUS. Sixty-two lesions were identified, with 34 located superficially and 28 deeply in the liver. While 13 patients underwent surgery for malignant liver metastases, two patients had operations for benign liver diseases. Seven patients underwent open or robotic liver resections, five laparoscopic microwave liver ablation, and three diagnostic laparoscopy. ICG identified all of the superficial lesions. IOUS identified 98% of all lesions. The most benefit of ICG was in showing the margins of the superficial lesions in real-time and guiding surgical treatment, which was limited by IOUS. This is the first North American study to evaluate the potential utility of ICG during liver surgery. Its major benefit seems to be in providing real-time feedback to the surgeon about the margins of superficial tumors for resection or ablation. J. Surg. Oncol. 2016;114:625-629. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

The efficacy of sentinel lymph node mapping with indocyanine green in cervical cancer.

PubMed

Kim, Ju-Hyun; Kim, Dae-Yeon; Suh, Dae-Shik; Kim, Jong-Hyeok; Kim, Yong-Man; Kim, Young-Tak; Nam, Joo-Hyun

2018-03-09

Lymph node metastasis is a significant predictive factor for disease recurrence and survival in cervical cancer patients. Given the importance of lymph node metastasis, it is imperative that patients harboring metastasis are identified and can undergo appropriate treatment. Sentinel lymph node (SLN) mapping has drawn attention as a lymph node mapping technique. We evaluated the feasibility and efficacy of (SLN) mapping using indocyanine green (ICG) in cervical cancer. We performed a single-center, retrospective study of 103 surgically treated cervical cancer patients who underwent SLN mapping. After using ICG to detect SLN during surgery, we removed the SLNs followed by laparoscopic or robotic-assisted radical surgery and bilateral pelvic lymphadenectomy. Stage IB1 was the most common (61.17%). At least one SLN was detected in all cases. Eighty-eight patients (85.44%) had bilateral pelvic SLNs. The mean number of SLN per patient was 2.34. The side-specific sensitivity was 71.43%, the specificity was 100%, the negative predictive value (NPV) was 93.98%, and the false negative rate (FNR) was 28.57%. In cases of tumors smaller than 2 cm with negative lymph node metastasis on imaging, the study revealed a side-specific sensitivity of 100%, a specificity of 100%, a NPV of 100%, and a FNR of 0%. Large tumor size (≥ 4 cm), a previous history of a loop electrosurgical excision procedure (LEEP), depth of invasion (≥ 50%), the microscopic parametrial (PM) invasion, and vaginal extension were significantly associated with the false-negative detection of SLN. Moreover, the microscopic PM invasion was the only risk factor of the false-negative detection of SLN in multivariate analysis. SLN mapping with ICG in cervical cancer is feasible and has high detection rate. The sensitivity of 100% was high enough to perform SLN biopsy alone in an early stage in which the tumor is less than 2 cm, with no lymphadenopathy on image examination. However, for large or invasive

Preparation study of indocyanine green-rituximab: A new receptor-targeted tracer for sentinel lymph node in breast cancer

PubMed Central

Cong, Bin-Bin; Sun, Xiao; Song, Xian-Rang; Liu, Yan-Bing; Zhao, Tong; Cao, Xiao-Shan; Qiu, Peng-Fei; Tian, Chong-Lin

2016-01-01

An appropriate receptor-targeted tracer for sentinel lymph node biopsy (SLNB) was prepared. We combined the fluorescence tracer (Indocyanine green, ICG) with Rituximab (a chimeric human/murine monoclonal antibody targeting the CD20 antigen on the surface of lymphocyte) directly to produce a new tracer (ICG-Rituximab). When the new tracer drains to the lymph node, Rituximab will combine with CD20 receptor on the B-cell surface in the lymph node. If the statue of antibody-receptor connection does not reach saturation, the number of Rituximab is less than CD20. With this appropriate injection dose, the new tracer could only stay in sentinel lymph node (SLN) and make it imaging. Positive fluorescence SLN was detected 12 minutes after injection with no other organs imaging. The imaging of SLN was stable and clear for 20–24 hours. Due to SLN stained with more ICG than the lymphatic vessel, the fluorescence situation of SLN would be brighter than the vessel. The surgeon can detect the positive fluorescence SLN easily without following the fluorescence imaging lymphatic vessel. The results of our preliminary study showed that the new tracer might be useful for improving SLN imaging and worth further clinical study. SLNB with the new tracer could be a convenient method for detecting SLN and would become a standard performance in clinical practice. PMID:27374088

Preparation study of indocyanine green-rituximab: A new receptor-targeted tracer for sentinel lymph node in breast cancer.

PubMed

Cong, Bin-Bin; Sun, Xiao; Song, Xian-Rang; Liu, Yan-Bing; Zhao, Tong; Cao, Xiao-Shan; Qiu, Peng-Fei; Tian, Chong-Lin; Yu, Jin-Ming; Wang, Yong-Sheng

2016-07-26

An appropriate receptor-targeted tracer for sentinel lymph node biopsy (SLNB) was prepared. We combined the fluorescence tracer (Indocyanine green, ICG) with Rituximab (a chimeric human/murine monoclonal antibody targeting the CD20 antigen on the surface of lymphocyte) directly to produce a new tracer (ICG-Rituximab). When the new tracer drains to the lymph node, Rituximab will combine with CD20 receptor on the B-cell surface in the lymph node. If the statue of antibody-receptor connection does not reach saturation, the number of Rituximab is less than CD20. With this appropriate injection dose, the new tracer could only stay in sentinel lymph node (SLN) and make it imaging. Positive fluorescence SLN was detected 12 minutes after injection with no other organs imaging. The imaging of SLN was stable and clear for 20-24 hours. Due to SLN stained with more ICG than the lymphatic vessel, the fluorescence situation of SLN would be brighter than the vessel. The surgeon can detect the positive fluorescence SLN easily without following the fluorescence imaging lymphatic vessel. The results of our preliminary study showed that the new tracer might be useful for improving SLN imaging and worth further clinical study. SLNB with the new tracer could be a convenient method for detecting SLN and would become a standard performance in clinical practice.

Co-registered photoacoustic and fluorescent imaging of a switchable nanoprobe based on J-aggregates of indocyanine green

NASA Astrophysics Data System (ADS)

Dumani, Diego S.; Brecht, Hans-Peter; Ivanov, Vassili; Deschner, Ryan; Harris, Justin T.; Homan, Kimberly A.; Cook, Jason R.; Emelianov, Stanislav Y.; Ermilov, Sergey A.

2018-02-01

We introduce a preclinical imaging platform - a 3D photoacoustic/fluorescence tomography (PAFT) instrument augmented with an environmentally responsive dual-contrast biocompatible nanoprobe. The PAFT instrument was designed for simultaneous acquisition of photoacoustic and fluorescence orthogonal projections at each rotational position of a biological object, enabling direct co-registration of the two imaging modalities. The nanoprobe was based on liposomes loaded with J-aggregates of indocyanine green (PAtrace). Once PAtrace interacts with the environment, a transition from J-aggregate to monomeric ICG is induced. The subsequent recovery of monomeric ICG is characterized by dramatic changes in the optical absorption spectrum and reinstated fluorescence. In the activated state, PAtrace can be simultaneously detected by both imaging modes of the PAFT instrument using 780 nm excitation and fluorescence detection at 810 nm. The fluorescence imaging component is used to boost detection sensitivity by providing lowresolution map of activated nanoprobes, which are then more precisely mapped in 3D by the photoacoustic imaging component. Activated vs non-activated particles can be distinguished based on their different optical absorption peaks, removing the requirements for complex image registration between reference and detection scans. Preliminary phantom and in vivo animal imaging results showed successful activation and visualization of PAtrace with high sensitivity and resolution. The proposed PAFT-PAtrace imaging platform could be used in various functional and molecular imaging applications including multi-point in vivo assessment of early metastasis.

Intestinal blood flow assessment by indocyanine green fluorescence imaging in a patient with the incarcerated umbilical hernia: Report of a case.

PubMed

Ryu, Shunjin; Yoshida, Masashi; Ohdaira, Hironori; Tsutsui, Nobuhiro; Suzuki, Norihiko; Ito, Eisaku; Nakajima, Keigo; Yanagisawa, Satoru; Kitajima, Masaki; Suzuki, Yutaka

2016-06-01

After reduction of the incarceration during surgery for incarcerated hernia, intestinal blood flow (IBF) and the need for bowel resection must be evaluated. We report the case of a patient with incarcerated umbilical hernia in whom the bowel was preserved after evaluating IBF using indocyanine green (ICG) fluorescence. A woman in her 40s with a chief complaint of abdominal pain visited our hospital, was diagnosed with incarcerated umbilical hernia and underwent surgery. Laparotomy was performed to reduce bowel incarceration. After reducing the incarceration, IBF was observed using ICG fluorescence detected using a brightfield full-color fluorescence camera. The small bowel that had been incarcerated showed deep-red discoloration on gross evaluation, but intravenous injection of ICG revealed uniform fluorescence of the mesentery and bowel wall. This indicated an absence of irreversible ischemic changes of the bowel, so no resection was performed. The patient showed a good postoperative course, including resumption of eating on day 4 and discharge on day 11. In surgery for incarcerated hernia, ICG fluorescence may offer a useful method to evaluate IBF after reducing the incarceration. This case implied that PINPOINT could be used in open conventional surgery.

Indocyanine green kinetics with near-infrared spectroscopy predicts cerebral hyperperfusion syndrome after carotid artery stenting

PubMed Central

Park, Hun Soo; Yokoyama, Shohei; Yamada, Shuichi; Motoyama, Yasushi; Park, Young Su; Wada, Takeshi; Kichikawa, Kimihiko; Nakase, Hiroyuki

2017-01-01

Background Cerebral hyperperfusion syndrome (HPS) is a potentially life-threatening complication following carotid artery stenting (CAS) and carotid endoarterectomy (CEA). Early prediction and treatment of patients at risk for HPS are required in patients undergoing CAS because HPS occurs significantly earlier after CAS than CEA. Near-infrared spectroscopy (NIRS) is often used for monitoring, and indocyanine green (ICG) kinetics by NIRS (ICG-NIRS) can detect reductions in cerebral perfusion in patients with acute stroke. However, whether ICG-NIRS can predict postoperative hyperperfusion phenomenon (HP) after carotid revascularization is unclear. Objective Here, we evaluated whether the blood flow index (BFI) ratio calculated from a time-intensity curve from ICG-NIRS monitoring can predict HPS after CAS. Methods The BFI ratio was prospectively monitored using ICG-NIRS in 135 patients undergoing CAS. Preoperative cerebrovascular reactivity (CVR) and the postoperative asymmetry index (AI) were also assessed with single-photon emission computed tomography before and after CAS, and the correlation was evaluated. In addition, patients were divided into two groups, a non-HP group (n = 113) and an HP group (n = 22), and we evaluated the correlation with hemodynamic impairment in the ipsilateral hemisphere and clinical results. Results Twenty-two cases (16%) showed HP, and four (3%) showed HPS after CAS. The BFI ratio calculated from ICG-NIRS showed a significant linear correlation with preoperative CVR and postoperative AI (r = −0.568, 0.538, P < 0.001, <0.001, respectively). The degree of stenosis, the rate of no cross flow, preoperative CVR, and the incidence of HPS were significantly different between the groups. Conclusions Measurement of ICG kinetics by NIRS is useful for detection of HPS in patients who underwent CAS. PMID:28704454

Sentinel lymph node detection rates using indocyanine green in women with early-stage cervical cancer.

PubMed

Beavis, Anna L; Salazar-Marioni, Sergio; Sinno, Abdulrahman K; Stone, Rebecca L; Fader, Amanda N; Santillan-Gomez, Antonio; Tanner, Edward J

2016-11-01

Our study objective was to determine feasibility and mapping rates using indocyanine green (ICG) for sentinel lymph node (SLN) mapping in early-stage cervical cancer. We performed a retrospective review of all women who underwent SLN mapping with ICG during primary surgical management of early-stage cervical cancer by robotic-assisted radical hysterectomy (RA-RH) or fertility-sparing surgery. Patients were treated at two high-volume centers from 10/2012 to 02/2016. Completion pelvic lymphadenectomy was performed after SLN biopsy; additionally, removal of clinically enlarged/suspicious nodes was part of the SLN treatment algorithm. Thirty women with a median age of 42.5 and BMI of 26.5 were included. Most (90%) had stage IB disease, and 67% had squamous histology. RA-RH was performed in 86.7% of cases. One patient underwent fertility-sparing surgery. Median cervical tumor size was 2.0cm. At least one SLN was detected in all cases (100%), with bilateral mapping achieved in 87%. SLN detection was not impacted by tumor size and was most commonly identified in the hypogastric (40.3%), obturator (26.0%), and external iliac (20.8%) regions. Five cases of lymphatic metastasis were identified (16.7%): three in clinically enlarged SLNs, one in a clinically enlarged non-SLN, and one case with cytokeratin positive cells in an SLN. All metastatic disease would have been detected even if full lymphadenectomy had been omitted from our treatment algorithm, CONCLUSIONS: SLN mapping with ICG is feasible and results in high detection rates in women with early-stage cervical cancer. Prospective studies are needed to determine if SLN mapping can replace lymphadenectomy in this setting. Copyright © 2016 Elsevier Inc. All rights reserved.

Near Infrared Imaging of Indocyanine Green Distribution in Pregnant Mice and Effects of Concomitant Medications.

PubMed

Bishara, Ameer; Meir, Michal; Portnoy, Emma; Shmuel, Miri; Eyal, Sara

2015-09-08

The transfer of indocyanine green (ICG) across the placenta is considered to be very low based on measurements in fetal blood. The goal of this study was to evaluate in mice ICG's distribution within fetuses themselves and effects of concomitant medications on fetal exposure. Mid-gestational (day 12.5) and late-gestational (day 17.5) age mice were imaged after administration of ICG (0.167 mg), in the presence and the absence of the organic anion transporting polypeptide (OATP) inhibitor rifampin (10 mg/kg, n = 11, or 20 mg/kg, n = 1) or the P-glycoprotein inhibitor valspodar (12.5 mg/kg). In vivo ICG emission intensity was followed by ex vivo analysis of blood and tissue emission. Both valspodar and rifampin increased ICG's emission intensity within maternal tissues. In addition, valspodar enhanced the ex vivo signal in mid-pregnancy placentae (2.1-fold; p < 0.01) and fetuses (2.4-fold; p < 0.01), and reduced late-pregnancy placenta:blood and fetus:blood ratios. Rifampin increased placental (1.4-fold, p < 0.05, and 2.3-fold, p < 0.01, in mid- and late-pregnancy, respectively) and fetal (2.2-fold, p < 0.01, and 3.2-fold, p < 0.01, in mid- and late-pregnancy) ICG signal. Similarly to valspodar, late-pregnancy placenta:blood and fetus:blood ratios were reduced by rifampin. Both inhibitors enhanced ICG's emission in fetal leg, liver, and brain. In conclusion, ICG distribution into the mouse fetus can be enhanced when used concomitantly with OATP or P-glycoprotein inhibitors. The greater distribution within individual fetal tissues is likely related to ICG's greater transplacental transfer. Until further data are available on ICG's safety when combined with medications that affect its maternal handling, such combinations should be used with caution.

Indocyanine Green Videoangiography for Surgery of a Ruptured Dissecting Aneurysm in the Precommunicating Anterior Cerebral Artery: A Technical Case Report.

PubMed

Nagai, Yasunori; Goto, Masanori; Toda, Hiroki; Nishida, Namiko; Yoshimoto, Naoya; Iwasaki, Koichi

2017-08-01

Indocyanine green videoangiography (ICG-VA) is an important intraoperative adjunct for saccular aneurysm surgery, but its efficacy in surgery for dissecting aneurysms has rarely been reported. The authors describe the usefulness of preclipping ICG-VA in a rare case of a ruptured dissecting aneurysm located at the precommunicating (A1) segment of the anterior cerebral artery. A 52-year-old woman, with no history of connective tissue diseases or vascular disorders, presented with sudden headache and convulsion. The CT scan showed that the patient had subarachnoid hemorrhage. Angiography showed a dissecting aneurysm in the left A1 segment of the anterior cerebral artery. Thus, the patient underwent trapping of the dissecting aneurysm. ICG-VA was used as an intraoperative adjunct before and after clipping. The preclipping ICG-VA showed the heterogeneously bright dissecting aneurysm and branching arteries even in the presence of hematoma. Preclipping ICG-VA may enhance the advantage of direct surgery for dissecting aneurysm by allowing visualization of the extent of the dissected vascular wall and the related branching arteries. ICG-VA can be an indispensable adjunct to minimize the compromise from the surgical treatment for intracranial dissecting aneurysms. Copyright © 2017 by the Congress of Neurological Surgeons

Use of Indocyanine Green for Detecting the Sentinel Lymph Node in Breast Cancer Patients: From Preclinical Evaluation to Clinical Validation

PubMed Central

Chi, Chongwei; Ye, Jinzuo; Ding, Haolong; He, De; Huang, Wenhe; Zhang, Guo-Jun; Tian, Jie

2013-01-01

Assessment of the sentinel lymph node (SLN) in patients with early stage breast cancer is vital in selecting the appropriate surgical approach. However, the existing methods, including methylene blue and nuclides, possess low efficiency and effectiveness in mapping SLNs, and to a certain extent exert side effects during application. Indocyanine green (ICG), as a fluorescent dye, has been proved reliable usage in SLN detection by several other groups. In this paper, we introduce a novel surgical navigation system to detect SLN with ICG. This system contains two charge-coupled devices (CCD) to simultaneously capture real-time color and fluorescent video images through two different bands. During surgery, surgeons only need to follow the fluorescence display. In addition, the system saves data automatically during surgery enabling surgeons to find the registration point easily according to image recognition algorithms. To test our system, 5 mice and 10 rabbits were used for the preclinical setting and 22 breast cancer patients were utilized for the clinical evaluation in our experiments. The detection rate was 100% and an average of 2.7 SLNs was found in 22 patients. Our results show that the usage of our surgical navigation system with ICG to detect SLNs in breast cancer patients is technically feasible. PMID:24358319

Comparison of sentinel lymph node biopsy guided by blue dye with or without indocyanine green in early breast cancer.

PubMed

Shen, Songjie; Xu, Qianqian; Zhou, Yidong; Mao, Feng; Guan, Jinghong; Sun, Qiang

2018-05-22

There were limited data available for a head-to-head comparison of the identification rate and survival between the combined method of indocyanine green fluorescence and blue dye versus the traditional blue dye alone method for sentinel lymph node (SLN) biopsy. From January 2013 to December 2015, 523 eligible breast cancer patients were included in this nonrandomized prospective analysis. The identification rates, the number of SLNs identified, and the disease-free survival (DFS) between the two mapping methods were compared. The identification rate of SLNs was significantly higher with the combined method than that with the blue dye alone method (99.2% vs 93.3%, respectively; P < 0.001). The average number of SLNs identified per patient in the combined method group was 3.7 ± 2.4, which was more than that in the blue dye alone group (3.2 ± 1.6; P = 0.004). With a median follow-up of 29 months, 0.5% patients in the combined group, and 1.3% patients in the blue dye group had axillary recurrences. The DFS between the two groups showed no significant difference (P = 0.161). The combined method achieved a higher identification rate and lower rate of axillary recurrence compared to the blue dye alone method. © 2018 Wiley Periodicals, Inc.

Preliminary study of laser welding for aortic dissection in a porcine model using a diode laser with indocyanine green.

PubMed

Fujita, Masanori; Morimoto, Yuji; Ohmori, Sayaka; Usami, Noriko; Arai, Tsunenori; Maehara, Tadaaki; Kikuchi, Makoto

2003-01-01

The objective of this study was to determine whether a dissected aorta could be welded by a diode laser with a solder using an in vitro porcine aortic dissection model. Porcine aortic strips were dissected into two flaps and the dissected faces were immersed in a solution of indocyanine green. The two flaps were pressed at 0.2 kg/cm2 with contact between the two immersed faces. The pressed flaps were irradiated with a diode laser (810 nm) at intensities of 170-425 W/cm2 for 8 seconds. The welded flaps were studied by light microscopy and the adhesive strengths were measured. The irradiated flaps were successfully welded. The breaking stress, the maximum stress recorded in a stress-strain curve, increased with increase in irradiation intensity up to 396 W/cm2 (2.7 x 10(2) mmHg) and decreased when the intensity reached 425 W/cm2. In the specimen irradiated at 396 W/cm2, the welded faces showed continuous fusion of elastin layers, while some voids were seen between the welded faces in the specimen irradiated at 425 W/cm2. The dissected porcine aortas were successfully welded using a laser with solder. The results suggest that the welded aorta can bear physiological blood pressure. Copyright 2003 Wiley-Liss, Inc.

Indocyanine green-augmented diode laser therapy of telangiectatic leg veins: a randomized controlled proof-of-concept trial.

PubMed

Klein, Annette; Bäumler, Wolfgang; Koller, Michael; Shafirstein, Gal; Kohl, Elisabeth A; Landthaler, Michael; Babilas, Philipp

2012-07-01

Telangiectatic leg veins, which affect about 40-50% of adults, represent a frequent cosmetic rather than a medical problem. Besides sclerotherapy, various laser devices are common treatment options. However, complete clearance rates can only be achieved in a small number of patients. In this proof-of-concept study, the safety and efficacy of indocyanine green (ICG)-augmented diode laser therapy (808 nm) was evaluated for the treatment of telangiectatic leg veins. ICG (2 mg/kg body weight) was intravenously administered in 15 female patients (skin type II to III) with telangiectatic leg veins (measuring between 0.25 and 3 mm in diameter). Immediately after ICG injection, diode laser pulses with different radiant exposures (50-110 J/cm(2)) were applied as one single treatment. Safety and efficacy were assessed 1 and 3 months after treatment by a blinded investigator and the patient. Treatments with the pulsed dye laser (PDL) and the diode laser without ICG served as reference therapies. The safety of ICG application and diode laser treatment was excellent in all patients with no persisting side effects. Vessel clearance was dose-dependent. Diode laser treatment at radiant exposures between 100 and 110 J/cm(2) resulted in good vessel clearance, which even improved to excellent after the application of double pulses. Diode laser therapy without ICG and PDL treatment induced poor to moderate clearance of telangiectatic leg veins. ICG-augmented diode laser therapy has proved to be a safe and effective treatment option for telangiectatic leg veins. Copyright © 2012 Wiley Periodicals, Inc.

A simple method for in vivo labelling of infiltrating leukocytes in the mouse retina using indocyanine green dye.

PubMed

Sim, Dawn A; Chu, Colin J; Selvam, Senthil; Powner, Michael B; Liyanage, Sidath; Copland, David A; Keane, Pearse A; Tufail, Adnan; Egan, Catherine A; Bainbridge, James W B; Lee, Richard W; Dick, Andrew D; Fruttiger, Marcus

2015-11-01

We have developed a method to label and image myeloid cells infiltrating the mouse retina and choroid in vivo, using a single depot injection of indocyanine green dye (ICG). This was demonstrated using the following ocular models of inflammation and angiogenesis: endotoxin-induced uveitis, experimental autoimmune uveoretinitis and laser-induced choroidal neovascularization model. A near-infrared scanning ophthalmoscope was used for in vivo imaging of the eye, and flow cytometry was used on blood and spleen to assess the number and phenotype of labelled cells. ICG was administered 72 h before the induction of inflammation to ensure clearance from the systemic circulation. We found that in vivo intravenous administration failed to label any leukocytes, whereas depot injection, either intraperitoneal or subcutaneous, was successful in labelling leukocytes infiltrating into the retina. Progression of inflammation in the retina could be traced over a period of 14 days following a single depot injection of ICG. Additionally, bright-field microscopy, spectrophotometry and flow cytometric analysis suggest that the predominant population of cells stained by ICG are circulating myeloid cells. The translation of this approach into clinical practice would enable visualization of immune cells in situ. This will not only provide a greater understanding of pathogenesis, monitoring and assessment of therapy in many human ocular diseases but might also open the ability to image immunity live for neurodegenerative disorders, cardiovascular disease and systemic immune-mediated disorders. © 2015. Published by The Company of Biologists Ltd.

Sulfobutyl ether β-cyclodextrin (Captisol(®) ) and methyl β-cyclodextrin enhance and stabilize fluorescence of aqueous indocyanine green.

PubMed

DeDora, Daniel J; Suhrland, Cassandra; Goenka, Shilpi; Mullick Chowdhury, Sayan; Lalwani, Gaurav; Mujica-Parodi, Lilianne R; Sitharaman, Balaji

2016-10-01

As the only FDA-approved near-infrared fluorophore, indocyanine green (ICG) is commonly used to image vasculature in vivo. ICG degrades rapidly in solution, which limits its usefulness in certain applications, including time-sensitive surgical procedures. We propose formulations that address this shortcoming via complexation with β-cyclodextrin derivatives (β-CyD), which are known to create stabilizing inclusion complexes with hydrophobic molecules. Here, we complexed ICG with highly soluble methyl β-CyD and FDA-approved sulfobutyl ether β-CyD (Captisol(®) ) in aqueous solution. We measured the fluorescence of the complexes over 24 h. We found that both CyD+ICG complexes exhibit sustained fluorescence increases of >2.0× versus ICG in water and >20.0× in PBS. Using transmission electron microscopy, we found evidence of reduced aggregation in complexes versus ICG alone. We thus conclude that this reduction in aggregation helps mitigate fluorescence autoquenching of CyD+ICG complexes compared in ICG alone. We also found that while ICG complexed with methyl β-CyD severely reduced the viability of MRC-5 fibroblasts, ICG complexed with sulfobutyl ether β-CyD had no effect on viability. These results represent an important first step toward enhancing the utility of aqueous ICG by reducing aggregation-dependent fluorescence degradation. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 104B: 1457-1464, 2016. © 2015 Wiley Periodicals, Inc.

Intraoperative Matas test using microscope-integrated intraoperative indocyanine green videoangiography with temporary unilateral occlusion of the A1 segment of the anterior cerebral artery.

PubMed

Murai, Yasuo; Adachi, Koji; Takagi, Ryo; Koketsu, Kenta; Matano, Fumihiro; Teramoto, Akira

2011-11-01

The aim of the present study was to assess a new technique of surgical microscope-based indocyanine green (ICG) videoangiography (VAG) to confirm the patency of the anterior communicating artery (AcomA) after clipping AcomA aneurysms. Aneurysmal clipping of five cases of unruptured, broad-neck AcomA aneurysm was performed using the Carl Zeiss Surgical Microscope OPMI Pentero INFRARED 800. In all five patients, after clipping AcomA aneurysms, the patency of AcomA was confirmed using ICGVAG findings and temporary unilateral occlusion of the A1 segment of the anterior cerebral artery using temporary clips. Images were excellent and enabled a real-time surgical assessment because the structures of interest, including vessels, perforating arteries, or residual aneurysm neck, were visible to the surgeon's eye under the microscope in all five patients. ICGVAG and temporary unilateral occlusion with clips provides a simple, reliable, real-time, and rapid intraoperative assessment of the patency of AcomA. This technique may help to improve the quality of neurosurgical procedures. Copyright © 2011 Elsevier Inc. All rights reserved.

Understanding Green Purchase Behavior: College Students and Socialization Agents

ERIC Educational Resources Information Center

Yan, Ruoh-Nan; Xu, Huimin

2010-01-01

Taking the perspective of consumer socialization theory, this study examined the influences of different socialization agents on consumers' purchases of green products. A total of 224 surveys were distributed to students enrolled in a business-related course at a major university in the northeastern United States. The objectives were twofold. The…

Anterior segment angiography of the normal canine eye: a comparison between indocyanine green and sodium fluorescein.

PubMed

Pirie, C G; Alario, A

2014-03-01

The objective of this study was to assess and compare indocyanine green (IG) and sodium fluorescein (SF) angiographic findings in the normal canine anterior segment using a digital single lens reflex (dSLR) camera adaptor. Images were obtained from 10 brown-eyed Beagles, free of ocular and systemic disease. All animals received butorphanol (0.2 mg/kg IM), maropitant citrate (1.0 mg/kg SC) and diphenhydramine (2.0 mg/kg SC) 20 min prior to propofol (4 mg/kg IV bolus, 0.2 mg/kg/min continuous rate infusion). Standard color imaging was performed prior to the administration of 0.25% IG (1 mg/kg IV). Imaging was performed using a full spectrum dSLR camera, dSLR camera adaptor, camera lens (Canon 60 mm f/2.8 Macro) and an accessory flash. Images were obtained at a rate of 1/s immediately following IG bolus for 30 s, then at 1, 2, 3, 4 and 5 min. Ten minutes later, 10% SF (20 mg/kg IV) was administered. Imaging was repeated using the same adaptor system and imaging sequence protocol. Arterial, capillary and venous phases were identified during anterior segment IG angiography (ASIGA) and their time sequences were recorded. ASIGA offered improved visualization of the iris vasculature in heavily pigmented eyes compared to anterior segment SF angiography (ASSFA), since visualization of the vascular pattern during ASSFA was not possible due to pigment masking. Leakage of SF was noted in a total of six eyes. The use of IG and SF was not associated with any observed adverse events. The adaptor described here provides a cost-effective alternative to existing imaging systems. Copyright © 2013 Elsevier Ltd. All rights reserved.

Near-infrared indocyanine dye permits real-time characterization of both venous and lymphatic circulation

NASA Astrophysics Data System (ADS)

Kurahashi, Toshikazu; Iwatsuki, Katsuyuki; Onishi, Tetsuro; Arai, Tetsuya; Teranishi, Katsunori; Hirata, Hitoshi

2016-08-01

We investigated the optical properties of a near-infrared (NIR) fluorochrome, di-β-cyclodextrin-binding indocyanine derivative (TK-1), and its pharmacokinetic differences with indocyanine green (ICG). TK-1 was designed to have hydrophilic cyclodextrin molecules and, thus, for higher water solubility and smaller particle sizes than the plasma protein-bound ICG. We compared optical properties such as the absorption and fluorescence spectra, quantum yield, and photostability between both dyes in vitro. In addition, we subcutaneously injected a 1 mM solution of TK-1 or ICG into the hind footpad of rats and observed real-time NIR fluorescence intensities in their femoral veins and accompanying lymphatics at the exposed groin site to analyze the dye pharmacokinetics. These optical experiments demonstrated that TK-1 has high water solubility, a low self-aggregation tendency, and high optical and chemical stabilities. Our in vivo imaging showed that TK-1 was transported via peripheral venous flow and lymphatic flow, whereas ICG was drained only through lymphatics. The results of this study showed that lymphatic and venous transport can be differentially regulated and is most likely influenced primarily by particle size, and that TK-1 can enable real-time NIR fluorescence imaging of whole fluids and solute movement via both microvessels and lymphatics, which conventional ICG cannot achieve.

The utility of indocyanine green near infrared fluorescent imaging in the identification of parathyroid glands during surgery for primary hyperparathyroidism.

PubMed

Zaidi, Nisar; Bucak, Emre; Okoh, Alexis; Yazici, Pinar; Yigitbas, Hakan; Berber, Eren

2016-06-01

Intraoperative adjuncts for the localization of parathyroid glands in parathyroid surgery are limited. The aim of this study is to assess the usefulness of indocyanine green (ICG) near-infrared (NIR) fluorescent imaging in patients undergoing surgery for primary hyperparathyroidism (PHPT). ICG imaging was performed in 33 patients undergoing parathyroidectomy (PTX). Thyroid and parathyroid ICG uptake were assessed and independently verified on a grading scale. Clinical variables were recorded and analyzed for factors associated with ICG uptake. Of 112 glands identified by naked eye, 104 (92.9%) demonstrated ICG uptake. Concomitant ICG fluorescence was identified in the thyroid in all patients. There was a trend toward increased ICG fluorescence in patients <60 years of age (P = 0.05). A higher degree of fluorescence was seen in patients presenting with pre-operative calcium values >11 mg/dl (P = 0.04) and in those parathyroids larger than 10 mm (P < 0.01). All patients had biochemically proven cure. No patients who underwent subtotal PTX (n = 6) developed postoperative hypoparathyroidism. ICG can reliably localize parathyroid glands during PTX and additionally allow for assessment of parathyroid perfusion in patients undergoing subtotal resection. Concomitant fluorescence of the thyroid gland limits ICG's usefulness in directing the course of PTX. J. Surg. Oncol. 2016;113:771-774. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

The feasibility of indocyanine green fluorescence imaging for identifying and assessing the perfusion of parathyroid glands during total thyroidectomy.

PubMed

Zaidi, Nisar; Bucak, Emre; Yazici, Pinar; Soundararajan, Sarah; Okoh, Alexis; Yigitbas, Hakan; Dural, Cem; Berber, Eren

2016-06-01

There are limited adjuncts available for identifying and assessing the viability of parathyroid glands (PGs) during total thyroidectomy (TT). The aim of this study is to determine the feasibility of indocyanine green (ICG) imaging in identifying and assessing perfusion of PGs during TT. ICG was administered in patients undergoing TT and fluorescence of PGs was assessed. A grading scale was developed for assessing degree of ICG uptake. Patients were evaluated for hypocalcemia and hypoparathyroidism on post-operative day (POD) #1. Twenty-seven patients underwent TT with ICG imaging for multinodular goiter (n = 13), thyroid cancer (n = 10), and Graves' disease (n = 4). Eight-five PGs were identified visually, 71 (84%) of which showed ICG fluorescence. False negative rate was 6%. Post-operatively, three patients (11%) had a serum calcium value <8 mg/dl. ICG uptake after TT correlated with post-operative PTH levels: mean POD#1 PTH of those patients with at least two PGs exhibiting <30% fluorescence was 9 pg/ml; whereas those with fewer than two demonstrating <30% fluorescence had a POD#1 PTH of 19.5 pg/ml (P = 0.05). ICG imaging of PGs during TT is feasible. ICG might be a useful adjunct in identifying those patients at risk for post-thyroidectomy hypoparathyroidism. J. Surg. Oncol. 2016;113:775-778. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Navigation surgery for intraoperative sentinel lymph node detection using Indocyanine green (ICG) fluorescence real-time imaging in breast cancer.

PubMed

Toh, U; Iwakuma, N; Mishima, M; Okabe, M; Nakagawa, S; Akagi, Y

2015-09-01

A new sensitive fluorescence imaging system was developed for the real-time identification of sentinel lymph nodes (SLNs) in patients with early breast cancer. The purpose of this study was to evaluate the utility of a color charge-coupled device camera system for the intraoperative detection of SLNs and to determine its clinical efficacy and sensitivity in patients with operable breast cancer. We assessed a total of 168 patients diagnosed with or suspected of having early-stage breast cancer without metastasis in SLNs. The intraoperative detection of SLNs was performed using the conventional Indigo Carmine dye (indigotindisulfonate sodium) technique combined with a new Indocyanine green (ICG) imaging system (HyperEye Medical System: HEMS, MIZUHO IKAKOGYO, Japan) to map SLNs, in which the lymphatic vessels and SLNs were visualized transcutaneously with illuminating ICG fluorescence. Between January 2012 and May 2013, SLNs were successfully identified in all 168 patients (detection rate: 100%). By histopathology, the sensitivity was 93.8% for the detection of the metastatic involvement of SLNs (15 of 16 nodal-positive patients). After a median follow-up of 30.5 months, none of the patients presented with axillary recurrence. These results suggest that the HEMS imaging system is a feasible and effective method for the detection of SLNs in breast cancer. Furthermore, the HEMS device permitted the transcutaneous visualization of lymphatic vessels under light conditions, thus facilitating the identification and detection of SLNs without affecting the surgical procedure, together with a high sensitivity and specificity.

Comparing quantitative values of two generations of laser-assisted indocyanine green dye angiography systems: can we predict necrosis?

PubMed

Phillips, Brett T; Fourman, Mitchell S; Rivara, Andrew; Dagum, Alexander B; Huston, Tara L; Ganz, Jason C; Bui, Duc T; Khan, Sami U

2014-01-01

Several devices exist today to assist the intraoperative determination of skin flap perfusion. Laser-Assisted Indocyanine Green Dye Angiography (LAICGA) has been shown to accurately predict mastectomy skin flap necrosis using quantitative perfusion values. The laser properties of the latest LAICGA device (SPY Elite) differ significantly from its predecessor system (SPY 2001), preventing direct translation of previous published data. The purpose of this study was to establish a mathematical relationship of perfusion values between these 2 devices. Breast reconstruction patients were prospectively enrolled into a clinical trial where skin flap evaluation and excision was based on quantitative SPY Q values previously established in the literature. Initial study patients underwent mastectomy skin flap evaluation using both SPY systems simultaneously. Absolute perfusion unit (APU) values at identical locations on the breast were then compared graphically. 210 data points were identified on the same patients (n = 4) using both SPY systems. A linear relationship (y = 2.9883x + 12.726) was identified with a high level or correlation (R(2) = 0.744). Previously published values using SPY 2001 (APU 3.7) provided a value of 23.8 APU on the SPY Elite. In addition, postoperative necrosis in these patients correlated to regions of skin identified with the SPY Elite with APU less than 23.8. Intraoperative comparison of LAICGA systems has provided direct correlation of perfusion values predictive of necrosis that were previously established in the literature. An APU value of 3.7 from the SPY 2001 correlates to a SPY Elite APU value of 23.8.

Comparing Quantitative Values of Two Generations of Laser-Assisted Indocyanine Green Dye Angiography Systems: Can We Predict Necrosis?

PubMed Central

Fourman, Mitchell S.; Rivara, Andrew; Dagum, Alexander B.; Huston, Tara L.; Ganz, Jason C.; Bui, Duc T.; Khan, Sami U.

2014-01-01

Objective: Several devices exist today to assist the intraoperative determination of skin flap perfusion. Laser-Assisted Indocyanine Green Dye Angiography (LAICGA) has been shown to accurately predict mastectomy skin flap necrosis using quantitative perfusion values. The laser properties of the latest LAICGA device (SPY Elite) differ significantly from its predecessor system (SPY 2001), preventing direct translation of previous published data. The purpose of this study was to establish a mathematical relationship of perfusion values between these 2 devices. Methods: Breast reconstruction patients were prospectively enrolled into a clinical trial where skin flap evaluation and excision was based on quantitative SPY Q values previously established in the literature. Initial study patients underwent mastectomy skin flap evaluation using both SPY systems simultaneously. Absolute perfusion unit (APU) values at identical locations on the breast were then compared graphically. Results: 210 data points were identified on the same patients (n = 4) using both SPY systems. A linear relationship (y = 2.9883x + 12.726) was identified with a high level or correlation (R2 = 0.744). Previously published values using SPY 2001 (APU 3.7) provided a value of 23.8 APU on the SPY Elite. In addition, postoperative necrosis in these patients correlated to regions of skin identified with the SPY Elite with APU less than 23.8. Conclusion: Intraoperative comparison of LAICGA systems has provided direct correlation of perfusion values predictive of necrosis that were previously established in the literature. An APU value of 3.7 from the SPY 2001 correlates to a SPY Elite APU value of 23.8. PMID:25525483

Feasibility of simultaneous sodium fluorescein and indocyanine green injection in neurosurgical procedures.

PubMed

Acerbi, F; Restelli, F; Broggi, M; Schiariti, M; Ferroli, P

2016-07-01

The objective of this study is to assess the feasibility of simultaneous Sodium Fluorescein (SF) and Indocyanine Green (ICG) injection during neurosurgical procedures. Three patients harboring a high-grade glioma (HGG) were retrospectively identified in the surgical database of the Neurosurgical Unit 2 at the Foundation IRCCS Istituto Neurologico C. Besta in Milan, by having received intraoperatively both SF for tumor resection and ICG for vasculature angiographic studies in the same surgical procedure. We identified 2 males and 1 female (age range 25-60). Lesions were located in the left temporo-polar area and hippocampus (1 case), right superior frontal gyrus (1 case), left supplementary motor area (1 case). All the three lesions showed Magnetic Resonance Imaging (MRI) characteristics of HGG and, for this reason, in all patients a fluorescein-guided tumor removal was proposed. In the same surgical procedure ICG videoangiography was considered necessary in order to study arterial and venous vasculature, given by the strict relation of the tumor with an unexpected Posterior Communicating Artery (PComA) aneurysm in one case and with cortical drainage veins complexes in the other two cases. In all cases a microscope equipped with both YELLOW560 and IR800 integrated filters (Pentero 900, Carl Zeiss, Oberkorchen, Germany) was used. Fluorescein was i.v. injected at a dose of 5mg/kg immediately after patient intubation. ICG was i.v. injected in bolus on demand of the operating surgeon at a dose of 12.5mg. No side-effects related to simultaneous injection of SF and ICG were identified. In all three cases, the use of SF allowed to better visualize the tumor areas during surgical removal, thus leading to a radical resection until no macroscopic appearance of residual tumor mass and no fluorescence was visible in the surgical cavity. ICG videoangiography confirmed the patency of branches of internal carotid artery after clipping of an unexpected small PComA aneurysm found

The Application of Heptamethine Cyanine Dye DZ-1 and Indocyanine Green for Imaging and Targeting in Xenograft Models of Hepatocellular Carcinoma

PubMed Central

Zhang, Caiqin; Zhao, Yong; Zhang, He; Chen, Xue; Zhao, Ningning; Tan, Dengxu; Zhang, Hai; Shi, Changhong

2017-01-01

Near infrared fluorescence (NIRF) imaging has strong potential for widespread use in noninvasive tumor imaging. Indocyanine green (ICG) is the only Food and Drug Administration (FDA) -approved NIRF dye for clinical diagnosis; however, it is unstable and poorly targets tumors. DZ-1 is a novel heptamethine cyanine NIRF dye, suitable for imaging and tumor targeting. Here, we compared the fluorescence intensity and metabolism of DZ-1 and ICG. Additionally, we assayed their specificities and abilities to target tumor cells, using cultured hepatocellular carcinoma (HCC) cell lines, a nude mouse subcutaneous xenograft model of liver cancer, and a rabbit orthotopic transplantation model. We found that DZ-1 accumulates in tumor tissue and specifically recognizes HCC in subcutaneous and orthotopic models. The NIRF intensity of DZ-1 was one order of magnitude stronger than that of ICG, and DZ-1 showed excellent intraoperative tumor targeting in the rabbit model. Importantly, ICG accumulated at tumor sites, as well as in the liver and kidney. Furthermore, DZ-1 analog-gemcitabine conjugate (NIRG) exhibited similar tumor-specific targeting and imaging properties, including inhibition of tumor growth, in HCC patient-derived xenograft (PDX) mice. DZ-1 and NIRG demonstrated superior tumor-targeting specificity, compared to ICG. We show that DZ-1 is an effective molecular probe for specific imaging, targeting, and therapy in HCC. PMID:28635650

The Application of Heptamethine Cyanine Dye DZ-1 and Indocyanine Green for Imaging and Targeting in Xenograft Models of Hepatocellular Carcinoma.

PubMed

Zhang, Caiqin; Zhao, Yong; Zhang, He; Chen, Xue; Zhao, Ningning; Tan, Dengxu; Zhang, Hai; Shi, Changhong

2017-06-21

Near infrared fluorescence (NIRF) imaging has strong potential for widespread use in noninvasive tumor imaging. Indocyanine green (ICG) is the only Food and Drug Administration (FDA) -approved NIRF dye for clinical diagnosis; however, it is unstable and poorly targets tumors. DZ-1 is a novel heptamethine cyanine NIRF dye, suitable for imaging and tumor targeting. Here, we compared the fluorescence intensity and metabolism of DZ-1 and ICG. Additionally, we assayed their specificities and abilities to target tumor cells, using cultured hepatocellular carcinoma (HCC) cell lines, a nude mouse subcutaneous xenograft model of liver cancer, and a rabbit orthotopic transplantation model. We found that DZ-1 accumulates in tumor tissue and specifically recognizes HCC in subcutaneous and orthotopic models. The NIRF intensity of DZ-1 was one order of magnitude stronger than that of ICG, and DZ-1 showed excellent intraoperative tumor targeting in the rabbit model. Importantly, ICG accumulated at tumor sites, as well as in the liver and kidney. Furthermore, DZ-1 analog-gemcitabine conjugate (NIRG) exhibited similar tumor-specific targeting and imaging properties, including inhibition of tumor growth, in HCC patient-derived xenograft (PDX) mice. DZ-1 and NIRG demonstrated superior tumor-targeting specificity, compared to ICG. We show that DZ-1 is an effective molecular probe for specific imaging, targeting, and therapy in HCC.

Comparison of indocyanine green fluorescence and parathyroid autofluorescence imaging in the identification of parathyroid glands during thyroidectomy.

PubMed

Kahramangil, Bora; Berber, Eren

2017-12-01

Indocyanine green fluorescence (ICGF) and parathyroid autofluorescence (AF) are two new techniques that aid in the identification of parathyroid glands (PG) intraoperatively during thyroidectomy. There is no study comparing the efficacy of these techniques. This was an IRB-approved clinical study comparing the utility of ICGF and AF for identification of PGs during thyroidectomy. Data were collected prospectively. Both techniques were compared to naked eye (NE) for PG detection. Standard statistical methods were used for data analysis. Twenty-two patients in each group underwent a total of 39 total thyroidectomies and 5 thyroid lobectomies. AF and ICGF had similar detection rates for PGs [98% (61 of 62) and 95% (60 of 63) of PGs, respectively; P=0.31]. The location of PGs was suggested before detection with NE more frequently by AF than ICGF [52% (32 of 62) vs. 6% (4 of 63) of PGs; P<0.001]. In 82% (18 of 22) of patients at least one PG was detected by AF before NE, as opposed to 14% (3 of 22) by ICGF (P<0.001). The median (range) number of PGs detected before NE per patient was greater with AF than ICGF [2 (0-3) vs. 0 (0-2)];. Upper PGs were more likely to be detected by AF before recognition with NE than the lower ones (P=0.03). There was no predictive factor for ICGF detection. Postoperative hypocalcemia rates were similar [9% (2 of 22) and 5% (1 of 22) for AF and ICGF, respectively; P>0.99]. To the best of our knowledge, this is the first comparative study between parathyroid AF and ICGF in detection of PGs during thyroidectomy. Our data suggest both techniques have similarly high detection rates and that the main difference lies in the timing of detection. AF more frequently detects PGs before recognition with NE compared to ICGF.

Intraoperative tumor localization and tissue distinction during robotic adrenalectomy using indocyanine green fluorescence imaging: a feasibility study.

PubMed

Sound, Sara; Okoh, Alexis K; Bucak, Emre; Yigitbas, Hakan; Dural, Cem; Berber, Eren

2016-02-01

To investigate the feasibility of a method for intraoperative tumor localization and tissue distinction during robotic adrenalectomy (RA) via indocyanine green (ICG) imaging under near-infrared light. Ten patients underwent RA. After exposure of the retroperitoneal space, but before adrenal dissection was started, ICG was given intravenously (IV). Fluorescence Firefly™ imaging was performed at 1-, 5-, 10-, and 20-min time points. The precision with which the borders of the adrenal tissue were distinguished with ICG imaging was compared to that with the conventional robotic view. The number and the total volume of injections for each patient were recorded. There were six male and four female patients. Diagnosis was primary hyperaldosteronism in four patients and myelolipoma, adrenocortical neoplasm, adrenocortical hyperplasia, Cushing's syndrome, pheochromocytoma, and metastasis in one patient each. Procedures were done through a robotic lateral transabdominal approach in nine and through a robotic posterior retroperitoneal approach in one patient. Dose per injection ranged between 2.5 and 6.3 mg and total dose per patient 7.5-18.8 mg. The adrenal gland took up the dye in 1 min, with contrast between adrenal mass and surrounding retroperitoneal fat becoming most distinguished at 5 min. Fluorescence of adrenal tissue lasted up to 20 min after injection. Overall, ICG imaging was felt to help with the conduct of operation in 8 out of 10 procedures. There were no conversions to open or morbidity. There were no immediate or delayed adverse effects attributable to IV ICG administration. In this pilot study, we demonstrated the feasibility and safety of ICG imaging in a small group of patients undergoing RA. We described a method that enabled an effective fluorescence imaging to localize the adrenal glands and guide dissection. Future research is necessary to study how this imaging affects perioperative outcomes.

Treatment of Near-Infrared Photodynamic Therapy Using a Liposomally Formulated Indocyanine Green Derivative for Squamous Cell Carcinoma

PubMed Central

Maruyama, Tetsuro; Akutsu, Yasunori; Suganami, Akiko; Tamura, Yutaka; Fujito, Hiromichi; Ouchi, Tomoki; Akanuma, Naoki; Isozaki, Yuka; Takeshita, Nobuyoshi; Hoshino, Isamu; Uesato, Masaya; Toyota, Taro; Hayashi, Hideki; Matsubara, Hisahiro

2015-01-01

Introduction Photodynamic therapy (PDT) is a less invasive option for cancer treatment that has evolved through recent developments in nanotechnology. We have designed and synthesized a novel liposome system that includes an indocyanine green (ICG) derivative, ICG-C18, in its bilayer. In addition to its use as an optical imager to visualize blood, lymphatic, and bile flow, ICG has also been used as an optical sensitizer. In the present report, we evaluate the use of our novel liposome system, LP-ICG-C18, in PDT for squamous cell carcinoma in an autologous murine model. Materials and Methods An excitation pulse beam (300 μJ/pulse) of a single band (800 nm) was used for sensitization. The cytotoxicity of the photodynamic therapy was evaluated in terms of cellular morphology changes, methyl thiazolyl tetrazolium (MTT) assay results, and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick end labeling (TUNEL) staining. We tested the enhanced permeability and retention effect of LP-ICG-C18 in tumor-bearing C3H/He mice using a near-infrared fluorescence imaging system and fluorescence microscopy. We also examined the antitumor effect of PDT by measuring tumor volume in tumor-bearing mice. Results Cell death and apoptosis were only observed in the PDT group receiving LP-ICG-C18. LP-ICG-C18 itself had no cytotoxic activity and showed good biocompatibility. LP-ICG-C18 accumulated on the tumor 24 hours after injection and was retained for approximately 3 weeks. Tumor cell apoptosis following PDT with LP-ICG-C18 was also observed under optical microscopy, MTT assay, and TUNEL staining. Conclusion These findings suggest that LP-ICG-C18 may be an effective intervening material in PDT for malignant disease. PMID:25850029

Indocyanine green (ICG) as a new adjuvant for the antimicrobial photo-dynamic therapy (aPDT) in dentistry

NASA Astrophysics Data System (ADS)

Meister, Joerg; Hopp, Michael; Schäfers, Johannes; Verbeek, Jonas; Kraus, Dominik; Frentzen, Matthias

2014-02-01

Clinical surveys show a continuous increase of antimicrobial resistance related to the frequency of the administrated medication. The antimicrobial photodynamic therapy (aPDT) is an effective adjuvant to reduce the need of antibiotics in dentistry, especially in periodontics. The antimicrobial effect of lightactivated photosensitizers in periodontics is demonstrated in clinical studies and case reports. Indocyanine green (ICG) as a new adjuvant shows the high potential of antiphlogistic and antimicrobial effects in combination with laser-light activation. In trying to answer the question of just how far the influence of temperature is acting on bacteria, this study was carried out. The influences of ICG at different concentrations (0.01 up to 1 mg/ml) in combination with a culture medium (brain-heart-infusion) and a bacteria culture (Streptococcus salivarius) at different optical densities (OD600 0.5 and 0.1) were investigated under laser-light activation. Laser activation was carried out with diode laser at 810 nm and two different power settings (100 mW/300 mW). The pulse repetition rate was 2 kHz. Taking account of the fiber diameter, distance and spot size on the sample surface, the applicated intensities were 6.2 and 18.7 W/cm2. Total irradiation time was 20 s for all meaurements. Transmitted laser power and temperature increase in the culture medium as well as in the bacteria culture were determined. Additionally the influence of ICG regarding bacterial growth and bactericidal effect was investigated in the bacteria culture without laser irradiation. Without laser, no bactericidal effect of ICG was observed. Only a bacteriostatic effect could be proved. In dependence of the ICG concentration and the applied intensities a temperature increase of ΔT up to 80°C was measured.

Treatment of near-infrared photodynamic therapy using a liposomally formulated indocyanine green derivative for squamous cell carcinoma.

PubMed

Maruyama, Tetsuro; Akutsu, Yasunori; Suganami, Akiko; Tamura, Yutaka; Fujito, Hiromichi; Ouchi, Tomoki; Akanuma, Naoki; Isozaki, Yuka; Takeshita, Nobuyoshi; Hoshino, Isamu; Uesato, Masaya; Toyota, Taro; Hayashi, Hideki; Matsubara, Hisahiro

2015-01-01

Photodynamic therapy (PDT) is a less invasive option for cancer treatment that has evolved through recent developments in nanotechnology. We have designed and synthesized a novel liposome system that includes an indocyanine green (ICG) derivative, ICG-C18, in its bilayer. In addition to its use as an optical imager to visualize blood, lymphatic, and bile flow, ICG has also been used as an optical sensitizer. In the present report, we evaluate the use of our novel liposome system, LP-ICG-C18, in PDT for squamous cell carcinoma in an autologous murine model. An excitation pulse beam (300 μJ/pulse) of a single band (800 nm) was used for sensitization. The cytotoxicity of the photodynamic therapy was evaluated in terms of cellular morphology changes, methyl thiazolyl tetrazolium (MTT) assay results, and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick end labeling (TUNEL) staining. We tested the enhanced permeability and retention effect of LP-ICG-C18 in tumor-bearing C3H/He mice using a near-infrared fluorescence imaging system and fluorescence microscopy. We also examined the antitumor effect of PDT by measuring tumor volume in tumor-bearing mice. Cell death and apoptosis were only observed in the PDT group receiving LP-ICG-C18. LP-ICG-C18 itself had no cytotoxic activity and showed good biocompatibility. LP-ICG-C18 accumulated on the tumor 24 hours after injection and was retained for approximately 3 weeks. Tumor cell apoptosis following PDT with LP-ICG-C18 was also observed under optical microscopy, MTT assay, and TUNEL staining. These findings suggest that LP-ICG-C18 may be an effective intervening material in PDT for malignant disease.

Noninvasive in vivo multispectral optoacoustic imaging of apoptosis in triple negative breast cancer using indocyanine green conjugated phosphatidylserine monoclonal antibody

NASA Astrophysics Data System (ADS)

Kannadorai, Ravi Kumar; Udumala, Sunil Kumar; Sidney, Yu Wing Kwong

2016-12-01

Noninvasive and nonradioactive imaging modality to track and image apoptosis during chemotherapy of triple negative breast cancer is much needed for an effective treatment plan. Phosphatidylserine (PS) is a biomarker transiently exposed on the outer surface of the cells during apoptosis. Its externalization occurs within a few hours of an apoptotic stimulus by a chemotherapy drug and leads to presentation of millions of phospholipid molecules per apoptotic cell on the cell surface. This makes PS an abundant and accessible target for apoptosis imaging. In the current work, we show that PS monoclonal antibody tagged with indocyanine green (ICG) can help to track and image apoptosis using multispectral optoacoustic tomography in vivo. When compared to saline control, the doxorubicin treated group showed a significant increase in uptake of ICG-PS monoclonal antibody in triple negative breast tumor xenografted in NCr nude female mice. Day 5 posttreatment had the highest optoacoustic signal in the tumor region, indicating maximum apoptosis and the tumor subsequently shrank. Since multispectral optoacoustic imaging does not involve the use of radioactivity, the longer the circulatory time of the PS antibody can be exploited to monitor apoptosis over a period of time without multiple injections of commonly used imaging probes such as Tc-99m Annexin V or F-18 ML10. The proposed apoptosis imaging technique involving multispectral optoacoustic tomography, monoclonal antibody, and near-infrared absorbing fluorescent marker can be an effective tool for imaging apoptosis and treatment planning.

Real-time navigation system for sentinel lymph node biopsy in breast cancer patients using projection mapping with indocyanine green fluorescence.

PubMed

Takada, Masahiro; Takeuchi, Megumi; Suzuki, Eiji; Sato, Fumiaki; Matsumoto, Yoshiaki; Torii, Masae; Kawaguchi-Sakita, Nobuko; Nishino, Hiroto; Seo, Satoru; Hatano, Etsuro; Toi, Masakazu

2018-05-09

Inability to visualize indocyanine green fluorescence images in the surgical field limits the application of current near-infrared fluorescence imaging (NIR) systems for real-time navigation during sentinel lymph node (SLN) biopsy in breast cancer patients. The aim of this study was to evaluate the usefulness of the Medical Imaging Projection System (MIPS), which uses active projection mapping, for SLN biopsy. A total of 56 patients (59 procedures) underwent SLN biopsy using the MIPS between March 2016 and November 2017. After SLN biopsy using the MIPS, residual SLNs were removed using a conventional NIR camera and/or radioisotope method. The primary endpoint of this study was identification rate of SLNs using the MIPS. In all procedures, at least one SLN was detected by the MIPS, giving an SLN identification rate of 100% [95% confidence interval (CI) 94-100%]. SLN biopsy was successfully performed without operating lights in all procedures. In total, 3 positive SLNs were excised using MIPS, but were not included in the additional SLNs excised by other methods. The median number of SLNs excised using the MIPS was 3 (range 1-7). Of procedures performed after preoperative systemic therapy, the median number of SLNs excised using the MIPS was 3 (range 2-6). The MIPS is effective in detecting SLNs in patients with breast cancer, providing continuous and accurate projection of fluorescence signals in the surgical field, without need for operating lights, and could be useful in real-time navigation surgery for SLN biopsy.

Hybrid lymph node imaging using 64Cu-labeled mannose-conjugated human serum albumin with and without indocyanine green.

PubMed

Kang, Choong Mo; An, Gwang Il; Choe, Yearn Seong

2015-10-01

Human serum albumin (HSA), which has 58 Lys residues, one Cys residue, and indocyanine green (ICG) adsorption sites, can be used as a multifunctional platform for the development of hybrid imaging probes. In this study, we prepared 64Cu-labeled mannose-conjugated HSA with and without ICG ([64Cu]1-ICG and [64Cu]1, respectively) and compared hybrid PET/near-infrared fluorescence (NIRF) imaging with positron emission tomography (PET)/Cerenkov luminescence (CL) imaging of lymph nodes (LNs). 1,4,7,10-Tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid (DOTA)/mannose-conjugated HSA (1) was synthesized by conjugating mannose molecules to Lys residues and a DOTA molecule to a Cys residue of HSA. Compound 1 was then labeled with Cu ([64Cu]1), and the resulting [64Cu]1 was adsorbed with ICG ([64Cu]1-ICG). PET/NIRF or PET/CL imaging and subsequent biodistribution studies were performed in ICR mice after injection of the probes into the foot pads. The numbers of mannose and DOTA molecules conjugated to HSA were 7.17 ± 0.49 and 0.95 ± 0.18, respectively. The site-specific conjugation of one DOTA molecule to HSA was sufficient for 64Cu-labeling with high efficiency (96.0 ± 1.1%). PET/NIRF and PET/CL imaging and subsequent biodistribution studies demonstrated that the probes were avidly taken up by the popliteal LNs (PO), with a slightly higher uptake ratio of the PO to the lumbar LNs by [64Cu]1. In-vivo studies suggest that [64Cu]1 has more specific and selective binding to mannose receptors in the PO than [64Cu]1-ICG.

Prefabricated Cervical Skin Flaps for Hemi-Facial Resurfacing: Elucidating the Natural History of Postoperative Edema Using Indocyanine Green.

PubMed

Li, Ke; Min, Peiru; Sadigh, Parviz; Grassetti, Luca; Lazzeri, Davide; Torresetti, Matteo; Marsili, Riccardo; Feng, Shaoqing; Liu, Ningfei; Zhang, Yi Xin

2018-02-01

The increases in capillary wall permeability and capillary hydrostatic pressure are considered to be the causes for the acute swelling seen in flaps; however, disruption of the circulating flap lymphatics could be another contributory factor. In this study we monitor the development of flap edema in a series of 18 prefabricated flaps and aim to delineate the natural history of this phenomenon by use of lymphography. Postoperative swelling was monitored in a series of 18 pre-expanded prefabricated cervical skin flaps used for hemi-facial burns-scar resurfacing. Time to spontaneous resolution, presence or absence of venous congestion, and clinical outcome were recorded. In two cases, indocyanine-green (ICG) lymphography was used to monitor the dermal backflow pattern until swelling had completely resolved. Average moving velocity of ICG after injection as well as flap thickness was also recorded over the follow-up period. The average moving velocity of ICG in the flap lymphatics improved from 0.48 cm/min to 1.5 cm/min in the first 12 days after flap transfer. The dermal backflow pattern was stardust in the first 12 days, indicating moderate lymphedema, transforming to splash from week three, and a robust collecting lymphatic vessel occurring from the fifth month, indicating mild lymphedema and lymphatic channel recovery, respectively. Transient swelling was observed in all prefabricated flaps in our series. We postulate that this is mostly secondary to lymphatic disruption that subsides as lymphangiogenesis takes place. ICG lymphography is an inexpensive, safe, and easy-to-use imaging technology that could be used in the monitoring of postoperative lymphedema seen in prefabricated flaps.

Volumetric analysis and indocyanine green retention rate at 15 min as predictors of post-hepatectomy liver failure

PubMed Central

Kim, Hee Joon; Kim, Choong Young; Park, Eun Kyu; Hur, Young Hoe; Koh, Yang Seok; Kim, Hyun Jong; Cho, Chol Kyoon

2015-01-01

Objectives The actual future liver remnant (aFLR) is calculated as the ratio of remnant liver volume (RLV) to total functional liver volume (TFLV). The standardized future liver remnant (sFLR) is calculated as the ratio of RLV to standard liver volume (SLV). The aims of this study were to compare the aFLR with the sFLR and to determine criteria for safe hepatectomy using computed tomography volumetry and indocyanine green retention rate at 15 min (ICG R15). Methods Medical records and volumetric measurements were obtained retrospectively for 81 patients who underwent right hemi-hepatectomy for malignant hepatic tumours from January 2010 to November 2013. The sFLR was compared with the aFLR, and a ratio of sFLR to ICG R15 as a predictor of postoperative hepatic function was established. Results In patients without cirrhosis, the sFLR showed a stronger correlation with the total serum bilirubin level than the aFLR (R2 = 0.499 versus R2 = 0.239). Post-hepatectomy liver failure developed only in the group with an sFLR of <25%, regardless of ICG R15. In patients with cirrhosis, the aFLR and sFLR had no correlation with postoperative total serum bilirubin. An sFLR : ICG R15 ratio of >1.9 showed 66.7% sensitivity and 100% specificity. Conclusions Regardless of ICG R15, an sFLR of ≥25% in patients without cirrhosis, and an sFLR of ≥25% with an sFLR : ICG R15 ratio of >1.9 in patients with cirrhosis indicate acceptable levels of safety in major hepatectomy. PMID:24964188

Biliary tract visualization using near-infrared imaging with indocyanine green during laparoscopic cholecystectomy: results of a systematic review.

PubMed

Vlek, S L; van Dam, D A; Rubinstein, S M; de Lange-de Klerk, E S M; Schoonmade, L J; Tuynman, J B; Meijerink, W J H J; Ankersmit, M

2017-07-01

Near-infrared imaging with indocyanine green (ICG) has been extensively investigated during laparoscopic cholecystectomy (LC). However, methods vary between studies, especially regarding patient selection, dosage and timing. The aim of this systematic review was to evaluate the potential of the near-infrared imaging technique with ICG to identify biliary structures during LC. A comprehensive systematic literature search was performed. Prospective trials examining the use of ICG during LC were included. Primary outcome was biliary tract visualization. Risk of bias was assessed using ROBINS-I. Secondly, a meta-analysis was performed comparing ICG to intraoperative cholangiography (IOC) for identification of biliary structures. GRADE was used to assess the quality of the evidence. Nineteen studies were included. Based upon the pooled data from 13 studies, cystic duct (Lusch et al. in J Endourol 28:261-266, 2014) visualization was 86.5% (95% CI 71.2-96.6%) prior to dissection of Calot's triangle with a 2.5-mg dosage of ICG and 96.5% (95% CI 93.9-98.4%) after dissection. The results were not appreciably different when the dosage was based upon bodyweight. There is moderate quality evidence that the CD is more frequently visualized using ICG than IOC (RR 1.16; 95% CI 1.00-1.35); however, this difference was not statistically significant. This systematic review provides equal results for biliary tract visualization with near-infrared imaging with ICG during LC compared to IOC. Near-infrared imaging with ICG has the potential to replace IOC for biliary mapping. However, methods of near-infrared imaging with ICG vary. Future research is necessary for optimization and standardization of the near-infrared ICG technique.

Clinical utility of the additional use of blue dye for indocyanine green for sentinel node biopsy in breast cancer.

PubMed

Ji, Yinan; Luo, Ningbin; Jiang, Yi; Li, Qiuyun; Wei, Wei; Yang, Huawei; Liu, Jianlun

2017-07-01

Indocyanine green (ICG) is widely used as a tracer in sentinel lymph node biopsy (SLNB) of patients with breast cancer. Whether SLNB performance can be improved by supplementing ICG with methylene blue dye remains controversial. This study compared the performance of SLNB when ICG was used alone or with blue dye. Consecutive patients with T1-3 primary breast cancer at our hospital were recruited into our study and randomized to undergo SLNB with ICG alone (n = 62) or with the combination of ICG and blue dye (n = 65). We compared the two methods in terms of identification rate, number and detection time of sentinel lymph nodes (SLNs) removed. SLN identification rate were similar in the absence (95.2%) or presence of blue dye (98.5%, P = 0.578) but significantly, more average nodes were removed when blue dye was used (3.8 ± 1.5 versus 2.7 ± 1.2, P = 0.000), and the average time for detecting each SLN was significantly shorter (3.91 ± 1.87 versus 5.65 ± 2.95 min; P = 0.000). No patient in the study experienced severe adverse reactions or complications. Recurrence of axillary node was detected in one patient (1.6%) using ICG alone but not in any patients using ICG and blue dye. The efficiency and sensitivity of SLNB can be improved by combining ICG with blue dye. Copyright © 2017 Elsevier Inc. All rights reserved.

Smart human serum albumin-indocyanine green nanoparticles generated by programmed assembly for dual-modal imaging-guided cancer synergistic phototherapy.

PubMed

Sheng, Zonghai; Hu, Dehong; Zheng, Mingbin; Zhao, Pengfei; Liu, Huilong; Gao, Duyang; Gong, Ping; Gao, Guanhui; Zhang, Pengfei; Ma, Yifan; Cai, Lintao

2014-12-23

Phototherapy, including photodynamic therapy (PDT) and photothermal therapy (PTT), is a light-activated local treatment modality that is under intensive preclinical and clinical investigations for cancer. To enhance the treatment efficiency of phototherapy and reduce the light-associated side effects, it is highly desirable to improve drug accumulation and precision guided phototherapy for efficient conversion of the absorbed light energy to reactive oxygen species (ROS) and local hyperthermia. In the present study, a programmed assembly strategy was developed for the preparation of human serum albumin (HSA)-indocyanine green (ICG) nanoparticles (HSA-ICG NPs) by intermolecular disulfide conjugations. This study indicated that HSA-ICG NPs had a high accumulation with tumor-to-normal tissue ratio of 36.12±5.12 at 24 h and a long-term retention with more than 7 days in 4T1 tumor-bearing mice, where the tumor and its margin, normal tissue were clearly identified via ICG-based in vivo near-infrared (NIR) fluorescence and photoacoustic dual-modal imaging and spectrum-resolved technology. Meanwhile, HSA-ICG NPs efficiently induced ROS and local hyperthermia simultaneously for synergetic PDT/PTT treatments under a single NIR laser irradiation. After an intravenous injection of HSA-ICG NPs followed by imaging-guided precision phototherapy (808 nm, 0.8 W/cm2 for 5 min), the tumor was completely suppressed, no tumor recurrence and treatments-induced toxicity were observed. The results suggest that HSA-ICG NPs generated by programmed assembly as smart theranostic nanoplatforms are highly potential for imaging-guided cancer phototherapy with PDT/PTT synergistic effects.

Assessment of tumor angiogenesis using fluorescence contrast agents

NASA Astrophysics Data System (ADS)

Chen, Yu; Liu, Qian; Huang, Ping; Hyman, Shay; Intes, Xavier; Lee, William; Chance, Britton

2003-12-01

Angiogenesis is an important factor for further tumor growth and thus could be an attractive therapeutic target. Optical imaging can provide a non-invasive way to measure the permeability of tumor blood vessels and assess the tumor vasculature. We have developed a dual-channel near-infrared fluorescence system for simultaneous measurement of the pharmacokinetics of tumorous and normal tissues with exogenous contrast agents. This frequency-domain system consists of the light source (780 nm laser diode), fiber optics, interference filter (830 nm) and the detector (PMT). The fluorescent contrast agent used in this study is Indocyanine Green (ICG), and the normal dosage is 100 μl at a concentration of 5 μM. In vivo animal study is performed on the K1735 melanoma-bearing mouse. The fluorescence signals both tumorous and normal tissues after the bolus injection of ICG through the tail vein are continuously recorded as a function of time. The data is fitted by a double-exponential model to reveal the wash-in and wash-out parameters of different tissues. We observed an elongated wash-out from the tumor compared with normal tissue (leg). The effect of radiation therapy on the tumor vasculature is also discussed.

Assessment of inflow and washout of indocyanine green in the adult human brain by monitoring of diffuse reflectance at large source-detector separation

NASA Astrophysics Data System (ADS)

Liebert, Adam; Sawosz, Piotr; Milej, Daniel; Kacprzak, Michał; Weigl, Wojciech; Botwicz, Marcin; MaCzewska, Joanna; Fronczewska, Katarzyna; Mayzner-Zawadzka, Ewa; Królicki, Leszek; Maniewski, Roman

2011-04-01

Recently, it was shown in measurements carried out on humans that time-resolved near-infrared reflectometry and fluorescence spectroscopy may allow for discrimination of information originating directly from the brain avoiding influence of contaminating signals related to the perfusion of extracerebral tissues. We report on continuation of these studies, showing that the near-infrared light can be detected noninvasively on the surface of the tissue at large interoptode distance. A multichannel time-resolved optical monitoring system was constructed for measurements of diffuse reflectance in optically turbid medium at very large source-detector separation up to 9 cm. The instrument was applied during intravenous injection of indocyanine green and the distributions of times of flight of photons were successfully acquired showing inflow and washout of the dye in the tissue. Time courses of the statistical moments of distributions of times of flight of photons are presented and compared to the results obtained simultaneously at shorter source-detector separations (3, 4, and 5 cm). We show in a series of experiments carried out on physical phantom and healthy volunteers that the time-resolved data acquisition in combination with very large source-detector separation may allow one to improve depth selectivity of perfusion assessment in the brain.

Intraoperative imaging using intravascular contrast agent

NASA Astrophysics Data System (ADS)

Watson, Jeffrey R.; Martirosyan, Nikolay; Garland, Summer; Lemole, G. Michael; Romanowski, Marek

2016-03-01

Near-infrared (NIR) contrast agents are becoming more frequently studied in medical imaging due to their advantageous characteristics, most notably the ability to capture near-infrared signal across the tissue and the safety of the technique. This produces a need for imaging technology that can be specific for both the NIR dye and medical application. Indocyanine green (ICG) is currently the primary NIR dye used in neurosurgery. Here we report on using the augmented microscope we described previously for image guidance in a rat glioma resection. Luc-C6 cells were implanted in a rat in the left-frontal lobe and grown for 22 days. Surgical resection was performed by a neurosurgeon using augmented microscopy guidance with ICG contrast. Videos and images were acquired to evaluate image quality and resection margins. ICG accumulated in the tumor tissue due to enhanced permeation and retention from the compromised bloodbrain- barrier. The augmented microscope was capable of guiding the rat glioma resection and intraoperatively highlighted tumor tissue regions via ICG fluorescence under normal illumination of the surgical field.

Combination of Near Infrared Light-Activated Photodynamic Therapy Mediated by Indocyanine Green with Etoposide to Treat Non-Small-Cell Lung Cancer

PubMed Central

Luo, Ting; Zhang, Qinrong; Lu, Qing-Bin

2017-01-01

Indocyanine green (ICG) has been reported as a potential near-infrared (NIR) photosensitizer for photodynamic therapy (PDT) of cancer. However the application of ICG-mediated PDT is both intrinsically and physiologically limited. Here we report a combination of ICG-PDT with a chemotherapy drug etoposide (VP-16), aiming to enhance the anticancer efficacy, to circumvent limitations of PDT using ICG, and to reduce side effects of VP-16. We found in controlled in vitro cell-based assays that this combination is effective in killing non-small-cell lung cancer cells (NSCLC, A549 cell line). We also found that the combination of ICG-PDT and VP-16 exhibits strong synergy in killing non-small-cell lung cancer cells partially through inducing more DNA double-strand breaks (DSBs), while it has a much weaker synergy in killing human normal cells (GM05757). Furthermore, by studying the treatment sequence dependence and the cytotoxicity of laser-irradiated mixtures of ICG and VP-16, we found that the observed synergy involves direct/indirect reactions between ICG and VP-16. We further propose that there exists an electron transfer reaction between ICG and VP-16 under irradiation. This study therefore shows the anticancer efficacy of ICG-PDT combined with VP-16. These findings suggest that ICG-mediated PDT may be applied in combination with the chemotherapy drug VP-16 to treat some cancers, especially the non-small-cell lung cancer. PMID:28587258

An investigation of the application of laser-assisted indocyanine green fluorescent dye angiography in pedicle transverse rectus abdominus myocutaneous breast reconstruction.

PubMed

Newman, Martin I; Samson, Michel C; Tamburrino, Joseph F; Swartz, Kimberly A; Brunworth, Louis

2011-01-01

Pedicle transverse rectus abdominus myocutaneous (pTRAM) flaps remain the most common method of autologous tissue breast reconstruction. Using pTRAM flaps, complications often arise postoperatively, secondary to inadequate circulation. Tissues from distant angiosomes are associated with poorer perfusion, but this differs among patients. Many modalities have been used to reduce the risk of complications, but none have achieved widespread application. The authors believe that laser-assisted indocyanine green fluorescent dye angiography (LA-ICGA) can potentially reduce the risk of complications. In two routine, single-pedicle, ipsilateral pTRAM flaps, LA-ICGA imaging was performed following the division of the distal rectus muscle and deep inferior epigastric pedicle. The resulting images were used to guide design of the flap and debridement. In case 1, good perfusion was observed in zone 1 and part of zone 2. In case 2, good perfusion was observed in zone 1 and 50% of zone 3, with little perfusion in zone 2. In both cases, tissues with poor perfusion were debrided before transfer and inset. In both patients, there were no issues with wound healing, tissue necrosis or fat necrosis. The variability of perfusion of the pTRAM flap among individuals is well appreciated. LA-ICGA helped to determine the limits of good perfusion and, therefore, the limits of tissue to be preserved for transfer and inset. This helped to avoid harvesting poorly perfused tissue that would have almost certainly experienced necrosis and, ultimately, would have reduced the risk of postoperative complications.

Erythrocyte-Derived Nanoparticles as a Theranostic Agent for Near-Infrared Fluorescence Imaging and Thrombolysis of Blood Clots.

PubMed

Vankayala, Raviraj; Corber, Samantha R; Mac, Jenny T; Rao, Masaru P; Shafie, Mohammad; Anvari, Bahman

2018-04-01

Ischemic stroke occurs when a blood clot obstructs or narrows the arteries that supply blood to the brain. Currently, tissue plasminogen activator (tPA), a thrombolytic agent, is the only United States Food and Drug Administration (FDA)-approved pharmacologic treatment for ischemic stroke. Despite its effective usage, the major limitation of tPA that stems from its short half-life in plasma (≈5 min) is the potential for increased risk of hemorrhagic complications. To circumvent these limitations, herein, the first proof-of-principle demonstration of a theranostic nanoconstruct system derived from erythrocytes doped with the FDA-approved near-infrared (NIR) imaging agent, indocyanine green, and surface-functionalized with tPA is reported. Using a clot model, the dual functionality of these nanoconstructs in NIR fluorescence imaging and clot lysis is demonstrated. These biomimetic theranostic nanoconstructs may ultimately be effective in imaging and treatment of blood clots involved in ischemic stroke. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Surgical excision of filum terminale arteriovenous fistulae after lumbar fusion: Value of indocyanine green and theory on origins (a technical note and report of two cases)

PubMed Central

Trinh, Victoria T.; Duckworth, Edward A.M

2011-01-01

Background: Intradural filum terminale arteriovenous fistulas (AVFs) are uncommon. We report two cases of this rare entity in which we used indocyanine green (ICG) videoangiography to identify the fistulous connection of each lesion. Case Description: Two male patients presented with unresolved lower extremity weakness and paresthesias following lumbar fusion surgery. In each case, angiography showed an AVF between the filum terminale artery (FTA), the distal segment of the anterior spinal artery (ASA), and an accompanying vein of the filum terminale. A magnetic resonance image (MRI) obtained before lumbar fusion was available in one of these cases and demonstrated evidence of the preexisting vascular malformation. Surgical obliteration of each fistulous connection was facilitated by the use of ICG videoangiography. This emerging technology was instrumental in pinpointing fistula anatomy and in choosing the exact segment of the filum for disconnection. Conclusion: Our findings indicate that intradural filum terminale AVFs may have a congenital origin and that ICG is a useful tool in their successful surgical management. As these cases demonstrate, spine surgeons should remain vigilant in evaluating patients based on their clinical symptomatology, even in the presence of obvious lumbar pathology. PMID:21697980

Fluorescence-enhanced robotic radical prostatectomy using real-time lymphangiography and tissue marking with percutaneous injection of unconjugated indocyanine green: the initial clinical experience in 50 patients.

PubMed

Manny, Ted B; Patel, Manish; Hemal, Ashok K

2014-06-01

Pilot studies have demonstrated the utility of indocyanine green (ICG) sentinel lymphadenectomy for prostate cancer. Prior work has used ICG with radiocontrast agents injected at a separate procedure and relied on assistant-controlled fluorescence systems, making the technique costly and cumbersome. To describe the initial optimization and feasibility of fluorescence-enhanced robotic radical prostatectomy (FERRP) using real-time injection of ICG for tissue marking and identification of sentinel lymphatic drainage visualized by a fully integrated surgeon-controlled system. Patients with clinically localized prostate cancer at a tertiary referral center were offered FERRP. Ten patients participated in a pilot arm in which ICG dosing and injection technique were optimized. Fifty consecutive patients then underwent FERRP. After development of the space of Retzius, 0.4 ml of a 2.5 mg/ml ICG solution were injected into each lobe of the prostate using a robotically guided percutaneous needle. After ICG was allowed to travel through the pelvic lymphatics, lymphadenectomy was performed from the endopelvic fascia to the aortic bifurcation. Parameters describing the time course of tissue fluorescence and pelvic lymphangiography were systematically recorded. Lymphatic packets containing fluorescent nodes were considered sentinel. Percutaneous, robotic-guided ICG injection proved superior to cystoscope or transrectal delivery. Tissue marking was achieved in all patients, positively identifying the prostate with uniform fluorescence relative to the obturator nerve, seminal vesicles, vas deferens, and neurovascular pedicles at a mean time of 10 min postinjection. Sentinel nodes were identified in 76% of patients at a mean time of 30 min postinjection and had 100% sensitivity, 75.4% specificity, 14.6% positive predictive value, and 100% negative predictive value for the detection of nodal metastasis. FERRP is safe, feasible, and allows for reliable prostate tissue marking and

pH triggered in vivo photothermal therapy and fluorescence nanoplatform of cancer based on responsive polymer-indocyanine green integrated reduced graphene oxide.

PubMed

Sharker, Shazid Md; Lee, Jung Eun; Kim, Sung Han; Jeong, Ji Hoon; In, Insik; Lee, Haeshin; Park, Sung Young

2015-08-01

We have synthesized a pH-dependent, NIR-sensitive, reduced graphene oxide (rGO) hybrid nano-composite via electrostatic interaction with indocyanine green (ICG) which is designed not only to destroy localized cancer cells but also be minimally invasive to surrounding normal cells. The near-infrared (NIR) irradiated hybrid nano-composites showed pH dependent photo-thermal heat generation capability from pH 5.0 to 7.4 due to the pH response relief and quenching effects of poly(2-dimethyl amino ethyl methacrylate) [poly(PDMAEMA)] with ICG on a single rGO sheet. This pH-triggered relief and quenching mechanism regulated in vitro photo-thermolysis as the pH changed from 5.0 to 7.4. The in vitro cellular uptake and confocal laser scan microscopic (CLSM) images at different pH values show promise for environment sensitive bio-imaging. The NIR-absorbing hybrid nanomaterials showed a remarkably improved in vitro cancer cell targeted photothermal destruction compared to free ICG. Upon local NIR irradiation, these hybrid nano-composites-treated tumors showed necrotic, shrunken, ablation of malignant cells and totally healed after 18 days treatment. Our finding regarding the acidic pH stimulus of cancer cellular environment has proven to be a wining platform for the fight against cancer. Copyright © 2015 Elsevier Ltd. All rights reserved.

A Real-Time Near-Infrared Fluorescence Imaging Method for the Detection of Oral Cancers in Mice Using an Indocyanine Green-Labeled Podoplanin Antibody.

PubMed

Ito, Akihiro; Ohta, Mitsuhiko; Kato, Yukinari; Inada, Shunko; Kato, Toshio; Nakata, Susumu; Yatabe, Yasushi; Goto, Mitsuo; Kaneda, Norio; Kurita, Kenichi; Nakanishi, Hayao; Yoshida, Kenji

2018-01-01

Podoplanin is distinctively overexpressed in oral squamous cell carcinoma than oral benign neoplasms and plays a crucial role in the pathogenesis and metastasis of oral squamous cell carcinoma but its diagnostic application is quite limited. Here, we report a new near-infrared fluorescence imaging method using an indocyanine green (ICG)-labeled anti-podoplanin antibody and a desktop/a handheld ICG detection device for the visualization of oral squamous cell carcinoma-xenografted tumors in nude mice. Both near-infrared imaging methods using a desktop (in vivo imaging system: IVIS) and a handheld device (photodynamic eye: PDE) successfully detected oral squamous cell carcinoma tumors in nude mice in a podoplanin expression-dependent manner with comparable sensitivity. Of these 2 devices, only near-infrared imaging methods using a handheld device visualized oral squamous cell carcinoma xenografts in mice in real time. Furthermore, near-infrared imaging methods using the handheld device (PDE) could detect smaller podoplanin-positive oral squamous cell carcinoma tumors than a non-near-infrared, autofluorescence-based imaging method. Based on these results, a near-infrared imaging method using an ICG-labeled anti-podoplanin antibody and a handheld detection device (PDE) allows the sensitive, semiquantitative, and real-time imaging of oral squamous cell carcinoma tumors and therefore represents a useful tool for the detection and subsequent monitoring of malignant oral neoplasms in both preclinical and some clinical settings.

Comparison of indocyanine green fluorescence and parathyroid autofluorescence imaging in the identification of parathyroid glands during thyroidectomy

PubMed Central

Kahramangil, Bora

2017-01-01

Background Indocyanine green fluorescence (ICGF) and parathyroid autofluorescence (AF) are two new techniques that aid in the identification of parathyroid glands (PG) intraoperatively during thyroidectomy. There is no study comparing the efficacy of these techniques. Methods This was an IRB-approved clinical study comparing the utility of ICGF and AF for identification of PGs during thyroidectomy. Data were collected prospectively. Both techniques were compared to naked eye (NE) for PG detection. Standard statistical methods were used for data analysis. Results Twenty-two patients in each group underwent a total of 39 total thyroidectomies and 5 thyroid lobectomies. AF and ICGF had similar detection rates for PGs [98% (61 of 62) and 95% (60 of 63) of PGs, respectively; P=0.31]. The location of PGs was suggested before detection with NE more frequently by AF than ICGF [52% (32 of 62) vs. 6% (4 of 63) of PGs; P<0.001]. In 82% (18 of 22) of patients at least one PG was detected by AF before NE, as opposed to 14% (3 of 22) by ICGF (P<0.001). The median (range) number of PGs detected before NE per patient was greater with AF than ICGF [2 (0–3) vs. 0 (0–2)];. Upper PGs were more likely to be detected by AF before recognition with NE than the lower ones (P=0.03). There was no predictive factor for ICGF detection. Postoperative hypocalcemia rates were similar [9% (2 of 22) and 5% (1 of 22) for AF and ICGF, respectively; P>0.99]. Conclusions To the best of our knowledge, this is the first comparative study between parathyroid AF and ICGF in detection of PGs during thyroidectomy. Our data suggest both techniques have similarly high detection rates and that the main difference lies in the timing of detection. AF more frequently detects PGs before recognition with NE compared to ICGF. PMID:29302480

The Predictive Value of Indocyanine Green Clearance in Future Liver Remnant for Posthepatectomy Liver Failure Following Hepatectomy with Extrahepatic Bile Duct Resection.

PubMed

Yokoyama, Yukihiro; Ebata, Tomoki; Igami, Tsuyoshi; Sugawara, Gen; Mizuno, Takashi; Yamaguchi, Junpei; Nagino, Masato

2016-06-01

Postoperative liver failure (PHLF) is one of the most common complications following major hepatectomy. The preoperative assessment of future liver remnant (FLR) function is critical to predict the incidence of PHLF. To determine the efficacy of the plasma clearance rate of indocyanine green clearance of FLR (ICGK-F) in predicting PHLF in cases of highly invasive hepatectomy with extrahepatic bile duct resection. Five hundred and eighty-five patients who underwent major hepatectomy with extrahepatic bile duct resection, from 2002 to 2014 in a single institution, were evaluated. Among them, 192 patients (33 %) had PHLF. The predictive value of ICGK-F for PHLF was determined and compared with other risk factors for PHLF. The incidence of PHLF was inversely proportional to the level of ICGK-F. With multivariate logistic regression analysis, ICGK-F, combined pancreatoduodenectomy, the operation time, and blood loss were identified as independent risk factors of PHLF. The risk of PHLF increased according to the decrement of ICGK-F (the odds ratio of ICGK-F for each decrement of 0.01 was 1.22; 95 % confidence interval 1.12-1.33; P < 0.001). Low ICGK-F was also identified as an independent risk factor predicting the postoperative mortality. ICGK-F is useful in predicting the PHLF and mortality in patients undergoing major hepatectomy with extrahepatic bile duct resection. This criterion may be useful for highly invasive hepatectomy, such as that with extrahepatic bile duct resection.

20 g PPV with indocyanine green-assisted ILM peeling versus 23 g PPV with brilliant blue G-assisted ILM peeling for epiretinal membrane.

PubMed

Manousaridis, Kleanthis; Peter, Silvia; Mennel, Stefan

2016-06-01

To compare the anatomical and visual outcomes of 20 gauge (g) pars plana vitrectomy (PPV) with indocyanine green (ICG)-assisted internal limiting membrane (ILM) peeling and 23 g PPV with brilliant blue G (BBG)-assisted ILM peeling for idiopathic epiretinal membrane (ERM). 38 eyes of 38 patients with idiopathic ERM were included. They were divided in two groups: group 1 (18 eyes) underwent 20 g PPV with ICG-assisted ILM peeling and group 2 (20 eyes) 23 g PPV with BBG-assisted ILM peeling. Postoperative best-corrected visual acuity (BCVA) and central macular thickness (CMT) were compared. Average BCVA in group 1 improved significantly from 0.60 logarithm of the minimal angle of resolution (log MAR) at baseline to 0.3 log MAR postoperatively. Average BCVA in group 2 improved significantly from 0.60 log MAR at baseline to 0.3 log MAR postoperatively. Mean CMT reduced significantly from 473 to 375 μm in group 1 and from 486 to 396 μm in group 2. There were no significant differences in the BCVA and CMT between the groups. Both surgical methods appeared to be safe and provided similar anatomical and visual outcomes.

Feasibility Study for the Use of Green, Bio-Based, Efficient Reactive Sorbent Material to Neutralize Chemical Warfare Agents

DTIC Science & Technology

2012-08-02

REPORT Feasibility study for the use of green, bio-based, efficient reactive sorbent material to neutralize chemical warfare agents 14. ABSTRACT 16...way cellulose, lignin and hemicelluloses interact as well as whole wood dissolution occurs in ILs. The present project was conducted to 1. REPORT...Feasibility study for the use of green, bio-based, efficient reactive sorbent material to neutralize chemical warfare agents Report Title ABSTRACT Over the

Fluorescence-enhanced robotic radical cystectomy using unconjugated indocyanine green for pelvic lymphangiography, tumor marking, and mesenteric angiography: the initial clinical experience.

PubMed

Manny, Ted B; Hemal, Ashok K

2014-04-01

To describe the initial feasibility of fluorescence-enhanced robotic radical cystectomy (FERRC) using real-time cystoscopic injection of unconjugated indocyanine green (ICG) for tumor marking and identification of sentinel lymphatic drainage with additional intravenous injection for mesenteric angiography. Ten patients with clinically localized high-grade bladder cancer underwent FERRC. Before robot docking, rigid cystoscopy was performed, during which a 2.5-mg/mL ICG solution was injected in the bladder submucosa and detrusor circumferentially around the tumor. After robot docking, parameters describing the time course of tissue fluorescence and pelvic lymphangiography were systematically recorded. Lymphatic packets containing fluorescent lymph nodes were considered the sentinel drainage. Eight patients underwent intracorporeal ileal conduit urinary diversion, during which an additional 2-mL ICG solution was given intravenously for mesenteric angiography, allowing maximal preservation of bowel vascularity to the conduit and remaining bowel segments. Bladder tumor marking and identification of sentinel drainage were achieved in 9 of 10 (90%) patients. The area of bladder tumor was identified at a median of 15 minutes after injection, whereas sentinel drainage was visualized at a median of 30 minutes. Mesenteric angiography was successful in 8 of 8 (100%) patients at a median time of <1 minutes after intravenous injection and enabled identification of bowel arcades before intracorporeal bowel stapling. FERRC using combined cystoscopic and intravenous injection of ICG is safe and feasible. FERRC allows for reliable bladder tumor marking, identification of sentinel lymphatic drainage, and identification of mesenteric vasculature in most patients. Copyright © 2014 Elsevier Inc. All rights reserved.

An investigation of the application of laser-assisted indocyanine green fluorescent dye angiography in pedicle transverse rectus abdominus myocutaneous breast reconstruction

PubMed Central

Newman, Martin I; Samson, Michel C; Tamburrino, Joseph F; Swartz, Kimberly A; Brunworth, Louis

2011-01-01

BACKGROUND: Pedicle transverse rectus abdominus myocutaneous (pTRAM) flaps remain the most common method of autologous tissue breast reconstruction. Using pTRAM flaps, complications often arise postoperatively, secondary to inadequate circulation. Tissues from distant angiosomes are associated with poorer perfusion, but this differs among patients. Many modalities have been used to reduce the risk of complications, but none have achieved widespread application. The authors believe that laser-assisted indocyanine green fluorescent dye angiography (LA-ICGA) can potentially reduce the risk of complications. METHODS: In two routine, single-pedicle, ipsilateral pTRAM flaps, LA-ICGA imaging was performed following the division of the distal rectus muscle and deep inferior epigastric pedicle. The resulting images were used to guide design of the flap and debridement. RESULTS: In case 1, good perfusion was observed in zone 1 and part of zone 2. In case 2, good perfusion was observed in zone 1 and 50% of zone 3, with little perfusion in zone 2. In both cases, tissues with poor perfusion were debrided before transfer and inset. In both patients, there were no issues with wound healing, tissue necrosis or fat necrosis. CONCLUSIONS: The variability of perfusion of the pTRAM flap among individuals is well appreciated. LA-ICGA helped to determine the limits of good perfusion and, therefore, the limits of tissue to be preserved for transfer and inset. This helped to avoid harvesting poorly perfused tissue that would have almost certainly experienced necrosis and, ultimately, would have reduced the risk of postoperative complications. PMID:22379372

Small animal optoacoustic tomography system for molecular imaging of contrast agents

NASA Astrophysics Data System (ADS)

Su, Richard; Liopo, Anton; Ermilov, Sergey A.; Oraevsky, Alexander A.

2016-03-01

We developed a new and improved Laser Optoacoustic Imaging System, LOIS-3D for preclinical research applications in small animal models. The advancements include (i) a new stabilized imaging module with a more homogeneous illumination of the mouse yielding a better spatial resolution (<0.2 mm) and (ii) a new low noise amplifier incorporated into the ultrasonic probe and providing the noise equivalent pressure around 2 Pa resulting in increased signal-to-noise ratio and the optical absorption sensitivity of about 0.15 cm-1. We also improved scan time and the image reconstruction times. This prototype has been commercialized for a number of biomedical research applications, such as imaging vascularization and measuring hemoglobin / oxyhemoglobin distribution in the organs as well as imaging exogenous or endogenous optoacoustic contrast agents. As examples, we present in vivo experiments using phantoms and mice with and without tumor injected with contrast agents with indocyanine green (ICG). LOIS-3D was capable of detecting ~1-2 pmole of the ICG, in tissues with relatively low blood content. With its high sensitivity and excellent spatial resolution LOIS-3D is an advanced alternative to fluorescence and bioluminescence based modalities for molecular imaging in live mice.

Microscope-integrated quantitative analysis of intraoperative indocyanine green fluorescence angiography for blood flow assessment: first experience in 30 patients.

PubMed

Kamp, Marcel A; Slotty, Philipp; Turowski, Bernd; Etminan, Nima; Steiger, Hans-Jakob; Hänggi, Daniel; Stummer, Walter

2012-03-01

Intraoperative measurements of cerebral blood flow are of interest during vascular neurosurgery. Near-infrared indocyanine green (ICG) fluorescence angiography was introduced for visualizing vessel patency intraoperatively. However, quantitative information has not been available. To report our experience with a microscope with an integrated dynamic ICG fluorescence analysis system supplying semiquantitative information on blood flow. We recorded ICG fluorescence curves of cortex and cerebral vessels using software integrated into the surgical microscope (Flow 800 software; Zeiss Pentero) in 30 patients undergoing surgery for different pathologies. The following hemodynamic parameters were assessed: maximum intensity, rise time, time to peak, time to half-maximal fluorescence, cerebral blood flow index, and transit times from arteries to cortex. For patients without obvious perfusion deficit, maximum fluorescence intensity was 177.7 arbitrary intensity units (AIs; 5-mg ICG bolus), mean rise time was 5.2 seconds (range, 2.9-8.2 seconds; SD, 1.3 seconds), mean time to peak was 9.4 seconds (range, 4.9-15.2 seconds; SD, 2.5 seconds), mean cerebral blood flow index was 38.6 AI/s (range, 13.5-180.6 AI/s; SD, 36.9 seconds), and mean transit time was 1.5 seconds (range, 360 milliseconds-3 seconds; SD, 0.73 seconds). For 3 patients with impaired cerebral perfusion, time to peak, rise time, and transit time between arteries and cortex were markedly prolonged (>20, >9 , and >5 seconds). In single patients, the degree of perfusion impairment could be quantified by the cerebral blood flow index ratios between normal and ischemic tissue. Transit times also reflected blood flow perturbations in arteriovenous fistulas. Quantification of ICG-based fluorescence angiography appears to be useful for intraoperative monitoring of arterial patency and regional cerebral blood flow.

Contribution of Dual Fluorescein and Indocyanine Green Angiography to the Appraisal of Presumed Tuberculous Chorioretinitis in a Non-endemic Area

PubMed Central

Massy, Raphael; Herbort, Carl P.

2017-01-01

Purpose: To assess the respective involvement of retina versus choroid in presumed ocular tuberculosis (POT) in a non-endemic area using dual fluorescein (FA) and indocyanine green angiography (ICGA). Methods: We retrospectively analyzed cases diagnosed with POT at the Centre for Ophthalmic Specialized Care, Lausanne, Switzerland. Angiography signs were quantified using an established dual FA and ICGA scoring system for uveitis. Results: Out of 1739 uveitis patients visited from 1995 to 2014, 53 (3%) were diagnosed with POT; of whom 28 patients (54 eyes) had sufficient data available to be included in this study. Of 54 affected eyes, 39 showed predominant choroidal involvement, 14 showed predominant retinal involvement and one had equal retinal and choroidal scores. Mean angiographic score was 6.97 ± 5.08 for the retina versus 13.48 ± 7.06 for the choroid (P < 0.0001). For patients with sufficient angiographic follow-up after combined anti-tuberculous and inflammation suppressive therapy, mean FA and ICGA scores decreased from 6.97 ± 5.08 to 3.63 ± 3.14 (P = 0.004), and 13.48 ± 7.06 to 7.47 ± 5.58 (P < 0.0001), respectively. Conclusion: These results represent the first report of the respective contributions of retinal and choroidal involvement in POT. Choroidal involvement was more common, for which ICGA is the preferred examination. In cases of compatible uveitis with positive results of an interferon-gamma release assay, particularly in a region that is non-endemic for TB, dual FA and ICGA should be performed to help establish the diagnosis of ocular tuberculosis and improve follow-up. PMID:28299004

Indocyanine Green Clearance Varies as a Function of N-Acetylcysteine Treatment in a Murine Model of Acetaminophen Toxicity

PubMed Central

Milesi-Hallé, Alessandra; Abdel-Rahman, Susan M.; Brown, Aliza; McCullough, Sandra S.; Letzig, Lynda; Hinson, Jack A.; James, Laura P.

2011-01-01

Standard assays to assess acetaminophen (APAP) toxicity in animal models include determination of ALT (alanine aminotransferase) levels and examination of histopathology of liver sections. However, these assays do not reflect the functional capacity of the injured liver. To examine a functional marker of liver injury, the pharmacokinetics of indocyanine green (ICG) were examined in mice treated with APAP, saline, or APAP followed by N-acetylcysteine (NAC) treatment. Male B6C3F1 mice were administered APAP (200 mg/kg IP) or saline. Two additional groups of mice received APAP followed by NAC at 1 or 4 h after APAP. At 24 h, mice were injected with ICG (10 mg/kg IV) and serial blood samples (0, 2, 10, 30, 50 and 75 min) were obtained for determination of serum ICG concentrations and ALT. Mouse livers were removed for measurement of APAP protein adducts and examination of histopathology. Toxicity (ALT values and histology) was significantly increased above saline treated mice in the APAP and APAP/NAC 4 h mice. Mice treated with APAP/NAC 1 h had complete protection from toxicity. APAP protein adducts were increased in all APAP treated groups and were highest in the APAP/NAC 1 h group. Pharmacokinetic analysis of ICG demonstrated that the total body clearance (ClT) of ICG was significantly decreased and the mean residence time (MRT) was significantly increased in the APAP mice compared to the saline mice. Mice treated with NAC at 1 h had ClT and MRT values similar to those of saline treated mice. Conversely, mice that received NAC at 4 h had a similar ICG pharmacokinetic profile to that of the APAP only mice. Prompt treatment with NAC prevented loss of functional activity while late treatment with NAC offered no improvement in ICG clearance at 24 h. ICG clearance in mice with APAP toxicity can be utilized in future studies testing the effects of novel treatments for APAP toxicity. PMID:21145883

Determination of plasma volume by indocyanine green--validation of the method and use in patients after cardiopulmonary bypass.

PubMed

Menth-Meier, S E; Imoberdorf, R; Regli, B; Kipfer, B; Turgay, M; Ballmer, P E

2001-05-01

Validation of plasma volume (PV) determination by indocyanine green (ICG) in comparison to the gold-standard method with radioiodinated albumin, and investigation of the effect of commonly used plasma expanders (albumin, hydroxyethyl starch, and polygelatine) on PV in the early postoperative phase in patients undergoing cardiac surgery. Prospective clinical study. Department of medicine and intensive care unit at a university hospital. Ten healthy volunteers and 21 patients after elective open-heart surgery. PV of subjects was measured by i.v. injecting 5 microCi [125I]albumin (I-ALB). One hour later, PV was determined by a peripheral i. v. injection of 0.25 mg/kg body weight ICG (ICG1). In five subjects PV was measured repeatedly by ICG (ICG2) 1 h after ICG1. Mean PV of I-ALB and ICG1 or ICG2 showed consistent results. Further, we investigated central vs peripheral intravenous injection of ICG in six patients after open-heart surgery compared to [125I]albumin. There was no difference between mean PV measured by [125I]albumin and peripheral ICG (P = 0.40). PV determined by central injection of ICG was significantly higher than by the other methods. In 15 patients PV was determined by [125I]albumin. Thereafter, patients were randomly divided into three groups. Group ALB was infused with 1.75 ml/kg body weight human albumin 20%, group HAES with 5.25 ml/kg body weight hydroxyethyl starch 6%, and group HAEM with 7.0 ml/kg body weight polygelatine 3.5%. PV was measured 1 h and 4 h after infusion by ICG. There were no significant changes in PV between the groups. PV determination by peripheral i. v. injection of ICG produced reliable and consistent results when a reactive hyperaemia was produced by a tourniquet prior to injection. Therefore, central venous injection of ICG may not be prerequisite for precise measurements of PV. The expected acute increase in PV after infusion of commonly used plasma expanders after cardiac surgery was not found.

Near-infrared lymphatic imaging demonstrates the dynamics of lymph flow and lymphangiogenesis during the acute versus chronic phases of arthritis in mice.

PubMed

Zhou, Quan; Wood, Ronald; Schwarz, Edward M; Wang, Yong-Jun; Xing, Lianping

2010-07-01

To develop an in vivo imaging method to assess lymphatic draining function in the K/BxN mouse model of inflammatory arthritis. Indocyanine green, a near-infrared fluorescent dye, was injected intradermally into the footpads of wild-type mice, mouse limbs were illuminated with an 806-nm near-infrared laser, and the movement of indocyanine green from the injection site to the draining popliteal lymph node (LN) was recorded with a CCD camera. Indocyanine green near-infrared images were analyzed to obtain 5 measures of lymphatic function across time. Images of K/BxN arthritic mice and control nonarthritic littermates were obtained at 1 month of age, when acute joint inflammation commenced, and again at 3 months of age, when joint inflammation became chronic. Lymphangiogenesis in popliteal LNs was assessed by immunochemistry. Indocyanine green and its transport within lymphatic vessels were readily visualized, and quantitative measures were derived. During the acute phase of arthritis, the lymphatic vessels were dilated, with increased indocyanine green signal intensity and lymphatic pulses, and popliteal LNs became fluorescent quickly. During the chronic phase, new lymphatic vessels were present near the foot. However, the appearance of indocyanine green in lymphatic vessels was delayed. The size and area of popliteal LN lymphatic sinuses progressively increased in the K/BxN mice. Our findings indicate that indocyanine green near-infrared lymphatic imaging is a valuable method for assessing the lymphatic draining function in mice with inflammatory arthritis. Indocyanine green-near-infrared imaging of K/BxN mice identified 2 distinct lymphatic phenotypes during the acute and chronic phase of inflammation. This technique can be used to assess new therapies for lymphatic disorders.

Superselective intra-arterial hepatic injection of indocyanine green (ICG) for fluorescence image-guided segmental positive staining: experimental proof of the concept.

PubMed

Diana, Michele; Liu, Yu-Yin; Pop, Raoul; Kong, Seong-Ho; Legnèr, Andras; Beaujeux, Remy; Pessaux, Patrick; Soler, Luc; Mutter, Didier; Dallemagne, Bernard; Marescaux, Jacques

2017-03-01

Intraoperative liver segmentation can be obtained by means of percutaneous intra-portal injection of a fluorophore and illumination with a near-infrared light source. However, the percutaneous approach is challenging in the minimally invasive setting. We aimed to evaluate the feasibility of fluorescence liver segmentation by superselective intra-hepatic arterial injection of indocyanine green (ICG). Eight pigs (mean weight: 26.01 ± 5.21 kg) were involved. Procedures were performed in a hybrid experimental operative suite equipped with the Artis Zeego ® , multiaxis robotic angiography system. A pneumoperitoneum was established and four laparoscopic ports were introduced. The celiac trunk was catheterized, and a microcatheter was advanced into different segmental hepatic artery branches. A near-infrared laparoscope (D-Light P, Karl Storz) was used to detect the fluorescent signal. To assess the correspondence between arterial-based fluorescence demarcation and liver volume, metallic markers were placed along the fluorescent border, followed by a 3D CT-scanning, after injecting intra-arterial radiological contrast (n = 3). To assess the correspondence between arterial and portal supplies, percutaneous intra-portal angiography and intra-arterial angiography were performed simultaneously (n = 1). Bright fluorescence signal enhancing the demarcation of target segments was obtained from 0.1 mg/mL, in matter of seconds. Correspondence between the volume of hepatic segments and arterial territories was confirmed by CT angiography. Higher background fluorescence noise was found after positive staining by intra-portal ICG injection, due to parenchymal accumulation and porto-systemic shunting. Intra-hepatic arterial ICG injection, rapidly highlights hepatic target segment borders, with a better signal-to-background ratio as compared to portal vein injection, in the experimental setting.

Indocyanine green retention test (ICG-r15) as a noninvasive predictor of portal hypertension in patients with different severity of cirrhosis.

PubMed

Pind, Marie-Louise L; Bendtsen, Flemming; Kallemose, Thomas; Møller, Søren

2016-08-01

Portal hypertension is a severe consequence of chronic liver disease, responsible for the main clinical complications of cirrhosis. Measurement of the hepatic venous pressure gradient (HVPG) provides important clinical information, but the procedure is invasive and demands expert skills of the staff.In the present study, we aimed to investigate the relationship between the constant infusion indocyanine green (ICG) clearance, the calculated ICG retention test after 15 min (ICG-r15), and HVPG in patients with different severity of cirrhosis for validation of ICG-r15 as a noninvasive predictor of portal hypertension. A total of 325 patients were studied. During a hemodynamic investigation, the ICG clearance was determined using the constant infusion technique and ICG-r15 was calculated. Assessment of the diagnostic performance of ICG clearance and ICG-r15 as predictors of HVPG above 10 mmHg was performed by receiver operating characteristic curve analyses.The ICG clearance and ICG-r15 performed well in all three Child classes, with the most significant results among Child class A patients [area under the receiver operating characteristic (AUROC)=0.832] and less significant results in Child class B (AUROC=0.7448) and Child class C patients (AUROC=0.7392). Only six out of 102 patients in Child class C had HVPG of less than 12 mmHg. ICG-r15 can be used as an indirect assessment of significant portal hypertension in compensated cirrhotic patients. ICG-r15 may be suitable as a screening tool for the identification of patients for endoscopy and measurement of HVPG.Further validation of ICG-r15 together with other predictors of portal hypertension and its clinical use is encouraged.

Near-infrared fluorescence cholangiography with indocyanine green for biliary atresia. Real-time imaging during the Kasai procedure: a pilot study.

PubMed

Hirayama, Yutaka; Iinuma, Yasushi; Yokoyama, Naoyuki; Otani, Tetsuya; Masui, Daisuke; Komatsuzaki, Naoko; Higashidate, Naruki; Tsuruhisa, Shiori; Iida, Hisataka; Nakaya, Kengo; Naito, Shinichi; Nitta, Koju; Yagi, Minoru

2015-12-01

Hepatoportoenterostomy (HPE) with the Kasai procedure is the treatment of choice for biliary atresia (BA) as the initial surgery. However, the appropriate level of dissection level of the fibrous cone (FC) of the porta hepatis (PH) is frequently unclear, and the procedure sometimes results in unsuccessful outcomes. Recently, indocyanine green near-infrared fluorescence imaging (ICG-FCG) has been developed as a form of real-time cholangiography. We applied this technique in five patients with BA to visualize the biliary flow at the PH intraoperatively. ICG was injected intravenously the day before surgery as the liver function test, and the liver was observed with a near-infrared camera system during the operation while the patient's feces was also observed. In all patients, the whole liver fluoresced diffusely with ICG-containing stagnant bile, whereas no extrahepatic structures fluoresced. The findings of the ICG fluorescence pattern of the PH after dissection of the FC were classified into three types: spotty fluorescence, one patient; diffuse weak fluorescence, three patients; and diffuse strong fluorescence, one patient. In all five patients, the feces evacuated after HPE showed distinct fluorescent spots, although that obtained before surgery showed no fluorescence. One patient with diffuse strong fluorescence who did not achieve JF underwent living related liver transplantation six months after the initial HPE procedure. Four patients, including three cases involving diffuse weak fluorescence and one case involving spotty fluorescence showed weak fluorescence compared to that of the surrounding liver surface. We were able to detect the presence of bile excretion at the time of HPE intraoperatively and successfully evaluated the extent of bile excretion using this new technique. Furthermore, the ICG-FCG findings may provide information leading to a new classification and potentially function as an indicator predicting the clinical outcomes after HPE.

Intraoperative use of indocyanine green angiography for selecting the more reliable perforator of the anterolateral thigh flap: A comparison study.

PubMed

La Padula, Simone; Hersant, Barbara; Meningaud, Jean Paul

2018-03-30

Anatomical variability of anterolateral thigh flap (ALT) perforators has been reported. The aim of this study is to assess if the use of intraoperative indocyanine green angiography (iICGA) can help surgeons to choose the ALT flap best perforator to be preserved. A retrospective study was conducted in 28 patients with open tibial fracture, following a road traffic crash, who had undergone ALT flap. Patients were classified into two groups: ICGA group (iICGA was used to select the more reliable perforator) and control group. The mean tissue loss size of the ICGA group (n = 13, 11 men and 2 women, mean age: 52 ± 6 years) was of 16.6 cm × 12.2 cm. The mean defect size of the control group (n = 15, 14 men and 1 women, mean age: 50 ± 5.52 years) was of 15.3 cm × 11.1 cm. Statistical analysis was performed to analyze and compare the results. ICGA allowed preserving only the most functional perforator, that provided the best ALT flap perfusion in 10 out of the 13 cases (77%). ICGA allowed a significant operative time reduction (160 ± 23 vs. 202 ± 48 minutes; P < .001). One case of distal necrosis was observed in the ICGA group (mean follow-up 12.3 months), while partial skin necrosis occurred in three cases of the control group (mean follow-up 13.1 months); P = .35. No additional coverage was required and a successful bone healing was observed in both groups. These findings suggest that iICGA is an effective method that allows to select the most reliable ALT flap perforators and to reduce operative time. © 2018 Wiley Periodicals, Inc.

Surgical Strategy Based on Indocyanine Green Test for Chemotherapy-Associated Liver Injury and Long-Term Outcome in Colorectal Liver Metastases.

PubMed

Takamoto, Takeshi; Hashimoto, Takuya; Ichida, Akihiko; Shimada, Kei; Maruyama, Yoshikazu; Makuuchi, Masatoshi

2018-06-01

It remains unclear whether the presence of chemotherapy-induced liver injury (CALI) or impaired liver functional reserve affects the long-term outcome. This study assessed the applicability and long-term effects of using criteria based on the indocyanine green (ICG) test results in selecting the operative procedure among patients with colorectal liver metastases (CRLM) who had a risk of CALI. CRLM patients who received preoperative chemotherapy including oxaliplatin and/or irinotecan prior to a curative hepatectomy between 2007 and 2017 were included. For each case, the minimum required future remnant liver volume and operative procedure were decided based on the ICG retention rate at 15 min (ICG R15). Patients with an ICG R15 > 10% and who had undergone a major hepatectomy were categorized in a marginal liver functional reserve (MHML) group. Overall, 161 patients were included; 77 of them had an ICG R15 > 10%, and 57 had pathological liver injury (PLI). After the median follow-up time of 30.9 months, the 5-year overall survival rate was 36.1%. The presence of an impaired ICG test result or CALI did not negatively impact the overall and recurrence-free survival outcomes. A multivariate analysis revealed that the presence of four or more nodules of liver metastases was the only independent predictor of a poor overall survival. A significantly larger proportion of patients in the MHML group (n = 37) had a 25% or larger increase in splenic volume (30 vs. 13%; P = 0.024). The presence of an impaired ICG test result or PLI did not affect the long-term outcome after individually selected operative procedure. However, patients undergoing MHML had a higher possibility of developing a > 25% splenic volume increase after hepatectomy.

Detection of rheumatoid arthritis in humans by fluorescence imaging

NASA Astrophysics Data System (ADS)

Ebert, Bernd; Dziekan, Thomas; Weissbach, Carmen; Mahler, Marianne; Schirner, Michael; Berliner, Birgitt; Bauer, Daniel; Voigt, Jan; Berliner, Michael; Bahner, Malte L.; Macdonald, Rainer

2010-02-01

The blood pool agent indo-cyanine green (ICG) has been investigated in a prospective clinical study for detection of rheumatoid arthritis using fluorescence imaging. Temporal behavior as well as spatial distribution of fluorescence intensity are suited to differentiate healthy and inflamed finger joints after i.v. injection of an ICG bolus.

Pilot Assessment of the Repeatability of Indocyanine Green Fluorescence Imaging and Correlation with Traditional Foot Perfusion Assessments.

PubMed

Venermo, M; Settembre, N; Albäck, A; Vikatmaa, P; Aho, P-S; Lepäntalo, M; Inoue, Y; Terasaki, H

2016-10-01

Ankle brachial index (ABI), toe pressures (TP), and transcutaneous oxygen pressure (TcPO 2 ) are traditionally used in the assessment of critical limb ischemia (CLI). Indocyanine green (ICG) fluorescence imaging can be used to evaluate local circulation in the foot and to evaluate the severity of ischemia. This prospective study analyzed the suitability of a fluorescence imaging system (photodynamic eye [PDE]) in CLI. Forty-one patients with CLI were included. Of the patients, 66% had diabetes and there was an ischemic tissue lesion in 70% of the limbs. ABI, toe pressures, TcPO 2 and ICG-fluorescence imaging (ICG-FI) were measured in each leg. To study the repeatability of the ICG-FI, each patient underwent the study twice. After the procedure, foot circulation was measured using a time-intensity curve, where T1/2 (the time needed to achieve half of the maximum fluorescence intensity) and PDE10 (increase of the intensity during the first 10 s) were determined. A time-intensity curve was plotted using the same areas as for the TcPO 2 probes (n=123). The mean ABI was 0.43, TP 21 mmHg, TcPO 2 23 mmHg, T1/2 38 s, and PDE10 19 AU. Time-intensity curves were repeatable. In a Bland-Altman scatter plot, the 95% limits of agreement of PDE10 was 9.9 AU and the corresponding value of T1/2 was 14 s. Correlation between ABI and TP was significant (R=.73, p<.001), and it was weaker in diabetic patients (R=.47, p=.048) compared with non-diabetic patients (R=.89, p=.002). Correlations between ABI and TcPO 2 and TP and TcPO 2 were weak (R=.37, p=.05 and R=.43, p=.037, respectively). Correlation between TcPO 2 and PDE10 was strong in diabetic patients (R=.70, p=.003). According to this pilot study, ICG-FI with PDE can be used in the assessment of blood supply in the ischemic foot. Copyright © 2016 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.

Targeted Delivery of Chemotherapeutic Agents Using Improved Radiosensitive Liquid Core Microcapsules and Assessment of Their Antitumor Effect

DOE Office of Scientific and Technical Information (OSTI.GOV)

Harada, Satoshi; Ehara, Shigeru; Ishii, Keizo

2009-10-01

Purpose: Radiation-sensitive microcapsules composed of alginate and hyaluronic acid are being developed. We report the development of improved microcapsules that were prepared using calcium- and yttrium-induced polymerization. We previously reported on the combined antitumor effect of carboplatin-containing microcapsules and radiotherapy. Methods and Materials: We mixed a 0.1% (wt/vol) solution of hyaluronic acid with a 0.2% alginate solution. Carboplatin (l mg) and indocyanine green (12.5 {mu}g) were added to this mixture, and the resultant material was used for capsule preparation. The capsules were prepared by spraying the material into a mixture containing a 4.34% CaCl{sub 2} solution supplemented with 0-0.01% yttrium.more » These capsules were irradiated with single doses of 0.5, 1.0, 1.5, or 2 Gy {sup 60}Co {gamma}-rays. Immediately after irradiation, the frequency of microcapsule decomposition was determined using a microparticle-induced X-ray emission camera. The amount of core content released was estimated by particle-induced X-ray emission and colorimetric analysis with 0.25% indocyanine green. The antitumor effect of the combined therapy was determined by monitoring its effects on the diameter of an inoculated Meth A fibrosarcoma. Results: Microcapsules that had been polymerized using a 4.34% CaCl{sub 2} solution supplemented with 5.0 x 10{sup -3}% (10{sup -3}% meant or 10%{sup -3}) yttrium exhibited the maximal decomposition, and the optimal release of core content occurred after 2-Gy irradiation. The microcapsules exhibited a synergistic antitumor effect combined with 2-Gy irradiation and were associated with reduced adverse effects. Conclusion: The results of our study have shown that our liquid core microcapsules can be used in radiotherapy for targeted delivery of chemotherapeutic agents.« less

A biomimetic hybrid nanoplatform for encapsulation and precisely controlled delivery of therasnostic agents

NASA Astrophysics Data System (ADS)

Wang, Hai; Agarwal, Pranay; Zhao, Shuting; Yu, Jianhua; Lu, Xiongbin; He, Xiaoming

2015-12-01

Nanoparticles have demonstrated great potential for enhancing drug delivery. However, the low drug encapsulation efficiency at high drug-to-nanoparticle feeding ratios and minimal drug loading content in nanoparticle at any feeding ratios are major hurdles to their widespread applications. Here we report a robust eukaryotic cell-like hybrid nanoplatform (EukaCell) for encapsulation of theranostic agents (doxorubicin and indocyanine green). The EukaCell consists of a phospholipid membrane, a cytoskeleton-like mesoporous silica matrix and a nucleus-like fullerene core. At high drug-to-nanoparticle feeding ratios (for example, 1:0.5), the encapsulation efficiency and loading content can be improved by 58 and 21 times, respectively, compared with conventional silica nanoparticles. Moreover, release of the encapsulated drug can be precisely controlled via dosing near infrared laser irradiation. Ultimately, the ultra-high (up to ~87%) loading content renders augmented anticancer capacity both in vitro and in vivo. Our EukaCell is valuable for drug delivery to fight against cancer and potentially other diseases.

Near-infrared dye marking for thoracoscopic resection of small-sized pulmonary nodules: comparison of percutaneous and bronchoscopic injection techniques.

PubMed

Anayama, Takashi; Hirohashi, Kentaro; Miyazaki, Ryohei; Okada, Hironobu; Kawamoto, Nobutaka; Yamamoto, Marino; Sato, Takayuki; Orihashi, Kazumasa

2018-01-12

Minimally invasive video-assisted thoracoscopic surgery for small-sized pulmonary nodules is challenging, and image-guided preoperative localisation is required. Near-infrared indocyanine green fluorescence is capable of deep tissue penetration and can be distinguished regardless of the background colour of the lung; thus, indocyanine green has great potential for use as a near-infrared fluorescent marker in video-assisted thoracoscopic surgery. Thirty-seven patients with small-sized pulmonary nodules, who were scheduled to undergo video-assisted thoracoscopic wedge resection, were enrolled in this study. A mixture of diluted indocyanine green and iopamidol was injected into the lung parenchyma as a marker, using either computed tomography-guided percutaneous or bronchoscopic injection techniques. Indications and limitations of the percutaneous and bronchoscopic injection techniques for marking nodules with indocyanine green fluorescence were examined and compared. In the computed tomography-guided percutaneous injection group (n = 15), indocyanine green fluorescence was detected in 15/15 (100%) patients by near-infrared thoracoscopy. A small pneumothorax occurred in 3/15 (20.0%) patients, and subsequent marking was unsuccessful after a pneumothorax occurred. In the bronchoscopic injection group (n = 22), indocyanine green fluorescence was detected in 21/22 (95.5%) patients. In 6 patients who underwent injection marking at 2 different lesion sites, 5/6 (83.3%) markers were successfully detected. Either computed tomography-guided percutaneous or bronchoscopic injection techniques can be used to mark pulmonary nodules with indocyanine green fluorescence. Indocyanine green is a safe and easily detectable fluorescent marker for video-assisted thoracoscopic surgery. Furthermore, the bronchoscopic injection approach enables surgeons to mark multiple lesion areas with less risk of causing a pneumothorax. UMIN-CTR R000027833 accepted by ICMJE. Registered 5 January

A comparison of indocyanine green fluorescence imaging plus blue dye and blue dye alone for sentinel node navigation surgery in breast cancer patients.

PubMed

Hirano, Akira; Kamimura, Mari; Ogura, Kaoru; Kim, Naomi; Hattori, Akinori; Setoguchi, Yumika; Okubo, Fumie; Inoue, Hiroaki; Miyamoto, Reiko; Kinoshita, Jun; Fujibayashi, Mariko; Shimizu, Tadao

2012-12-01

To evaluate two methods of sentinel node navigation surgery (SNNS) using blue dye with and without indocyanine green (ICG) fluorescence imaging (FI) to determine the usefulness of combined ICG and blue dye. Between 2005 and 2010, a total of 501 patients underwent SNNS in our hospital. Detection of sentinel lymph node (SLN) was performed with sulfan blue (SB) alone until 2008 and with a combination of SB and ICG-FI since 2009. ICG 5 mg and SB 15 mg were injected in the subareolar region, and FI was obtained by a fluorescence imaging device. We attempted to identify SLNs in 393 patients by SB alone and in 108 patients by a combination of SB and FI. The mean number of SLNs detected was 1.6 (0-5) for SB alone and 2.2 (1-6) for the combination method. The SLN identification rate was 95.7 % for SB alone and 100 % for the combination method so that the combination was significantly superior to SB in terms of the identification rate (p = 0.0037). In patients who received the combination method, detection of SLN was made through only SB in 1 patient, only ICG in 8 patients, and both in 99 patients. Lymph node metastasis was found in 56 patients with SB alone and in 16 patients with the combination method. Recurrence of an axillary node was observed in 3 patients (0.8 %) with SB alone and in no patients with the combination method. ICG-FI is a useful method and is especially recommended in cases where no radiotracers are available.

Is near infrared fluorescence imaging using indocyanine green dye useful in robotic partial nephrectomy: a prospective comparative study of 94 patients.

PubMed

Krane, L Spencer; Manny, Theodore B; Hemal, Ashok K

2012-07-01

To compare a consecutive prospective cohort of patients who underwent robotic partial nephrectomy (RPN) with near infrared fluorescence (NIRF) imaging with indocyanine green dye (ICG) with a previous consecutive patient cohort. A total of 47 consecutive patients with renal masses suspicious for malignancy undergoing RPN were given 5-7.5 mg of ICG before hilar clamping or tumor excision. This cohort of patients was compared with 47 immediate previous consecutive patients who had undergone RPN without NIRF real-time imaging using ICG. The intraoperative, perioperative, and postoperative parameters were collected in an institutional review board-approved prospective database. The preoperative demographics and tumor complexity according to the nephrometry or preoperative aspects and dimensions used for an anatomic (PADUA) scores were similar. The mean warm ischemia time was significantly decreased in the ICG group (15 vs 17 minutes, P = .01). The median hospital stay was 2 days in both groups. No significant difference was seen in the positive margin rate (ICG, 6% vs control, 8.5%; P = .69) or observed Clavien grade III-IV complications in these 2 cohorts (ICG, 4% vs control, 15%; P = .07). No adverse events were associated with ICG dye administration. Differential ICG uptake was observed with selective clamping or in patients with cystic tumors, hypofluorescent tumors with exophytic components, and angiomyelolipomas, but these benefits could not be quantified. NIRF-ICG was transiently helpful to identify the vascular anatomy and not helpful at all for endophytic tumors. RPN using NIRF-ICG can be performed safely and effectively. A decreased warm ischemia time in the ICG cohort was observed without specific measured advantages. Differential ICG uptake by different tumors did not lead to significant differences in the positive margin rate. Copyright © 2012 Elsevier Inc. All rights reserved.

Indocyanine Green Fluorescence for Free-Flap Perfusion Imaging Revisited: Advanced Decision Making by Virtual Perfusion Reality in Visionsense Fusion Imaging Angiography.

PubMed

Bigdeli, Amir Khosrow; Gazyakan, Emre; Schmidt, Volker Juergen; Hernekamp, Frederick Jochen; Harhaus, Leila; Henzler, Thomas; Kremer, Thomas; Kneser, Ulrich; Hirche, Christoph

2016-06-01

Near-infrared indocyanine green video angiography (ICG-NIR-VA) has been introduced for free-flap surgery and may provide intraoperative flap designing as well as postoperative monitoring. Nevertheless, the technique has not been established in clinical routine because of controversy over benefits. Improved technical features of the novel Visionsense ICG-NIR-VA surgery system are promising to revisit the field of application. It features a unique real-time fusion image of simultaneous NIR and white light visualization, with highlighted perfusion, including a color-coded perfusion flow scale for optimized anatomical understanding. In a feasibility study, the Visionsense ICG-NIR-VA system was applied during 10 free-flap surgeries in 8 patients at our center. Indications included anterior lateral thigh (ALT) flap (n = 4), latissimus dorsi muscle flap (n = 1), tensor fascia latae flap (n = 1), and two bilateral deep inferior epigastric artery perforator flaps (n = 4). The system was used intraoperatively and postoperatively to investigate its impact on surgical decision making and to observe perfusion patterns correlated to clinical monitoring. Visionsense ICG-NIR-VA aided assessing free-flap design and perfusion patterns in all cases and correlated with clinical observations. Additional interventions were performed in 2 cases (22%). One venous anastomosis was revised, and 1 flap was redesigned. Indicated by ICG-NIR-VA, 1 ALT flap developed partial flap necrosis (11%). The Visionsense ICG-NIR-VA system allowed a virtual view of flap perfusion anatomy by fusion imaging in real-time. The system improved decision making for flap design and surgical decisions. Clinical and ICG-NIR-VA parameters correlated. Its future implementation may aid in improving outcomes for free-flap surgery, but additional experience is needed to define its final role. © The Author(s) 2015.

Enhanced fluorescence diffuse optical tomography with indocyanine green-encapsulating liposomes targeted to receptors for vascular endothelial growth factor in tumor vasculature.

PubMed

Zanganeh, Saeid; Xu, Yan; Hamby, Carl V; Backer, Marina V; Backer, Joseph M; Zhu, Quing

2013-12-01

To develop an indocyanine green (ICG) tracer with slower clearance kinetics, we explored ICG-encapsulating liposomes (Lip) in three different formulations: untargeted (Lip/ICG), targeted to vascular endothelial growth factor (VEGF) receptors (scVEGF-Lip/ICG) by the receptor-binding moiety single-chain VEGF (scVEGF), or decorated with inactivated scVEGF (inactive-Lip/ICG) that does not bind to VEGF receptors. Experiments were conducted with tumor-bearing mice that were placed in a scattering medium with tumors located at imaging depths of either 1.5 or 2.0 cm. Near-infrared fluorescence diffuse optical tomography that provides depth-resolved spatial distributions of fluorescence in tumor was used for the detection of postinjection fluorescent signals. All liposome-based tracers, as well as free ICG, were injected intravenously into mice in the amounts corresponding to 5 nmol of ICG/mouse, and the kinetics of increase and decrease of fluorescent signals in tumors were monitored. A signal from free ICG reached maximum at 15-min postinjection and then rapidly declined with t1/2 of ~20 min. The signals from untargeted Lip/ICG and inactive-Lip/ICG also reached maximum at 15-min postinjection, however, declined somewhat slower than free ICG with t1/2 of ~30 min. By contrast, a signal from targeted scVEGF-Lip/ICG grew slower than that of all other tracers, reaching maximum at 30-min postinjection and declined much slower than that of other tracers with t1/2 of ~90 min, providing a more extended observation window. Higher scVEGF-Lip/ICG tumor accumulation was further confirmed by the analysis of fluorescence on cryosections of tumors that were harvested from animals at 400 min after injection with different tracers.

Biomcompatible gold nanorods conjugated with photosensitizers assisted for photostability and photodestructive ability

NASA Astrophysics Data System (ADS)

Kuo, Wen-Shuo; Chen, Shean-Jen

2012-02-01

Light-exposure-mediated higher temperatures that markedly accelerate the degradation of indocyanine green (ICG) in aqueous solutions by thermal decomposition have been a serious medical problem. In this work, we present the example of using gold nanorods (Au NRs) simultaneously serving as photodynamic and photothermal agents to destroy malignant cells. Au NRs were successfully conjugated with hydrophilic photosensitizer, indocyanine green (ICG), to achieve photodynamic therapy (PDT) and photothermal therapy (PTT). We also demonstrated that Au NRs conjugated with ICG displayed high chemical stability and acted as a promising diagnostic probe. Due to its stability even via higher temperatures mediated by laser irradiation, the combination of PDT and PTT proved to be efficiently killing cancer cells as compared to PDT or PTT treatment alone and enhanced the effectiveness of photodestruction and was demonstrated to enhance its photostability.

Neurosurgical confocal endomicroscopy: A review of contrast agents, confocal systems, and future imaging modalities

PubMed Central

Zehri, Aqib H.; Ramey, Wyatt; Georges, Joseph F.; Mooney, Michael A.; Martirosyan, Nikolay L.; Preul, Mark C.; Nakaji, Peter

2014-01-01

Background: The clinical application of fluorescent contrast agents (fluorescein, indocyanine green, and aminolevulinic acid) with intraoperative microscopy has led to advances in intraoperative brain tumor imaging. Their properties, mechanism of action, history of use, and safety are analyzed in this report along with a review of current laser scanning confocal endomicroscopy systems. Additional imaging modalities with potential neurosurgical utility are also analyzed. Methods: A comprehensive literature search was performed utilizing PubMed and key words: In vivo confocal microscopy, confocal endomicroscopy, fluorescence imaging, in vivo diagnostics/neoplasm, in vivo molecular imaging, and optical imaging. Articles were reviewed that discussed clinically available fluorophores in neurosurgery, confocal endomicroscopy instrumentation, confocal microscopy systems, and intraoperative cancer diagnostics. Results: Current clinically available fluorescent contrast agents have specific properties that provide microscopic delineation of tumors when imaged with laser scanning confocal endomicroscopes. Other imaging modalities such as coherent anti-Stokes Raman scattering (CARS) microscopy, confocal reflectance microscopy, fluorescent lifetime imaging (FLIM), two-photon microscopy, and second harmonic generation may also have potential in neurosurgical applications. Conclusion: In addition to guiding tumor resection, intraoperative fluorescence and microscopy have the potential to facilitate tumor identification and complement frozen section analysis during surgery by providing real-time histological assessment. Further research, including clinical trials, is necessary to test the efficacy of fluorescent contrast agents and optical imaging instrumentation in order to establish their role in neurosurgery. PMID:24872922

Hybrid radioguided occult lesion localization (hybrid ROLL) of (18)F-FDG-avid lesions using the hybrid tracer indocyanine green-(99m)Tc-nanocolloid.

PubMed

KleinJan, G H; Brouwer, O R; Mathéron, H M; Rietbergen, D D D; Valdés Olmos, R A; Wouters, M W; van den Berg, N S; van Leeuwen, F W B

2016-01-01

To assess if combined fluorescence- and radio-guided occult lesion localization (hybrid ROLL) is feasible in patients scheduled for surgical resection of non-palpable (18)F-FDG-avid lesions on PET/CT. Four patients with (18)F-FDG-avid lesions on follow-up PET/CT that were not palpable during physical examination but were suspected to harbor metastasis were enrolled. Guided by ultrasound, the hybrid tracer indocyanine green (ICG)-(99m)Tc-nanocolloid was injected centrally in the target lesion. SPECT/CT imaging was used to confirm tracer deposition. Intraoperatively, lesions were localized using a hand-held gamma ray detection probe, a portable gamma camera, and a fluorescence camera. After excision, the gamma camera was used to check the wound bed for residual activity. A total of six (18)F-FDG-avid lymph nodes were identified and scheduled for hybrid ROLL. Comparison of the PET/CT images with the acquired SPECT/CT after hybrid tracer injection confirmed accurate tracer deposition. No side effects were observed. Combined radio- and fluorescence-guidance enabled localization and excision of the target lesion in all patients. Five of the six excised lesions proved tumor-positive at histopathology. The hybrid ROLL approach appears to be feasible and can facilitate the intraoperative localization and excision of non-palpable lesions suspected to harbor tumor metastases. In addition to the initial radioguided detection, the fluorescence component of the hybrid tracer enables high-resolution intraoperative visualization of the target lesion. The procedure needs further evaluation in a larger cohort and wider range of malignancies to substantiate these preliminary findings. Copyright © 2016 Elsevier España, S.L.U. y SEMNIM. All rights reserved.

Near-infrared spectroscopy using indocyanine green dye for minimally invasive measurement of respiratory and leg muscle blood flow in patients with COPD.

PubMed

Louvaris, Zafeiris; Habazettl, Helmut; Wagner, Harrieth; Zakynthinos, Spyros G; Wagner, Peter D; Vogiatzis, Ioannis

2018-06-21

Reliability of Near-infrared spectroscopy (NIRS), measuring indocyanine green (ICG) for minimally invasive assessment of relative muscle blood flow during exercise has been examined in fit young individuals, but not in COPD. Here we ask whether it could be used to evaluate respiratory and locomotor muscle perfusion in COPD patients. Vastus lateralis muscle blood flow (MBF, the reference method calculated from arterial and muscle ICG concentration curves) and a blood flow index (BFI, calculated using only the (same) muscle ICG concentration curves) were compared in 10 patients (FEV 1 :51{plus minus}6%predicted) at rest and during cycling at 25%, 50%, 75% and 100% of WRpeak. Intercostal muscle MBF and BFI were also compared during isocapnic hyperpnea at rest, reproducing ventilation levels up to those at WRpeak. Intercostal and vastus lateralis BFI increased with increasing ventilation during hyperpnea (from 2.5{plus minus}0.3 to 4.5{plus minus}0.7nM/s) and cycling load (from 1.0{plus minus}0.2 to 12.8{plus minus}1.9nM/s), respectively. There were strong correlations between BFI and MBF for both intercostal (r=0.993 group mean data, r=0.872 individual data) and vastus lateralis (r=0.994 group mean data, r=0.895 individual data). Fold changes from rest in BFI and MBF did not differ for either the intercostal muscles or the vastus lateralis. Group mean BFI data showed strong interrelationships with respiratory and cycling workload, and whole body metabolic demand (r ranged from 0.913 to 0.989) simultaneously recorded during exercise. We conclude that BFI is a reliable and minimally invasive tool for evaluating relative changes in respiratory and locomotor muscle perfusion from rest to peak exercise in COPD patient groups.

Oral Administration and Detection of a Near-Infrared Molecular Imaging Agent in an Orthotopic Mouse Model for Breast Cancer Screening

PubMed Central

2018-01-01

Molecular imaging is advantageous for screening diseases such as breast cancer by providing precise spatial information on disease-associated biomarkers, something neither blood tests nor anatomical imaging can achieve. However, the high cost and risks of ionizing radiation for several molecular imaging modalities have prevented a feasible and scalable approach for screening. Clinical studies have demonstrated the ability to detect breast tumors using nonspecific probes such as indocyanine green, but the lack of molecular information and required intravenous contrast agent does not provide a significant benefit over current noninvasive imaging techniques. Here we demonstrate that negatively charged sulfate groups, commonly used to improve solubility of near-infrared fluorophores, enable sufficient oral absorption and targeting of fluorescent molecular imaging agents for completely noninvasive detection of diseased tissue such as breast cancer. These functional groups improve the pharmacokinetic properties of affinity ligands to achieve targeting efficiencies compatible with clinical imaging devices using safe, nonionizing radiation (near-infrared light). Together, this enables development of a “disease screening pill” capable of oral absorption and systemic availability, target binding, background clearance, and imaging at clinically relevant depths for breast cancer screening. This approach should be adaptable to other molecular targets and diseases for use as a new class of screening agents. PMID:29696981

Oral Administration and Detection of a Near-Infrared Molecular Imaging Agent in an Orthotopic Mouse Model for Breast Cancer Screening.

PubMed

Bhatnagar, Sumit; Verma, Kirti Dhingra; Hu, Yongjun; Khera, Eshita; Priluck, Aaron; Smith, David E; Thurber, Greg M

2018-05-07

Molecular imaging is advantageous for screening diseases such as breast cancer by providing precise spatial information on disease-associated biomarkers, something neither blood tests nor anatomical imaging can achieve. However, the high cost and risks of ionizing radiation for several molecular imaging modalities have prevented a feasible and scalable approach for screening. Clinical studies have demonstrated the ability to detect breast tumors using nonspecific probes such as indocyanine green, but the lack of molecular information and required intravenous contrast agent does not provide a significant benefit over current noninvasive imaging techniques. Here we demonstrate that negatively charged sulfate groups, commonly used to improve solubility of near-infrared fluorophores, enable sufficient oral absorption and targeting of fluorescent molecular imaging agents for completely noninvasive detection of diseased tissue such as breast cancer. These functional groups improve the pharmacokinetic properties of affinity ligands to achieve targeting efficiencies compatible with clinical imaging devices using safe, nonionizing radiation (near-infrared light). Together, this enables development of a "disease screening pill" capable of oral absorption and systemic availability, target binding, background clearance, and imaging at clinically relevant depths for breast cancer screening. This approach should be adaptable to other molecular targets and diseases for use as a new class of screening agents.

Preparation of tyrosinase inhibitors and antibrowning agents using green technology.

PubMed

Dong, Xue; Zhang, Yinan; He, Jia-Liang; Zhang, Shuang; Zeng, Mao-Mao; Chen, Jie; Zheng, Zong-Ping

2016-04-15

Chalcones and their derivatives have attracted great interests in recent years for their comprehensive biological activities. In this study, 2,4,2',4'-tetrahydroxychalcone and its two derivatives, 1,3,5-tris-(2,4-dihydroxy-phenyl)pentane-1,5-dione (new compound) and 7,2',4'-trihydroxyflavanone, were synthesized through one-pot green procedure catalyzed by boric acid in polyethylene glycol 400. Their structures were identified by ESI-MS and NMR spectral. Tyrosinase inhibitory activity and antibrowning test results showed that compounds 1-3 exhibited strong tyrosinase inhibitory activities and significant antibrowning effects on the fresh-cut lotus root slices at room temperature in 48 h. Among them, 0.01% 1,3,5-tris-(2,4-dihydroxy-phenyl)pentane-1,5-dione combined with 0.5% VC showed the best antibrowning ability. In brief, this study offers a protocol for one-pot green synthesis of high efficiency tyrosinase inhibitors which may be suitable as antibrowning agents for fresh-cut vegetables. More important, this study developed a new type of 1,5-dione derivative which may serve as new lead structures for novel tyrosinase inhibitors discovery. Copyright © 2015 Elsevier Ltd. All rights reserved.

Erythrocyte-derived optical nano-vesicles as theranostic agents

NASA Astrophysics Data System (ADS)

Mac, Jenny T.; Nunez, Vicente; Bahmani, Baharak; Guerrero, Yadir; Tang, Jack; Vullev, Valentine I.; Anvari, Bahman

2015-07-01

We have engineered nano-vesicles, derived from erythrocytes, which can be doped with various near infrared (NIR) organic chromophores, including the FDA-approved indocyanine green (ICG). We refer to these vesicles as NIR erythrocyte-mimicking transducers (NETS) since in response to NIR photo-excitation they can generate heat or emit fluorescent light. Using biochemical methods based on reduction amination, we have functionalized the surface of NET with antibodies to target specific biomolecules. We present results that demonstrate the effectiveness of NETs in targeted imaging of cancer cells that over-express the human epidermal growth factor receptor-2 (HER2).

Dynamic infrared thermography (DIRT) for assessment of skin blood perfusion in cranioplasty: a proof of concept for qualitative comparison with the standard indocyanine green video angiography (ICGA).

PubMed

Rathmann, P; Chalopin, C; Halama, D; Giri, P; Meixensberger, J; Lindner, D

2018-03-01

Complications in wound healing after neurosurgical operations occur often due to scarred dehiscence with skin blood perfusion disturbance. The standard imaging method for intraoperative skin perfusion assessment is the invasive indocyanine green video angiography (ICGA). The noninvasive dynamic infrared thermography (DIRT) is a promising alternative modality that was evaluated by comparison with ICGA. The study was carried out in two parts: (1) investigation of technical conditions for intraoperative use of DIRT for its comparison with ICGA, and (2) visual and quantitative comparison of both modalities in a proof of concept on nine patients. Time-temperature curves in DIRT and time-intensity curves in ICGA for defined regions of interest were analyzed. New perfusion parameters were defined in DIRT and compared with the usual perfusion parameters in ICGA. The visual observation of the image data in DIRT and ICGA showed that operation material, anatomical structures and skin perfusion are represented similarly in both modalities. Although the analysis of the curves and perfusion parameter values showed differences between patients, no complications were observed clinically. These differences were represented in DIRT and ICGA equivalently. DIRT has shown a great potential for intraoperative use, with several advantages over ICGA. The technique is passive, contactless and noninvasive. The practicability of the intraoperative recording of the same operation field section with ICGA and DIRT has been demonstrated. The promising results of this proof of concept provide a basis for a trial with a larger number of patients.

Application of albumin protein and indocyanine green chromophore for tissue soldering by using an IR diode laser: ex vivo and in vivo studies.

PubMed

Khosroshahi, M E; Nourbakhsh, M S; Saremi, S; Hooshyar, A; Rabbani, Sh; Tabatabai, F; Anvari, M Sotudeh

2010-12-01

We sought to examine the impact of different parameters of laser soldering on the thermophysical properties of the skin and to optimize these parameters for sealing a full-thickness incision in the rat skin under closed feedback control under in vivo conditions. Laser tissue soldering based on protein as biologic glues and other compounds can provide greater bond strength and less collateral damage. Endogenous and exogenous materials such as indocyanine green (ICG) are often added to solders to enhance light absorption. In ex vivo study, the temperature increase, number of scan (Ns), and scan velocity (Vs) were investigated. In ex vivo studies, four skin incisions were made over rat dorsa and were closed by using two different methods: (a) wound closure by suture and (b) closure by using an automated temperature-controlled system. An automated soldering system was developed based on a diode laser, IR detector, photodiode, digital thermocouple, and camera. The true temperature of heated tissue was determined by using a calibration software method. The results showed that at each laser irradiance (I), the tensile strength (σ) of incisions repaired in the static mode is higher than in the dynamic mode. It must also be noted that the tensile strength of the repaired skin wound was increased by increasing the irradiance in both static and dynamic modes. However, in parallel, an increase in the corresponding temperature was observed. The tensile strength was measured for sutured and laser-soldered tissue after 2 to 10 postoperative days. Histopathologic studies showed a better healing and less inflammatory reactions than with those caused by standard sutures after day 7. It is demonstrated that automated laser soldering technique can be practical provided the optothermal properties of tissue is carefully optimized.

Development of PLGA-lipid nanoparticles with covalently conjugated indocyanine green as a versatile nanoplatform for tumor-targeted imaging and drug delivery.

PubMed

Xin, Yu; Liu, Tie; Yang, Chenlong

We have prepared novel poly(d,l-lactide- co -glycolide) (PLGA) lipid nanoparticles (PNPs) that covalently conjugate folic acid (FA) and indocyanine green (ICG), in addition to encapsulating resveratrol (RSV) (FA-RSV/ICG-PLGA-lipid NPs, abbreviated as FA-RIPNPs); these nanoparticles have been developed for simultaneous targeted delivery of anticancer drug and fluorescence imaging. The FA-RIPNPs, with an average particle size of 92.8±2.1 nm, were prepared by a facile self-assembly-and-nanoprecipitation method, and they showed excellent stability and biocompatibility characteristics. The FA-RIPNPs exhibited an RSV encapsulation efficiency of approximately 65.6%±4.7% and a maximum release ratio of 78.2%±4.1% at pH 5.0 and 37°C. Confocal fluorescence images showed that FA-RIPNPs may facilitate a high cellular uptake via FA receptor-mediated endocytosis. Furthermore, FA-RIPNPs (containing 50 μg/mL RSV) induced a 81.4%±2.1% U87 cell inhibition rate via apoptosis, a value that proved to be higher than what has been shown for free RSV (53.1%±1.1%, equivalent RSV concentration). With a formulated polyethylene glycol (PEG) shell around the PLGA core, FA-RIPNPs prolonged the blood circulation of both free RSV and ICG, which approximately increased 6.96- and 39.4-fold ( t 1/2 ), respectively. Regarding FA-RIPNP use as a near-infrared probe, in vivo fluorescence images indicated a highly efficient accumulation of FA-RIPNPs in the tumor tissue, which proved to be approximately 2.8- and 12.6-fold higher than the RIPNPs and free ICG, respectively. Intravenous injection of FA-RIPNPs into U87 tumor-bearing mice demonstrated the best tumor inhibition effect for all tested drugs, including free RSV and RIPNPs, with no relapse, showing high biocompatibility and with no significant systemic in vivo toxicity over the course of the treatment (1 month). The results obtained demonstrate the versatility of the NPs, featuring stable fluorescence and tumor-targeting characteristics, with

Development of PLGA-lipid nanoparticles with covalently conjugated indocyanine green as a versatile nanoplatform for tumor-targeted imaging and drug delivery

PubMed Central

Xin, Yu; Liu, Tie; Yang, Chenlong

2016-01-01

We have prepared novel poly(d,l-lactide-co-glycolide) (PLGA) lipid nanoparticles (PNPs) that covalently conjugate folic acid (FA) and indocyanine green (ICG), in addition to encapsulating resveratrol (RSV) (FA-RSV/ICG-PLGA-lipid NPs, abbreviated as FA-RIPNPs); these nanoparticles have been developed for simultaneous targeted delivery of anticancer drug and fluorescence imaging. The FA-RIPNPs, with an average particle size of 92.8±2.1 nm, were prepared by a facile self-assembly-and-nanoprecipitation method, and they showed excellent stability and biocompatibility characteristics. The FA-RIPNPs exhibited an RSV encapsulation efficiency of approximately 65.6%±4.7% and a maximum release ratio of 78.2%±4.1% at pH 5.0 and 37°C. Confocal fluorescence images showed that FA-RIPNPs may facilitate a high cellular uptake via FA receptor-mediated endocytosis. Furthermore, FA-RIPNPs (containing 50 μg/mL RSV) induced a 81.4%±2.1% U87 cell inhibition rate via apoptosis, a value that proved to be higher than what has been shown for free RSV (53.1%±1.1%, equivalent RSV concentration). With a formulated polyethylene glycol (PEG) shell around the PLGA core, FA-RIPNPs prolonged the blood circulation of both free RSV and ICG, which approximately increased 6.96- and 39.4-fold (t1/2), respectively. Regarding FA-RIPNP use as a near-infrared probe, in vivo fluorescence images indicated a highly efficient accumulation of FA-RIPNPs in the tumor tissue, which proved to be approximately 2.8- and 12.6-fold higher than the RIPNPs and free ICG, respectively. Intravenous injection of FA-RIPNPs into U87 tumor-bearing mice demonstrated the best tumor inhibition effect for all tested drugs, including free RSV and RIPNPs, with no relapse, showing high biocompatibility and with no significant systemic in vivo toxicity over the course of the treatment (1 month). The results obtained demonstrate the versatility of the NPs, featuring stable fluorescence and tumor-targeting characteristics, with

Quantitative Primary Tumor Indocyanine Green Measurements Predict Osteosarcoma Metastatic Lung Burden in a Mouse Model.

PubMed

Fourman, Mitchell S; Mahjoub, Adel; Mandell, Jon B; Yu, Shibing; Tebbets, Jessica C; Crasto, Jared A; Alexander, Peter E; Weiss, Kurt R

2018-03-01

Current preclinical osteosarcoma (OS) models largely focus on quantifying primary tumor burden. However, most fatalities from OS are caused by metastatic disease. The quantification of metastatic OS currently relies on CT, which is limited by motion artifact, requires intravenous contrast, and can be technically demanding in the preclinical setting. We describe the ability for indocyanine green (ICG) fluorescence angiography to quantify primary and metastatic OS in a previously validated orthotopic, immunocompetent mouse model. (1) Can near-infrared ICG fluorescence be used to attach a comparable, quantitative value to the primary OS tumor in our experimental mouse model? (2) Will primary tumor fluorescence differ in mice that go on to develop metastatic lung disease? (3) Does primary tumor fluorescence correlate with tumor volume measured with CT? Six groups of 4- to 6-week-old immunocompetent Balb/c mice (n = 6 per group) received paraphyseal injections into their left hindlimb proximal tibia consisting of variable numbers of K7M2 mouse OS cells. A hindlimb transfemoral amputation was performed 4 weeks after injection with euthanasia and lung extraction performed 10 weeks after injection. Histologic examination of lung and primary tumor specimens confirmed ICG localization only within the tumor bed. Mice with visible or palpable tumor growth had greater hindlimb fluorescence (3.5 ± 2.3 arbitrary perfusion units [APU], defined as the fluorescence pixel return normalized by the detector) compared with those with a negative examination (0.71 ± 0.38 APU, -2.7 ± 0.5 mean difference, 95% confidence interval -3.7 to -1.8, p < 0.001). A strong linear trend (r = 0.81, p < 0.01) was observed between primary tumor and lung fluorescence, suggesting that quantitative ICG tumor fluorescence is directly related to eventual metastatic burden. We did not find a correlation (r = 0.04, p = 0.45) between normalized primary tumor fluorescence and CT volumetric measurements. We

Laparoscopic Sentinel Lymph Node Mapping with Indocyanine Green Using the iSpies Platform: Initial Experience Argentina.

PubMed

Di Guilmi, Julian; Darin, Maria Cecilia; Toscano, Maria; Maya, Gustavo

To demonstrate the initial experience in Argentina using the iSpies indocyanine green (ICG) platform in sentinel lymph node mapping in patients with early-stage cervical cancer. Step-by-step demonstration of the technique using a video and pictures (educative video) (Canadian Task Force classification III). Laparoscopic and robotic sentinel lymph node mapping using ICG has been shown to be safe and feasible; however, in developing countries, the opportunities to use fluorescent imaging through a minimally invasive approach are very limited, given the cost restrictions of acquiring the near-infrared technology and the fluorescent dyes. A 47-year-old woman presented with a stage IB1 squamous cervical cancer. Physical examination revealed a 1.5-cm tumor without evidence of parametrial involvement. Magnetic resonance imaging did not show any evidence of metastatic disease. The patient underwent laparoscopic radical hysterectomy with sentinel lymph node mapping. On laparoscopic exposure of the pelvic spaces, a cervical injection of ICG (1 mL superficial and deep) was administered using a spinal needle at the 3 o'clock and 9 o'clock positions. Sentinel lymph node mapping was then performed using the ICG (Pulsion Medical Systems, Feldkirchen, Germany) and an iSpies near-infrared camera (Karl Storz Endoskope, Tuttlingen, Germany). Bilateral sentinel lymph nodes were detected on the left external iliac artery and in the right obturator space. Both were confirmed ex vivo. The total operative time was 170 minutes. No intraoperative or postoperative complications were reported, and the patient was discharged at 48 hours after surgery. Estimated blood loss was minimal. Sentinel lymph node mapping alone is not the standard of care in our institution, and thus bilateral lymphadenectomy was performed. Ultrastaging is routinely performed when a sentinel lymph node is evaluated. Final pathology revealed a tumor confined to the cervix, with tumor-free margins, and a total of 10

Indocyanine green-encapsulating calcium phosphosilicate nanoparticles: Bifunctional theranostic vectors for near infrared diagnostic imaging and photodynamic therapy

NASA Astrophysics Data System (ADS)

Altinoglu, Erhan I.

The synthesis, laundering, and properties of calcium phosphosilicate nanoparticles (CPSNPs) that encapsulate the NIR fluorophore indocyanine green (ICG) related to multifunctional fluorescent photosensitization is presented. Imaging with transmission electron microscopy (TEM) revealed the well dispersed state of the nanoparticles, the spherical morphology, and the log normal mean particle diameter of 16 nm. Electron energy loss spectroscopy (EELS) mapping identified a Ca:P:Si ratio of 1:1.72:0.41 and a homogeneous composition without evidence of an element rich or deficient architecture. Zeta potential of the as-synthesized, citrate-functionalized CPSNPs was -29 +/-3 mV. A theoretical solids loading of 1.9 x 1013 CPSNP/mL was calculated for a standard suspension. The mean ICG content per suspension is 2 x 10 -6 M, which equates to approximately 63 fluorophore molecules encapsulated per CPSNP. For imaging and diagnostic considerations, the doped CPSNPs exhibited significantly greater intensity at the maximum emission wavelength relative to the free constituent fluorophore. The quantum efficiency of the fluorescent agent is 200% greater at 0.053+/-0.003 over the free fluorophore in PBS. Also, photostability based on fluorescence half-life of encapsulated ICG in PBS is 500% longer under typical clinical imaging conditions relative to the free dye. These performance enhancements are attributed to the matrix shielding effect of the NP around the internalized fluorophore molecules. The in vivo emission signal stability from ICG-CPSNPs was compared to the free fluorophore by whole animal NIR imaging. The duration of fluorescent signal from the ICG-CPSPNPs was extended to up to four days post-injection, highlighting the potential for long-term imaging and sensitive tracking applications using ICG when encapsulated within the protective matrix of CPSNPs. The surfaces of the ICG-CPSNPs were covalently bound with polyethylene glycol (PEG). The pharmacokinetic behavior of the

Host-guest chemistry of dendrimer-drug complexes: 7. Formation of stable inclusions between acetylated dendrimers and drugs bearing multiple charges.

PubMed

Fang, Min; Zhang, Jiahai; Wu, Qinglin; Xu, Tongwen; Cheng, Yiyun

2012-03-15

Drug molecules bearing multiple charges usually form precipitates with cationic dendrimers, which presents a challenge during the preparation of dendrimer inclusions for these drugs. In the present study, fully acetylated polyamidoamine (PAMAM) dendrimers were proposed as stable vehicles for drug molecules bearing two negative charges such as Congo red and indocyanine green. NMR techniques including (1)H NMR and (1)H-(1)H NOESY were used to characterize the host-guest chemistry of acetylated dendrimer and these guest molecules. The cationic PAMAM dendrimer was found to form a precipitate with Congo red and indocyanine green, but the acetylated one avoided the formation of cross-linking structures in aqueous solutions. NOESY studies revealed the encapsulation of Congo red and indocyanine green within the interior cavities of PAMAM dendrimers at mild acidic conditions and acetylated dendrimers show much stronger ability to encapsulate the guest molecules than cationic ones. Also, UV-vis-NIR studies suggest that acetylated dendrimers significantly improve the photostability of indocyanine green and prevent the formation of indocyanine green J-aggregates in aqueous solutions. The present study provides a new insight into dendrimer-based host-guest systems, especially for those guest molecules bearing multiple charges. © 2012 American Chemical Society

Feasibility and optimal dosage of indocyanine green fluorescence for sentinel lymph node detection using robotic single-site instrumentation: preclinical study.

PubMed

Levinson, Kimberly L; Mahdi, Haider; Escobar, Pedro F

2013-01-01

The present study was performed to determine the optimal dosage of indocyanine green (ICG) to accurately differentiate the sentinel node from surrounding tissue and then to test this dosage using novel single-port robotic instrumentation. The study was performed in healthy female pigs. After induction of anesthesia, all pigs underwent exploratory laparotomy, dissection of the bladder, and colpotomy to reveal the cervical os. With use of a 21-gauge needle, 0.5 mL normal saline solution was injected at the 3- and 9-o'clock positions as control. Four concentrations of ICG were constituted for doses of 1000, 500, 250, and 175 μg per 0.5 mL. ICG was then injected at the 3- and 9-o'clock positions on the cervix. The SPY camera was used to track ICG into the sentinel nodes and to quantify the intensity of light emitted. SPY technology uses an intensity scale of 1 to 256; this scale was used to determine the difference in intensity between the sentinel node and surrounding tissues. The optimal dosage was tested using single-port robotic instrumentation with the same injection techniques. A sentinel node was identified at all doses except 175 μg, at which ICG stayed in the cervix and vasculature only. For both the 500- and 250-μg doses, the sentinel node was identified before reaching maximum intensity. At maximum intensity, the difference between the surrounding tissue and the node was 207 (251 vs 44) for the 500-μg dose and 159 (251 vs 92) for the 250-μg dose. Sentinel lymph node (SLN) biopsy was successfully performed using single-port robotic technology with both the 250- and 500-μg doses. For SLN detection, the dose of ICG is related to the ability to differentiate the sentinel node from the surrounding tissue. An ICG dose of 250 to 500 μg enables identification of a SLN with more distinction from the surrounding tissues, and this procedure is feasible using single-port robotics instrumentation. Copyright © 2013 AAGL. Published by Elsevier Inc. All rights

Retinal Pigmented Epithelial Cells Cytotoxicity and Apoptosis through Activation of the Mitochondrial Intrinsic Pathway: Role Of Indocyanine Green, Brilliant Blue and Implications for Chromovitrectomy

PubMed Central

Penha, Fernando M.; Pons, Marianne; Costa, Elaine Fiod; Barros, Nilana Meza Tenório; Rodrigues, Eduardo B.; Cardoso, Emmerson Badaró; Dib, Eduardo; Maia, Mauricio; Marin-Castaño, Maria E.; Farah, Michel Eid

2013-01-01

Purpose To investigate the in vitro effect of four vital dyes on toxicity and apoptosis in a human retinal pigment epithelial (RPE) cell line. Methods ARPE-19 cells were exposed to brilliant blue (BriB), methyl blue (MetB), acid violet (AcV) and indocyanine green (ICG). Balanced salt solution was used as control. Five different concentrations of each dye (1, 0.5, 0.25, 0.05 and 0.005 mg/mL) and two exposure times (3 and 30 min) were tested. Cell viability was determined by cell count and MTS assay and cell toxicity by LDH assay. Real-time PCR and Western blotting were used to access the apoptosis process. Results ICG significantly reduced cell viability after 3 minutes of exposure at all concentrations (p<0.01). BriB was safe at concentrations up to 0.25 mg/mL and MetB at concentrations up to 0.5 mg/mL, while AcV was safe up to 0.05 mg/ml, after 3 minutes of exposure. Toxicity was higher, when the cells were treated for 30 minutes. Expression of Bax, cytochrome c and caspase-9 was upregulated at the mRNA and protein level after ICG exposure, while Bcl-2 was downregulated. AcV and MetB were similar to control. However, BriB resulted in upregulation of Bcl-2, an antiapoptotic protein. Conclusions The safest dye used on RPE cells was MetB followed by BriB and AcV. ICG was toxic at all concentrations and exposure times tested. Moreover, ICG was the only dye that induced apoptosis in ARPE-19 cells. BriB significantly increased Bcl-2 protein levels, which might protect against the apoptosis process. PMID:23675521

Indocyanine green-augmented diode laser therapy vs. long-pulsed Nd:YAG (1064 nm) laser treatment of telangiectatic leg veins: a randomized controlled trial.

PubMed

Klein, A; Buschmann, M; Babilas, P; Landthaler, M; Bäumler, W

2013-08-01

Telangiectatic leg veins (TLV) represent a common cosmetic problem. Near infrared lasers have been widely used in treatment because of their deeper penetration into the dermis, but with varying degrees of success, particularly because of different vessel diameters. Indocyanine green (ICG)-augmented diode laser treatment (ICG+DL) may present an alternative treatment option. This trial evaluates the efficacy of ICG+DL in the treatment of TLV and compares the safety and efficacy of therapy with the standard treatment, the long-pulsed neodymium-doped yttrium aluminium garnet (Nd:YAG) laser. In a prospective randomized controlled clinical trial, 29 study participants with TLV were treated with a Nd:YAG laser (λem = 1064 nm, 160-240 J cm(-2) , 65-ms pulse duration, 5-mm spot size) and ICG+DL (λem = 810 nm, 60-110 J cm(-2) , 48-87-ms pulse duration, 6-mm spot size; total ICG dose 4 mg kg(-1) ) in a side-by-side comparison in one single treatment setting that included histological examination in four participants. Two blinded investigators and the participants assessed clearance rate, cosmetic appearance and adverse events up to 3 months after treatment. According to both the investigators' and participants' assessment, clearance rates were significantly better after ICG+DL therapy than after Nd:YAG laser treatment (P < 0·05). On a 10-point scale indicating pain during treatment, participants rated ICG+DL therapy to be more painful (6·1 ± 2·0) than Nd:YAG laser (5·4 ± 2·0). ICG+DL therapy represents a new and promising treatment modality for TLV, with high clearance rates and a very good cosmetic outcome after one single treatment session. © 2013 British Association of Dermatologists.

Effect of fluorescent pseudomonades and Trichoderma sp. and their combination with two chemicals on Penicillium digitatum caused agent of citrus green mold.

PubMed

Zamani, M; Tehrani, A Sharifi; Ahmadzadeh, M; Abadi, A Alizadeh Ali

2006-01-01

Citrus green mold (Penicillium digitatum) causes economic losses. Chemical fungicides such as imazalil provide the primary means for controlling green mold decay of citrus fruits. Continuous use of fungicides has faced two major obstacles- increasing public concern regarding contamination of perishables with fungicidal residues, and proliferation of resistance in the pathogen populations. The aim of this research was to determine if the attacks of green mold on orange could be reduced by usage of biocontrol agent alone or in combination with low dosage of imazalil or sodium bicarbonate. Pseudomonas fluorescens isolate PN, P. fluorescens isolate PS and Trichoderma virens isolate TE were evaluated as potential biological agents for control of green mold of oranges caused by P. digitatum. Increasing concentration of SB decreased spore germination of P. digitatum. In laboratory tests, a cell suspension (10(8) cells per ml.) of bacterial strains reduced the incidence of green mold. On fruits surface biocontrol activity of antagonistic isolates was significantly increased when combined with low dosage of imazalil (500ppm) or sodium carbonate (5%). Effect of Trichoderma virens on controlling P. digitatum was better than others with or without these chemicals.

Binding of indocyanine green in polycaprolactone fibers using blend electrospinning for in vivo laser-assisted vascular anastomosis.

PubMed

Schönfeld, Annemarie; Kabra, Zacharia Mbäıdjol; Constantinescu, Mihai; Bosshardt, Dieter; Stoffel, Michael H; Peters, Kirsten; Frenz, Martin

2017-12-01

The clinical application of laser-assisted vascular anastomosis is afflicted by unreliable and low bonding strengths as well as tedious handling during microvascular surgery. The challenge to be met arises from the flow-off of the chromophore during soldering that changes the absorption and stains the surrounding tissue, leading to an uncontrollable thermal damage zone. In this study, we investigated the feasibility to produce an indocyanine green (ICG)-loaded patch by electrospinning and tested its applicability to both in vitro and in vivo microvascular laser soldering. A blend of polycaprolactone and ICG was electrospun to produce a pliable patch. Prior to soldering, the patch was soaked in 40% wt. bovine serum albumin solution. The solder patch was wrapped in vitro around blood vessel stumps of rabbit aortas. An intraluminal balloon catheter enabled an easy alignment and held the setup in place. The soldering energy was delivered via a diffusor fiber from the vessel lumen using a diode laser at 810 nm. During the procedure, the surface temperature was observed with an infrared camera. Afterward, samples were embedded in methylmethacrylate and epon to study thermal damage. The quality of the fusion was assessed by measuring the tensile strength. After in vitro tests with rabbit aortas, eight large white pigs were subjected to an acute in vivo experiment, and the artery of the latissimus dorsi flap was anastomosed to the distal femoral artery. The ICG-loaded patch, produced by electrospinning, has a thickness of 279 ± 62 μm, a fiber diameter of 1.20 ± 0.19 μm, and an attenuation coefficient of 1,119 ± 183 cm -1 at a wavelength of 790 nm. The patch was pliable and easy to handle during surgery. No leakage of the chromophore was observed. Thermal damage was restricted to the Tunica adventitia and Tunica media and the area of the vessel wall that was covered with the patch. Six pigs were successfully treated, without any bleeding and with

Gold nanorods/mesoporous silica-based nanocomposite as theranostic agents for targeting near-infrared imaging and photothermal therapy induced with laser

PubMed Central

Liu, Yang; Xu, Ming; Chen, Qing; Guan, Guannan; Hu, Wen; Zhao, Xiuli; Qiao, Mingxi; Hu, Haiyang; Liang, Ying; Zhu, Heyun; Chen, Dawei

2015-01-01

Photothermal therapy (PTT) is widely regarded as a promising technology for cancer treatment. Gold nanorods (GNRs), as excellent PTT agent candidates, have shown high-performance photothermal conversion ability under laser irradiation, yet two major obstacles to their clinical application are the lack of selective accumulation in the target site following systemic administration and the greatly reduced photothermal conversion efficiency caused by self-aggregating in aqueous environment. Herein, we demonstrate that tLyp-1 peptide-functionalized, indocyanine green (ICG)-containing mesoporous silica-coated GNRs (I-TMSG) possessed dual-function as tumor cells-targeting near-infrared (NIR) fluorescent probe and PTT agents. The construction of the nanostructure began with synthesis of GNRs by seed-mediated growth method, followed by the coating of mesoporous silica, the chemical conjugation of PEG and tLyp-1 peptide, and the enclosure of ICG as an NIR imaging agent in the mesoporous. The as-prepared nanoparticles could shield the GNRs against their self-aggregation, improve the stability of ICG, and exhibit negligible dark cytotoxicity. More importantly, such a theranostic nanocomposite could realize the combination of GNRs-based photothermal ablation under NIR illumination, ICG-mediated fluorescent imaging, and tLyp-1-enabled more easy endocytosis into breast cancer cells. All in all, I-TMSG nanoparticles, in our opinion, possessed the strong potential to realize the effective diagnosis and PTT treatment of human mammary cancer. PMID:26251596

Stabilization of green bodies via sacrificial gelling agent during electrophoretic deposition

DOEpatents

Worsley, Marcus A.; Kuntz, Joshua D.; Rose, Klint A.

2016-03-22

In one embodiment, a method for electrophoretic deposition of a three-dimensionally patterned green body includes suspending a first material in a gelling agent above a patterned electrode of an electrophoretic deposition (EPD) chamber, and gelling the suspension while applying a first electric field to the suspension to cause desired patterning of the first material in a resulting gelation. In another embodiment, a ceramic, metal, or cermet includes a plurality of layers, wherein each layer includes a gradient in composition, microstructure, and/or density in an x-y plane oriented parallel to a plane of deposition of the plurality of layers along a predetermined distance in a z-direction perpendicular to the plane of deposition.

Tailoring through Technology: A Retrospective Review of a Single Surgeon's Experience with Implant-Based Breast Reconstruction before and after Implementation of Laser-Assisted Indocyanine Green Angiography.

PubMed

Harless, Christin A; Jacobson, Steven R

2016-05-01

Reported complication rates of implant-based breast reconstruction in the literature exceed 50%, with mastectomy skin flap necrosis reported to occur in up to 25% of cases. Laser-assisted indocyanine green angiography (LA-ICGA) technology allows the surgeon to optimize preservation of the mastectomy skin flap while avoiding skin necrosis. The purpose of this study was to determine if outcomes of breast reconstruction are beneficially affected by using LA-ICGA. A total 269 consecutive women (467 breast reconstructions) undergoing implant-based breast reconstruction from 2008 to 2013 were examined. The complication rates of those who underwent reconstruction prior to the implementation of LA-ICGA were compared with those who were reconstructed after implementation of LA-ICGA. A total of 254 consecutive breast reconstructions were performed prior to implementation of LA-ICGA, and 213 breasts were reconstructed with the use of LA-ICGA. After implementation of LA-ICGA System, the rate of mastectomy skin flap necrosis decreased by 86% (6.7% versus 0.9%, p = 0.02). The overall complication rate prior to LA-ICGA was 13.8% compared with 6.6% with the use of LA-ICGA (p = 0.01). After LA-ICGA was incorporated, the percentage of patients undergoing single-stage reconstruction increased from 12% to 32% (p = <0.001). Implementation of LA-ICGA provides the surgeon with an objective assessment of mastectomy flap perfusion resulting in a trend toward overall reduction in complications as well as an 86% decrease in the rate of subsequent skin necrosis. The objective assessment of mastectomy flap perfusion allows the surgeon to tailor breast reconstruction intraoperatively, in real-time, adjusting for the individual patient's mastectomy flap perfusion. © 2016 Wiley Periodicals, Inc.

Accelerating the degradation of green plant waste with chemical decomposition agents.

PubMed

Kejun, Sun; Juntao, Zhang; Ying, Chen; Zongwen, Liao; Lin, Ruan; Cong, Liu

2011-10-01

Degradation of green plant waste is often difficult, and excess maturity times are typically required. In this study, we used lignin, cellulose and hemicellulose assays; scanning electron microscopy; infrared spectrum analysis and X-ray diffraction analysis to investigate the effects of chemical decomposition agents on the lignocellulose content of green plant waste, its structure and major functional groups and the mechanism of accelerated degradation. Our results showed that adding chemical decomposition agents to Ficus microcarpa var. pusillifolia sawdust reduced the contents of lignin by 0.53%-11.48% and the contents of cellulose by 2.86%-7.71%, and increased the contents of hemicellulose by 2.92%-33.63% after 24 h. With increasing quantities of alkaline residue and sodium lignosulphonate, the lignin content decreased. Scanning electron microscopy showed that, after F. microcarpa var. pusillifolia sawdust was treated with chemical decomposition agents, lignocellulose tube wall thickness increased significantlyIncreases of 29.41%, 3.53% and 34.71% were observed after treatment with NaOH, alkaline residue and sodium lignosulphonate, respectively. Infrared spectroscopy showed that CO and aromatic skeleton stretching absorption peaks were weakened and the C-H vibrational absorption peak from out-of-plane in positions 2 and 6 (S units) (890-900 cm(-1)) was strengthened after F. microcarpa var. pusillifolia sawdust was treated with chemical decomposition agents, indicating a reduction in lignin content. Several absorption peaks [i.e., C-H deformations (asymmetry in methyl groups, -CH(3)- and -CH(2)-) (1450-1460 cm(-1)); Aliphatic C-H stretching in methyl and phenol OH (1370-1380 cm(-1)); CO stretching (cellulose and hemicellulose) (1040-1060 cm(-1))] that indicate the presence of a chemical bond between lignin and cellulose was reduced, indicating that the chemical bond between lignin and cellulose had been partially broken. X-ray diffraction analysis showed that Na

Rapid measurement of indocyanine green retention by pulse spectrophotometry: a validation study in 70 patients with Child-Pugh A cirrhosis before hepatectomy for hepatocellular carcinoma.

PubMed

Cheung, Tan To; Chan, See Ching; Chok, Kenneth S H; Chan, Albert C Y; Yu, Wan Ching; Poon, Ronnie T P; Lo, Chung Mau; Fan, Sheung Tat

2012-06-01

The indocyanine green (ICG) retention test is the most popular liver function test for selecting patients for major hepatectomy. Traditionally, it is done using spectrophotometry with serial blood sampling. The newly-developed pulse spectrophotometry is a faster alternative, but its accuracy on Child-Pugh A cirrhotic patients undergoing hepatectomy for hepatocellular carcinoma has not been well documented. This study aimed to assess the accuracy of the LiMON(®), one of the pulse spectrophotometry systems, in measuring preoperative ICG retention in these patients and to devise an easy formula for conversion of the results so that they can be compared with classical literature records where ICG retention was measured by the traditional method. We measured the liver function of 70 Child-Pugh A cirrhotic patients before hepatectomy for hepatocellular carcinoma from September 2008 to January 2009. ICG retention at 15 minutes measured by traditional spectrophotometry (ICGR15) was compared with ICG retention at 15 minutes measured by the LiMON (ICGR15(L)). The median ICGR15 was 14.7% (5.6%-32%) and the median ICGR15(L) was 10.4% (1.2%-28%). The mean difference between them was -4.3606. There was a strong correlation between ICGR15 and ICGR15(L) (correlation coefficient, 0.844; 95% confidence interval, 0.762-0.899). The following formula was devised: ICGR15=1.16XICGR15(L)+2.73. The LiMON provides a fast and repeatable way to measure ICG retention at 15 minutes, but with constant underestimation of the real value. Therefore, when comparing results obtained by traditional spectrophotometry and the LiMON, adjustment of results from the latter is necessary, and this can be done with a simple mathematical calculation using the above formula.

Green tea extract as an anti-browning agent for cloudy apple juice.

PubMed

Klimczak, Inga; Gliszczyńska-Świgło, Anna

2017-03-01

Enzymatic browning of fruits and vegetables and their products is an important factor worsening their quality. The influence of five green tea extracts at the concentrations of 1 g L -1 , 2 g L -1 and 3 g L -1 on polyphenol oxidase (PPO) activity in fresh cloudy apple juice was investigated. Moreover, PPO inhibition by tea extract and colour stability of juice during short-time refrigerated storage was studied. The changes of juice colour during storage was expressed as the total colour differences (ΔE*), browning index (BI), yellowness index (YI), and the absorbance at 420 nm (A 420 ). All extracts inhibited PPO activity in fresh apple juice in concentration-dependent manner. PPO activity in pure apple juice decreased by 7% after 48 h, whereas PPO activity in samples with 1 g L -1 , 2 g L -1 and 3 g L -1 tea extract decreased by 53%, 74%, and 96%, respectively. Browning of apple juice during storage decreased with increased concentration of green tea extract. After 48 h, extract at 1 g L -1 , 2 g L -1 and 3 g L -1 inhibited browning of juice expressed as BI by 48%, 60%, and 86%, respectively, comparing to pure apple juice. Green tea extract may be an effective anti-browning agent for short-time stored cloudy apple juices. © 2016 Society of Chemical Industry. © 2016 Society of Chemical Industry.

Synthesis, Characterization, and Biological Evaluation of Anti-HER2 Indocyanine Green-Encapsulated PEG-Coated PLGA Nanoparticles for Targeted Phototherapy of Breast Cancer Cells.

PubMed

Lee, Yu-Hsiang; Lai, Yun-Han

2016-01-01

Human epidermal growth factor receptor 2 (HER2)-overexpressed breast cancer is known to be more aggressive and resistant to medicinal treatment and therefore to whom an alternative therapeutics is needed. Indocyanine green (ICG) has been widely exploited in breast cancer phototherapy. However, drawbacks of accelerated degradation and short half-life (2-4 min) in blood seriously hamper its use in the clinic. To overcome these challenges, an anti-HER2 ICG-encapsulated polyethylene glycol-coated poly(lactic-co-glycolic acid) nanoparticles (HIPPNPs) were developed in this study. Through the analyses of degradation rate coefficients of ICG with and without polymeric encapsulation, the photostability of HIPPNP-entrapped ICG significantly enhanced 4 folds (P < 0.05) while its thermal stabilities at 4 and 37°C significantly enhanced 5 and 3 (P < 0.05 for each) folds, respectively, under equal lighting and/or heating treatment for 48 h. The target specificity of HIPPNPs to HER2-positive cells was demonstrated based on a 6-fold (P < 0.05) enhancement of uptake efficiency of HIPPNPs in MDA-MB-453/HER2(+) cells within 4 h as compared with that in MCF7/HER2(-) cells. Moreover, the HIPPNPs with ≤ 25 μM ICG equivalent were nontoxic to cells in the absence of light illumination, and enabled to generate similar amount of singlet oxygen and hyperthermia effect as compared with that used by free ICG upon NIR irradiation. After 808 nm-laser irradiation with intensity of 6 W/cm2 for 5 min, the viability of MDA-MB-453 cells pre-treated by HIPPNPs with ≥ 5 μM ICG equivalent for 4 h significantly reduced as compared with that treated by equal concentration of free ICG (P < 0.05) and > 90% of the cells were eradicated while the dose of HIPPNPs was increased to 25 μM ICG equivalent. In summary, the developed HIPPNPs are anticipated as a feasible tool for use in phototherapy of breast cancer cells with HER2 expression.

Preclinical evaluation of biodegradable macromolecular contrast agents for magnetic resonance imaging

NASA Astrophysics Data System (ADS)

Feng, Yi

Macromolecular contrast agents have been shown to be superior to small molecular weight contrast agents for MRI in blood pool imaging, tumor diagnosis and grading. However, none has been approved by the FDA because they circulate in the bloodstream much longer than small molecular weight contrast agents and result in high tissue accumulation of toxic Gd(III) ions. Biodegradable macromolecular contrast agents (BMCA) were invented to alleviate the toxic accumulation. They have a cleavable disulfide bond based backbone that can be degraded in vivo and excreted out of the body via renal filtration. Furthermore, the side chain of the backbone can be modified to achieve various degradation rates. Three BMCA, (Gd-DTPA)-cystamine copolymers (GDCC), Gd-DTPA cystine copolymers (GDCP), and Gd-DTPA cystine diethyl ester copolymers (GDCEP), were evaluated as blood pool contrast agents in a rat model. They have excellent blood pool enhancement, preferred pharmacokinetics, and only minimal long-term tissue retention of toxic Gd(III) ions. GDCC and GDCP, the lead agents with desired degradation rates, with molecular weights of 20 KDa and 70 KDa, were chosen for dynamic contrast enhanced MRI (DCE-MRI) to differentiate human prostate tumor models of different malignancy and growth rates. GDCC and GDCP could differentiate these tumor models, providing more accurate estimations of plasma volume, flow leakage rate, and permeability surface area product than a small molecular weight contrast agent Gd-DTPA-BMA when compared to the prototype macromolecular contrast agent albumin-Gd-DTPA. GDCC was favored for its neutral charge side chain and reasonable uptake rate by the tumors. GDCC with a molecular weight of 40 KDa (GDCC-40, above the renal filtration cutoff size) was used to assess the efficacy of two photothermal therapies (interstitial and indocyanine green enhanced). GDCC-40 provided excellent tumor enhancement shortly after its injection. Acute tumor response (4 hr) after therapies

Localization of near-infrared contrast agents in tumors by intravital microscopy

NASA Astrophysics Data System (ADS)

Becker, Andreas; Schneider, Guenther; Riefke, Bjoern; Licha, Kai; Semmler, Wolfhard

1999-01-01

In this contribution we use intravital microscopy to study the dynamics of extravasation into normal and tumor tissue of several hydrophilic cyanine dyes used as near-infrared (NIR) contrast agents. The technique provides information about the angiographic properties of the dyes and about their interaction with tumor tissue under dynamic conditions in vivo. In our previous work we demonstrated that several NIR- absorbing fluorescent dyes enable in vivo fluorescence detection of tumors in mice and rats. However, the mechanism leading to dye accumulation and enhanced fluorescence in tumors is not fully understood. Increased extravasation of dyes into tumor tissue due to pathologically altered tumor vessels may be an important factor in this process. Indocyanine green (ICG) displayed predominantly intravascular distribution and rapid elimination resulting in enhanced fluorescence signal of vessels during the first 15 min after administration only. No elevated extravasation into tumor tissue was observed with ICG. A hydrophilic indotricarbocyanine derivative with a high molecular weight displayed prolonged intravascular distribution and increased fluorescence signal of the vasculature compared to surrounding tissue for up to five hours. Rapid extravasation and accumulation in tumor areas, yielding elevated contrast of tumors up to 15 min after administration, was observed with hydrophilic, low molecular weight indotricarbocyanine derivatives.

Pure laparoscopic hepatectomy with augmented reality-assisted indocyanine green fluorescence versus open hepatectomy for hepatocellular carcinoma with liver cirrhosis: A propensity analysis at a single center.

PubMed

Cheung, Tan To; Ma, Ka Wing; She, Wong Hoi; Dai, Wing Chiu; Tsang, Simon Hing Yin; Chan, Albert Chi Yan; Chok, Kenneth Siu Ho; Lo, Chung Mau

2018-05-10

Laparoscopic hepatectomy is considered an acceptable treatment of choice in selected patients with primary hepatocellular carcinoma (HCC). Whether indocyanine green (ICG) immunofluorescence, a new technology, may improve surgery outcomes has yet to be tested. The aim of the present study was to investigate and compare the effect of ICG fluorescence imaging on the outcomes of pure laparoscopic hepatectomy and open hepatectomy for primary HCC with background cirrhosis. From January 2015 to June 2016, 20 patients with HCC and liver cirrhosis underwent laparoscopic hepatectomy with ICG immunofluorescence. The outcomes of pure laparoscopic hepatectomy with ICG immunofluorescence were compared with those of open hepatectomy. To avoid selection bias, patients were propensity score matched in a ratio of 1 : 6, with 20 patients in the laparoscopic group and 120 in the open group. The laparoscopic group had 20 patients, and the open group had 120 patients. The laparoscopic group had less blood loss (125 vs 450 mL, P < 0.001), a shorter operation time (200 vs 250 min, P = 0.003), and a shorter hospital stay (5 vs 6 days, P < 0.001). The complication rate was 0% in the laparoscopic group compared to 15.0% in the open group (P = 0.135). All patients in the laparoscopic group had negative margin involvement. Four patients (3.3%) in the open resection group had positive margin involvement. Two patients in the ICG immunofluorescence group had additional lesions identified and resected during operation. Pure laparoscopic hepatectomy with ICG immunofluorescence for primary HCC can be carried out safely with favorable short-term outcomes even in cirrhotic patients. Better identification of the bile duct structure and better assessment of the tumor resection margin and perfusion are advantages of this new technique. © 2018 Japan Society for Endoscopic Surgery, Asia Endosurgery Task Force and John Wiley & Sons Australia, Ltd.

Evaluation of antifungal activity of carbonate and bicarbonate salts alone or in combination with biocontrol agents in control of citrus green mold.

PubMed

Zamani, M; Sharifi Tehrani, A; Ali Abadi, A Alizadeh

2007-01-01

The aim of this research was to determine if the attacks of green mold on orange could be reduced by edible salts alone or in combination with biocontrol agent. For this purpose toxicity to Pantoea digitatum and practical use of sodium carbonate (SC), sodium bicarbonate (SBC) and potassium carbonate, and potassium bicarbonate alone or in combination with antagonistic bacteria (Pseudomonas fluorescens isolate PN, Bacillus subtilis isolate VHN, Pantoea agglomerans isolate CA) to control green mold were determined. All were fungistatic. SC and SBC were equal and superior to the other salts for control of green mold on oranges inoculated 6h before treatment and were chosen for subsequent trails under cold storage conditions. The biocontrol agents were found completely tolerant to 3% sodium bicarbonate and sodium carbonate at room temperature; although their culturability was reduced by > 1000-fold after 60 min in 1% other salt solutions. Satisfactory results were also obtained with the combined treatment for control of green mold. A significant increase in biocontrol activity of all isolate was observed when combined with sodium carbonate and sodium bicarbonate. The treatments comprising CA combined with SB was as effective as fungicide treatment. Thus, use of sodium bicarbonate treatment at 3% followed by the antagonist P. agglomerans CA could be an alternative to chemical fungicides for control of green mold on oranges.

SENSITIVITY AND SPECIFICITY OF DETECTING POLYPOIDAL CHOROIDAL VASCULOPATHY WITH EN FACE OPTICAL COHERENCE TOMOGRAPHY AND OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY.

PubMed

de Carlo, Talisa E; Kokame, Gregg T; Kaneko, Kyle N; Lian, Rebecca; Lai, James C; Wee, Raymond

2018-03-20

Determine sensitivity and specificity of polypoidal choroidal vasculopathy (PCV) diagnosis with structural en face optical coherence tomography (OCT) and OCT angiography (OCTA). Retrospective review of the medical records of eyes diagnosed with PCV by indocyanine green angiography with review of diagnostic testing with structural en face OCT and OCTA by a trained reader. Structural en face OCT, cross-sectional OCT angiograms alone, and OCTA in its entirety were reviewed blinded to the findings of indocyanine green angiography and each other to determine if they could demonstrate the PCV complex. Sensitivity and specificity of PCV diagnosis was determined for each imaging technique using indocyanine green angiography as the ground truth. Sensitivity and specificity of structural en face OCT were 30.0% and 85.7%, of OCT angiograms alone were 26.8% and 96.8%, and of the entire OCTA were 43.9% and 87.1%, respectively. Sensitivity and specificity were improved for OCT angiograms and OCTA when looking at images taken within 1 month of PCV diagnosis. Sensitivity of detecting PCV was low using structural en face OCT and OCTA but specificity was high. Indocyanine green angiography remains the gold standard for PCV detection.

Measuring hepatic functional reserve using low temporal resolution Gd-EOB-DTPA dynamic contrast-enhanced MRI: a preliminary study comparing galactosyl human serum albumin scintigraphy with indocyanine green retention.

PubMed

Saito, Kazuhiro; Ledsam, Joseph; Sourbron, Steven; Hashimoto, Tsuyoshi; Araki, Yoichi; Akata, Soichi; Tokuuye, Koichi

2014-01-01

To investigate if tracer kinetic modelling of low temporal resolution dynamic contrast-enhanced (DCE) MRI with Gd-EOB-DTPA could replace technetium-99 m galactosyl human serum albumin (GSA) single positron emission computed tomography (SPECT) and indocyanine green (ICG) retention for the measurement of liver functional reserve. Twenty eight patients awaiting liver resection for various cancers were included in this retrospective study that was approved by the institutional review board. The Gd-EOB-DTPA MRI sequence acquired five images: unenhanced, double arterial phase, portal phase, and 4 min after injection. Intracellular contrast uptake rate (UR) and extracellular volume (Ve) were calculated from DCE-MRI, along with the ratio of GSA radioactivity of liver to heart-plus-liver and per cent of cumulative uptake from 15-16 min (LHL15 and LU15, respectively) from GSA-scintigraphy. ICG retention at 15 min, Child-Pugh cirrhosis score (CPS) and postoperative Inuyama fibrosis criteria were also recorded. Statistical analysis was with Spearman rank correlation analysis. Comparing MRI parameters with the reference methods, significant correlations were obtained for UR and LHL15, LU15, ICG15 (all 0.4-0.6, P < 0.05); UR and CPS (-0.64, P < 0.001); Ve and Inuyama (0.44, P < 0.05). Measures of liver function obtained by routine Gd-EOB-DTPA DCE-MRI with tracer kinetic modelling may provide a suitable method for the evaluation of liver functional reserve. • Magnetic resonance imaging (MRI) provides new methods of measuring hepatic functional reserve. • DCE-MRI with Gd-EOB-DTPA offers the possibility of replacing scintigraphy. • The analysis method can be used for preoperative liver function evaluation.

Impact of Indocyanine Green for Sentinel Lymph Node Mapping in Early Stage Endometrial and Cervical Cancer: Comparison with Conventional Radiotracer (99m)Tc and/or Blue Dye.

PubMed

Buda, Alessandro; Crivellaro, Cinzia; Elisei, Federica; Di Martino, Giampaolo; Guerra, Luca; De Ponti, Elena; Cuzzocrea, Marco; Giuliani, Daniela; Sina, Federica; Magni, Sonia; Landoni, Claudio; Milani, Rodolfo

2016-07-01

To compare the detection rate (DR) and bilateral optimal mapping (OM) of sentinel lymph nodes (SLNs) in women with endometrial and cervical cancer using indocyanine green (ICG) versus the standard technetium-99m radiocolloid ((99m)Tc) radiotracer plus methylene or isosulfan blue, or blue dye alone. From October 2010 to May 2015, 163 women with stage I endometrial or cervical cancer (118 endometrial and 45 cervical cancer) underwent SLN mapping with (99m)Tc with blue dye, blue dye alone, or ICG. DR and bilateral OM of ICG were compared respectively with the results obtained using the standard (99m)Tc radiotracer with blue dye, or blue dye alone. SLN mapping with (99m)Tc radiotracer with blue dye was performed on 77 of 163 women, 38 with blue dye only and 48 with ICG. The overall DR of SLN mapping was 97, 89, and 100 % for (99m)Tc with blue dye, blue dye alone, and ICG, respectively. The bilateral OM rate for ICG was 85 %-significantly higher than the 58 % obtained with (99m)Tc with blue dye (p = 0.003) and the 54 % for blue dye (p = 0.001). Thirty-one women (19 %) had positive SLNs. Sensitivity and negative predictive value of SLN were 100 % for all techniques. SLNs mapping using ICG demonstrated higher DR compared to other modalities. In addition, ICG was significantly superior to (99m)Tc with blue dye in terms of bilateral OM in women with early stage endometrial and cervical cancer. The higher number of bilateral OM may consequently reduce the overall number of complete lymphadenectomies, reducing the duration and additional costs of surgical treatment.

Quantitative cerebral perfusion assessment using microscope-integrated analysis of intraoperative indocyanine green fluorescence angiography versus positron emission tomography in superficial temporal artery to middle cerebral artery anastomosis.

PubMed

Kobayashi, Shinya; Ishikawa, Tatsuya; Tanabe, Jun; Moroi, Junta; Suzuki, Akifumi

2014-01-01

Intraoperative qualitative indocyanine green (ICG) angiography has been used in cerebrovascular surgery. Hyperperfusion may lead to neurological complications after superficial temporal artery to middle cerebral artery (STA-MCA) anastomosis. The purpose of this study is to quantitatively evaluate intraoperative cerebral perfusion using microscope-integrated dynamic ICG fluorescence analysis, and to assess whether this value predicts hyperperfusion syndrome (HPS) after STA-MCA anastomosis. Ten patients undergoing STA-MCA anastomosis due to unilateral major cerebral artery occlusive disease were included. Ten patients with normal cerebral perfusion served as controls. The ICG transit curve from six regions of interest (ROIs) on the cortex, corresponding to ROIs on positron emission tomography (PET) study, was recorded. Maximum intensity (IMAX), cerebral blood flow index (CBFi), rise time (RT), and time to peak (TTP) were evaluated. RT/TTP, but not IMAX or CBFi, could differentiate between control and study subjects. RT/TTP correlated (|r| = 0.534-0.807; P < 0.01) with mean transit time (MTT)/MTT ratio in the ipsilateral to contralateral hemisphere by PET study. Bland-Altman analysis showed a wide limit of agreement between RT and MTT and between TTP and MTT. The ratio of RT before and after bypass procedures was significantly lower in patients with postoperative HPS than in patients without postoperative HPS (0.60 ± 0.032 and 0.80 ± 0.056, respectively; P = 0.017). The ratio of TTP was also significantly lower in patients with postoperative HPS than in patients without postoperative HPS (0.64 ± 0.081 and 0.85 ± 0.095, respectively; P = 0.017). Time-dependent intraoperative parameters from the ICG transit curve provide quantitative information regarding cerebral circulation time with quality and utility comparable to information obtained by PET. These parameters may help predict the occurrence of postoperative HPS.

Thromboresistant surface coatings for the measurement of cardiac output through continuous low flow peripheral A-V shunts.

PubMed Central

Deeb, G M; Borovetz, H S; Griffith, B P; Hardesty, R L

1980-01-01

The dilution technique for determining cardiac output using indocyanine green dye is limited in patients weighing less than 20 kg because of the obligatory volume loss. Reproducible achieved using the green dye dilution method by the establishment of a low flow peripheral arteriovenous shunt. The shunt materials were treated with thromboresistant agents--TDMAC (7%) and albumin (1 g/dl)--to facilitate the use of this technique without heparin. For A-V shunt flow rates of 8-30 cc/min reproducible values of cardiac output were obtained for up to 38 hours which were in good agreement with determinations made using the conventional technique of dye dilution. PMID:6986120

Photodynamic inactivation of microorganisms which cause pulmonary diseases with infrared light: an in vitro study

NASA Astrophysics Data System (ADS)

Leite, Ilaiáli S.; Geralde, Mariana C.; Salina, Ana C.; Medeiros, Alexandra I.; Kurachi, Cristina; Bagnato, Vanderlei S.; Inada, Natalia M.

2014-03-01

Lower respiratory infections are among the leading causes of death worldwide. In this study, it was evaluated the interaction of indocyanine green, a photosensitizer activated by infrared light, with alveolar macrophages and the effectiveness of the photodynamic therapy using this compound against Streptococcus pneumoniae . Initial experiments analyzed indocyanine green toxicity to alveolar macrophages in the dark with different drug concentrations and incubation times, and macrophage viability was obtained with the MTT method. The average of the results showed viability values below 90% for the two highest concentrations. Experiments with Streptococcus pneumoniae showed photodynamic inactivation with 10 μM indocyanine green solution. Further experiments with the bacteria in co-culture with AM will be conducted verifying the photodynamic inactivation effectiveness of the tested drug concentrations and incubation periods using infrared light.

Comparison of Laser Doppler and Laser-Assisted Indocyanine Green Angiography Prediction of Flap Survival in a Novel Modification of the McFarlane Flap.

PubMed

Fourman, Mitchell Stephen; Gersch, Robert P; Phillips, Brett T; Nasser, Ahmed; Rivara, Andrew; Verma, Richa; Dagum, Alexander B; Rosengart, Todd K; Bui, Duc T

2015-07-01

The McFarlane rat ischemic dorsal skin flap model has been commonly used for clinical vector studies, as well as the testing of noninvasive diagnostics. However, variability of this model secondary to flap contact with the wound bed has led many to question its validity. Here we present a novel modification to the McFarlane skin flap using sterile silicone. We also use this model to test the prognostic efficacy of laser-assisted indocyanine green (ICG) angiography and laser Doppler imaging (LDI). A 3 × 9-cm dorsal skin flap with a cranially based pedicle was created, centered 1 cm distal to the scapulae. The flap was undermined, and in one of the 2 groups, a sterile silicone sheet was placed onto the wound bed. All flaps were then reapproximated with sutures 1-cm intervals. Clinical assessment and perfusion imaging was performed immediately postoperative, and at 24, 48, and 72 hours postsurgery. Postoperative day 7 clinical assessment was obtained before euthanasia. A comparative study using silicone blocked versus unblocked models (n = 6 per group) showed that, clinically, both models had equivalent flap survival [8.5 (0.913) vs 9.5 (1.01) cm]. However, a statistically significant increase in perfusion in the mid-third of unblocked models was observed on POD3 [20.28% (2.7%) vs blocked 13.45% (2.5%), P < 0.05], with a similar increase in the distal third on POD7 [18.73% (2.064%) vs 10.91% (4.19%), P < 0.05]. A prognostic study comparing LDI and ICG angiography prediction of POD7 survival at early time points (n = 10) found that LDI underpredicted flap survival at early time points [84.2% (12.03%) on POD0, 87.35% (16.11%) on POD1]. In contrast, ICG was more proficient [100.1% (10.1%) on POD0]. We present a modification of the McFarlane skin flap model that results in similar clinical results, but with a noted reduction in perfusion inconsistencies noted in unblocked models. The ICG angiography is superior to LDI in predicting POD7 flap necrosis within the first 48

Synthesis and spectroscopic investigations of hydroxyapatite using a green chelating agent as template

NASA Astrophysics Data System (ADS)

Gopi, D.; Bhuvaneshwari, N.; Indira, J.; Kavitha, L.

2013-03-01

Hydroxyapatite [Ca10(PO4)6(OH)2, HAP] particles have been successfully synthesized by a cost-effective, eco-friendly green template method using natural and commercially available sucrose as a chelating agent. The sucrose used in this method has been extracted from various sources, three from natural and one from commercially available sources are exploited in our study to achieve a controlled crystallinity, particle size as well as uniform morphology. Spectral characterizations involving Fourier transform infrared spectroscopy (FT-IR) for the functional group analysis of sucrose and HAP; carbon-13 nuclear magnetic resonance spectroscopy (13C NMR) for the identification of the carbon atoms in sucrose and in HAP; liquid chromatography/mass spectrometry (LC-MS) for the determination of the hydrolyzed products of sucrose; and X-ray diffraction (XRD) techniques for the phase identification of the HAP particles were performed. The morphology of the HAP particles were assessed thoroughly using a scanning electron microscope (SEM) equipped with energy dispersive X-ray analysis (EDAX). The experimental results indicate that the obtained HAP using the natural sucrose as a chelating agent is of phase pure, with a well defined morphology having discrete particles without any agglomeration than the HAP from commercially available sucrose. Further, the reduced particle size can be achieved from the stem sugarcane extract as the source of the chelating agent.

Synthesis and spectroscopic investigations of hydroxyapatite using a green chelating agent as template.

PubMed

Gopi, D; Bhuvaneshwari, N; Indira, J; Kavitha, L

2013-03-01

Hydroxyapatite [Ca(10)(PO(4))(6)(OH)(2), HAP] particles have been successfully synthesized by a cost-effective, eco-friendly green template method using natural and commercially available sucrose as a chelating agent. The sucrose used in this method has been extracted from various sources, three from natural and one from commercially available sources are exploited in our study to achieve a controlled crystallinity, particle size as well as uniform morphology. Spectral characterizations involving Fourier transform infrared spectroscopy (FT-IR) for the functional group analysis of sucrose and HAP; carbon-13 nuclear magnetic resonance spectroscopy ((13)C NMR) for the identification of the carbon atoms in sucrose and in HAP; liquid chromatography/mass spectrometry (LC-MS) for the determination of the hydrolyzed products of sucrose; and X-ray diffraction (XRD) techniques for the phase identification of the HAP particles were performed. The morphology of the HAP particles were assessed thoroughly using a scanning electron microscope (SEM) equipped with energy dispersive X-ray analysis (EDAX). The experimental results indicate that the obtained HAP using the natural sucrose as a chelating agent is of phase pure, with a well defined morphology having discrete particles without any agglomeration than the HAP from commercially available sucrose. Further, the reduced particle size can be achieved from the stem sugarcane extract as the source of the chelating agent. Copyright © 2012 Elsevier B.V. All rights reserved.

Optical see-through cancer vision goggles enable direct patient visualization and real-time fluorescence-guided oncologic surgery

PubMed Central

Mondal, Suman B.; Gao, Shengkui; Zhu, Nan; Hebimana-Griffin, LeMoyne; Akers, Walter J.; Liang, Rongguang; Gruev, Viktor; Margenthaler, Julie; Achilefu, Samuel

2017-01-01

Background The inability to directly visualize the patient and surgical site limits the use of current near infrared fluorescence-guided surgery systems for real-time sentinel lymph node biopsy and tumor margin assessment. Methods We evaluated an optical see-through goggle augmented imaging and navigation system (GAINS) for near-infrared fluorescence-guided surgery. Tumor-bearing mice injected with a near infrared cancer-targeting agent underwent fluorescence-guided tumor resection. Female Yorkshire pigs received hind leg intradermal indocyanine green injection and underwent fluorescence-guided popliteal lymph node resection. Four breast cancer patients received 99mTc-sulfur colloid and indocyanine green retroareolarly, before undergoing sentinel lymph node biopsy using radioactive tracking and fluorescence imaging. Three other breast cancer patients received indocyanine green retroareolarly before undergoing standard-of-care partial mastectomy, followed by fluorescence imaging of resected tumor and tumor cavity for margin assessment. Results Using near-infrared fluorescence from the dyes, the optical see-through GAINS accurately identified all mouse tumors, pig lymphatics, and 4 pig popliteal lymph nodes with high signal-to-background ratio. In 4 human breast cancer patients, 11 sentinel lymph nodes were identified with a detection sensitivity of 86.67± 0.27% for radioactive tracking and 100% for GAINS. Tumor margin status was accurately predicted by GAINS in all three patients, including clear margins in patients 1 and 2 and positive margins in patient 3 as confirmed by paraffin embedded section histopathology. Conclusions The optical see-through GAINS prototype enhances near infrared fluorescence-guided surgery for sentinel lymph node biopsy and tumor margin assessment in breast cancer patients without disrupting the surgical workflow in the operating room. PMID:28213790

Mechanism of the beneficial effects of ATP-MgCl2 following trauma-hemorrhage and resuscitation: downregulation of inflammatory cytokine (TNF, IL-6) release.

PubMed

Wang, P; Ba, Z F; Morrison, M H; Ayala, A; Dean, R E; Chaudry, I H

1992-04-01

Although ATP-MgCl2 improves hepatocellular function in a nonheparinized model of trauma-hemorrhage and crystalloid resuscitation, it remains unknown whether the beneficial effects of this agent are due to downregulation of the release of the inflammatory cytokines, tumor necrosis factor (TNF), and interleukin-6 (IL-6) under those conditions. To study this, rats underwent a 5-cm laparotomy (i.e., trauma induced) and were bled to and maintained at a mean arterial pressure of 40 mm Hg until 40% of maximum bleedout volume was returned in the form of Ringer's lactate (RL). The animals were then resuscitated with four times the volume of shed blood with RL over 60 min. ATP-MgCl2 (50 mumoles/kg body weight each) or an equivalent volume of normal saline was infused intravenously for 95 min. This infusion was started during the last 15 min of RL resuscitation. Plasma levels of TNF and IL-6 were measured at 1.5 hr after the completion of resuscitation by cytokine-dependent cellular assays. Hepatic blood flow was determined by in vivo indocyanine green clearance (corrected by hepatic extraction ratio for indocyanine green), radioactive microspheres, and [3H]-galactose clearance techniques. The results indicate that the levels of circulating TNF and IL-6 increased significantly in the hemorrhaged-resuscitated animals. ATP-MgCl2 treatment, however, markedly decreased the synthesis and/or release of these cytokines to levels similar to the sham group. The markedly decreased hepatic blood flow (as determined by three different methods) and hepatic extraction ratio for indocyanine green were also restored by ATP-MgCl2 treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Optical See-Through Cancer Vision Goggles Enable Direct Patient Visualization and Real-Time Fluorescence-Guided Oncologic Surgery.

PubMed

Mondal, Suman B; Gao, Shengkui; Zhu, Nan; Habimana-Griffin, LeMoyne; Akers, Walter J; Liang, Rongguang; Gruev, Viktor; Margenthaler, Julie; Achilefu, Samuel

2017-07-01

The inability to visualize the patient and surgical site directly, limits the use of current near infrared fluorescence-guided surgery systems for real-time sentinel lymph node biopsy and tumor margin assessment. We evaluated an optical see-through goggle augmented imaging and navigation system (GAINS) for near-infrared, fluorescence-guided surgery. Tumor-bearing mice injected with a near infrared cancer-targeting agent underwent fluorescence-guided, tumor resection. Female Yorkshire pigs received hind leg intradermal indocyanine green injection and underwent fluorescence-guided, popliteal lymph node resection. Four breast cancer patients received 99m Tc-sulfur colloid and indocyanine green retroareolarly before undergoing sentinel lymph node biopsy using radioactive tracking and fluorescence imaging. Three other breast cancer patients received indocyanine green retroareolarly before undergoing standard-of-care partial mastectomy, followed by fluorescence imaging of resected tumor and tumor cavity for margin assessment. Using near-infrared fluorescence from the dyes, the optical see-through GAINS accurately identified all mouse tumors, pig lymphatics, and four pig popliteal lymph nodes with high signal-to-background ratio. In 4 human breast cancer patients, 11 sentinel lymph nodes were identified with a detection sensitivity of 86.67 ± 0.27% for radioactive tracking and 100% for GAINS. Tumor margin status was accurately predicted by GAINS in all three patients, including clear margins in patients 1 and 2 and positive margins in patient 3 as confirmed by paraffin-embedded section histopathology. The optical see-through GAINS prototype enhances near infrared fluorescence-guided surgery for sentinel lymph node biopsy and tumor margin assessment in breast cancer patients without disrupting the surgical workflow in the operating room.

Detection of rheumatoid arthritis by evaluation of normalized variances of fluorescence time correlation functions

NASA Astrophysics Data System (ADS)

Dziekan, Thomas; Weissbach, Carmen; Voigt, Jan; Ebert, Bernd; MacDonald, Rainer; Bahner, Malte L.; Mahler, Marianne; Schirner, Michael; Berliner, Michael; Berliner, Birgitt; Osel, Jens; Osel, Ilka

2011-07-01

Fluorescence imaging using the dye indocyanine green as a contrast agent was investigated in a prospective clinical study for the detection of rheumatoid arthritis. Normalized variances of correlated time series of fluorescence intensities describing the bolus kinetics of the contrast agent in certain regions of interest were analyzed to differentiate healthy from inflamed finger joints. These values are determined using a robust, parameter-free algorithm. We found that the normalized variance of correlation functions improves the differentiation between healthy joints of volunteers and joints with rheumatoid arthritis of patients by about 10% compared to, e.g., ratios of areas under the curves of raw data.

In vivo antimicrobial activity of silver nanoparticles produced via a green chemistry synthesis using Acacia rigidula as a reducing and capping agent.

PubMed

Escárcega-González, Carlos Enrique; Garza-Cervantes, J A; Vázquez-Rodríguez, A; Montelongo-Peralta, Liliana Zulem; Treviño-González, M T; Díaz Barriga Castro, E; Saucedo-Salazar, E M; Chávez Morales, R M; Regalado Soto, D I; Treviño González, F M; Carrazco Rosales, J L; Cruz, Rocío Villalobos; Morones-Ramírez, José Rubén

2018-01-01

One of the main issues in the medical field and clinical practice is the development of novel and effective treatments against infections caused by antibiotic-resistant bacteria. One avenue that has been approached to develop effective antimicrobials is the use of silver nanoparticles (Ag-NPs), since they have been found to exhibit an efficient and wide spectrum of antimicrobial properties. Among the main drawbacks of using Ag-NPs are their potential cytotoxicity against eukaryotic cells and the latent environmental toxicity of their synthesis methods. Therefore, diverse green synthesis methods, which involve the use of environmentally friendly plant extracts as reductive and capping agents, have become attractive to synthesize Ag-NPs that exhibit antimicrobial effects against resistant bacteria at concentrations below toxicity thresholds for eukaryotic cells. In this study, we report a green one-pot synthesis method that uses Acacia rigidula extract as a reducing and capping agent, to produce Ag-NPs with applications as therapeutic agents to treat infections in vivo. The Ag-NPs were characterized using transmission electron microscopy (TEM), high-resolution TEM, selected area electron diffraction, energy-dispersive spectroscopy, ultraviolet-visible, and Fourier transform infrared. We show that Ag-NPs are spherical with a narrow size distribution. The Ag-NPs show antimicrobial activities in vitro against Gram-negative ( Escherichia coli , Pseudomonas aeruginosa , and a clinical multidrug-resistant strain of P. aeruginosa ) and Gram-positive ( Bacillus subtilis ) bacteria. Moreover, antimicrobial effects of the Ag-NPs, against a resistant P. aeruginosa clinical strain, were tested in a murine skin infection model. The results demonstrate that the Ag-NPs reported in this work are capable of eradicating pathogenic resistant bacteria in an infection in vivo. In addition, skin, liver, and kidney damage profiles were monitored in the murine infection model, and the

In vivo antimicrobial activity of silver nanoparticles produced via a green chemistry synthesis using Acacia rigidula as a reducing and capping agent

PubMed Central

Escárcega-González, Carlos Enrique; Garza-Cervantes, JA; Vázquez-Rodríguez, A; Montelongo-Peralta, Liliana Zulem; Treviño-González, MT; Díaz Barriga Castro, E; Saucedo-Salazar, EM; Chávez Morales, RM; Regalado Soto, DI; Treviño González, FM; Carrazco Rosales, JL; Cruz, Rocío Villalobos; Morones-Ramírez, José Rubén

2018-01-01

Introduction One of the main issues in the medical field and clinical practice is the development of novel and effective treatments against infections caused by antibiotic-resistant bacteria. One avenue that has been approached to develop effective antimicrobials is the use of silver nanoparticles (Ag-NPs), since they have been found to exhibit an efficient and wide spectrum of antimicrobial properties. Among the main drawbacks of using Ag-NPs are their potential cytotoxicity against eukaryotic cells and the latent environmental toxicity of their synthesis methods. Therefore, diverse green synthesis methods, which involve the use of environmentally friendly plant extracts as reductive and capping agents, have become attractive to synthesize Ag-NPs that exhibit antimicrobial effects against resistant bacteria at concentrations below toxicity thresholds for eukaryotic cells. Purpose In this study, we report a green one-pot synthesis method that uses Acacia rigidula extract as a reducing and capping agent, to produce Ag-NPs with applications as therapeutic agents to treat infections in vivo. Materials and methods The Ag-NPs were characterized using transmission electron microscopy (TEM), high-resolution TEM, selected area electron diffraction, energy-dispersive spectroscopy, ultraviolet–visible, and Fourier transform infrared. Results We show that Ag-NPs are spherical with a narrow size distribution. The Ag-NPs show antimicrobial activities in vitro against Gram-negative (Escherichia coli, Pseudomonas aeruginosa, and a clinical multidrug-resistant strain of P. aeruginosa) and Gram-positive (Bacillus subtilis) bacteria. Moreover, antimicrobial effects of the Ag-NPs, against a resistant P. aeruginosa clinical strain, were tested in a murine skin infection model. The results demonstrate that the Ag-NPs reported in this work are capable of eradicating pathogenic resistant bacteria in an infection in vivo. In addition, skin, liver, and kidney damage profiles were

Sentinel lymph nodes and lymphatic vessels: noninvasive dual-modality in vivo mapping by using indocyanine green in rats--volumetric spectroscopic photoacoustic imaging and planar fluorescence imaging.

PubMed

Kim, Chulhong; Song, Kwang Hyun; Gao, Feng; Wang, Lihong V

2010-05-01

To noninvasively map sentinel lymph nodes (SLNs) and lymphatic vessels in rats in vivo by using dual-modality nonionizing imaging-volumetric spectroscopic photoacoustic imaging, which measures optical absorption, and planar fluorescence imaging, which measures fluorescent emission-of indocyanine green (ICG). Institutional animal care and use committee approval was obtained. Healthy Sprague-Dawley rats weighing 250-420 g (age range, 60-120 days) were imaged by using volumetric photoacoustic imaging (n = 5) and planar fluorescence imaging (n = 3) before and after injection of 1 mmol/L ICG. Student paired t tests based on a logarithmic scale were performed to evaluate the change in photoacoustic signal enhancement of SLNs and lymphatic vessels before and after ICG injection. The spatial resolutions of both imaging systems were compared at various imaging depths (2-8 mm) by layering additional biologic tissues on top of the rats in vivo. Spectroscopic photoacoustic imaging was applied to identify ICG-dyed SLNs. In all five rats examined with photoacoustic imaging, SLNs were clearly visible, with a mean signal enhancement of 5.9 arbitrary units (AU) + or - 1.8 (standard error of the mean) (P < .002) at 0.2 hour after injection, while lymphatic vessels were seen in four of the five rats, with a signal enhancement of 4.3 AU + or - 0.6 (P = .001). In all three rats examined with fluorescence imaging, SLNs and lymphatic vessels were seen. The average full width at half maximum (FWHM) of the SLNs in the photoacoustic images at three imaging depths (2, 6, and 8 mm) was 2.0 mm + or - 0.2 (standard deviation), comparable to the size of a dissected lymph node as measured with a caliper. However, the FWHM of the SLNs in fluorescence images widened from 8 to 22 mm as the imaging depth increased, owing to strong light scattering. SLNs were identified spectroscopically in photoacoustic images. These two modalities, when used together with ICG, have the potential to help map SLNs in

Accuracy and reproducibility of the measurement of actively circulating blood volume with an integrated fiberoptic monitoring system.

PubMed

Kisch, H; Leucht, S; Lichtwarck-Aschoff, M; Pfeiffer, U J

1995-05-01

Bedside monitoring of circulating blood volume has become possible with the introduction of an integrated fiberoptic monitoring system that calculates blood volume from the changes in blood concentration of indocyanine green dye 4 mins after injection. The aim of this investigation was to compare the blood volume estimate of the integrated fiberoptic monitoring system (group 1) with the standard methods of blood volume measurement using Evans blue (group 2), and indocyanine green measured photometrically (group 3). Prospective laboratory study. Animal laboratory of a University's institute for experimental surgery. Eleven anesthetized, paralyzed, and mechanically ventilated piglets. A central venous catheter was used for the injection of the indicator dyes (Evans blue and indocyanine green). A fiberoptic thermistor catheter was advanced into the thoracic aorta. The fiberoptic catheter detects indocyanine green by reflection densitometry for the estimation of blood volume of the integrated fiberoptic monitoring system. Samples for the determination of Evans blue and indocyanine green concentrations were drawn from an arterial catheter in the femoral artery over a period of 17 mins after injection. Measurements were performed during normovolemia, hypovolemia (blood withdrawal of < or = 30 mL/kg), and hypervolemia (retransfusion of the withdrawn blood plus an infusion of 10% hydroxyethyl starch [45 mL/kg]). Linear regression, correlation, and bias were calculated for the comparison of the blood volume estimates by the fiberoptic monitoring system (group 1) vs. the total blood volume estimates using Evans blue (group 2) and indocyanine green (group 3): group 1 = 0.82.group 2-26 mL; r2 = 82.71%; r = .91; n = 40; group 1-group 2 +/- 1 SD = -435 +/- 368 mL; group 1 = 0.79.group 3 + 50 mL; r2 = 74.81%; r = .87; n = 28; group 1-group 3 +/- 1 SD = -506 +/- 374 mL. The results demonstrate that the blood volume estimate of the fiberoptic monitoring system (group 1) correlates

From Conventional Radiotracer Tc-99(m) with Blue Dye to Indocyanine Green Fluorescence: A Comparison of Methods Towards Optimization of Sentinel Lymph Node Mapping in Early Stage Cervical Cancer for a Laparoscopic Approach.

PubMed

Buda, Alessandro; Papadia, Andrea; Zapardiel, Ignacio; Vizza, Enrico; Ghezzi, Fabio; De Ponti, Elena; Lissoni, Andrea Alberto; Imboden, Sara; Diestro, Maria Dolores; Verri, Debora; Gasparri, Maria Luisa; Bussi, Beatrice; Di Martino, Giampaolo; de la Noval, Begoña Diaz; Mueller, Michael; Crivellaro, Cinzia

2016-09-01

The credibility of sentinel lymph node (SLN) mapping is becoming increasingly more established in cervical cancer. We aimed to assess the sensitivity of SLN biopsy in terms of detection rate and bilateral mapping in women with cervical cancer by comparing technetium-99 radiocolloid (Tc-99(m)) and blue dye (BD) versus fluorescence mapping with indocyanine green (ICG). Data of patients with cervical cancer stage 1A2 to 1B1 from 5 European institutions were retrospectively reviewed. All centers used a laparoscopic approach with the same intracervical dye injection. Detection rate and bilateral mapping of ICG were compared, respectively, with results obtained by standard Tc-99(m) with BD. Overall, 76 (53 %) of 144 of women underwent preoperative SLN mapping with radiotracer and intraoperative BD, whereas 68 of (47 %) 144 patients underwent mapping using intraoperative ICG. The detection rate of SLN mapping was 96 % and 100 % for Tc-99(m) with BD and ICG, respectively. Bilateral mapping was achieved in 98.5 % for ICG and 76.3 % for Tc-99(m) with BD; this difference was statistically significant (p < 0.0001). The fluorescence SLN mapping with ICG achieved a significantly higher detection rate and bilateral mapping compared to standard radiocolloid and BD technique in women with early stage cervical cancer. Nodal staging with an intracervical injection of ICG is accurate, safe, and reproducible in patients with cervical cancer. Before replacing lymphadenectomy completely, the additional value of fluorescence SLN mapping on both perioperative morbidity and survival should be explored and confirmed by ongoing controlled trials.

Cracking the perfusion code?: Laser-assisted Indocyanine Green angiography and combined laser Doppler spectrophotometry for intraoperative evaluation of tissue perfusion in autologous breast reconstruction with DIEP or ms-TRAM flaps.

PubMed

Ludolph, Ingo; Arkudas, Andreas; Schmitz, Marweh; Boos, Anja M; Taeger, Christian D; Rother, Ulrich; Horch, Raymund E; Beier, Justus P

2016-10-01

The aim of this prospective study was to assess the correlation of flap perfusion analysis based on laser-assisted Indocyanine Green (ICG) angiography with combined laser Doppler spectrophotometry in autologous breast reconstruction using free DIEP/ms-TRAM flaps. Between February 2014 and July 2015, 35 free DIEP/ms-TRAM flaps were included in this study. Besides the clinical evaluation of flaps, intraoperative perfusion dynamics were assessed by means of laser-assisted ICG angiography and post-capillary oxygen saturation and relative haemoglobin content (rHb) using combined laser Doppler spectrophotometry. Correlation of the aforementioned parameters was analysed, as well as the impact on flap design and postoperative complications. Flap survival rate was 100%. There were no partial flap losses. In three cases, flap design was based on the angiography, contrary to clinical evaluation and spectrophotometry. The final decision on the inclusion of flap areas was based on the angiographic perfusion pattern. Angiography and spectrophotometry showed a correlation in most of the cases regarding tissue perfusion, post-capillary oxygen saturation and relative haemoglobin content. Laser-assisted ICG angiography is a useful tool for intraoperative evaluation of flap perfusion in autologous breast reconstruction with DIEP/ms-TRAM flaps, especially in decision making in cases where flap perfusion is not clearly assessable by clinical signs and exact determination of well-perfused flap margins is difficult to obtain. It provides an objective real-time analysis of flap perfusion, with high sensitivity for the detection of poorly perfused flap areas. Concerning the topographical mapping of well-perfused flap areas, laser-assisted angiography is superior to combined laser Doppler spectrophotometry. Copyright © 2016 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.

Fluorescence measurement of diode (805 nm) laser-induced release of 5,6-CF from DSPC liposomes for monitoring of temperature: an in vivo study in rat liver using indocyanine green potentiation

NASA Astrophysics Data System (ADS)

Mordon, Serge R.; Desmettre, Thomas; Devoisselle, Jean-Marie; Soulie-Begu, Sylvie

1995-05-01

This in-vivo study examines the validity of fluorescence measurement of laser-induced release of temperature sensitive liposome-encapsulated dye for monitoring of temperature and prediction of tissue thermal damage. It is performed in rat liver after i.v. injection of liposomes loaded with a fluorescent dye and i.v. injection of Indocyanine Green (ICG) for diode laser potentiation. Temperature sensitive liposomes (DSPC: Di- Stearoyl-Phosphatidyl-Choline) are loaded with 5,6-Carboxyfluorescein (5,6-CF). These liposomes (1.5 ml solution) and ICG (1.5 ml solution-5 mg/kg) are injected to adult male wistar rats. Two hours later, the liver is exposed and irradiated with a 0.8 W diode laser using pulses lasting from 1 s to 6 s (fluence ranging from 16 to 98 J/cm+2)). Simultaneously, the fluorescence emission is measured with a fluorescent imaging system. Results show that the fluorescence intensity increases linearly form 18 J/cm2 up to 75 J/cm2. These fluences correspond to surface temperatures between 42°C to 64°C. The measurements appear to be highly reproducible. In this temperature range, the accuracy is +/- 3°C. The maximum intensity is observed immediately after the laser is switched off and a decrease of the fluorescence intensity is observed (27% in 20 minutes) due to the 5.6-CF clearance. However, the ratio (IF/Ibck) remains almost stable over this period of time and the determination of the temperature is still possible with a good accuracy even 20 minutes after laser irradiation. In conclusion, temperature monitoring by using fluorescence measurement of laser-induced release of liposome-encapsulated dye is clearly demonstrated. This procedure could conceivably prove useful for controlling the thermal coagulation of biological tissues.

Axillary lymph node recurrence after sentinel lymph node biopsy performed using a combination of indocyanine green fluorescence and the blue dye method in early breast cancer.

PubMed

Inoue, Tomoo; Nishi, Toshio; Nakano, Yoshiaki; Nishimae, Ayaka; Sawai, Yuka; Yamasaki, Masaru; Inaji, Hideo

2016-03-01

There is limited information on indocyanine green (ICG) fluorescence and blue dye for detecting sentinel lymph node (SLN) in early breast cancer. A retrospective study was conducted to assess the feasibility of an SLN biopsy using the combination of ICG fluorescence and the blue dye method. Seven hundred and fourteen patients with clinically node-negative breast cancer were included in this study. They underwent SLN biopsy using a combination of ICG fluorescence and the blue dye method from March 2007 to February 2014. The ICG (a fluorescence-emitting source) and patent blue (the blue dye) were injected into the patients' subareolar region. The removed lymph nodes that had ICG fluorescence and/or blue dye uptake were defined as SLNs. The results of the SLN biopsies and follow-up results of patients who underwent SLN biopsy alone were investigated. In 711 out of 714 patients, SLNs were identified by a combination of ICG fluorescence and the blue dye method (detection rate, 99.6 %). The average number of SLNs was 2.4 (range 1-7), and the average number of resected swollen para-SLNs was 0.4 (range 0-5). Ninety-nine patients with an SLN and/or para-SLN involvement during the intraoperative pathological diagnosis underwent axillary lymph node resection (ALND). In addition, two of three patients whose SLN was not identified also underwent ALND. In 46 of 101 patients with an ALND, non-SLN involvement was not found. Follow-up results were analyzed in 464 patients with invasive carcinoma excluding those with ductal carcinoma in situ (n = 148) and those who underwent ALND (n = 101). During the follow-up period (range 4.4-87.7 months; median, 38 months), two patients (0.4 %) developed axillary lymph node recurrence. They were successfully salvaged, and to date, no further locoregional recurrence has been observed. A high rate of SLN detection and low rate of axillary lymph node recurrence were confirmed by an SLN biopsy using a combination of ICG fluorescence and the blue dye

Effects of petroleum hydrocarbons on hepatic function in the duck

USGS Publications Warehouse

Patton, J.F.; Dieter, M.P.

1980-01-01

1. The indocyanine green dye clearance test for hepatic function was determined in mallard ducks before and during the chronic ingestion (7 months) of representative paraffinic or aromatic petroleum hydrocarbons (PH).2. No mortality or visible symptoms of toxicity occured in any of the tests. Ingestion of 4000 ppm aromatic PH produced significant increases in liver (25%), plasma clearance of indocyanine green (33%) and hepatic blood flow (30%).3. Although the aromatics elicited a greater hepatic stress response than the paraffins, the ducks tolerated high concentrations of PH for extended periods.

Evaluation of liver function using gadoxetate disodium (Gd-EOB-DTPA) enhanced MR imaging

NASA Astrophysics Data System (ADS)

Yamada, Akira; Hara, Takeshi; Li, Feng; Doi, Kunio

2010-03-01

Indocyanine green (ICG) is widely used for its clearance test in the evaluation of liver function. Gadoxetate disodium (Gd-EOB-DTPA) is a targeted MR contrast agent partially taken up by hepatocytes. The objective of this study was to evaluate the feasibility of an estimation of the liver function corresponding to plasma disappearance rate of indocyanine green (ICG-PDR) by use of the signal intensity of the liver alone in Gd-EOB-DTPA enhanced MR imaging (EOB-MRI). We evaluated fourteen patients who had EOB-MRI and ICG clearance test within 1 month. 2D-GRE T1 weighted images were obtained at pre contrast, 3 min (equilibrium phase) and 20 min (hepatobiliary phase) after the intravenous administration of Gd-EOB-DTPA, and the mean signal intensity of the liver was measured. The correlation between ICG-PDR and many parameters derived from the signal intensity of the liver in EOB-MRI was evaluated. The correlation coefficient between ICG-PDR and many parameters derived from the signal intensity of the liver in EOBMRI was low and not significant. The estimation of the liver function corresponding to ICG-PDR by use of the signal intensity of the liver alone in EOB-MRI would not be reliable.

Uncaria gambir Roxb. mediated green synthesis of silver nanoparticles using diethanolamine as capping agent

NASA Astrophysics Data System (ADS)

Labanni, A.; Zulhadjri; Handayani, D.; Arief, S.

2018-01-01

Studies of silver nanoparticles preparation has been developed increasingly due to the wide application in various areas and field, such as medicine, energy, catalysis, and electronic. An environmental-friendly method is needed to fabricate biocompatible silver nanoparticles without producing hazardous materials to the environment. In this study, we synthesized silver nanoparticles by green synthesis method, using leaf extract of gambir (Uncaria gambir Roxb.) as bioreducing agent and aqueous diethanolamine (DEA) solution as capping agents. The AgNO3/DEA molar ratio was varied to investigate the effect of DEA concentration to the properties of silver nanoparticles. The formation of silver nanoparticles was indicated by colour changes to yellowish brown and confirmed by result of UV-Vis spectrophotometer analysis which shown absorption band at 400 to 410 nm. The absorbance was increased to the reaction time of 24 hours, and was decrease by the increasing of DEA concentration in reaction. TEM analysis showed that prepared silver nanoparticles were spherical in shape with diameter of 3,5 - 45,5 nm. The diameter of DEA capped silver nanoparticles was 13 nm, smaller than uncapped silver nanoparticles which was 26 nm It exhibited good stability to time reaction of one month which was potential to be developed in some fields.

Sentinel Node Mapping Using Indocyanine Green and Near-infrared Fluorescence Imaging Technology for Uterine Malignancies: Preliminary Experience With the Da Vinci Xi System.

PubMed

Siesto, Gabriele; Romano, Fabrizio; Fiamengo, Barbara; Vitobello, Domenico

2016-01-01

Sentinel lymph node (SLN) mapping has emerged as the new frontier for the surgical staging of apparently early-stage cervical and endometrial cancer. Different colorimetric and radioactive tracers, alone and in combination, have been proposed with encouraging results. Fluorometric mapping using indocyanine green (ICG) appears to be a suitable and attractive alternative to provide reliable staging [1-4]. In this video, we present the technique of SLN mapping in 2 cases (1 endometrial and 1 cervical cancer, respectively) using ICG and the near-infrared technology provided by the newest Da Vinci Xi robotic system (Intuitive Surgical Inc., Sunnyvale, CA). Together we report the results of our preliminary experience on the first 20 cases performed. The new robotic Da Vinci Xi system was available at our institution since May 2015. Upon institutional review board/ethical committee approval, all consecutive patients with early-stage endometrial and cervical cancer who were judged suitable for robotic surgery have been enrolled for SLN mapping with ICG. We adopted the Memorial Sloan Kettering Cancer Center SLN algorithm; the tracer was delivered into the cervix in all cases. Four milliliters (1.25 mg/mL) of ICG was injected divided into the 3- and 9-o'clock positions of the cervix alone, with 1 mL deep into the stroma and 1 mL submucosally at the skin incision. Sentinel lymph nodes were examined with a protocol including both ultrastaging with immunohistochemistry [3] and 1-step nucleic acid amplification assay [5,6] under a parallel protocol of study. During the study period, 20 cases were managed; 14 and 6 patients had endometrial and cervical cancer, respectively. SLN was detected in all cases (20/20, 100%). Bilateral SLNs were detected in 17 of 20 (85.0%) cases. Based on preoperative and intraoperative findings, 13 (65.0%) patients received systematic pelvic lymphadenectomy after SLN mapping. Three (15.0%) patients had microscopic nodal metastases on SLN. No

Application of glucose as a green capping agent and reductant to fabricate CuI micro/nanostructures

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tavakoli, Farnosh; Salavati-Niasari, Masoud, E-mail: salavati@kashanu.ac.ir; Ghanbari, Davood

Graphical abstract: - Highlights: • CuI nanostructures were prepared via a simple precipitation method. • Glucose as a green capping agent and reductant was applied. • The effect of glucose concentration on the morphology of CuI was investigated. • According to XRD results, pure cubic phase CuI have been formed by using glucose. - Abstract: In this work, CuI micro/nanostructures have been successfully prepared via a simple precipitation route at room temperature. By using glucose as a clean reducing agent with different concentrations, CuI micro/nanostructures with various morphologies were obtained. Besides glucose, Na{sub 2}SO{sub 3}, KBH{sub 4} and N{sub 2}H{submore » 4}·H{sub 2}O have been applied as reductant. X-ray diffraction (XRD), scanning electron microscopy (SEM), photoluminescence spectroscopy, X-ray energy dispersive spectroscopy (EDS) and Fourier transformed infrared (FT-IR) spectroscopy were used to characterize the as-produced CuI micro/nanostructures. According to the XRD results, it was found that pure cubic phase CuI have been formed by using glucose.« less

Synthesis, characterization, and biological verification of anti-HER2 indocyanine green-doxorubicin-loaded polyethyleneimine-coated perfluorocarbon double nanoemulsions for targeted photochemotherapy of breast cancer cells.

PubMed

Lee, Yu-Hsiang; Ma, Yun-Ting

2017-05-18

Breast cancer is the most frequently diagnosed cancer and the leading cause of cancer death among females worldwide. Among various types of breast cancer, the human epidermal growth factor receptor 2 (HER2)-overexpressing breast cancer is known to be more aggressive and often resistant to medicinal treatment, leading to an insufficient prognosis and poor susceptibility to chemotherapy and/or hormonal therapy in the current clinic. These circumstances implicate that developing an improved therapeutic strategy rather than persistently changing the anticancer drugs for trying is truly needed to successfully cure this type of breast cancer. In this study, we aimed to fabricate anti-HER2 indocyanine green (ICG)-doxorubicin (DOX)-loaded polyethyleneimine-coated perfluorocarbon double nanoemulsions (HIDPPDNEs) to explore the co-administration of phototherapy and chemotherapy for HER2-overexpressing breast cancer in vitro. The HIDPPDNE was first characterized as a sphere-like nanoparticle with surface charge of -57.1 ± 5.6 mV and size of 340.6 ± 4.5 nm, whereas the DOX release rates for the nanodroplets within 48 h in 4 and 37 °C were obtained by 8.13 ± 2.46% and 19.88 ± 2.75%, respectively. We then examined the target-ability of the nanostructure and found that the adhesion efficiency of the HIDPPDNEs onto HER2+ MDA-MB-453 cells was threefold higher than the nanodroplets without anti-HER2 antibody, indicating that the HIDPPDNEs are the product with HER2 binding specificity. In comparison to freely dissolved ICG, the HIDPPDNEs conferred an enhanced thermal stability to the entrapped ICG, and were able to provide a comparable hyperthermia effect and markedly increased production of singlet oxygen under near infrared irradiation (808 nm; 6 W/cm 2 ). Based on the viability analyses, the results showed that the HIDPPDNEs were effective on cell eradication upon near infrared irradiation (808 nm; 6 W/cm 2 ), and the resulting cell mortality was even higher

Spectroscopy by joint spectral and time domain optical coherence tomography

NASA Astrophysics Data System (ADS)

Szkulmowski, Maciej; Tamborski, Szymon; Wojtkowski, Maciej

2015-03-01

We present the methodology for spectroscopic examination of absorbing media being the combination of Spectral Optical Coherence Tomography and Fourier Transform Spectroscopy. The method bases on the joint Spectral and Time OCT computational scheme and simplifies data analysis procedure as compared to the mostly used windowing-based Spectroscopic OCT methods. The proposed experimental setup is self-calibrating in terms of wavelength-pixel assignment. The performance of the method in measuring absorption spectrum was checked with the use of the reflecting phantom filled with the absorbing agent (indocyanine green). The results show quantitative accordance with the controlled exact results provided by the reference method.

Photodynamic therapy for polypoidal choroidal vasculopathy secondary to choroidal nevus.

PubMed

Wong, James G; Lai, Xin Jie; Sarafian, Richard Y; Wong, Hon Seng; Smith, Jeremy B

2017-01-01

We report a case of a Caucasian female who developed active polypoidal choroidal vasculopathy (PCV) at the edge of a stable choroidal nevus and was successfully treated with verteporfin photodynamic therapy. No active polyp was detectable on indocyanine green angiography 2 years after treatment, and good vision was maintained. Indocyanine green angiography is a useful investigation to diagnose PCV and may be underutilized. Unlike treatment of choroidal neovascularization secondary to choroidal nevus, management of PCV secondary to nevus may not require intravitreal anti-vascular endothelial growth factor therapy. Photodynamic monotherapy may be an effective treatment of secondary PCV.

Influence of bulking agents on physical, chemical, and microbiological properties during the two-stage composting of green waste.

PubMed

Zhang, Lu; Sun, Xiangyang

2016-02-01

A recyclable organic bulking agent (BA) that can be screened and was developed to optimize green waste (GW) composting. This study investigated the use of wood chips (WC) (at 0%, 15%, and 25%) and/or composted green waste (CGW) (at 0%, 25%, and 35%) as the BAs in the two-stage composting of GW. The combined addition of WC and CGW improved the conditions of composting process and the quality of compost product in terms of composting temperature, porosity, water retention, particle-size distribution, pH, electrical conductivity (EC), cation exchange capacity (CEC), nitrogen losses, humification indices, microbial numbers, enzyme activities, macro- and micro-nutrient contents, and toxicity to germinating seeds. The compost matured in only 22days with the optimized two-stage composting method rather than in the 90-270days typically required for traditional composting. The optimal two-stage composting process and the best quality of compost product were obtained with the combined addition of 15% WC and 35% CGW. Copyright © 2015 Elsevier Ltd. All rights reserved.

Dual-modality imaging with 99mTc and fluorescent indocyanine green using surface-modified silica nanoparticles for biopsy of the sentinel lymph node: an animal study

PubMed Central

2013-01-01

Background We propose a new approach to facilitate sentinel node biopsy examination by multimodality imaging in which radioactive and near-infrared (NIR) fluorescent nanoparticles depict deeply situated sentinel nodes and fluorescent nodes with anatomical resolution in the surgical field. For this purpose, we developed polyamidoamine (PAMAM)-coated silica nanoparticles loaded with technetium-99m (99mTc) and indocyanine green (ICG). Methods We conducted animal studies to test the feasibility and utility of this dual-modality imaging probe. The mean diameter of the PAMAM-coated silica nanoparticles was 30 to 50 nm, as evaluated from the images of transmission electron microscopy and scanning electron microscopy. The combined labeling with 99mTc and ICG was verified by thin-layer chromatography before each experiment. A volume of 0.1 ml of the nanoparticle solution (7.4 MBq, except for one rat that was injected with 3.7 MBq, and 1 μg of an ICG derivative [ICG-sulfo-OSu]) was injected submucosally into the tongue of six male Wistar rats. Results Scintigraphic images showed increased accumulation of 99mTc in the neck of four of the six rats. Nineteen lymph nodes were identified in the dissected neck of the six rats, and a contact radiographic study showed three nodes with a marked increase in uptake and three nodes with a weak uptake. NIR fluorescence imaging provided real-time clear fluorescent images of the lymph nodes in the neck with anatomical resolution. Six lymph nodes showed weak (+) to strong (+++) fluorescence, whereas other lymph nodes showed no fluorescence. Nodes showing increased radioactivity coincided with the fluorescent nodes. The radioactivity of 15 excised lymph nodes from the four rats was assayed using a gamma well counter. Comparisons of the levels of radioactivity revealed a large difference between the high-fluorescence-intensity group (four lymph nodes; mean, 0.109% ± 0.067%) and the low- or no-fluorescence-intensity group (11 lymph nodes

Imaging of Lymph Flow in Breast Cancer Patients after Microdose Administration of a Near-Infrared Fluorophore: Feasibility Study1

PubMed Central

Sevick-Muraca, Eva M.; Sharma, Ruchi; Rasmussen, John C.; Marshall, Milton V.; Wendt, Juliet A.; Pham, Hoang Q.; Bonefas, Elizabeth; Houston, Jessica P.; Sampath, Lakshmi; Adams, Kristen E.; Blanchard, Darlene Kay; Fisher, Ronald E.; Chiang, Stephen B.; Elledge, Richard; Mawad, Michel E.

2011-01-01

Purpose To prospectively demonstrate the feasibility of using indocyanine green, a near-infrared (NIR) fluorophore at the minimum dose needed for noninvasive optical imaging of lymph nodes (LNs) in breast cancer patients undergoing sentinel lymph node mapping (SLNM). Materials and Methods Informed consent was obtained from 24 women (age range, 30–85 years) who received intradermal subcutaneous injections of 0.31–100 μg indocyanine green in the breast in this IRB-approved, HIPAA-compliant, dose escalation study to find the minimum microdose for imaging. The breast, axilla, and sternum were illuminated with NIR light and the fluorescence generated in the tissue was collected with an NIR-sensitive intensified charged-coupled device. Lymphoscintigraphy was also performed. Resected LNs were evaluated for the presence of radioactivity, blue dye accumulation, and fluorescence. The associations between the resected LNs that were fluorescent and (a) the time elapsed between NIR fluorophore administration and resection and (b) the dosage of NIR fluorophores were tested with the Spearman rank and Pearson product moment correlation tests, respectively. Results Lymph imaging consistently failed with indocyanine green microdosages between 0.31 and 0.77 μg. When indocyanine green dosages were 10 μg or higher, lymph drainage pathways from the injection site to LNs were imaged in eight of nine women; lymph propulsion was observed in seven of those eight. When propulsion in the breast and axilla regions was present, the mean apparent velocities ranged from 0.08 to 0.32 cm/sec, the time elapsed between “packets” of propelled fluid varied from 14 to 92 seconds. In patients who received 10 μg of indocyanine green or more, a weak negative correlation between the fluorescence status of resected LNs and the time between NIR fluorophore administration and LN resection was found. No statistical association was found between the fluorescence status of resected LNs and the dose of

Accuracy of indocyanine green pulse spectrophotometry clearance test for liver function prediction in transplanted patients

PubMed Central

Hsieh, Chung-Bao; Chen, Chung-Jueng; Chen, Teng-Wei; Yu, Jyh-Cherng; Shen, Kuo-Liang; Chang, Tzu-Ming; Liu, Yao-Chi

2004-01-01

AIM: To investigate whether the non-invasive real-time Indocynine green (ICG) clearance is a sensitive index of liver viability in patients before, during, and after liver transplantation. METHODS: Thirteen patients were studied, two before, three during, and eight following liver transplantation, with two patients suffering acute rejection. The conventional invasive ICG clearance test and ICG pulse spectrophotometry non-invasive real-time ICG clearance test were performed simultaneously. Using linear regression analysis we tested the correlation between these two methods. The transplantation condition of these patients and serum total bilirubin (T. Bil), alanine aminotransferase (ALT), and platelet count were also evaluated. RESULTS: The correlation between these two methods was excellent (r2 = 0.977). CONCLUSION: ICG pulse spectrophotometry clearance is a quick, non-invasive, and reliable liver function test in transplantation patients. PMID:15285026

FIGO stage IIIC endometrial cancer identification among patients with complex atypical hyperplasia, grade 1 and 2 endometrioid endometrial cancer: laparoscopic indocyanine green sentinel lymph node mapping versus frozen section of the uterus, why get around the problem?

PubMed

Papadia, Andrea; Gasparri, Maria Luisa; Siegenthaler, Franziska; Imboden, Sara; Mohr, Stefan; Mueller, Michael D

2017-03-01

To compare two surgical strategies used to identify lymph node metastases in patients with preoperative diagnosis of complex atypical hyperplasia (CAH), grade 1 and 2 endometrial cancer (EC). Data on patients with preoperative diagnosis of CAH, grade 1 and 2 EC undergoing laparoscopic indocyanine green (ICG) sentinel lymph node (SLN) mapping followed by frozen section of the uterus were collected. When risk factors were identified at frozen section, patients were subjected to a systematic lymphadenectomy. False negative (FN) rates, negative predictive values (NPV), positive predictive values (PPV) and correlation with stage IIIC EC were calculated for the systematic lymphadenectomy based on frozen section of the uterus and for the SLN mapping. Six (9.5%) out of 63 patients had lymph nodal metastases. Based on frozen section of the uterus, 22 (34.9%) and 15 (22.2%) patients underwent a pelvic and a pelvic and paraaortic lymphadenectomy, respectively. Five patients with stage IIIC disease were identified with a FN rate of 16.7% and a NPV and PPV of 97.6 and 27.3%, respectively. Overall and bilateral detection rates of ICG SLN mapping were 100 and 97.6%, respectively; no FN were recorded. The identification of patients with stage IIIC disease with ICG SLN mapping showed a NPV and PPV of 100%. Correlation between indication to lymphadenectomy and stage IIIC disease was poor (κ = 0.244) when based on frozen section of the uterus and excellent (κ = 1) when based on SLN mapping. ICG SLN mapping reduces the number of unnecessary systematic lymphadenectomies and the risk of underdiagnosing patients with metastatic lymph nodes.

Nonclinical Profile of BLZ-100, a Tumor-Targeting Fluorescent Imaging Agent.

PubMed

Parrish-Novak, Julia; Byrnes-Blake, Kelly; Lalayeva, Narine; Burleson, Stefanie; Fidel, Janean; Gilmore, Rhonda; Gayheart-Walsten, Pamela; Bricker, Gregory A; Crumb, William J; Tarlo, K S; Hansen, Stacey; Wiss, Valorie; Malta, Errol; Dernell, William S; Olson, James M; Miller, Dennis M

BLZ-100 is a single intravenous use, fluorescent imaging agent that labels tumor tissue to enable more complete and precise surgical resection. It is composed of a chlorotoxin peptide covalently bound to the near-infrared fluorophore indocyanine green. BLZ-100 is in clinical development for intraoperative visualization of human tumors. The nonclinical safety and pharmacokinetic (PK) profile of BLZ-100 was evaluated in mice, rats, canines, and nonhuman primates (NHP). Single bolus intravenous administration of BLZ-100 was well tolerated, and no adverse changes were observed in cardiovascular safety pharmacology, PK, and toxicology studies in rats and NHP. The single-dose no-observed-adverse-effect-levels (NOAELs) were 7 mg (28 mg/kg) in rats and 60 mg (20 mg/kg) in NHP, corresponding to peak concentration values of 89 400 and 436 000 ng/mL and area-under-the-curve exposure values of 130 000 and 1 240 000 h·ng/mL, respectively. Based on a human imaging dose of 3 mg, dose safety margins are >100 for rat and monkey. BLZ-100 produced hypersensitivity reactions in canine imaging studies (lethargy, pruritus, swollen muzzle, etc). The severity of the reactions was not dose related. In a follow-up study in dogs, plasma histamine concentrations were increased 5 to 60 minutes after BLZ-100 injection; this coincided with signs of hypersensitivity, supporting the conclusion that the reactions were histamine based. Hypersensitivity reactions were not observed in other species or in BLZ-100 human clinical studies conducted to date. The combined imaging, safety pharmacology, PK, and toxicology studies contributed to an extensive initial nonclinical profile for BLZ-100, supporting first-in-human clinical trials.

Biocompatible magnetite/gold nanohybrid contrast agents via green chemistry for MRI and CT bioimaging.

PubMed

Narayanan, Sreeja; Sathy, Binulal N; Mony, Ullas; Koyakutty, Manzoor; Nair, Shantikumar V; Menon, Deepthy

2012-01-01

Magnetite/gold (Fe(3)O(4)/Au) hybrid nanoparticles were synthesized from a single iron precursor (ferric chloride) through a green chemistry route using grape seed proanthocyanidin as the reducing agent. Structural and physicochemical characterization proved the nanohybrid to be crystalline, with spherical morphology and size ~35 nm. Magnetic resonance imaging and magnetization studies revealed that the Fe(3)O(4) component of the hybrid provided superparamagnetism, with dark T(2) contrast and high relaxivity (124.2 ± 3.02 mM(-1) s(-1)). Phantom computed tomographic imaging demonstrated good X-ray contrast, which can be attributed to the presence of the nanogold component in the hybrid. Considering the potential application of this bimodal nanoconstruct for stem cell tracking and imaging, we have conducted compatibility studies on human Mesenchymal Stem Cells (hMSCs), wherein cell viability, apoptosis, and intracellular reactive oxygen species (ROS) generation due to the particle-cell interaction were asessed. It was noted that the material showed good biocompatibility even for high concentrations of 500 μg/mL and up to 48 h incubation, with no apoptotic signals or ROS generation. Cellular uptake of the nanomaterial was visualized using confocal microscopy and prussian blue staining. The presence of the nanohybrids were clearly visualized in the intracytoplasmic region of the cell, which is desirable for efficient imaging of stem cells in addition to the cytocompatible nature of the hybrids. Our work is a good demonstrative example of the use of green aqueous chemistry through the employment of phytochemicals for the room temperature synthesis of complex hybrid nanomaterials with multimodal functionalities. © 2011 American Chemical Society

Presidential Green Chemistry Challenge: 2009 Academic Award

EPA Pesticide Factsheets

Presidential Green Chemistry Challenge 2009 award winner, Professor Krzysztof Matyjaszewski, developed Atom Transfer Radical Polymerization to make polymers with copper catalysts and environmentally friendly reducing agents.

Plant mediated green synthesis: modified approaches.

PubMed

Das, Ratul Kumar; Brar, Satinder Kaur

2013-11-07

Plant mediated green synthesis of different metallic nanoparticles has emerged as one of the options for implementation of green chemistry principles, and successfully made an important contribution towards green nanotechnology. However, beyond the synthesis and application aspects, the science of green synthesis has carried some wrong perceptions in an unforeseen fashion. In this review, some of the key issues related to the green synthesis of metallic nanoparticles employing plants as reducing/capping agents have been addressed. Random selection of plants and its overall impact on the different aspects of green synthesis have been discussed. Emphasis is given to the setting of some standard selection criteria to be adopted for selecting a plant for use in green synthesis. How selection of a plant can positively or negatively influence both procedure and products of a green synthesis process is the prime concern of this article. In addition to selection, the key issue of biocompatibility associated with green synthesized metallic nanoparticles has been considered. Both selection of plant and biocompatibility were reconsidered for their minute details in terms of synthesis, analysis and data interpretation in the green synthesis approach. The key factors capable of fine tuning the core meaning of "green" in the synthesis of any metallic nanoparticles were taken into consideration. This article is an effort towards keeping the core meaning of green synthesis.

The Supraclavicular Artery Perforator Flap: A Comparative Study of Imaging Techniques Used in Preoperative Mapping.

PubMed

Sheriff, Hemin Oathman; Mahmood, Kawa Abdullah; Hamawandi, Nzar; Mirza, Aram Jamal; Hawas, Jawad; Moreno, Esther Granell; Clavero, Juan Antonio; Hankins, Christopher; Masia, Jaume

2018-05-18

 The supraclavicular artery flap is an excellent flap for head and neck reconstruction. The aim of this study is to assess imaging techniques to define the precise vascular boundaries of this flap.  Six imaging techniques were used for supraclavicular artery mapping in 65 cases; handheld Doppler, triplex ultrasound, computed tomography angiography, magnetic resonance angiography, digital subtraction angiography, and indocyanine green angiography. We checked the site of the perforators, the course of a supraclavicular artery, and anatomical mapping of the supraclavicular artery.  Handheld Doppler identified perforators' sites in 80% of the cases but showed no results for the course of the vessel. Triplex ultrasound identified the site of perforators in 52.9%, and partial mapping of the course of a supraclavicular artery in 64.7% of the cases. Computerized tomography angiography showed the site of perforators in 60%, and the course of supraclavicular artery completely in 45%, and partially in an additional 30%of the cases examined. Magnetic resonance angiography showed negative results for all parameters. Digital subtraction angiography showed the partial course of a supraclavicular artery in 62.5%, but showed no perforators. Indocyanine green angiography showed the site of perforators in 60% and a partial course of supraclavicular artery distal to perforators in 60%.Anatomical mapping of the vessel was possible with computerized tomography angiogram completely in 45%, and partially in 30%, and was also possible with indocyanine green angiography partially in 60%.  Computerized tomography angiography showed best results in the mapping of the supraclavicular artery, but with an inability to define the perforator perfusion territories, and also with risks of irradiation, while indocyanine green angiography is a good alternative as it could precisely map the superficial course of the artery and angiosomes, with no radiation exposure. Thieme Medical Publishers

Fully integrated high-speed intravascular optical coherence tomography/near-infrared fluorescence structural/molecular imaging in vivo using a clinically available near-infrared fluorescence-emitting indocyanine green to detect inflamed lipid-rich atheromata in coronary-sized vessels.

PubMed

Lee, Sunki; Lee, Min Woo; Cho, Han Saem; Song, Joon Woo; Nam, Hyeong Soo; Oh, Dong Joo; Park, Kyeongsoon; Oh, Wang-Yuhl; Yoo, Hongki; Kim, Jin Won

2014-08-01

Lipid-rich inflamed coronary plaques are prone to rupture. The purpose of this study was to assess lipid-rich inflamed plaques in vivo using fully integrated high-speed optical coherence tomography (OCT)/near-infrared fluorescence (NIRF) molecular imaging with a Food and Drug Administration-approved indocyanine green (ICG). An integrated high-speed intravascular OCT/NIRF imaging catheter and a dual-modal OCT/NIRF system were constructed based on a clinical OCT platform. For imaging lipid-rich inflamed plaques, the Food and Drug Administration-approved NIRF-emitting ICG (2.25 mg/kg) or saline was injected intravenously into rabbit models with experimental atheromata induced by balloon injury and 12- to 14-week high-cholesterol diets. Twenty minutes after injection, in vivo OCT/NIRF imaging of the infrarenal aorta and iliac arteries was acquired only under contrast flushing through catheter (pullback speed up to ≤20 mm/s). NIRF signals were strongly detected in the OCT-visualized atheromata of the ICG-injected rabbits. The in vivo NIRF target-to-background ratio was significantly larger in the ICG-injected rabbits than in the saline-injected controls (P<0.01). Ex vivo peak plaque target-to-background ratios were significantly higher in ICG-injected rabbits than in controls (P<0.01) on fluorescence reflectance imaging, which correlated well with the in vivo target-to-background ratios (P<0.01; r=0.85) without significant bias (0.41). Cellular ICG uptake, correlative fluorescence microscopy, and histopathology also corroborated the in vivo imaging findings. Integrated OCT/NIRF structural/molecular imaging with a Food and Drug Administration -approved ICG accurately identified lipid-rich inflamed atheromata in coronary-sized vessels. This highly translatable dual-modal imaging approach could enhance our capabilities to detect high-risk coronary plaques. © 2014 American Heart Association, Inc.

Roadmap to Implementing Green Cleaning in Districts and Schools

ERIC Educational Resources Information Center

Davis, Rochelle, Ed.

2012-01-01

Bill Thompson, Director of Facilities for Lockport Township High School in Illinois, first considered starting a green cleaning program after his janitors became dizzy when using a traditional chemical floor stripper. Thompson started introducing green products gradually at Lockport Township High, and now almost all of the cleaning agents used at…

Determination of adulteration of malachite green in green pea and some prepared foodstuffs by micellar liquid chromatography.

PubMed

Ashok, Vipin; Agrawal, Nitasha; Durgbanshi, Abhilasha; Esteve-Romero, Josep; Bose, Devasish

2014-01-01

A simple, fast, and robust micellar LC method was developed for the separation and identification of the nonpermitted color malachite green in green pea and some ready-to-eat foodstuffs. Malachite green (4-[(4-dimethylaminophenyl) phenyl-methyl]-N,N-dimethylaniline) is a hazardous dye that is used to treat fungal and protozoan infections in fish and is a common adulterant (coloring agent) in green pea and other green vegetables because of its green color. In the present work, malachite green was determined in various foodstuffs using a direct injection technique on an RP C18 column with isocratic elution. The optimum mobile phase consisted of 0.15 M sodium dodecyl sulfate (SDS), 6% pentanol buffered at pH 5. Detection was carried out at 620 nm. Malachite green was eluted in 9.2 min without any interference caused by endogenous compounds. Linearities (r > 0.9999), intraday and interday precision (RSD less than 1.00%) in micellar media, and robustness were studied for method validation. LOD and LOQ were 0.10 and 0.25 ppm, respectively. The simplicity of the developed method makes it useful for routine analysis in the area of food QC.

Sensitivity and specificity of detecting reticular pseudodrusen in multimodal imaging in Japanese patients.

PubMed

Ueda-Arakawa, Naoko; Ooto, Sotaro; Tsujikawa, Akitaka; Yamashiro, Kenji; Oishi, Akio; Yoshimura, Nagahisa

2013-03-01

To identify reticular pseudodrusen (RPD) in age-related macular degeneration using multiple imaging modalities, including the blue channel image of fundus photography, infrared reflectance (IR), fundus autofluorescence, near-infrared fundus autofluorescence, confocal blue reflectance, indocyanine green angiography, and spectral-domain optical coherence tomography (SD-OCT), and to compare the sensitivities and specificities of these modalities for detecting RPD. This study included 220 eyes from 114 patients with newly diagnosed age-related macular degeneration. Patients underwent fundus photography, IR, fundus autofluorescence, near-infrared fundus autofluorescence, confocal blue reflectance, indocyanine green angiography, and SD-OCT in both eyes. Eyes were diagnosed with RPD if they showed reticular patterns on at least two of the seven imaging modalities. Thirty-seven eyes were diagnosed with RPD. However, SD-OCT and IR had the highest sensitivity (94.6%), and at the same time, SD-OCT had a high specificity (98.4%). The blue channel of color fundus photography, confocal blue reflectance, and indocyanine green angiography had a specificity of 100% but had lower sensitivity than that of SD-OCT and IR. For detecting RPD, IR and SD-OCT had the highest sensitivity. Although SD-OCT had the highest sensitivity and specificity, RPD detection should be confirmed using more than one modality for increased accuracy.

Green synthesis of nanomaterials and sustainable applications of nano-catalysts

EPA Science Inventory

Green synthesis efforts involving the use of vitamins B1, B2, C, and tea and wine polyphenols which function both as reducing and capping agents will be presented which enables extremely simple, one-pot, green synthetic methods to nanomaterials in water.1a Shape-controlled synth...

Augmented microscopy: real-time overlay of bright-field and near-infrared fluorescence images

PubMed Central

Watson, Jeffrey R.; Gainer, Christian F.; Martirosyan, Nikolay; Skoch, Jesse; Lemole, G. Michael; Anton, Rein; Romanowski, Marek

2015-01-01

Abstract. Intraoperative applications of near-infrared (NIR) fluorescent contrast agents can be aided by instrumentation capable of merging the view of surgical field with that of NIR fluorescence. We demonstrate augmented microscopy, an intraoperative imaging technique in which bright-field (real) and electronically processed NIR fluorescence (synthetic) images are merged within the optical path of a stereomicroscope. Under luminance of 100,000 lx, representing typical illumination of the surgical field, the augmented microscope detects 189 nM concentration of indocyanine green and produces a composite of the real and synthetic images within the eyepiece of the microscope at 20 fps. Augmentation described here can be implemented as an add-on module to visualize NIR contrast agents, laser beams, or various types of electronic data within the surgical microscopes commonly used in neurosurgical, cerebrovascular, otolaryngological, and ophthalmic procedures. PMID:26440760

Augmented microscopy: real-time overlay of bright-field and near-infrared fluorescence images.

PubMed

Watson, Jeffrey R; Gainer, Christian F; Martirosyan, Nikolay; Skoch, Jesse; Lemole, G Michael; Anton, Rein; Romanowski, Marek

2015-10-01

Intraoperative applications of near-infrared (NIR) fluorescent contrast agents can be aided by instrumentation capable of merging the view of surgical field with that of NIR fluorescence. We demonstrate augmented microscopy, an intraoperative imaging technique in which bright-field (real) and electronically processed NIR fluorescence (synthetic) images are merged within the optical path of a stereomicroscope. Under luminance of 100,000 lx, representing typical illumination of the surgical field, the augmented microscope detects 189 nM concentration of indocyanine green and produces a composite of the real and synthetic images within the eyepiece of the microscope at 20 fps. Augmentation described here can be implemented as an add-on module to visualize NIR contrast agents, laser beams, or various types of electronic data within the surgical microscopes commonly used in neurosurgical, cerebrovascular, otolaryngological, and ophthalmic procedures.

Augmented microscopy: real-time overlay of bright-field and near-infrared fluorescence images

NASA Astrophysics Data System (ADS)

Watson, Jeffrey R.; Gainer, Christian F.; Martirosyan, Nikolay; Skoch, Jesse; Lemole, G. Michael, Jr.; Anton, Rein; Romanowski, Marek

2015-10-01

Intraoperative applications of near-infrared (NIR) fluorescent contrast agents can be aided by instrumentation capable of merging the view of surgical field with that of NIR fluorescence. We demonstrate augmented microscopy, an intraoperative imaging technique in which bright-field (real) and electronically processed NIR fluorescence (synthetic) images are merged within the optical path of a stereomicroscope. Under luminance of 100,000 lx, representing typical illumination of the surgical field, the augmented microscope detects 189 nM concentration of indocyanine green and produces a composite of the real and synthetic images within the eyepiece of the microscope at 20 fps. Augmentation described here can be implemented as an add-on module to visualize NIR contrast agents, laser beams, or various types of electronic data within the surgical microscopes commonly used in neurosurgical, cerebrovascular, otolaryngological, and ophthalmic procedures.

Catalytic and antibacterial properties of silver nanoparticles green biosynthesized using soluble green tea powder

NASA Astrophysics Data System (ADS)

Xu, Wei; Fan, Yapei; Liu, Xinfang; Luo, Denglin; Liu, Huan; Yang, Ningning

2018-04-01

Silver nanoparticles (Ag NPs) were green fabricated using soluble green tea powder (SGTP) as stabilizer and reducing agent. The properties and morphology of Ag NPs were investigated through UV–visible spectroscopy, field emission transmission electron microscope (FE-TEM) and fourier transform infrared (FT-IR). The spectroscopy showed surface plasmon resonance around at 420 nm revealing the synthesis of Ag NPs. FE-TEM results confirmed that the Ag NPs are spherical and face-centered cubic structure. FT-IR spectroscopy identified the role of various functional groups in the nanoparticle synthesis. The one spot biosynthesized Ag NPs showed favourable antibacterial properties on Escherichia coli and Staphyloccocus aureus, and excellent catalytic reduction of 4-nitrophenol. This work provided a feasible, green method to fabricate Ag NPs with promising photocatalytic and antimicrobial activities.

Towards green loyalty: the influences of green perceived risk, green image, green trust and green satisfaction

NASA Astrophysics Data System (ADS)

Chrisjatmiko, K.

2018-01-01

The paper aims to present a comprehensive framework for the influences of green perceived risk, green image, green trust and green satisfaction to green loyalty. The paper also seeks to account explicitly for the differences in green perceived risk, green image, green trust, green satisfaction and green loyalty found among green products customers. Data were obtained from 155 green products customers. Structural equation modeling was used in order to test the proposed hypotheses. The findings show that green image, green trust and green satisfaction has positive effects to green loyalty. But green perceived risk has negative effects to green image, green trust and green satisfaction. However, green perceived risk, green image, green trust and green satisfaction also seems to be a good device to gain green products customers from competitors. The contributions of the paper are, firstly, a more complete framework of the influences of green perceived risk, green image, green trust and green satisfaction to green loyalty analyses simultaneously. Secondly, the study allows a direct comparison of the difference in green perceived risk, green image, green trust, green satisfaction and green loyalty between green products customers.

Dynamic in vivo imaging of small animal brain using pulsed laser diode-based photoacoustic tomography system

NASA Astrophysics Data System (ADS)

Upputuri, Paul Kumar; Pramanik, Manojit

2017-09-01

We demonstrate dynamic in vivo imaging using a low-cost portable pulsed laser diode (PLD)-based photoacoustic tomography system. The system takes advantage of an 803-nm PLD having high-repetition rate ˜7000 Hz combined with a fast-scanning single-element ultrasound transducer leading to a 5 s cross-sectional imaging. Cortical vasculature is imaged in scan time of 5 s with high signal-to-noise ratio ˜48. To examine the ability for dynamic imaging, we monitored the fast uptake and clearance process of indocyanine green in the rat brain. The system will find applications to study neurofunctional activities, characterization of pharmacokinetic, and biodistribution profiles in the development process of drugs or imaging agents.

Near-infrared intraoperative imaging during resection of an anterior mediastinal soft tissue sarcoma.

PubMed

Predina, Jarrod D; Newton, Andrew D; Desphande, Charuhas; Singhal, Sunil

2018-01-01

Sarcomas are rare malignancies that are generally treated with multimodal therapy protocols incorporating complete local resection, chemotherapy and radiation. Unfortunately, even with this aggressive approach, local recurrences are common. Near-infrared intraoperative imaging is a novel technology that provides real-time visual feedback that can improve identification of disease during resection. The presented study describes utilization of a near-infrared agent (indocyanine green) during resection of an anterior mediastinal sarcoma. Real-time fluorescent feedback provided visual information that helped the surgeon during tumor localization, margin assessment and dissection from mediastinal structures. This rapidly evolving technology may prove useful in patients with primary sarcomas arising from other locations or with other mediastinal neoplasms.

The first report on mushroom green mould disease in Croatia.

PubMed

Hatvani, Lóránt; Sabolić, Petra; Kocsubé, Sándor; Kredics, László; Czifra, Dorina; Vágvölgyi, Csaba; Kaliterna, Joško; Ivić, Dario; Đermić, Edyta; Kosalec, Ivan

2012-12-01

Green mould disease, caused by Trichoderma species, is a severe problem for mushroom growers worldwide, including Croatia. Trichoderma strains were isolated from green mould-affected Agaricus bisporus (button or common mushroom) compost and Pleurotus ostreatus (oyster mushroom) substrate samples collected from Croatian mushroom farms. The causal agents of green mould disease in the oyster mushroom were T. pleurotum and T. pleuroticola, similar to other countries. At the same time, the pathogen of A. bisporus was exclusively the species T. harzianum, which is different from earlier findings and indicates that the range of mushroom pathogens is widening. The temperature profiles of the isolates and their hosts overlapped, thus no range was found that would allow optimal growth of the mushrooms without mould contamination. Ferulic acid and certain phenolic compounds, such as thymol showed remarkable fungistatic effect on the Trichoderma isolates, but inhibited the host mushrooms as well. However, commercial fungicides prochloraz and carbendazim were effective agents for pest management. This is the first report on green mould disease of cultivated mushrooms in Croatia.

Green chemistry approach for the synthesis of biocompatible graphene

PubMed Central

Gurunathan, Sangiliyandi; Han, Jae Woong; Kim, Jin-Hoi

2013-01-01

Background Graphene is a single-atom thick, two-dimensional sheet of hexagonally arranged carbon atoms isolated from its three-dimensional parent material, graphite. One of the most common methods for preparation of graphene is chemical exfoliation of graphite using powerful oxidizing agents. Generally, graphene is synthesized through deoxygenation of graphene oxide (GO) by using hydrazine, which is one of the most widespread and strongest reducing agents. Due to the high toxicity of hydrazine, it is not a promising reducing agent in large-scale production of graphene; therefore, this study focused on a green or sustainable synthesis of graphene and the biocompatibility of graphene in primary mouse embryonic fibroblast cells (PMEFs). Methods Here, we demonstrated a simple, rapid, and green chemistry approach for the synthesis of reduced GO (rGO) from GO using triethylamine (TEA) as a reducing agent and stabilizing agent. The obtained TEA reduced GO (TEA-rGO) was characterized by ultraviolet (UV)–visible absorption spectroscopy, X-ray diffraction (XRD), particle size dynamic light scattering (DLS), scanning electron microscopy (SEM), Raman spectroscopy, and atomic force microscopy (AFM). Results The transition of graphene oxide to graphene was confirmed by UV–visible spectroscopy. XRD and SEM were used to investigate the crystallinity of graphene and the surface morphologies of prepared graphene respectively. The formation of defects further supports the functionalization of graphene as indicated in the Raman spectrum of TEA-rGO. Surface morphology and the thickness of the GO and TEA-rGO were analyzed using AFM. The presented results suggest that TEA-rGO shows significantly more biocompatibility with PMEFs cells than GO. Conclusion This is the first report about using TEA as a reducing as well as a stabilizing agent for the preparation of biocompatible graphene. The proposed safe and green method offers substitute routes for large-scale production of graphene

Green tea and the skin.

PubMed

Hsu, Stephen

2005-06-01

Plant extracts have been widely used as topical applications for wound-healing, anti-aging, and disease treatments. Examples of these include ginkgo biloba, echinacea, ginseng, grape seed, green tea, lemon, lavender, rosemary, thuja, sarsaparilla, soy, prickly pear, sagebrush, jojoba, aloe vera, allantoin, feverwort, bloodroot, apache plume, and papaya. These plants share a common character: they all produce flavonoid compounds with phenolic structures. These phytochemicals are highly reactive with other compounds, such as reactive oxygen species and biologic macromolecules, to neutralize free radicals or initiate biological effects. A short list of phenolic phytochemicals with promising properties to benefit human health includes a group of polyphenol compounds, called catechins, found in green tea. This article summarizes the findings of studies using green tea polyphenols as chemopreventive, natural healing, and anti-aging agents for human skin, and discusses possible mechanisms of action.

New Paradigm Shift for the Green Synthesis of Antibacterial Silver Nanoparticles Utilizing Plant Extracts

PubMed Central

2014-01-01

This review covers general information regarding the green synthesis of antibacterial silver nanoparticles. Owing to their antibacterial properties, silver nanoparticles are widely used in many areas, especially biomedical applications. In green synthesis practices, the chemical reducing agents are eliminated, and biological entities are utilized to convert silver ions to silver nanoparticles. Among the various biological entities, natural plant extracts have emerged as green reducing agents, providing eco-friendly routes for the preparation of silver nanomaterials. The most obvious merits of green synthesis are the increased biocompatibility of the resulting silver nanoparticles and the ease with which the reaction can be carried out. This review summarizes some of the plant extracts that are used to produce antibacterial silver nanoparticles. Additionally, background information regarding the green synthesis and antibacterial activity of silver nanoparticles is provided. Finally, the toxicological aspects of silver nanoparticles are briefly mentioned. PMID:25343010

A Real-Time Near-Infrared Fluorescence Imaging Method for the Detection of Oral Cancers in Mice Using an Indocyanine Green–Labeled Podoplanin Antibody

PubMed Central

Ito, Akihiro; Ohta, Mitsuhiko; Kato, Yukinari; Inada, Shunko; Kato, Toshio; Nakata, Susumu; Yatabe, Yasushi; Goto, Mitsuo; Kaneda, Norio; Kurita, Kenichi; Nakanishi, Hayao; Yoshida, Kenji

2018-01-01

Podoplanin is distinctively overexpressed in oral squamous cell carcinoma than oral benign neoplasms and plays a crucial role in the pathogenesis and metastasis of oral squamous cell carcinoma but its diagnostic application is quite limited. Here, we report a new near-infrared fluorescence imaging method using an indocyanine green (ICG)–labeled anti-podoplanin antibody and a desktop/a handheld ICG detection device for the visualization of oral squamous cell carcinoma–xenografted tumors in nude mice. Both near-infrared imaging methods using a desktop (in vivo imaging system: IVIS) and a handheld device (photodynamic eye: PDE) successfully detected oral squamous cell carcinoma tumors in nude mice in a podoplanin expression–dependent manner with comparable sensitivity. Of these 2 devices, only near-infrared imaging methods using a handheld device visualized oral squamous cell carcinoma xenografts in mice in real time. Furthermore, near-infrared imaging methods using the handheld device (PDE) could detect smaller podoplanin-positive oral squamous cell carcinoma tumors than a non-near-infrared, autofluorescence-based imaging method. Based on these results, a near-infrared imaging method using an ICG-labeled anti-podoplanin antibody and a handheld detection device (PDE) allows the sensitive, semiquantitative, and real-time imaging of oral squamous cell carcinoma tumors and therefore represents a useful tool for the detection and subsequent monitoring of malignant oral neoplasms in both preclinical and some clinical settings. PMID:29649929

POLYPOIDAL CHOROIDAL VASCULOPATHY SECONDARY TO A STABLE CHOROIDAL NEVUS.

PubMed

Wong, James G; Lai, Xin Jie; Sarafian, Richard Y; Wong, Hon Seng; Smith, Jeremy B

2016-01-01

Choroidal nevus is the most common ocular fundus tumor in adults. Previous studies have widely discussed the features of choroidal neovascularization secondary to nevus and its treatment options. Polypoidal choroidal vasculopathy (PCV) is an exudative chorioretinopathy that is often underdiagnosed. Clinical features, natural history, and treatment response of PCV are distinct from occult choroidal neovascularization. Polypoidal choroidal vasculopathy secondary to choroidal nevus has not been previously documented. We report a patient with a history of stable choroidal nevus who developed a polypoidal lesion at the edge of the nevus lesion. A white woman who presented with a choroidal nevus and clinical features of PCV was examined using fundoscopy, optical coherence tomography, fluorescein angiography, and indocyanine green angiography. A polypoidal lesion with an associated branching vascular network adjacent to the nevus was demonstrated by optical coherence tomography, fluorescein angiography, and indocyanine green angiography. The patient was asymptomatic and was managed conservatively. Our case showed that PCV developing in association with a stable choroidal nevus. Pathogenic mechanisms of this condition may include chronic degenerative or inflammatory changes at the level of the retinal pigment epithelium resulting in vascular changes. Unlike treatment of occult choroidal neovascularization secondary to nevus, optimal management of PCV secondary to nevus may vary. Indocyanine green angiography is the gold standard for the diagnosis of PCV and is a useful investigation in atypical choroidal neovascularization.

Angiographic lesion size associated with LOC387715 A69S genotype in subfoveal polypoidal choroidal vasculopathy.

PubMed

Sakurada, Yoichi; Kubota, Takeo; Imasawa, Mitsuhiro; Tsumura, Toyoaki; Mabuchi, Fumihiko; Tanabe, Naohiko; Iijima, Hiroyuki

2009-01-01

To investigate whether the LOC387715/ARMS2 variants are associated with an angiographic phenotype, including lesion size and composition, in subfoveal polypoidal choroidal vasculopathy. Ninety-two subjects with symptomatic subfoveal polypoidal choroidal vasculopathy, whose visual acuity was from 0.1 to 0.5 on the Landolt chart, were genotyped for the LOC387715 polymorphism (rs10490924) using denaturing high-performance chromatography. The angiographic phenotype, including lesion composition and size, was evaluated by evaluators who were masked for the genotype. Lesion size was assessed by the greatest linear dimension based on fluorescein or indocyanine green angiography. Although there was no statistically significant difference in lesion size on indocyanine green angiography (P = 0.36, Kruskal-Wallis test) and in lesion composition (P = 0.59, chi-square test) among the 3 genotypes, there was a statistically significant difference in lesion size on fluorescein angiography (P = 0.0022, Kruskal-Wallis test). The LOC387715 A69S genotype is not associated with lesion composition or size on indocyanine green angiography but with lesion size on fluorescein angiography in patients with subfoveal polypoidal choroidal vasculopathy. Because fluorescein angiography findings represent secondary exudative changes, including subretinal hemorrhages and retinal pigment epithelial detachment, the results in the present study likely indicate that the T allele at the LOC387715 gene is associated with the exudative activity of polypoidal lesions.

Presidential Green Chemistry Challenge: 2001 Greener Synthetic Pathways Award

EPA Pesticide Factsheets

Presidential Green Chemistry Challenge 2001 award winners, Bayer Corporation and Bayer AG, developed a waste-free manufacturing process for sodium iminodisuccinate (Baypure CX), a biodegradable, nontoxic chelating agent.

Use Of Green Porphyrinsto Treat Neovasculature In The Eyes

DOEpatents

Levy, Julia; Miller, Joan W.; Gradoudas, Evangelos S.; Hasan, Tayyaba; Schmidt-Erfurth, Ursula

1998-08-25

Photodynamic therapy of conditions of the eye characterized by unwanted neovasculature, such as age-related macular degeneration, is effective using green porphyrins as photoactive agents, preferably as liposomal compositions.

Changes In Arterial Hemoglobin Oxygen Saturation During Transport From the Operating Room to the Postanesthesia Care Unit In Healthy Patients Breathing Room Air

DTIC Science & Technology

1998-12-16

motion artifact, electrical noise from the electrocautery, intravenous dyes such as methylene blue and indocyanine green, carboxyhemoglobin and... carboxyhemoglobin because the oximeter fails to distinguish between oxyhemoglobin and carboxyhemoglobin (Patel, Norden, & Hannallah, 1988) . Thus

Fluorescence-guided mapping of sentinel lymph nodes in gynecological malignancies

NASA Astrophysics Data System (ADS)

Hirsch, Ole; Szyc, Łukasz; Muallem, Mustafa Zelal; Ignat, Iulia; Chekerov, Radoslav; Macdonald, Rainer; Sehouli, Jalid; Braicu, Ioana; Grosenick, Dirk

2017-07-01

We have successfully applied a custom-made handheld fluorescence camera for intraoperative fluorescence detection of indocyanine green in a feasibility study on sentinel lymph node mapping in patients with vulvar, cervical, endometrial and ovarian cancer.

A game theory analysis of green infrastructure stormwater management policies

NASA Astrophysics Data System (ADS)

William, Reshmina; Garg, Jugal; Stillwell, Ashlynn S.

2017-09-01

Green stormwater infrastructure has been demonstrated as an innovative water resources management approach that addresses multiple challenges facing urban environments. However, there is little consensus on what policy strategies can be used to best incentivize green infrastructure adoption by private landowners. Game theory, an analysis framework that has historically been under-utilized within the context of stormwater management, is uniquely suited to address this policy question. We used a cooperative game theory framework to investigate the potential impacts of different policy strategies used to incentivize green infrastructure installation. The results indicate that municipal regulation leads to the greatest reduction in pollutant loading. However, the choice of the "best" regulatory approach will depend on a variety of different factors including politics and financial considerations. Large, downstream agents have a disproportionate share of bargaining power. Results also reveal that policy impacts are highly dependent on agents' spatial position within the stormwater network, leading to important questions of social equity and environmental justice.

Green chemistry synthesis of nano-cuprous oxide.

PubMed

Ceja-Romero, L R; Ortega-Arroyo, L; Ortega Rueda de León, J M; López-Andrade, X; Narayanan, J; Aguilar-Méndez, M A; Castaño, V M

2016-04-01

Green chemistry and a central composite design, to evaluate the effect of reducing agent, temperature and pH of the reaction, were employed to produce controlled cuprous oxide (Cu2O) nanoparticles. Response surface method of the ultraviolet-visible spectroscopy is allowed to determine the most relevant factors for the size distribution of the nanoCu2O. X-ray diffraction reflections correspond to a cubic structure, with sizes from 31.9 to 104.3 nm. High-resolution transmission electron microscopy reveals that the different shapes depend strongly on the conditions of the green synthesis.

Differentiation between Prototheca and morphologically similar green algae in tissue.

PubMed

Chandler, F W; Kaplan, W; Callaway, C S

1978-07-01

Evidence that algae are pathogens was provided by the results of electron microscopic studies of tissues from five cattle and sheep suspected of having green algal infections. Chloroplasts were demonstrated in the algae in each case. Prototheca organisms, considered by some to be achloric mutants of green algae, are causative agents of disease in man and animals and may appear morphologically similar to green algae in tissue. However, electron microscopy showed that chloroplasts were absent in these organisms. Light microscopy revealed not only similarities in size, shape, and mode of reproduction, but also a striking difference between the Prototheca organisms and green algae. Unlike Prototheca, the green algae contained abundant cytoplasmic starch granules that were strongly positive by several staining procedures; these granules, which were PAS-negative following diastase digestion, provide a means of differentiating green algae from Prototheca cells in tissue.

Environmental Concerns, Environmental Policy and Green Investment.

PubMed

Gao, Xuexian; Zheng, Haidong

2017-12-13

Environmental regulators often use environmental policy to induce green investment by firms. However, if an environmental policy fails to exert a long-run effect on regulating the economic agents' behavior, it may be more reasonable to think of the firm as the leader in the game, since the investment in green technology is usually a strategic decision. In this paper, we consider a three-stage Stackelberg game to address the interaction between a profit-maximizing firm (Stackelberg leader) facing emission-dependent demand, and the environmental regulator (Stackelberg follower). The firm decides on the green technology level in the first stage of the game based on its understanding of the regulator's profits function, especially an environmental concern that is introduced as an exogenous variable. In the current research, we show that high levels of the regulator's environmental concerns do not necessarily lead to the choice of green technology by the firm, and green investment level depends on the combined effects of the market and operational factors for a given level of the regulator's environmental concerns. The result also shows that increasing environmental awareness amongst the consumers is an effective way to drive the firm's green investment.

Green Synthesis of Ag, Cu and AgCu Nanoparticles using Palm Leaves Extract as the Reducing and Stabilizing Agents

NASA Astrophysics Data System (ADS)

Mohamad, N. A. N.; Arham, N. A.; Junaidah, J.; Hadi, A.; Idris, S. A.

2018-05-01

This paper reports the green synthesis of Ag, Cu and AgCu nanoparticles at room temperature using palm leaves extract. The purpose of this study is to eliminate the use of chemicals in the synthesis of nanoparticles and evaluate the efficiency of the palm leaves extract as the reducing and stabilizing agents. The palm leaves extract was added to metal salt solution and continuously stirred until reaction completed. The produced nanoparticles were analyzed using atomic absorption spectroscopy (AAS), Fourier transform infrared spectroscopy (FTIR), energy dispersive X-ray spectroscopy (EDS), scanning electron microscopy (SEM) and transmission electron microscopy (TEM). The analyses revealed that palm leaves extract has efficiently reduced the silver ions, but not the copper ions. During synthesis of AgCu nanoparticles, simultaneous reduction was occurred leading to formation of alloyed nanoparticles. Biomolecules from the palm leaves extract adsorbed on the surface of nanoparticles forming a capping layer thus stabilized the nanoparticles. The produced Ag and Cu nanoparticles were predominantly spherical with the particle size of Cu nanoparticles were larger than Ag nanoparticles. The AgCu nanoparticles closely resembled the Ag nanoparticles due to high Ag content with average size of 13nm. Therefore, palm leaves extract has a potential to be a good reducing and stabilizing agents.

Failure to Integrate Quantitative Measurement Methods of Ocular Inflammation Hampers Clinical Practice and Trials on New Therapies for Posterior Uveitis.

PubMed

Herbort, Carl P; Tugal-Tutkun, Ilknur; Neri, Piergiorgio; Pavésio, Carlos; Onal, Sumru; LeHoang, Phuc

2017-05-01

Uveitis is one of the fields in ophthalmology where a tremendous evolution took place in the past 25 years. Not only did we gain access to more efficient, more targeted, and better tolerated therapies, but also in parallel precise and quantitative measurement methods developed allowing the clinician to evaluate these therapies and adjust therapeutic intervention with a high degree of precision. Objective and quantitative measurement of the global level of intraocular inflammation became possible for most inflammatory diseases with direct or spill-over anterior chamber inflammation, thanks to laser flare photometry. The amount of retinal inflammation could be quantified by using fluorescein angiography to score retinal angiographic signs. Indocyanine green angiography gave imaging insight into the hitherto inaccessible choroidal compartment, rendering possible the quantification of choroiditis by scoring indocyanine green angiographic signs. Optical coherence tomography has enabled measurement and objective monitoring of retinal and choroidal thickness. This multimodal quantitative appraisal of intraocular inflammation represents an exquisite security in monitoring uveitis. What is enigmatic, however, is the slow pace with which these improvements are integrated in some areas. What is even more difficult to understand is the fact that clinical trials to assess new therapeutic agents still mostly rely on subjective parameters such as clinical evaluation of vitreous haze as a main endpoint; whereas a whole array of precise, quantitative, and objective modalities are available for the design of clinical studies. The scope of this work was to review the quantitative investigations that improved the management of uveitis in the past 2-3 decades.

Green and energy-efficient methods for the production of metallic nanoparticles.

PubMed

Naghdi, Mitra; Taheran, Mehrdad; Brar, Satinder Kaur; Verma, M; Surampalli, R Y; Valero, J R

2015-01-01

In the last decade, researchers paid great attention to the concept of "Green Chemistry", which aims at development of efficient methods for the synthesis of nanoparticles (NPs) in terms of the least possible impact on human life and environment. Generally, several reagents including precursors, reducing agents, stabilizing agents and solvents are used for the production of NPs and in some cases, energy is needed to reach the optimum temperature for reduction. Therefore, to develop a green approach, researchers had the opportunity to investigate eco-friendly reagents and new energy transfer techniques. In order to substitute the harmful reagents with green ones, researchers worked on different types of saccharides, polyols, carboxylic acids, polyoxometalates and extracts of various plants that can play the role of reducers, stabilizers or solvents. Also, there are some reports on using ultraviolet (UV), gamma and microwave irradiation that are capable of reducing and provide uniform heating. According to the literature, it is possible to use green reagents and novel energy transfer techniques for production of NPs. However, these new synthesis routes should be optimized in terms of performance, cost, product quality (shape and size distribution) and scale-up capability. This paper presents a review on most of the employed green reagents and new energy transfer techniques for the production of metallic NPs.

The Toxicity of Soman in the African Green Monkey (Chlorocebus aethiops)

DTIC Science & Technology

2007-01-01

M., and Mestries, 1. C. 1998. Nerve agent poisoning in primates: antilethal, anti -epileptic and neuroprotective effects of GK-11. Arch. Toxico/. 72...toxicity in African green monkeys (Chlorocebus aethiops) and is the first step in exploring the suitability of this species as a model for nerve agent ...rhesus monkey (Macaca mulatta) has traditionally served as the NHP research species of choice to assess nerve agent toxicity and the effectiveness of

Intraoperative spatial frequency domain diffuse optical tomography with indo-cyanine green (ICG) fluorescence contrast (Conference Presentation)

NASA Astrophysics Data System (ADS)

Chong, Sang Hoon; Parthasarathy, Ashwin B.; Kavuri, Venkaiah C.; Moscatelli, Frank A.; Singhal, Sunil; Yodh, Arjun G.

2017-02-01

Surgical resection is the most effective treatment strategy for solid tumors, but complete removal of the tumor is critical for post-surgical recovery/long-term survival and is dependent on correct identification of the tumor margin and accurate excision of microscopic residual tumor in the surgical field. Fluorescence image guided surgery is an emerging technique that has shown promise for intraoperative location of tumors and tumor margins. Current versions of such intraoperative fluorescence imaging, however, are generally limited to 2D near-surface images, i.e., without information about tumor depth. Here we present an intraoperative fluorescence imaging system for 3D volumetric imaging of tumors; the system uses spatial frequency domain diffuse optical tomography with an analytic inversion reconstruction method. The new instrument can derive depth-sensitive 3D tumor images at depths up to 1 cm, and it employs compact epi-imaging and illumination suitable for the operating room, with quasi-real-time image reconstruction for surgical visualization. We present experimental results with FDA-approved Indocynanine Green using an extensive array of tissue phantoms and in a pilot in-vivo study.

Presidential Green Chemistry Challenge: 1996 Greener Reaction Conditions Award

EPA Pesticide Factsheets

Presidential Green Chemistry Challenge 1996 award winner, Dow Chemical Company, developed a process to manufacture polystyrene foam sheet packaging that uses carbon dioxide (CO2) as a blowing agent, eliminating CFC-12 and HCFC-22.

In vivo and ex vivo sentinel node mapping does not identify the same lymph nodes in colon cancer.

PubMed

Andersen, Helene Schou; Bennedsen, Astrid Louise Bjørn; Burgdorf, Stefan Kobbelgaard; Eriksen, Jens Ravn; Eiholm, Susanne; Toxværd, Anders; Riis, Lene Buhl; Rosenberg, Jacob; Gögenur, Ismail

2017-07-01

Identification of lymph nodes and pathological analysis is crucial for the correct staging of colon cancer. Lymph nodes that drain directly from the tumor area are called "sentinel nodes" and are believed to be the first place for metastasis. The purpose of this study was to perform sentinel node mapping in vivo with indocyanine green and ex vivo with methylene blue in order to evaluate if the sentinel lymph nodes can be identified by both techniques. Patients with colon cancer UICC stage I-III were included from two institutions in Denmark from February 2015 to January 2016. In vivo sentinel node mapping with indocyanine green during laparoscopy and ex vivo sentinel node mapping with methylene blue were performed in all patients. Twenty-nine patients were included. The in vivo sentinel node mapping was successful in 19 cases, and ex vivo sentinel node mapping was successful in 13 cases. In seven cases, no sentinel nodes were identified. A total of 51 sentinel nodes were identified, only one of these where identified by both techniques (2.0%). In vivo sentinel node mapping identified 32 sentinel nodes, while 20 sentinel nodes were identified by ex vivo sentinel node mapping. Lymph node metastases were found in 10 patients, and only two had metastases in a sentinel node. Placing a deposit in relation to the tumor by indocyanine green in vivo or of methylene blue ex vivo could only identify sentinel lymph nodes in a small group of patients.

Reconstruction of Anterolateral Thigh Defects Using Perforator-Based Propeller Flaps.

PubMed

Iida, Takuya; Yoshimatsu, Hidehiko; Koshima, Isao

2017-10-01

Usually, anterolateral thigh (ALT) defects with width more than 8 cm cannot be closed directly. Although several methods of using local flaps exist, flap mobility of these methods is limited. We introduced a perforator-based propeller flap for such reconstruction. Their maximal mobility, which minimizes their size, is their greatest advantage. In addition, we present our technical refinements including double-axes propeller flap, the use of indocyanine green real-time angiography, and supercharged propeller flap for safer flap transfer. Seven patients underwent perforator-based propeller flap reconstruction of ALT defects. Flaps were designed cranial or caudal to the defect according to the perforator locations. To maximize mobility, flaps were designed so that the perforator was located at the periphery and closer to the defect. After rotating the flap to the defect, indocyanine green angiography was performed to determine the need for supercharge. In all cases, all flaps survived completely. Defect size ranged from 12 × 11 cm to 18 × 16 cm, and flap size ranged from 7 × 5 cm to 15 × 7 cm. The number of perforators in the flap was 1 in 3 cases and 2 in 4 cases. Supercharging was performed in 3 cases. Donor-site complications, including gait disturbance, were not observed. This method achieves ALT defect closure with minimal donor-site morbidity and can provide prompt and aesthetically acceptable results. Indocyanine green real-time angiography and supercharging technique are also useful for safer and reliable flap transfer.

Hexaphyrin as a Potential Theranostic Dye for Photothermal Therapy and 19 F Magnetic Resonance Imaging.

PubMed

Higashino, Tomohiro; Nakatsuji, Hirotaka; Fukuda, Ryosuke; Okamoto, Haruki; Imai, Hirohiko; Matsuda, Tetsuya; Tochio, Hidehito; Shirakawa, Masahiro; Tkachenko, Nikolai V; Hashida, Mitsuru; Murakami, Tatsuya; Imahori, Hiroshi

2017-05-18

Two features of meso-Aryl-substituted expanded porphyrins suggest suitability as theranostic agents. They have excellent absorption in near infrared (NIR) region, and they offer the possibility of introduction of multiple fluorine atoms at structurally equivalent positions. Here, hexaphyrin (hexa) was synthesized from 2,6-bis(trifluoromethyl)-4-formyl benzoate and pyrrole and evaluated as a novel expanded porphyrin with the above features. Under NIR illumination hexa showed intense photothermal and weak photodynamic effects, which were most likely due to its low excited states, close to singlet oxygen. The sustained photothermal effect caused ablation of cancer cells more effectively than the photodynamic effect of indocyanine green (a clinical dye). In addition, hexa showed potential for use in the visualization of tumors by 19 F magnetic resonance imaging (MRI), because of the multiple fluorine atoms. Our results strongly support the utility of expanded porphyrins as theranostic agents in both photothermal therapy and 19 F MRI. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Enhanced visualization of the bile duct via parallel white light and indocyanine green fluorescence laparoscopic imaging

NASA Astrophysics Data System (ADS)

Demos, Stavros G.; Urayama, Shiro

2014-03-01

Despite best efforts, bile duct injury during laparoscopic cholecystectomy is a major potential complication. Precise detection method of extrahepatic bile duct during laparoscopic procedures would minimize the risk of injury. Towards this goal, we have developed a compact imaging instrumentation designed to enable simultaneous acquisition of conventional white color and NIR fluorescence endoscopic/laparoscopic imaging using ICG as contrast agent. The capabilities of this system, which offers optimized sensitivity and functionality, are demonstrated for the detection of the bile duct in an animal model. This design could also provide a low-cost real-time surgical navigation capability to enhance the efficacy of a variety of other image-guided minimally invasive procedures.

Green chemistry for nanoparticle synthesis.

PubMed

Duan, Haohong; Wang, Dingsheng; Li, Yadong

2015-08-21

The application of the twelve principles of green chemistry in nanoparticle synthesis is a relatively new emerging issue concerning the sustainability. This field has received great attention in recent years due to its capability to design alternative, safer, energy efficient, and less toxic routes towards synthesis. These routes have been associated with the rational utilization of various substances in the nanoparticle preparations and synthetic methods, which have been broadly discussed in this tutorial review. This article is not meant to provide an exhaustive overview of green synthesis of nanoparticles, but to present several pivotal aspects of synthesis with environmental concerns, involving the selection and evaluation of nontoxic capping and reducing agents, the choice of innocuous solvents and the development of energy-efficient synthetic methods.

Green-Tea and Epigallocatechin-3-Gallate are Bactericidal against Bacillus anthracis

DTIC Science & Technology

2017-06-13

EGCG, catechins such 245 as epigallocatechin and epicatechin gallate are also antibacterial agents. Moreover, the 246 bactericidal activity of green...Sharma A, Gupta S, Sarethy IP, Dang S, Gabrani R. 2012. Green tea extract: possible mechanism 285 and antibacterial activity on skin pathogens. Food...was shown to be responsible for this activity , against 30 both the attenuated B. anthracis ANR and the virulent, encapsulated strain B. anthracis

Green route for synthesis of multifunctional fluorescent carbon dots from Tulsi leaves and its application as Cr(VI) sensors, bio-imaging and patterning agents.

PubMed

Bhatt, Shreya; Bhatt, Madhuri; Kumar, Anshu; Vyas, Gaurav; Gajaria, Tejal; Paul, Parimal

2018-07-01

We report a one pot green strategy for the synthesis of carbon dots using tulsi leaves and their potential application in sensing of Cr(VI) selectively. The detection mechanism is based on the phenomenon called inner filter effect (IFE) and a good linear static quenching was observed in the range of 1.6 μM to 50 μM with a detection limit of 4.5 ppb. The reversible switching in fluorescence has been tested and a good recovery in fluorescence was observed up to three consecutive cycles upon addition of ascorbic acid as reducing agent. Also the low toxicity, high fluorescence and photostabilty of the CDs make them excellent imaging and patterning agent. The acid and alkali resistant property of these CDs makes it suitable for real sample analysis. The fluorescent CDs were applied for successful detection of Cr(VI) in water with spike-recoveries ranging from 93 to 99%. Copyright © 2018 Elsevier B.V. All rights reserved.

Highly specific spectroscopic photoacoustic molecular imaging of dynamic optical absorption shifts of an antibody-ICG contrast agent (Conference Presentation)

NASA Astrophysics Data System (ADS)

Wilson, Katheryne E.; Bachawal, Sunitha; Abou-Elkacem, Lotfi; Jensen, Kristen C.; Machtaler, Steven; Tian, Lu; Willmann, Juergen K.

2017-03-01

Improved techniques for breast cancer screening are critically needed as current methods lack diagnostic accuracy. Using spectroscopic photoacoustic (sPA) molecular imaging with a priori knowledge of optical absorption spectra allows suppression of endogenous background signal, increasing the overall sensitivity and specificity of the modality to exogenous contrast agents. Here, sPA imaging was used to monitor antibody-indocyanine green (ICG) conjugates as they undergo optical absorption spectrum shifts after cellular endocytosis and degradation to allow differentiation between normal murine mammary glands from breast cancer by enhancing molecular imaging signal from target (B7-H3)-bound antibody-ICG. First, B7-H3 was shown to have highly specific (AUC of 0.93) expression on both vascular endothelium and tumor stroma in malignant lesions through quantitative immunohistochemical staining of B7-H3 on 279 human samples (normal (n=53), benign lesions (11 subtypes, n=182), breast cancers (4 subtypes, n=97)), making B7-H3 a promising target for sPA imaging. Second, absorption spectra of intracellular and degraded B7-H3-ICG and Isotype control (Iso-ICG) were characterized through in vitro and in vivo experiments. Finally, a transgenic murine breast cancer model (FVB/N-Tg(MMTVPyMT)634Mul) was imaged, and sPA imaging in found a 3.01 (IQR 2.63, 3.38, P<0.001) fold increase in molecular B7-H3-ICG signal in tumors (n=80) compared to control conditions (B7-H3-ICG in tumor negative animals (n=60), Iso-ICG (n=30), blocking B7-H3+B7-H3-ICG (n=20), and free ICG (n=20)) despite significant tumor accumulation of Iso-ICG, confirmed through ex vivo histology. Overall, leveraging anti-B7-H3 antibody-ICG contrast agents, which have dynamic optical absorption spectra representative of molecular interactions, allows for highly specific sPA imaging of murine breast cancer.

Green synthesis of anisotropic gold nanoparticles for photothermal therapy of cancer.

PubMed

Fazal, Sajid; Jayasree, Aswathy; Sasidharan, Sisini; Koyakutty, Manzoor; Nair, Shantikumar V; Menon, Deepthy

2014-06-11

Nanoparticles of varying composition, size, shape, and architecture have been explored for use as photothermal agents in the field of cancer nanomedicine. Among them, gold nanoparticles provide a simple platform for thermal ablation owing to its biocompatibility in vivo. However, the synthesis of such gold nanoparticles exhibiting suitable properties for photothermal activity involves cumbersome routes using toxic chemicals as capping agents, which can cause concerns in vivo. Herein, gold nanoparticles, synthesized using green chemistry routes possessing near-infrared (NIR) absorbance facilitating photothermal therapy, would be a viable alternative. In this study, anisotropic gold nanoparticles were synthesized using an aqueous route with cocoa extract which served both as a reducing and stabilizing agent. The as-prepared gold nanoparticles were subjected to density gradient centrifugation to maximize its NIR absorption in the wavelength range of 800-1000 nm. The particles also showed good biocompatibility when tested in vitro using A431, MDA-MB231, L929, and NIH-3T3 cell lines up to concentrations of 200 μg/mL. Cell death induced in epidermoid carcinoma A431 cells upon irradiation with a femtosecond laser at 800 nm at a low power density of 6 W/cm(2) proved the suitability of green synthesized NIR absorbing anisotropic gold nanoparticles for photothermal ablation of cancer cells. These gold nanoparticles also showed good X-ray contrast when tested using computed tomography (CT), proving their feasibility for use as a contrast agent as well. This is the first report on green synthesized anisotropic and cytocompatible gold nanoparticles without any capping agents and their suitability for photothermal therapy.

Green and energy-efficient methods for the production of metallic nanoparticles

PubMed Central

Naghdi, Mitra; Taheran, Mehrdad; Verma, M; Surampalli, R Y; Valero, J R

2015-01-01

Summary In the last decade, researchers paid great attention to the concept of “Green Chemistry”, which aims at development of efficient methods for the synthesis of nanoparticles (NPs) in terms of the least possible impact on human life and environment. Generally, several reagents including precursors, reducing agents, stabilizing agents and solvents are used for the production of NPs and in some cases, energy is needed to reach the optimum temperature for reduction. Therefore, to develop a green approach, researchers had the opportunity to investigate eco-friendly reagents and new energy transfer techniques. In order to substitute the harmful reagents with green ones, researchers worked on different types of saccharides, polyols, carboxylic acids, polyoxometalates and extracts of various plants that can play the role of reducers, stabilizers or solvents. Also, there are some reports on using ultraviolet (UV), gamma and microwave irradiation that are capable of reducing and provide uniform heating. According to the literature, it is possible to use green reagents and novel energy transfer techniques for production of NPs. However, these new synthesis routes should be optimized in terms of performance, cost, product quality (shape and size distribution) and scale-up capability. This paper presents a review on most of the employed green reagents and new energy transfer techniques for the production of metallic NPs. PMID:26734527

Development of a fast ELISA for the specific detection of both leucomalachite green and malachite green

NASA Astrophysics Data System (ADS)

Jiang, Yousheng; Chen, Li; Hu, Kun; Yu, Wenjuan; Yang, Xianle; Lu, Liqun

2015-04-01

Malachite green (MG), a dye, is an antifungal agent that has been used to treat and prevent fish diseases. It is metabolized into reduced leucomalachite green forms (LMG) that may reside in fish muscles for a long period, thus being harmful to human health. The aim of this study was to develop a competitive and direct enzyme-linked immunosorbent assay (ELISA) to detect MG and LMG specifically. The monoclonal antibody (mAb) to LMG was generated using a hybridoma technique. The obtained mAb showed good cross-reactivity (CR) to malachite green (MG), but not to crystal violet (CV) and Brilliant Green (BG). The mAb was used to develop a fast detecting ELISA of MG and LMG in fish. By introducing the conjugation LMG-HRP, the detection capability was 0.37 ng mL-1 for MG and LMG. The mean recovery from spiked grass carp tissues ranged from 76.2% to 82.9% and the coefficients of variation varied between 1.8% and 7.5%. The stable and efficient monoclonal cell line obtained is a sustainable source of sensitive and specific antibody to MG and LMG.

Primary cancer prevention by green tea, and tertiary cancer prevention by the combination of green tea catechins and anticancer compounds.

PubMed

Fujiki, Hirota; Sueoka, Eisaburo; Watanabe, Tatsuro; Suganuma, Masami

2015-03-01

Green tea is a daily beverage, a non-oxidized non-fermented product containing at least four green tea catechins. Considering our first results when repeated applications of (-)-epigallocatechin gallate (EGCG) prevented tumor promotion in mouse skin, we have continued to look at green tea as a possible cancer preventive agent. 1) The 10-year prospective cohort study by Drs. K. Nakachi and K. Imai revealed that drinking 10 Japanese-size cups (120 mL/cup) of green tea per day delayed cancer onset in humans by 7.3 years among females and by 3.2 years among males. The delay of cancer onset is of course significant evidence of primary cancer prevention in humans. 2) In collaboration with Dr. H. Moriwaki's group we successfully presented a prototype of tertiary cancer prevention showing that 10 Japanese-size cups of green tea daily, supplemented with tablets of green tea extract (G.T.E), reduced recurrence of colorectal adenomas in polypectomy patients by 51.6% (from 31% to 15%). 3) In 1999, we first reported that the combination of green tea catechins and non-steroidal anti-inflammatory drugs showed synergistic anticancer effects in both in vitro and in vivo experiments, along with elucidation of the mechanism. 4) Further studies by other investigators have revealed that various combinations of EGCG or green tea extract and anticancer compounds inhibit tumor volume in xenograft mouse models implanted with various human cancer cell lines. Green tea is a cancer preventive, and green tea catechins act as synergists with anticancer compounds.

Low-intensity LED (625 and 405 nm) and laser (805 nm) killing of Propionibacterium acnes and Staphylococcus epidermidis

NASA Astrophysics Data System (ADS)

Tuchina, Elena S.; Tuchin, Valery V.

2009-02-01

In the present work we have investigated in vitro sensitivity of microorganisms P. acnes and S. epidermidis to action of red (625 nm and 405 nm) and infrared (805 nm) radiations in combination with photosensitizes Methylene Blue and Indocyanine Green.

The clinical use of indocyanine green as a near-infrared fluorescent contrast agent for image-guided oncologic surgery