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Sample records for agent indocyanine green

  1. In Vitro Efficacy and Mechanistic Role of Indocyanine Green as a Photodynamic Therapy Agent for Human Melanoma

    SciTech Connect

    Mamoon, A.; Gamal-Eldeen, A; Ruppel, M; Smith, R; Tsang, T; Miller, L

    2009-01-01

    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 (700-800nm) 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.

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

    SciTech Connect

    Mamoon, A.M.; Miller, L.; Gamal-Eldeen, A. M.; Ruppel, M. E.; Smith, R. J.; Tsang, T.; Miller, L. 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 and 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.

  3. 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.

  4. Indocyanine green fluorescence-guided redo parathyroidectomy.

    PubMed

    Chakedis, Jeffery M; Maser, Christina; Brumund, Kevin T; Bouvet, Michael

    2015-09-02

    Re-operative neck surgery for hyperparathyroidism is a technically difficult operation that requires adjunctive studies to assist with finding the parathyroid tissues. Intraoperative tests help minimise exploration of the neck and decrease injuries to the surrounding structures. Indocyanine green is a near-infrared fluorescent dye that in pre-clinical models was found to be useful in locating the parathyroid glands of dogs. No study has yet reported its use as a tool for parathyroid localisation in humans. We investigated the use of indocyanine green to assist with localisation of a recurrent parathyroid adenoma using a near-infrared imaging system. After exposure of the neck tissues, the parathyroid gland fluoresced brightly and directed our dissection. Exploration of the neck was minimal, and allowed for fast localisation and excision of the adenoma. Overall, use of indocyanine green is a simple and safe technique of intraoperative parathyroid localisation that warrants further investigation.

  5. Indocyanine green fluorescence-guided redo parathyroidectomy.

    PubMed

    Chakedis, Jeffery M; Maser, Christina; Brumund, Kevin T; Bouvet, Michael

    2015-01-01

    Re-operative neck surgery for hyperparathyroidism is a technically difficult operation that requires adjunctive studies to assist with finding the parathyroid tissues. Intraoperative tests help minimise exploration of the neck and decrease injuries to the surrounding structures. Indocyanine green is a near-infrared fluorescent dye that in pre-clinical models was found to be useful in locating the parathyroid glands of dogs. No study has yet reported its use as a tool for parathyroid localisation in humans. We investigated the use of indocyanine green to assist with localisation of a recurrent parathyroid adenoma using a near-infrared imaging system. After exposure of the neck tissues, the parathyroid gland fluoresced brightly and directed our dissection. Exploration of the neck was minimal, and allowed for fast localisation and excision of the adenoma. Overall, use of indocyanine green is a simple and safe technique of intraoperative parathyroid localisation that warrants further investigation. PMID:26336189

  6. Efficiency of staining hair with indocyanine green

    NASA Astrophysics Data System (ADS)

    Kulyabina, Tatyana V.; Kochubey, Vyacheslav I.

    2005-06-01

    The efficiency of staining hair with indocyanine green (ICG) solution depending on type of hair, natural color, staining time and other parameters was investigated. Bonding ICG with hair material occurs due to interaction between ICG molecules and keratinocyte albumin. The penetration of ICG dye into hair meets with difficulties owing to surface protective layer.

  7. Monocytes loaded with indocyanine green as active homing contrast agents permit optical differentiation of infectious and non-infectious inflammation.

    PubMed

    Christensen, Joani M; Brat, Gabriel A; Johnson, Kristine E; Chen, Yongping; Buretta, Kate J; Cooney, Damon S; Brandacher, Gerald; Lee, W P Andrew; Li, Xingde; Sacks, Justin M

    2013-01-01

    Distinguishing cutaneous infection from sterile inflammation is a diagnostic challenge and currently relies upon subjective interpretation of clinical parameters, microbiological data, and nonspecific imaging. Assessing characteristic variations in leukocytic infiltration may provide more specific information. In this study, we demonstrate that homing of systemically administered monocytes tagged using indocyanine green (ICG), an FDA-approved near infrared dye, may be assessed non-invasively using clinically-applicable laser angiography systems to investigate cutaneous inflammatory processes. RAW 264.7 mouse monocytes co-incubated with ICG fluoresce brightly in the near infrared range. In vitro, the loaded cells retained the ability to chemotax toward monocyte chemotactic protein-1. Following intravascular injection of loaded cells into BALB/c mice with induced sterile inflammation (Complete Freund's Adjuvant inoculation) or infection (Group A Streptococcus inoculation) of the hind limb, non-invasive whole animal imaging revealed local fluorescence at the inoculation site. There was significantly higher fluorescence of the inoculation site in the infection model than in the inflammation model as early as 2 hours after injection (p<0.05). Microscopic examination of bacterial inoculation site tissue revealed points of near infrared fluorescence, suggesting the presence of ICG-loaded cells. Development of a non-invasive technique to rapidly image inflammatory states without radiation may lead to new tools to distinguish infectious conditions from sterile inflammatory conditions at the bedside.

  8. Study of diffusion of indocyanine green as a photodynamic dye into skin using backscattering spectroscopy

    NASA Astrophysics Data System (ADS)

    Genina, E. A.; Bashkatov, A. N.; Tuchin, V. V.

    2014-07-01

    One of the lines of development of modern medicine is theranostics consisting in simultaneous diagnosis and laser treatment with the use of multifunctional agents such as fluorescent indocyanine green that has photodynamic and photothermal properties. Diffusion of indocyanine green dissolved in water and aqueous solutions of alcohols (glycerol, propylene glycol and ethanol) into the dermis is studied by using backscattering spectroscopy. The coefficients of the dye diffusion into the dermis are obtained for the first time by using these solvents.

  9. Study of diffusion of indocyanine green as a photodynamic dye into skin using backscattering spectroscopy

    SciTech Connect

    Genina, E A; Bashkatov, A N; Tuchin, V V

    2014-07-31

    One of the lines of development of modern medicine is theranostics consisting in simultaneous diagnosis and laser treatment with the use of multifunctional agents such as fluorescent indocyanine green that has photodynamic and photothermal properties. Diffusion of indocyanine green dissolved in water and aqueous solutions of alcohols (glycerol, propylene glycol and ethanol) into the dermis is studied by using backscattering spectroscopy. The coefficients of the dye diffusion into the dermis are obtained for the first time by using these solvents. (laser biophotonics)

  10. 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. PMID:27349352

  11. Erythrocyte-derived photo-theranostic agents: hybrid nano-vesicles containing indocyanine green for near infrared imaging and therapeutic applications

    NASA Astrophysics Data System (ADS)

    Bahmani, Baharak; Bacon, Danielle; Anvari, Bahman

    2013-07-01

    Development of theranostic nano-constructs may enable diagnosis and treatment of diseases at high spatial resolution. Some key requirements for clinical translation of such constructs are that they must be non-toxic, non-immunogenic, biodegradable, with extended circulating lifetime. Cell-based structures, particularly those derived from erythrocytes, are promising candidate carrier systems to satisfy these requirements. One particular type of theranostic materials utilize light-sensitive agents that once photo-activated can provide diagnostic imaging capability, and elicit therapeutic effects. Here we demonstrate the first successful engineering of hybrid nano-scale constructs derived from membranes of hemoglobin-depleted erythrocytes that encapsulate the near infrared chromophore, indocyanine green. We show the utility of the constructs as photo-theranostic agents in fluorescence imaging and photothermal destruction of human cells. These erythrocyte-mimicking nano-structures can be derived autologously, and may have broad applications in personal nanomedicine ranging from imaging and photo-destruction of cancerous tissues to vascular abnormalities, and longitudinal evaluations of therapeutic interventions.

  12. 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.

  13. Erythrocyte-derived photo-theranostic agents: hybrid nano-vesicles containing indocyanine green for near infrared imaging and therapeutic applications.

    PubMed

    Bahmani, Baharak; Bacon, Danielle; Anvari, Bahman

    2013-01-01

    Development of theranostic nano-constructs may enable diagnosis and treatment of diseases at high spatial resolution. Some key requirements for clinical translation of such constructs are that they must be non-toxic, non-immunogenic, biodegradable, with extended circulating lifetime. Cell-based structures, particularly those derived from erythrocytes, are promising candidate carrier systems to satisfy these requirements. One particular type of theranostic materials utilize light-sensitive agents that once photo-activated can provide diagnostic imaging capability, and elicit therapeutic effects. Here we demonstrate the first successful engineering of hybrid nano-scale constructs derived from membranes of hemoglobin-depleted erythrocytes that encapsulate the near infrared chromophore, indocyanine green. We show the utility of the constructs as photo-theranostic agents in fluorescence imaging and photothermal destruction of human cells. These erythrocyte-mimicking nano-structures can be derived autologously, and may have broad applications in personal nanomedicine ranging from imaging and photo-destruction of cancerous tissues to vascular abnormalities, and longitudinal evaluations of therapeutic interventions.

  14. Erythrocyte-derived photo-theranostic agents: hybrid nano-vesicles containing indocyanine green for near infrared imaging and therapeutic applications

    PubMed Central

    Bahmani, Baharak; Bacon, Danielle; Anvari, Bahman

    2013-01-01

    Development of theranostic nano-constructs may enable diagnosis and treatment of diseases at high spatial resolution. Some key requirements for clinical translation of such constructs are that they must be non-toxic, non-immunogenic, biodegradable, with extended circulating lifetime. Cell-based structures, particularly those derived from erythrocytes, are promising candidate carrier systems to satisfy these requirements. One particular type of theranostic materials utilize light-sensitive agents that once photo-activated can provide diagnostic imaging capability, and elicit therapeutic effects. Here we demonstrate the first successful engineering of hybrid nano-scale constructs derived from membranes of hemoglobin-depleted erythrocytes that encapsulate the near infrared chromophore, indocyanine green. We show the utility of the constructs as photo-theranostic agents in fluorescence imaging and photothermal destruction of human cells. These erythrocyte-mimicking nano-structures can be derived autologously, and may have broad applications in personal nanomedicine ranging from imaging and photo-destruction of cancerous tissues to vascular abnormalities, and longitudinal evaluations of therapeutic interventions. PMID:23846447

  15. Photoacoustic tomography of human hepatic malignancies using intraoperative indocyanine green fluorescence imaging.

    PubMed

    Miyata, Akinori; Ishizawa, Takeaki; Kamiya, Mako; Shimizu, Atsushi; Kaneko, Junichi; Ijichi, Hideaki; Shibahara, Junji; Fukayama, Masashi; Midorikawa, Yutaka; Urano, Yasuteru; Kokudo, Norihiro

    2014-01-01

    Recently, fluorescence imaging following the preoperative intravenous injection of indocyanine green has been used in clinical settings to identify hepatic malignancies during surgery. The aim of this study was to evaluate the ability of photoacoustic tomography using indocyanine green as a contrast agent to produce representative fluorescence images of hepatic tumors by visualizing the spatial distribution of indocyanine green on ultrasonographic images. Indocyanine green (0.5 mg/kg, intravenous) was preoperatively administered to 9 patients undergoing hepatectomy. Intraoperatively, photoacoustic tomography was performed on the surface of the resected hepatic specimens (n = 10) under excitation with an 800 nm pulse laser. In 4 hepatocellular carcinoma nodules, photoacoustic imaging identified indocyanine green accumulation in the cancerous tissue. In contrast, in one hepatocellular carcinoma nodule and five adenocarcinoma foci (one intrahepatic cholangiocarcinoma and 4 colorectal liver metastases), photoacoustic imaging delineated indocyanine green accumulation not in the cancerous tissue but rather in the peri-cancerous hepatic parenchyma. Although photoacoustic tomography enabled to visualize spatial distribution of ICG on ultrasonographic images, which was consistent with fluorescence images on cut surfaces of the resected specimens, photoacoustic signals of ICG-containing tissues decreased approximately by 40% even at 4 mm depth from liver surfaces. Photoacoustic tomography using indocyanine green also failed to identify any hepatocellular carcinoma nodules from the body surface of model mice with non-alcoholic steatohepatitis. In conclusion, photoacoustic tomography has a potential to enhance cancer detectability and differential diagnosis by ultrasonographic examinations and intraoperative fluorescence imaging through visualization of stasis of bile-excreting imaging agents in and/or around hepatic tumors. However, further technical advances are needed

  16. 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

  17. Degradation kinetics of indocyanine green in aqueous solution.

    PubMed

    Saxena, Vishal; Sadoqi, Mostafa; Shao, Jun

    2003-10-01

    The degradation kinetics of a near-infrared fluorescent, diagnostic, and photodynamic agent, indocyanine green (ICG), was investigated in aqueous solution by steady-state fluorescence technique. The influence of ICG concentration on its fluorescence spectrum was determined. The degradation kinetics of ICG in aqueous solution was studied as a function of light exposure, type of light exposed, temperature, and ICG concentration. The degradation of ICG was found to follow first-order kinetics. Exposure to light and high temperatures caused acceleration in the degradation. The type and intensity of exposed light also affected degradation. ICG aqueous solutions were found to be more stable in dark, at low temperatures, and at higher ICG concentrations.

  18. Toxicity of indocyanine green in vitreoretinal surgery.

    PubMed

    Gandorfer, Arnd; Haritoglou, Christos; Kampik, Anselm

    2008-01-01

    Indocyanine green (ICG) selectively stains the internal limiting membrane (ILM) of the retina, and helps to visualize and remove the membrane from the retina. Toxicity and damage to the retina has been reported in in vitro and in vivo studies, and following macular surgery. Toxic effects can occur to retinal glial cells, to the nerve fiber layer, to retinal ganglion cells, and to the optic nerve. In case of subretinal application, the retinal pigment epithelium can be affected. The mechanisms of toxicity are unclear. Whether the dye itself or some preparations only are causing harm to the retina is subject of an ongoing debate. ICG changes the light absorption properties of the ILM and enhances the stiffness of the membrane, probably by crosslinking of collagen fibers. Beside better visualization, this effect is responsible for the ease of membrane removal compared to unaided ILM peeling. Whether a phototoxic effect, which has been demonstrated in vitro and in vivo, plays a clinically significant role in macular surgery has neither been proven nor ruled out yet. ICG at concentrations higher than 1.25% or application of the dye in air are very likely causing retinal damage. In addition, lower concentrations also carry the risk of iatrogenic damage, depending on the final concentration of potentially toxic substances at the vitreomacular interface and on other mechanisms. Due to its instability and the unpredictable effects of ICG at the macula, it cannot be recommended for clinical use before its safety has been proven. This chapter reviews the literature related to ICG toxicity, and summarizes dye-related untoward effects in postmortem eyes and ex vivo models, in in vitro and in vivo animal models, and in macular surgery.

  19. 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

  20. 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.

  1. Monocytes Loaded with Indocyanine Green as Active Homing Contrast Agents Permit Optical Differentiation of Infectious and Non-Infectious Inflammation

    PubMed Central

    Christensen, Joani M.; Brat, Gabriel A.; Johnson, Kristine E.; Chen, Yongping; Buretta, Kate J.; Cooney, Damon S.; Brandacher, Gerald; Lee, W. P. Andrew; Li, Xingde; Sacks, Justin M.

    2013-01-01

    Distinguishing cutaneous infection from sterile inflammation is a diagnostic challenge and currently relies upon subjective interpretation of clinical parameters, microbiological data, and nonspecific imaging. Assessing characteristic variations in leukocytic infiltration may provide more specific information. In this study, we demonstrate that homing of systemically administered monocytes tagged using indocyanine green (ICG), an FDA-approved near infrared dye, may be assessed non-invasively using clinically-applicable laser angiography systems to investigate cutaneous inflammatory processes. RAW 264.7 mouse monocytes co-incubated with ICG fluoresce brightly in the near infrared range. In vitro, the loaded cells retained the ability to chemotax toward monocyte chemotactic protein-1. Following intravascular injection of loaded cells into BALB/c mice with induced sterile inflammation (Complete Freund’s Adjuvant inoculation) or infection (Group A Streptococcus inoculation) of the hind limb, non-invasive whole animal imaging revealed local fluorescence at the inoculation site. There was significantly higher fluorescence of the inoculation site in the infection model than in the inflammation model as early as 2 hours after injection (p<0.05). Microscopic examination of bacterial inoculation site tissue revealed points of near infrared fluorescence, suggesting the presence of ICG-loaded cells. Development of a non-invasive technique to rapidly image inflammatory states without radiation may lead to new tools to distinguish infectious conditions from sterile inflammatory conditions at the bedside. PMID:24282595

  2. 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.

  3. [The indocyanine green (Ujoviridin) test in patients with hyperemesis gravidarum].

    PubMed

    Rudolf, K; Rudolf, H; Töwe, J

    1982-01-01

    A dose of 0.5 mg/kg body weight of indocyanine-green (Ujoviridin), a chromodiagnostic, was applied in one single injection under standardised conditions to 16 patients, aged between 21 and 31 years (25.9 years on average), with slight to moderate hyperemesis gravidarum, with the view to making an assessment of hepatic excretion.--Also determined were aminotransferases, alanine-aminopeptidase, and bilirubin in serum, accompanied by thymol turbidity tests.--The values of indocyanine-green half-life were all, but for one patient, within or at the upper limit of normal.--While the informative value of individual measurements is limited, the above findings seem to suggest that in cases of slight or moderate hyperemesis the laboratory parameters tested are unlikely to rise to pathological levels, except for slight increases which may be associated to certain individual cases. PMID:6126975

  4. 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

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

    SciTech Connect

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

    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)

  6. 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.

  7. 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.

  8. Indocyanine green angiography in chronic central serous chorioretinopathy

    PubMed Central

    Gajdzik-Gajdecka, Urszula; Dorecka, Mariola; Nita, Ewa; Michalska, Anna; Miniewicz-Kurkowska, Joanna; Romaniuk, Wanda

    2012-01-01

    Summary Background Central serous chorioretinopathy (CSC) is a condition that originates from alterations of the choroidal circulation. The aim of this paper was to evaluate the use of indocyanine green angiography (ICGA) in patients with chronic CSC. Material/Methods The analysis included 17 patients (34 eyes) with chronic CSC in at least 1 eye. The eye examination included: distance and near visual acuity, biomicroscopy, applanation tonometry, fundus examination, colored and red-free fundus photography, evaluation of autofluorescence, optical coherence tomography, and fluorescein and indocyanine green angiography. Results In 34 eyes (100%) involved in the ICGA study the results revealed zones of transient increased choroidal vessels permeability. In 18 eyes (52.9%) choroidal changes were accompanied by a focal serous pigment epithelial detachment. In 4 eyes (11.8%) of 3 patients’ the ICGA examination confirmed the presence of occult choroidal neovascularization (CNV). In the patient with bilateral diffuse retinal pigment epitheliopathy, CNV was present in 1 eye, in the patient with unilateral chronic CSC it was also present in 1 eye, and in the third patient with bilateral chronic CSC it was detected in both eyes. Conclusions ICGA is a very useful examination that enables ophthalmologists to visualize choroidal changes due to chronic CSC, as well as to diagnose occult CNV in chronic CSC. PMID:22293877

  9. Indocyanine Green Loaded Nanoconstructs for Optical Imaging and Phototherapeutic Applications

    NASA Astrophysics Data System (ADS)

    Bahmani, Baharak

    Development of theranostic nano-constructs may enable diagnosis and treatment of diseases at high spatial resolution. Optically active nanoparticles are widely pursued as exogenous chromophores in diagnostic imaging and phototherapeutic applications. However, the blood circulation time of nanoparticles remains limited due to the rapid clearance of the nanoparticles by reticuloendothelial system (RES). Coating with Polyethylene glycol (PEG) is a strategy to extend the circulation time of nanoparticles. Here, we report PEGylation of polymeric-based nanocapsules loaded with Indocyanine green (ICG) and effect of PEG's molecular weight on the uptake of these nanocapsules by human spleen macrophages and hepatocytes using flow cytometry. To characterize the biodistribution of the constructs, we performed in vivo quantitative fluorescence imaging in mice 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, offers the potential of extending the clinical applications of ICG. Targeted delivery of therapeutic and imaging agents using surface modified nanovectors has been explored immensely in recent years. The growing demand for site-specific and efficient delivery of nanovectors entails stable surface conjugation of targeting moieties. Our ICG-loaded polymeric nanocapsules (ICG-NCs) have potential for covalent coupling of various targeting moieties and materials due to presence of amine groups on the surface. Here, we covalently bioconjugate PEG-coated ICG-NCs with monoclonal anti- HER2 through reductive amination-mediated procedures. The targeting abilities of HER2 functionalized ICG-NCs toward ovarian cancer was investigated in-vitro. Since these functionalized nanoconstructs have potential applications in laser-induced photodestruction of ovarian cancer cells, we

  10. 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.

  11. 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.

  12. Pharmacokinetic study of indocyanine Green after intravenous administration by UPLC-MS/MS.

    PubMed

    Chen, Yu; Chen, Dongxin; Hu, Wenhao; Lin, Guanyang; Huang, Shiyong

    2015-01-01

    Indocyanine Green is widely used in medical diagnosis and to evaluate liver function and other regional blood flows in clinical application or animal experiments. In this work, a sensitive and selective ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method for determination of Indocyanine Green in rat plasma was developed and validated. After addition of rutin as an internal standard (IS), protein precipitation by acetonitrile-methanol (9:1, v/v) was used to prepare samples. Chromatographic separation was achieved on a UPLC BEH C18 column (2.1 mm × 100 mm, 1.7 μm) with 0.1% formic acid and acetonitrile as the mobile phase with gradient elution. An electrospray ionization source was applied and operated in positive ion mode; multiple reactions monitoring (MRM) mode was used for quantification using target fragment ions m/z 753.4→330.2 for Indocyanine Green, and m/z 611.1→303.1 for IS. Calibration plots were linear throughout the range 20-5000 ng/mL for Indocyanine Green in rat plasma. Mean recoveries of Indocyanine Green in rat plasma ranged from 79.5% to 85.4%. RSD of intra-day and inter-day precision were both < 12%. The accuracy of the method was between 95.9% and 113.9%. The method was successfully applied to pharmacokinetic study of Indocyanine Green after intravenous administration.

  13. Pharmacokinetic study of indocyanine Green after intravenous administration by UPLC-MS/MS

    PubMed Central

    Chen, Yu; Chen, Dongxin; Hu, Wenhao; Lin, Guanyang; Huang, Shiyong

    2015-01-01

    Indocyanine Green is widely used in medical diagnosis and to evaluate liver function and other regional blood flows in clinical application or animal experiments. In this work, a sensitive and selective ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method for determination of Indocyanine Green in rat plasma was developed and validated. After addition of rutin as an internal standard (IS), protein precipitation by acetonitrile-methanol (9:1, v/v) was used to prepare samples. Chromatographic separation was achieved on a UPLC BEH C18 column (2.1 mm × 100 mm, 1.7 μm) with 0.1% formic acid and acetonitrile as the mobile phase with gradient elution. An electrospray ionization source was applied and operated in positive ion mode; multiple reactions monitoring (MRM) mode was used for quantification using target fragment ions m/z 753.4→330.2 for Indocyanine Green, and m/z 611.1→303.1 for IS. Calibration plots were linear throughout the range 20-5000 ng/mL for Indocyanine Green in rat plasma. Mean recoveries of Indocyanine Green in rat plasma ranged from 79.5% to 85.4%. RSD of intra-day and inter-day precision were both < 12%. The accuracy of the method was between 95.9% and 113.9%. The method was successfully applied to pharmacokinetic study of Indocyanine Green after intravenous administration. PMID:26629038

  14. 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.

  15. The use of diffuse laser photonic energy and indocyanine green photosensitiser as an adjunct to periodontal therapy.

    PubMed

    Parker, S

    2013-08-01

    Light-activated chemical therapy - generally known as photodynamic therapy (PDT) - has been developed within medicine, to allow the use of an applied agent (photosensitiser) that could be activated using laser photonic energy, leading to the destruction of target cellular structures. In clinical dentistry, PDT has been utilised within a wide scope of topical application in endodontic, periodontal and oral epithelial pathology where specifically, anti-bacterial action may prove useful. Underlying the complex and multi-factorial aetiology, periodontal disease remains of essentially-bacterial origin and anti-bacterial PDT (aPDT) has been investigated as an adjunctive to other periodontal treatment therapies. Of several topically-applied photosensitisers, one agent, indocyanine green, may be activated using a diode laser wavelength (810 nm) that is commonly-available in clinical dental practice, to provide generalised bacteriocidal effect. Unlike antibiotics and antibacterial mouthwashes, the mode of action appears to be nonspecific to bacterial species and is linked to cell death through a process of oxidative stress. Additionally, indocyanine green has otherwise low toxicity to non-target host tissue and dental restorative materials. This paper explores the background to this therapy, its position within the broader delivery of periodontal treatment and the specific application of indocyanine green in clinical dental practice.

  16. Indocyanine-green-loaded microballoons for biliary imaging in cholecystectomy

    PubMed Central

    Mitra, Kinshuk; Melvin, James; Chang, Shufang; Park, Kyoungjin; Yilmaz, Alper; Melvin, Scott

    2012-01-01

    Abstract. 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. PMID:23214186

  17. Quantitative imaging of lymphatic function with liposomal indocyanine green.

    PubMed

    Proulx, Steven T; Luciani, Paola; Derzsi, Stefanie; Rinderknecht, Matthias; Mumprecht, Viviane; Leroux, Jean-Christophe; Detmar, Michael

    2010-09-15

    Lymphatic vessels play a major role in cancer progression and in postsurgical lymphedema, and several new therapeutic approaches targeting lymphatics are currently being developed. Thus, there is a critical need for quantitative imaging methods to measure lymphatic flow. Indocyanine green (ICG) has been used for optical imaging of the lymphatic system, but it is unstable in solution and may rapidly enter venous capillaries after local injection. We developed a novel liposomal formulation of ICG (LP-ICG), resulting in vastly improved stability in solution and an increased fluorescence signal with a shift toward longer wavelength absorption and emission. When injected intradermally to mice, LP-ICG was specifically taken up by lymphatic vessels and allowed improved visualization of deep lymph nodes. In a genetic mouse model of lymphatic dysfunction, injection of LP-ICG showed no enhancement of draining lymph nodes and slower clearance from the injection site. In mice bearing B16 luciferase-expressing melanomas expressing vascular endothelial growth factor-C (VEGF-C), sequential near-IR imaging of intradermally injected LP-ICG enabled quantification of lymphatic flow. Increased flow through draining lymph nodes was observed in mice bearing VEGF-C-expressing tumors without metastases, whereas a decreased flow pattern was seen in mice with a higher lymph node tumor burden. This new method will likely facilitate quantitative studies of lymphatic function in preclinical investigations and may also have potential for imaging of lymphedema or improved sentinel lymph detection in cancer. PMID:20823159

  18. 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

  19. 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.

  20. Intraoperative Indocyanine Green Laser Angiography in Pediatric Autologous Ear Reconstruction

    PubMed Central

    Martins, Deborah B.; Farias-Eisner, Gina; Mandelbaum, Rachel S.; Hoang, Han; Bradley, James P.

    2016-01-01

    Summary: Skin flap vascularity is a critical determinant of aesthetic results in autologous ear reconstruction. In this study, we investigate the use of intraoperative laser-assisted indocyanine green angiography (ICGA) as an adjunctive measure of skin flap vascularity in pediatric autologous ear reconstruction. Twenty-one consecutive pediatric patients undergoing first-stage autologous total ear reconstruction were retrospectively evaluated. The first 10 patients were treated traditionally (non-ICGA), and the latter 11 patients were evaluated with ICGA intraoperatively after implantation of the cartilage construct and administration of suction. Relative and absolute perfusion units in the form of contour maps were generated. Statistical analyses were performed using independent sample Student t test. Statistically significant differences in exposure and infection were not found between the 2 groups. However, decreased numbers of surgical revisions were required in cases with ICGA versus without ICGA (P = 0.03), suggesting that greater certainty in skin flap perfusion correlated with a reduction in revision surgeries. In cases of exposure, we found an average lowest absolute perfusion unit of 14.3, whereas cases without exposure had an average of 26.1 (P = 0.02), thereby defining objective parameters for utilizing ICGA data in tailoring surgical decision making for this special population of patients. Defined quantitative parameters for utilizing ICGA in evaluating skin flap vascularity may be a useful adjunctive technique in pediatric autologous ear reconstruction. PMID:27579233

  1. 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.

  2. Indocyanine green alters transepithelial electrical parameters of the distal colon.

    PubMed

    Hameed, Burhan; Smith, David M; Verrechio, Jon J; Schmidt, J David; Gillooley, Leesa E; Valenzano, Mary Carmen; Lewis, Simon A; Mullin, James M

    2004-09-01

    Indocyanine green (ICG) is used as a dye marker of the vascular space in gastroenterology, ophthalmology, neurology, and critical care medicine. It is widely regarded to be inert. We report, however, that ICG demonstrates effects on colonic transepithelial electrical parameters which could form a basis for a growing number of deleterious gastrointestinal and other clinical effects. Short-circuit current (Iscc), transepithelial conductance (gt), and transepithelial paracellular flux of 14C-D-mannitol were monitored across sheets of rat distal colon. Dye was introduced to mucosal or serosal tissue surfaces at a concentration similar to that used in vivo (10 microg/ml). ICG decreased Iscc by over 50% and gt by over 10%. Transepithelial mannitol flux was not altered. Dye was effective only from the serosal surface. Cyclic AMP-induced spiking of Iscc was not affected by ICG. Preincubation with amiloride or furosemide did not affect the action of the dye on gt or Iscc. ICG at in vivo dosages is clearly capable of inhibiting ion transport across colon epithelial tissue. The serosal site of action indicates activity on a basal-lateral transport system or diffusion into the cell only across the basal-lateral membrane followed by inhibition of a transporter from the intracellular side. ICG should not be considered inert in vivo. Leakage of ICG from the vascular space into the interstitial fluid space will likely result in tissue morbidity. PMID:15481307

  3. Intraoperative Indocyanine Green Laser Angiography in Pediatric Autologous Ear Reconstruction.

    PubMed

    Martins, Deborah B; Farias-Eisner, Gina; Mandelbaum, Rachel S; Hoang, Han; Bradley, James P; Lee, Justine C

    2016-05-01

    Skin flap vascularity is a critical determinant of aesthetic results in autologous ear reconstruction. In this study, we investigate the use of intraoperative laser-assisted indocyanine green angiography (ICGA) as an adjunctive measure of skin flap vascularity in pediatric autologous ear reconstruction. Twenty-one consecutive pediatric patients undergoing first-stage autologous total ear reconstruction were retrospectively evaluated. The first 10 patients were treated traditionally (non-ICGA), and the latter 11 patients were evaluated with ICGA intraoperatively after implantation of the cartilage construct and administration of suction. Relative and absolute perfusion units in the form of contour maps were generated. Statistical analyses were performed using independent sample Student t test. Statistically significant differences in exposure and infection were not found between the 2 groups. However, decreased numbers of surgical revisions were required in cases with ICGA versus without ICGA (P = 0.03), suggesting that greater certainty in skin flap perfusion correlated with a reduction in revision surgeries. In cases of exposure, we found an average lowest absolute perfusion unit of 14.3, whereas cases without exposure had an average of 26.1 (P = 0.02), thereby defining objective parameters for utilizing ICGA data in tailoring surgical decision making for this special population of patients. Defined quantitative parameters for utilizing ICGA in evaluating skin flap vascularity may be a useful adjunctive technique in pediatric autologous ear reconstruction. PMID:27579233

  4. Micellar formulation of indocyanine green for phototherapy of melanoma.

    PubMed

    Mundra, Vaibhav; Peng, Yang; Rana, Sandeep; Natarajan, Amarnath; Mahato, Ram I

    2015-12-28

    Phototherapy (PT), a light activated treatment modality, is a potential therapeutic option for the treatment of melanoma. In spite of the excellent safety profile and absorption in the near infrared (NIR) range, clinical potential of indocyanine green (ICG) as PT is limited by its short half-life and inefficient tumor accumulation. In this study, we have covalently conjugated ICG-NH2 to the pendant carboxyl groups of poly (ethylene glycol)-block-poly(2-methyl-2-carboxyl-propylene carbonate) (PEG-PCC) copolymer using carbodiimide coupling, which self-assembled into micelles with a particle size of 30-50 nm and high ICG loading. These ICG conjugated micelles exhibited significant in vitro photodynamic cytotoxicity. Use of sodium azide and NIR radiate on at 4 °C revealed photodynamic and photothermal as mechanism of cytotoxicity of ICG solution and ICG conjugated micelles, respectively. In vivo NIR imaging demonstrated that ICG conjugated micelles prolonged its circulation and increased tumor accumulation through enhanced permeability and retention (EPR) effect. Enhanced tumor accumulation improved therapeutic efficacy with complete tumor regression in NIR irradiated ICG conjugated micelles compared to ICG solution and control in a A375 human melanoma tumor model in athymic nude mice. These results suggest that ICG conjugated micelles can be potentially utilized for PT and imaging of melanoma.

  5. 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.

  6. 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

  7. 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.

  8. 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

  9. Selective Uptake of Indocyanine Green by Reticulocytes in Circulation

    PubMed Central

    Wei, Xunbin; Runnels, Judith M.; Lin, Charles P.

    2010-01-01

    Purpose Hyperfluorescent cells labeled with indocyanine green (ICG) have been observed in retinal and choroidal circulation using scanning laser ophthalmoscopy. It has been suggested that ICG labels leukocytes and that ICG can be used to track leukocyte movement in vivo. The purpose of this study is to identify the cell population that takes up ICG and to study their trafficking pattern in vivo by confocal fluorescence microscopy. Methods ICG was injected into the mouse tail vein, and images were taken by in vivo confocal microscopy. The trafficking pattern of ICG-labeled cells was compared with that of rhodamine 6G-labeled leukocytes. In vitro labeling of human blood cells with antibodies against cell lineage markers and with DNA stains was further used to identify the ICG-labeled cells. Antibodies against the following cell surface markers were used: CD45 (leukocytes), CD3 (T lymphocytes), CD19 (B lymphocytes), CD16 (Fc receptor), glycophorin A (erythroid lineage cells), and CD71 (transferrin receptor). Results The ICG-labeled cells were made up of two blood cell populations with distinct levels of ICG uptake. The strongly ICG-labeled cells did not roll on dermal vascular endothelium in vivo, in contrast to rhodamine 6G–labeled leukocytes. They were identified as reticulocytes because antibody staining showed that they were CD 45−, glycophorin A+ and CD 71+. The weakly ICG-labeled cells were identified as neutrophils because they were CD45+, CD16+, CD3−, and CD19−. Conclusions ICG strongly labels reticulocytes and weakly labels neutrophils. To the authors' knowledge, this is the first report of selective staining of reticulocytes by ICG. PMID:14507897

  10. Indocyanine green as an adjunct for resection of insular gliomas

    PubMed Central

    Shah, Abhidha; Rangarajan, Vithal; Kaswa, Amol; Jain, Sonal; Goel, Atul

    2016-01-01

    Objective: Many controversies exist regarding the extent of resection for insular gliomas and the timing of resection. Several techniques and adjuncts are used to maximize safety during resection of these tumors. We describe the use of indocyanine green (ICG) to identify the branches of the middle cerebral artery and discuss its utility to increase safety for resection for insular gliomas. Materials and Methods: Five patients with insular gliomas were surgically treated by the authors from June 2013 to June 2014. The patients presented with complaints of either a headache or recurring episodes of convulsions. All the patients were operated with the aid of neuronavigation and tractography. The long perforating branches of the middle cerebral artery course through the insula and pass onward to supply the corona radiata. It is essential to preserve these vessels to prevent postoperative neurological deficits. ICG (Aurogreen) was used to identify and preserve the long perforating arteries of the middle cerebral artery. Results: ICG dye correctly identified the long perforating branches of the middle cerebral artery and easily distinguished these vessels from the short perforating branches. All the branches of the middle cerebral artery that coursed through the tumor and had an onward course were preserved in all the patients. Only one patient developed a transient right sided hemiparesis that had improved at follow-up. Conclusions: Surgery for insular gliomas is challenging due to its location adjacent to eloquent areas, important white fiber tracts and the course of the middle cerebral artery within it. ICG is useful to identify and preserve the long perforating branches of the middle cerebral artery that course through the tumor and traverse onward to supply the corona radiata. PMID:27366256

  11. Development of a polymeric nanoparticulate delivery system for indocyanine green

    NASA Astrophysics Data System (ADS)

    Saxena, Vishal

    Purpose. The objective of this project was to develop an intravenously administrable poly(dl-lactic-co-glycolic acid) (PLGA) nanoparticulate delivery system for Indocyanine Green (ICG), to enhance the potential for ICG use in tumor imaging and therapy. Methods. For this purpose PLGA nanoparticles entrapping ICG were engineered by spontaneous emulsification solvent diffusion method. ICG entrapment in nanoparticles was determined and physicochemical characterization of nanoparticles was performed. The stability of ICG in nanoparticles formulation under various conditions was determined. The intracellular uptake of ICG in nanoparticles by B16-F10 and C-33A cancer cell lines was studied in comparison with the free ICG solution. Anti-proliferation studies against cancer cells were performed to prove the photodynamic activity of ICG in nanoparticles. Biodistribution of ICG when delivered through nanoparticles and solution were evaluated in mice after tail vein injection. Results. PLGA nanoparticles with a mean diameter of 350 nm and 74% ICG entrapment were obtained. The nanoparticles were nearly spherical in shape with zeta potential of -16 mV. The nanoparticles formulation provided overall stability to ICG with degradation half-lives of 2.5--3.5 days as compared to 10--20 hr of free ICG solutions. The intracellular uptake of ICG through nanoparticles was directly proportional to time and extracellular nanoparticle concentration. The intracellular uptake of ICG was enhanced about 100-fold by nanoparticles formulation as compared to the free ICG solution. Nanoparticles formulation showed significant photodynamic effect at nano-molar ICG concentrations and very low light dose (fluence: 0.22 W/cm2 and energy density: 1.1 J/cm2). In-vivo, the blood circulation-time and retention-time of ICG in various organs was enhanced 2--5 times by nanoparticles formulation as compared to the free ICG solution. Conclusions. A PLGA nanoparticlute delivery system was developed for ICG

  12. (177)Lu-Labeled Cerasomes Encapsulating Indocyanine Green for Cancer Theranostics.

    PubMed

    Jing, Lijia; Shi, Jiyun; Fan, Di; Li, Yaqian; Liu, Renfa; Dai, Zhifei; Wang, Fan; Tian, Jie

    2015-10-01

    This Article reported the fabrication of a robust theranostic cerasome encapsulating indocyanine green (ICG) by incorporating 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[carboxy(polyethylene glycol)2000]-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid monoamide (DSPE-PEG2000-DOTA), followed by chelating radioisotope of (177)Lu. Its applications in optical and nuclear imaging of tumor uptake and biodistribution, as well as photothermal killing of cancer cells, were investigated. It was found that the obtained cerasome could act efficiently as fluorescence contrast agent as well as nuclear imaging tracer. Encapsulating ICG into cerasome could protect ICG from degradation, aggregation, and fast elimination from body, resulting in remarkable improvement in near-infrared fluorescence imaging, photothermal stability, and in vivo pharmacokinetic profile. Both fluorescence and nuclear imaging showed that such agent could selectively accumulate in tumor site after intravenous injection of the cerasome agent into Lewis lung carcinoma tumor bearing mice, resulting in efficient photothermal ablation of tumor through a one-time NIR laser irradiation at the best time window. The ability to track the uptake of cerasomes on a whole body basis could provide researchers with an excellent tool for developing cerasome-based drug delivery agents, especially the strategy of labeling cerasomes with theranostic radionuclide (177)Lu, enabling the ability of the (177)Lu-labeled cerasomes for radionuclide cancer therapy and even the combined therapy.

  13. (177)Lu-Labeled Cerasomes Encapsulating Indocyanine Green for Cancer Theranostics.

    PubMed

    Jing, Lijia; Shi, Jiyun; Fan, Di; Li, Yaqian; Liu, Renfa; Dai, Zhifei; Wang, Fan; Tian, Jie

    2015-10-01

    This Article reported the fabrication of a robust theranostic cerasome encapsulating indocyanine green (ICG) by incorporating 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[carboxy(polyethylene glycol)2000]-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid monoamide (DSPE-PEG2000-DOTA), followed by chelating radioisotope of (177)Lu. Its applications in optical and nuclear imaging of tumor uptake and biodistribution, as well as photothermal killing of cancer cells, were investigated. It was found that the obtained cerasome could act efficiently as fluorescence contrast agent as well as nuclear imaging tracer. Encapsulating ICG into cerasome could protect ICG from degradation, aggregation, and fast elimination from body, resulting in remarkable improvement in near-infrared fluorescence imaging, photothermal stability, and in vivo pharmacokinetic profile. Both fluorescence and nuclear imaging showed that such agent could selectively accumulate in tumor site after intravenous injection of the cerasome agent into Lewis lung carcinoma tumor bearing mice, resulting in efficient photothermal ablation of tumor through a one-time NIR laser irradiation at the best time window. The ability to track the uptake of cerasomes on a whole body basis could provide researchers with an excellent tool for developing cerasome-based drug delivery agents, especially the strategy of labeling cerasomes with theranostic radionuclide (177)Lu, enabling the ability of the (177)Lu-labeled cerasomes for radionuclide cancer therapy and even the combined therapy. PMID:26398723

  14. Vital staining with indocyanine green: a review of the clinical and experimental studies relating to safety.

    PubMed

    Stanescu-Segall, D; Jackson, T L

    2009-03-01

    Indocyanine green (ICG) is extremely effective when used as a vital stain during macular hole surgery. By staining the internal limiting membrane, ICG facilitates removal of this delicate and sometimes hard to visualize structure. There is, however, considerable debate regarding its safety. This review considers the clinical and experimental studies of ICG and a related agent, infracyanine green. Some clinical papers show visual field defects, reduced visual acuity, and persistence of ICG at the macula and optic nerve. Other clinical studies fail to demonstrate toxicity. The experimental studies are also conflicting, but there are emerging trends. These suggest that surgeons who continue to use ICG should use concentrations not greater than 0.05 mg/ml, in fluid-filled eyes, with short exposure times, iso-osmolar solutions, and avoid proximal or prolonged endoillumination of stained tissue. A smaller number of studies suggest that infracyanine green produces similar staining to ICG, and may possibly be safer, but there are too few well-designed studies to reach a conclusion. Although the use of ICG continues, on the balance of evidence, this review suggests that it is has the potential to produce subtle visual damage.

  15. Hepatectomy Based on Future Liver Remnant Plasma Clearance Rate of Indocyanine Green.

    PubMed

    Uchida, Yuichiro; Furuyama, Hiroaki; Yasukawa, Daiki; Nishino, Hiroto; Ando, Yasuhisa; Hata, Toshiyuki; Machimoto, Takafumi; Yoshimura, Tsunehiro

    2016-01-01

    Background. Hepatectomy, an important treatment modality for liver malignancies, has high perioperative morbidity and mortality rates. Safe, comprehensive criteria for selecting patients for hepatectomy are needed. Since June 2011, we have used a cut-off value of ≧ 0.05 for future liver remnant plasma clearance rate of indocyanine green as a criterion for hepatectomy. The aim of this study was to verify the validity of this criterion. Methods. From June 2011 to December 2015, 212 hepatectomies were performed in Tenri Yorozu Hospital. Of these 212 patients, 107 who underwent preoperative computed tomography imaging volumetry, indocyanine green clearance test, and hepatectomy (excluding partial resection or enucleation) were retrospectively analyzed. Results. There was no postoperative mortality. Posthepatectomy liver failure occurred in 59 patients (55.1%) (International Study Group of Liver Surgery Grade A: 43 cases (40.2%), Grade B: 16 cases (15.0%), and Grade C: no cases). Operative morbidity greater than Clavien-Dindo Grade 3 occurred in 23 patients (21.5%). A low future liver remnant plasma clearance rate of indocyanine green was a good predictor for Grade B cases (area under curve = 0.804; 95% confidence interval, 0.712-0.895). Conclusion. Liver remnant plasma clearance rate of indocyanine green is a valid criterion for hepatectomy.

  16. Photoacoustic imaging enhanced by indocyanine green-conjugated single-wall carbon nanotubes.

    PubMed

    Zanganeh, Saeid; Li, Hai; Kumavor, Patrick D; Alqasemi, Umar; Aguirre, Andres; Mohammad, Innus; Stanford, Courtney; Smith, Michael B; Zhu, Quing

    2013-09-01

    A photoacoustic contrast agent that is based on bis-carboxylic acid derivative of indocyanine green (ICG) covalently conjugated to single-wall carbon nanotubes (ICG/SWCNT) is presented. Covalently attaching ICG to the functionalized SWCNT provides a more robust system that delivers much more ICG to the tumor site. The detection sensitivity of the new contrast agent in a mouse tumor model is demonstrated in vivo by our custom-built photoacoustic imaging system. The summation of the photoacoustic tomography (PAT) beam envelope, referred to as the "PAT summation," is used to demonstrate the postinjection light absorption of tumor areas in ICG- and ICG/SWCNT-injected mice. It is shown that ICG is able to provide 33% enhancement at approximately 20 min peak response time with reference to the preinjection PAT level, while ICG/SWCNT provides 128% enhancement at 80 min and even higher enhancement of 196% at the end point of experiments (120 min on average). Additionally, the ICG/SWCNT enhancement was mainly observed at the tumor periphery, which was confirmed by fluorescence images of the tumor samples. This feature is highly valuable in guiding surgeons to assess tumor boundaries and dimensions in vivo and to achieve clean tumor margins to improve surgical resection of tumors.

  17. 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

    2016-06-01

    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. PMID:27097108

  18. Fabrication of indocyanine green encapsulated biodegradable microbubbles for structural and functional imaging of cancer

    NASA Astrophysics Data System (ADS)

    Xu, Ronald X.; Huang, Jiwei; Xu, Jeff S.; Sun, Duxin; Hinkle, George H.; Martin, Edward W.; Povoski, Stephen P.

    2009-05-01

    We developed a novel dual-modal contrast agent for the structural and functional imaging of cancer. The contrast agent was fabricated by encapsulating indocyanine green (ICG) in poly(lactic-co-glycolic acid) (PLGA) microbubbles using a modified double-emulsion method. More stabilized absorption and fluorescence emission characteristics were observed for aqueous and plasma suspensions of ICG-encapsulated microbubbles. The technical feasibility of concurrent structural and functional imaging was demonstrated through a series of benchtop tests in which the aqueous suspension of ICG-encapsulated microbubbles was injected into a transparent tube embedded in an Intralipid phantom at different flow rates and concentrations. Concurrent fluorescence imaging and B-mode ultrasound imaging successfully captured the changes of microbubble flow rate and concentration with high linearity and accuracy. One potential application of the proposed ICG-encapsulated PLGA microbubbles is for the identification and characterization of peritumoral neovasculature for enhanced coregistration between tumor structural and functional boundaries in ultrasound-guided near-infrared diffuse optical tomography.

  19. 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. PMID:26743660

  20. 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.

  1. 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.

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

    PubMed

    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

    2014-12-01

    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.

  3. Cell tolerability and biodistribution in mice of indocyanine green-loaded lipid nanoparticles.

    PubMed

    Navarro, Fabrice P; Mittler, Frédérique; Berger, Michel; Josserand, Véronique; Gravier, Julien; Vinet, Françoise; Texier, Isabelle

    2012-08-01

    Considering toxicity requirements for clinical translation of fluorescence imaging applications, the use of biocompatible carriers for designing near infrared emitting contrast agents appears as an attractive alternative to semiconductor nanocrystals. Lipid nanoparticles (LNP) have been designed to serve as carriers for indocyanine green (ICG), the presently only human-use approved near infrared dye. The cytotoxicity and hemocompatibility of these nanoparticle-based probes are determined in vitro, respectively in mouse 3T3 fibroblasts and human blood samples. Comparative biodistribution of free ICG and ICG-LNP in mice is monitored, and an ex vivo fluorescence organ quantification is performed considering large animal cohorts. Good tolerability and very low hemolytic activity are demonstrated for naked and ICG-loaded LNP. Interestingly, ICG-LNP lead to long-term plasma fluorescence (> 24 hours) but also a partial intestinal reabsorption of ICG between 5 and 24 hours after injection. This novel ICG nanoformulation is foreseen to expand rapidly the field of clinical fluorescence imaging applications.

  4. Gadolinium-doped silica nanoparticles encapsulating indocyanine green for near infrared and magnetic resonance imaging.

    PubMed

    Sharma, Parvesh; Bengtsson, Niclas E; Walter, Glenn A; Sohn, Han-Byul; Zhou, Guangyin; Iwakuma, Nobutaka; Zeng, Huadong; Grobmyer, Stephen R; Scott, Edward W; Moudgil, Brij M

    2012-09-24

    Clinical applications of the indocyanine green (ICG) dye, the only near infrared (NIR) imaging dye approved by the Food and Drug Administration (FDA) in the USA, are limited due to rapid protein binding, fast clearance, and instability in physiologically relevant conditions. Encapsulating ICG in silica particles can enhance its photostability, minimize photobleaching, increase the signal-to-noise (S/N) ratio and enable in vivo studies. Furthermore, a combined magnetic resonance (MR) and NIR imaging particulate can integrate the advantage of high-resolution 3D anatomical imaging with high-sensitivity deep-tissue in-vivo fluorescent imaging. In this report, a novel synthesis technique that can achieve these goals is presented. A reverse-microemulsion-based synthesis protocol is employed to produce 25 nm ICG-doped silica nanoparticles (NPs). The encapsulation of ICG is achieved by manipulating coulombic attractions with bivalent ions and aminated silanes and carrying out silica synthesis in salt-catalyzed, mildly basic pH conditions using dioctyl sulfosuccinate (AOT)/heptane/water microemulsion system. Furthermore, paramagnetic properties are imparted by chelating paramagnetic Gd to the ICG-doped silica NPs. Aqueous ICG-dye-doped silica NPs show increased photostability (over a week) and minimal photobleaching as compared to the dye alone. The MR and optical imaging capabilities of these particles are demonstrated through phantom, in vitro and in vivo experiments. The described particles have the potential to act as theranostic agents by combining photodynamic therapy through the absorption of NIR irradiated light.

  5. Pilot Clinical Trial of Indocyanine Green Fluorescence-Augmented Colonoscopy in High Risk Patients.

    PubMed

    Sheth, Rahul A; Heidari, Pedram; Woods, Kevin; Chung, Daniel; Chan, Andrew T; Mahmood, Umar

    2016-01-01

    White light colonoscopy is the current gold standard for early detection and treatment of colorectal cancer, but emerging data suggest that this approach is inherently limited. Even the most experienced colonoscopists, under optimal conditions, miss at least 15-25% of adenomas. There is an unmet clinical need for an adjunctive modality to white light colonoscopy with improved lesion detection and characterization. Optical molecular imaging with exogenously administered organic fluorochromes is a burgeoning imaging modality poised to advance the capabilities of colonoscopy. In this proof-of-principle clinical trial, we investigated the ability of a custom-designed fluorescent colonoscope and indocyanine green, a clinically approved fluorescent blood pool imaging agent, to visualize polyps in high risk patients with polyposis syndromes or known distal colonic masses. We demonstrate (1) the successful performance of real-time, wide-field fluorescence endoscopy using off-the-shelf equipment, (2) the ability of this system to identify polyps as small as 1 mm, and (3) the potential for fluorescence imaging signal intensity to differentiate between neoplastic and benign polyps. PMID:26989406

  6. In vivo photoacoustic molecular imaging of breast carcinoma with folate receptor-targeted indocyanine green nanoprobes.

    PubMed

    Wang, Huina; Liu, Chengbo; Gong, Xiaojing; Hu, Dehong; Lin, Riqiang; Sheng, Zonghai; Zheng, Cuifang; Yan, Meng; Chen, Jingqin; Cai, Lintao; Song, Liang

    2014-11-01

    As an optical-acoustic hybrid imaging technology, photoacoustic imaging uniquely combines the advantages of rich optical contrast with high ultrasonic resolution in depth, opening up many new possibilities not attainable with conventional pure optical imaging technologies. To perform photoacoustic molecular imaging, optically absorbing exogenous contrast agents are needed to enhance the signals from specifically targeted disease activity. In this work, we designed and developed folate receptor targeted, indocyanine green dye doped poly(d,l-lactide-co-glycolide) lipid nanoparticles (FA-ICG-PLGA-lipid NPs) for molecular photoacoustic imaging of tumor. The fabricated FA-ICG-PLGA-lipid NPs exhibited good aqueous stability, a high folate-receptor targeting efficiency, and remarkable optical absorption in near-infrared wavelengths, providing excellent photoacoustic signals in vitro. Furthermore, after intravenous administration of FA-ICG-PLGA-lipid NPs, mice bearing MCF-7 breast carcinomas showed significantly enhanced photoacoustic signals in vivo in the tumor regions, compared with those using non-targeted ICG-PLGA-lipid NPs. Given the existing wide clinical use of ICG and PLGA, the developed FA-ICG-PLGA-lipid NPs, in conjunction with photoacoustic imaging technology, offer a great potential to be translated into the clinic for non-ionizing molecular imaging of breast cancer in vivo.

  7. In vivo photoacoustic molecular imaging of breast carcinoma with folate receptor-targeted indocyanine green nanoprobes

    NASA Astrophysics Data System (ADS)

    Wang, Huina; Liu, Chengbo; Gong, Xiaojing; Hu, Dehong; Lin, Riqiang; Sheng, Zonghai; Zheng, Cuifang; Yan, Meng; Chen, Jingqin; Cai, Lintao; Song, Liang

    2014-11-01

    As an optical-acoustic hybrid imaging technology, photoacoustic imaging uniquely combines the advantages of rich optical contrast with high ultrasonic resolution in depth, opening up many new possibilities not attainable with conventional pure optical imaging technologies. To perform photoacoustic molecular imaging, optically absorbing exogenous contrast agents are needed to enhance the signals from specifically targeted disease activity. In this work, we designed and developed folate receptor targeted, indocyanine green dye doped poly(d,l-lactide-co-glycolide) lipid nanoparticles (FA-ICG-PLGA-lipid NPs) for molecular photoacoustic imaging of tumor. The fabricated FA-ICG-PLGA-lipid NPs exhibited good aqueous stability, a high folate-receptor targeting efficiency, and remarkable optical absorption in near-infrared wavelengths, providing excellent photoacoustic signals in vitro. Furthermore, after intravenous administration of FA-ICG-PLGA-lipid NPs, mice bearing MCF-7 breast carcinomas showed significantly enhanced photoacoustic signals in vivo in the tumor regions, compared with those using non-targeted ICG-PLGA-lipid NPs. Given the existing wide clinical use of ICG and PLGA, the developed FA-ICG-PLGA-lipid NPs, in conjunction with photoacoustic imaging technology, offer a great potential to be translated into the clinic for non-ionizing molecular imaging of breast cancer in vivo.

  8. In vivo measurement of Indocyanine green biodistribution in mammalian organs using fiber based system

    NASA Astrophysics Data System (ADS)

    Chen, Qixiao; Mao, Shuo; Bai, Jing

    2009-11-01

    Indocyanine green (ICG) is a fluorescent probe widely used in recent years, and it is also the fluorescent dye that can be clinical used, in both imaging and treatment. So it is important to study its biodistribution and metabolism in mammalian organs, but the accuracy and sampling speed is limited by the traditional in-vitro methods. Now we present a design of an in-vivo multi-channel fluorescence intensity measurement system and an algorism of data processing, to achieve the accurate measurement of fluorescence intensity, continuous sampling, real time monitoring and curve fitting. This system design is based on customized fiber bundles and the principle of reflective fluorescence microscopy. We also present a mouse experiment using this system to study the Indocyanine green (ICG) biodistribution in small mammalian liver, in order to demonstrate the potential applications of this system and also present a new experiment method in the study of dye biodistribution and metabolism.

  9. [INDOCYANINE GREEN (ICG) IN THE DETECTION OF SENTINEL LYMPH NODES IN ENDOMETRIAL AND CERVIX CANCER].

    PubMed

    Berlev, I V; Ulrikh, E A; Ibragimov, Z N; Guseinov, K D; Gorodnova, T V; Korolkova, E N; Trifanov, Yu N; Nekrasova, E A; Saparov, A B; Khadzhimba, A V; Mikaya, N A; Urmancheeva, A F

    2015-01-01

    We analyzed the international and our own experience of using different dyes in the identification of sentinel lymph nodes in oncogynecological practice. We evaluated the possibility of using indocyanine green (ICG) in the detection of sentinel lymph nodes in patients with endometrial and cervical cancer. The first results of the use of ICG at the Oncogynecology Department of the N.N.Petrov Research Institute of Oncology are presented.

  10. 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

    2016-03-01

    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

  11. A novel indocyanine green nanoparticle probe for non invasive fluorescence imaging in vivo

    NASA Astrophysics Data System (ADS)

    Navarro, Fabrice P.; Berger, Michel; Goutayer, Mathieu; Guillermet, Stéphanie; Josserand, Véronique; Rizo, Philippe; Vinet, Françoise; Texier, Isabelle

    2009-02-01

    Fluorescence imaging (FLI) allows the in vivo monitoring of biological events associated with disease and represents a new promising tool for drug discovery. In particular, it speeds up the development and assessment of new therapies in oncology, helps in diagnosis, and improves surgery by fluorescence-guided tumor resection. This technique is highly sensitive, non-ionizing, easy to use and relatively inexpensive. Nevertheless, the main limitation of FLI lies in the optical properties of biological tissues. Mainly because of haemoglobin and water absorption, only near-infrared (NIR) light is adapted to image tissues in depth. Using a contrasting agent absorbing and emitting in the NIR region is therefore necessary to improve the background signal ratio, and thus the image contrast. Among many commercially available NIR optical contrast agents, only indocyanine green (ICG), has been approved by the United State Food and Drug Administration (FDA) for various medical applications. However, its instability (photo-degradation, thermal-degradation and low aqueous solubility) limits its applications as a fluorescent probe for imaging purposes. In order to improve the effectiveness of ICG, we engineered ICG-doped lipid nanoparticles (LNP). In this communication, we will report the design of these novel fluorescent nanoparticle probes. These low cost nanocarriers have numerous advantages, including their high chemical stability and biocompatibility. The characterization of the optical properties of the nanoparticles entrapping ICG will also be discussed. Finally, the biodistribution in mice of ICG when delivered through nanoparticles in comparison to free ICG in solution is presented. It demonstrates the efficient accumulation of ICG-doped nanoparticles in the tumor site.

  12. The effect of mannosylation of liposome-encapsulated indocyanine green on imaging of sentinel lymph node.

    PubMed

    Jeong, Hwan-Seok; Lee, Chang-Moon; Cheong, Su-Jin; Kim, Eun-Mi; Hwang, Hyosook; Na, Kyung Sook; Lim, Seok Tae; Sohn, Myung-Hee; Jeong, Hwan-Jeong

    2013-12-01

    The imaging of sentinel lymph nodes (SLN) has been researched for its role in assessing cancer progression and postsurgical lymphedema. Indocyanine green (ICG) is a near-infrared (NIR) optical dye that has been approved by the Food and Drug Administration. It is known that liposome-encapsulated ICG (LP-ICG) has improved stability and fluorescence signal compared with ICG. We designed mannosylated liposome-encapsulated ICG (M-LP-ICG) as an optical contrast agent for SLN. M-LP-ICG has a higher UV absorbance spectrum and fluorescence intensity than LP-ICG. The stability of M-LP-ICG measured in 50% fetal bovine serum solution by a dialysis method was better than that of LP-ICG. M-LP-ICG demonstrated a high uptake in RAW 264.7 macrophage cell because the density of mannose is high. There were differences between M-LP-ICG and glucosylated liposome-encapsulated ICG (G-LP-ICG), which are geometrical isomers. The result of an inhibition study of M-LP-ICG showed a statistically significant decrease in uptake in RAW 264.7 cells after either co-treatment or pre-treatment with D-(+)-mannose as an inhibitor. Results from an in vitro experiment demonstrated that M-LP-ICG was specifically taken up by macrophage cells through the mannose receptor on its surface. The time-series images acquired from a normal mouse model after subcutaneous injection showed that the signal from M-LP-ICG in SLN and other organs appeared early and disappeared quickly in comparison with signals from LP-ICG. Not only the sentinel but also the draining lymph nodes were observed partly in M-LP-ICG. M-LP-ICG appears to increase the specificity of uptake and retention in macrophages, making it a good candidate contrast agent for an optic imaging system for SLN and the lymphatic system.

  13. Indocyanine green enhanced co-registered diffuse optical tomography and photoacoustic tomography

    NASA Astrophysics Data System (ADS)

    Xu, Chen; Kumavor, Patrick D.; Alqasemi, Umar; Li, Hai; Xu, Yan; Zanganeh, Saeid; Zhu, Quing

    2013-12-01

    To overcome the intensive light scattering in biological tissue, diffuse optical tomography (DOT) in the near-infrared range for breast lesion detection is usually combined with other imaging modalities, such as ultrasound, x-ray, and magnetic resonance imaging, to provide guidance. However, these guiding imaging modalities may depend on different contrast mechanisms compared to the optical contrast in the DOT. As a result, they cannot provide reliable guidance for DOT because some lesions may not be detectable by a nonoptical modality but may have a high optical contrast. An imaging modality that relies on optical contrast to provide guidance is desirable for DOT. We present a system that combines a frequency-domain DOT and real-time photoacoustic tomography (PAT) systems to detect and characterize deeply seated targets embedded in a turbid medium. To further improve the contrast, the exogenous contrast agent, indocyanine green (ICG), is used. Our experimental results show that the combined system can detect a tumor-mimicking phantom, which is immersed in intralipid solution with the concentrations ranging from 100 to 10 μM and with the dimensions of 0.8 cm×0.8 cm×0.6 cm, up to 2.5 cm in depth. Mice experiments also confirmed that the combined system can detect tumors and monitor the ICG uptake and washout in the tumor region. This method can potentially improve the accuracy to detect small breast lesions as well as lesions that are sensitive to background tissue changes, such as the lesions located just above the chest wall.

  14. Indocyanine green enhanced co-registered diffuse optical tomography and photoacoustic tomography.

    PubMed

    Xu, Chen; Kumavor, Patrick D; Alqasemi, Umar; Li, Hai; Xu, Yan; Zanganeh, Saeid; Zhu, Quing

    2013-12-01

    To overcome the intensive light scattering in biological tissue, diffuse optical tomography (DOT) in the near-infrared range for breast lesion detection is usually combined with other imaging modalities, such as ultrasound, x-ray, and magnetic resonance imaging, to provide guidance. However, these guiding imaging modalities may depend on different contrast mechanisms compared to the optical contrast in the DOT. As a result, they cannot provide reliable guidance for DOT because some lesions may not be detectable by a nonoptical modality but may have a high optical contrast. An imaging modality that relies on optical contrast to provide guidance is desirable for DOT. We present a system that combines a frequency-domain DOT and real-time photoacoustic tomography (PAT) systems to detect and characterize deeply seated targets embedded in a turbid medium. To further improve the contrast, the exogenous contrast agent, indocyanine green (ICG), is used. Our experimental results show that the combined system can detect a tumor-mimicking phantom, which is immersed in intralipid solution with the concentrations ranging from 100 to 10 μM and with the dimensions of 0.8 cm × 0.8 cm × 0.6 cm, up to 2.5 cm in depth. Mice experiments also confirmed that the combined system can detect tumors and monitor the ICG uptake and washout in the tumor region. This method can potentially improve the accuracy to detect small breast lesions as well as lesions that are sensitive to background tissue changes, such as the lesions located just above the chest wall.

  15. 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.

  16. 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. PMID:27006261

  17. [Intraoperative verification of a perforator flap vascularization by indocyanine green angiography].

    PubMed

    Royer, E; Rausky, J; Binder, J-P; May, P; Virzi, D; Revol, M

    2014-02-01

    After Koshima and Soeda first described perforator flaps in 1988, Wei has improved the technique by describing the "free style perforator flap". These flaps have the advantage of being performed on all skin perforators and in reducing donor site morbidity. The disadvantage, however is that the size of their angiosome is not defined and the evaluation of their relay on the experience of the surgeon. An evaluation of the size of an angiosome by conducting intraoperative angiography is proposed. Intraoperative angiography is performed after injection of indocyanine green. Stimulation of the indocyanine green by infrared causes the emission of fluorescent radiation. This fluorescence is then detected by a specific camera that displays real-time visualization of the skin's perfusion. We present the case of a 39-year-old patient who had an open tibial pilon fracture, for which we performed a pedicled propeller flap based on a posterior tibial perforator. Angiography was used to determine accurately the optimal skin perfusion of the propeller flap, which was based on a perforator from the posterior tibial artery. Angiography identified several levels of skin perfusion with a high fluorescence, intermediate and absent. The non-vascularized part of the skin paddle was resected. Given the unreliability of this technique, hypoperfused area was retained. Debridment of this area, however was necessary at day 5 postoperative with repositionning of the flap. Indocyanine green angiography may be a useful decision-making tool for intraoperative surgeon. It allows to adjust the size of the propeller flap's skin paddle to it angiosome. However, this evaluation method needs to be improved with the introduction of a quantitative threshold.

  18. In vivo investigation of interaction of indocyanine green solutions with human epidermis

    NASA Astrophysics Data System (ADS)

    Kulyabina, Tatyana V.; Kochubey, Vyacheslav I.

    2004-08-01

    The main mechanism of penetration of the indocyanine green dye (ICG) (1) in upper human skin layers was determined for ICG water, ethanol and glycerol solutions. Some experiments with/without clearance of protection skin fat coat were carried out. We stained hand skin then we did several series of epidermis detachments by scotch. The spectra of stained skin were recorded by standard CARY-2415 spectrophotometer with an integrating sphere. The conclusion about the main mechanism of penetration of the ICG in human epidermis has been drown by analyze of the experiment results.

  19. Control of optical transmittance of fat tissue slices at NIR photodynamic action mediated by indocyanine green

    NASA Astrophysics Data System (ADS)

    Yanina, I. Y.; Doubrovsky, V. A.; Tuchin, V. V.

    2013-02-01

    The changes in optical transmittance of human adipose cell layers sensitized by indocyanine green (ICG) as a result of photodynamic action were found and studied. It was revealed experimentally that due to the selective action of laser radiation on fat tissue sensitized by ICG the spatial distribution of its optical transmittance becomes more homogeneous. The statistical computer processing of digital images allowed one to estimate tissue optical transmittance, its spatial and temporal distributions. These quantitative estimations correlated well with the visible changes of tissue images. The measurements carried out gave an opportunity to suggest the interpretation of the phenomenon observed.

  20. Laparoscopic Indocyanine Green Sentinel Lymph Node Mapping in Pregnant Cervical Cancer Patients.

    PubMed

    Papadia, Andrea; Mohr, Stefan; Imboden, Sara; Lanz, Susanne; Bolla, Daniele; Mueller, Michael D

    2016-02-01

    We present cases of 2 pregnant patients with early-stage cervical cancer who have undergone indocyanine green (ICG) sentinel lymph node (SLN) mapping followed by laparoscopic SLN biopsy, pelvic lymphadenectomy, and cervical conization. Eight milliliters of ICG were injected in the 4 quadrants of the cervix after having obtained an adequate pneumoperitoneum and having inspected the abdominal cavity. SLNs were identified in both hemipelvises in both patients. In the final pathologic analysis, both SLNs and non-SLNs were negative for metastatic disease. No adverse events from ICG injection were recorded. ICG SLN mapping seems to be feasible in pregnant cervical cancer patients.

  1. Liposomally formulated phospholipid-conjugated indocyanine green for intra-operative brain tumor detection and resection.

    PubMed

    Suganami, Akiko; Iwadate, Yasuo; Shibata, Sayaka; Yamashita, Masamichi; Tanaka, Tsutomu; Shinozaki, Natsuki; Aoki, Ichio; Saeki, Naokatsu; Shirasawa, Hiroshi; Okamoto, Yoshiharu; Tamura, Yutaka

    2015-12-30

    Some tumor-specific near-infrared (NIR) fluorescent dyes such as indocyanine green (ICG), IDRye800CW, and 5-aminolevulinic acid have been used clinically for detecting tumor margins or micro-cancer lesions. In this study, we evaluated the physicochemical properties of liposomally formulated phospholipid-conjugated ICG, denoted by LP-iDOPE, as a clinically translatable NIR imaging nanoparticle for brain tumors. We also confirmed its brain-tumor-specific biodistribution and its characteristics as the intra-operative NIR imaging nanoparticles for brain tumor surgery. These properties of LP-iDOPE may enable neurosurgeons to achieve more accurate identification and more complete resection of brain tumor.

  2. Combined Epiretinal and Internal Limiting Membrane Peeling Facilitated by High Dilution Indocyanine Green Negative Staining

    PubMed Central

    Kaehr, Mark M.; Apte, Rajendra S.

    2015-01-01

    We describe the utilization of indocyanine green (ICG) dye to facilitate combined/en bloc removal of epiretinal membranes (ERM) along with internal limiting membranes (ILM). The method utilizes a highly diluted preparation of ICG in dextrose water solvent (D5W). Elimination of fluid air exchange step facilitating staining in the fluid phase and low intensity lighting help minimize potential ICG toxicity. The technique demonstrates how ICG facilitates negative staining of ERMs and how ILM peeling concomitantly can allow complete and efficient ERM removal minimizing surgical time and the necessity for dual or sequential staining. PMID:27051499

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

    SciTech Connect

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

    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 of laser illumination ({lambda} = 808 nm) of bacteria, treated with conjugates of indocyanine green and nanocages. (optical technologies in biophysics and medicine)

  4. Indocyanine Green Near-Infrared Laser Angiography Predicts Timing for the Division of a Forehead Flap

    PubMed Central

    Christensen, Joani M.; Baumann, Donald P.; Myers, Jeffrey N.; Buretta, Kate; Sacks, Justin M.

    2012-01-01

    Introduction: Reconstruction with flaps requiring delayed division remains common, even with increasing use of free tissue transfer. Patient quality of life and function are significantly decreased during the delay period. Delay could be minimized by developing methods to reliably determine when the flap has developed sufficient vascular supply to undergo successful division. We report the use of laser angiography to determine the appropriate time for division of a forehead flap pedicle. Methods: The patient who had risk factors for microvascular disease underwent near-infrared laser angiography using indocyanine green on postoperative day 21 to assess vascular perfusion of the flap. Although traditional clinical examination indicated the flap was not adequately perfused, laser angiography revealed perfusion to all areas of the flap, so the pedicle was divided. Results: Pedicle division was successful, with no epidermolysis or necrosis. Conclusion: Near-infrared laser angiography with indocyanine green can assess perfusion status of the entire flap and inform the decision to divide the flap in an objective manner. PMID:22977676

  5. 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.

  6. 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.

  7. Indocyanine green encapsulated nanogels for hyaluronidase activatable and selective near infrared imaging of tumors and lymph nodes.

    PubMed

    Mok, Hyejung; Jeong, Hyunkyung; Kim, Sun-Jung; Chung, Bong Hyun

    2012-09-01

    Indocyanine green (ICG) encapsulated hyaluronic acid (HA) nanogels were first studied for highly selective detection of specific cancers and lymph nodes via hyaluronidase sensitive switch-on of near infrared fluorescence as a long-lasting and stimuli-responsive imaging probe.

  8. Multifunctionality of indocyanine green-loaded biodegradable nanoparticles for enhanced optical imaging and hyperthermia intervention of cancer.

    PubMed

    Patel, Ronak H; Wadajkar, Aniket S; Patel, Nimit L; Kavuri, Venkaiah C; Nguyen, Kytai T; Liu, Hanli

    2012-04-01

    The aim of this study was to develop and characterize multifunctional biodegradable and biocompatible poly lactic-co-glycolic acid (PLGA) nanoparticles loaded with indocyanine green (ICG) as an optical-imaging contrast agent for cancer imaging and as a photothermal therapy agent for cancer treatment. PLGA-ICG nanoparticles (PIN) were synthesized with a particle diameter of 246±11 nm, a polydispersity index of 0.10±0.03, and ICG loading efficiency of 48.75±5.48%. PIN were optically characterized with peak excitation and emission at 765 and 810±5 nm, a fluorescence lifetime of 0.30±0.01 ns, and peak absorbance at 780 nm. The cytocompatibility study of PIN showed 85% cell viability till 1-mg/ml concentration of PIN. Successful cellular uptake of ligand conjugated PIN by prostate cancer cells (PC3) was also obtained. Both phantom-based and in vitro cell culture results demonstrated that PIN (1) have the great potential to induce local hyperthermia (i.e., temperature increase of 8 to 10°C) in tissue within 5 mm both in radius and in depth; (2) result in improved optical stability, excellent biocompatibility with healthy cells, and a great targeting capability; (3) have the ability to serve as an image contrast agent for deep-tissue imaging in diffuse optical tomography.

  9. Multifunctionality of indocyanine green-loaded biodegradable nanoparticles for enhanced optical imaging and hyperthermia intervention of cancer

    NASA Astrophysics Data System (ADS)

    Patel, Ronak H.; Wadajkar, Aniket S.; Patel, Nimit L.; Kavuri, Venkaiah C.; Nguyen, Kytai T.; Liu, Hanli

    2012-04-01

    The aim of this study was to develop and characterize multifunctional biodegradable and biocompatible poly lactic-co-glycolic acid (PLGA) nanoparticles loaded with indocyanine green (ICG) as an optical-imaging contrast agent for cancer imaging and as a photothermal therapy agent for cancer treatment. PLGA-ICG nanoparticles (PIN) were synthesized with a particle diameter of 246+/-11 nm, a polydispersity index of 0.10+/-0.03, and ICG loading efficiency of 48.75+/-5.48%. PIN were optically characterized with peak excitation and emission at 765 and 810+/- 5 nm, a fluorescence lifetime of 0.30+/-0.01 ns, and peak absorbance at 780 nm. The cytocompatibility study of PIN showed 85% cell viability till 1-mg/ml concentration of PIN. Successful cellular uptake of ligand conjugated PIN by prostate cancer cells (PC3) was also obtained. Both phantom-based and in vitro cell culture results demonstrated that PIN (1) have the great potential to induce local hyperthermia (i.e., temperature increase of 8 to 10°C) in tissue within 5 mm both in radius and in depth; (2) result in improved optical stability, excellent biocompatibility with healthy cells, and a great targeting capability; (3) have the ability to serve as an image contrast agent for deep-tissue imaging in diffuse optical tomography.

  10. Near infrared dye indocyanine green doped silica nanoparticles for biological imaging.

    PubMed

    Quan, Bo; Choi, Kihwan; Kim, Young-Hwa; Kang, Keon Wook; Chung, Doo Soo

    2012-09-15

    Indocyanine green (ICG) is an FDA-approved near infrared (NIR) fluorescent dye used in clinical imaging. However, its applications remain limited due to its short half-life, nonspecific plasma binding, optical instability, and poor aqueous stability. Dye doped silica nanoparticles provide an effective barrier in keeping the dye away from the surrounding environment, but ICG cannot be encapsulated into silica easily by conventional methods. In this study, ICG molecules ion-paired with a cationic polymer polyethylenimine (PEI) were successfully encapsulated into a silica matrix to form ICG doped silica nanoparticles by using the Stöber method. Pairing with PEI reduced self-quenching of fluorescence by preventing the aggregation of ICG molecules in silica nanoparticles. Dye leakage was also reduced to the level of 3-6% loss in 5 days. NIR fluorescence images of ICG doped silica NPs below a 2.0 cm thick porcine muscle sample illuminated by NIR light were obtained.

  11. Retention of indocyanine green as a potential marker for optical detection of blood brain barrier disruption

    NASA Astrophysics Data System (ADS)

    Ergin, A.; Joshi, S.; Wang, M.; Bigio, I. J.

    2011-03-01

    Preliminary studies have shown that there is great variability in the degree of disruption of blood-brain barrier (BBBD) after the intraarterial injection of mannitol in rabbit models. The disruption of blood-brain barrier (BBB) is affected by a number of factors, and the variations could have a profound impact on regional delivery of chemotherapeutics. Optically measured brain tissue concentrations of indocyanine green (ICG) and Evan's blue (EB) enable the quantification of BBBD after intraarterial administration of mannitol. Using the optical pharmacokinetics technique, a variation of diffuse reflectance spectroscopy, we are able to track in vivo brain tissue concentrations of ICG and EB in rabbits, before and after barrier disruption. This study shows the feasibility of optical monitoring of BBBD, a method that can help improve intraarterial delivery of chemotherapeutic drugs.

  12. Preparation and characterization of phospholipid-conjugated indocyanine green as a near-infrared probe.

    PubMed

    Suganami, Akiko; Toyota, Taro; Okazaki, Shigetoshi; Saito, Kengo; Miyamoto, Katsuhiko; Akutsu, Yasunori; Kawahira, Hiroshi; Aoki, Akira; Muraki, Yutaka; Madono, Tomoyuki; Hayashi, Hideki; Matsubara, Hisahiro; Omatsu, Takashige; Shirasawa, Hiroshi; Tamura, Yutaka

    2012-12-15

    We have rationally designed and synthesized a novel near-infrared (NIR) photoactivating probe, designated by iDOPE, in which an indocyanine green (ICG) fluorophore is covalently conjugated with a phospholipid moiety, 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE), to incorporate into liposome bilayers. NIR irradiation showed that iDOPE retained the optical and fluorescence properties of ICG and demonstrated photoactivator characteristics: fluorescence emission at around 820 nm in a solvent, singlet oxygen production, and concentration-dependent heat generation. Additionally, iDOPE was incorporated into liposome bilayers and maintained stable liposomally formulated iDOPE (LP-iDOPE) over 1week under physiological conditions. We also observed the tumor-specific biodistribution of LP-iDOPE of in vivo xenografts. These findings suggest that LP-iDOPE might be a promising tool for NIR optical imaging, photodynamic therapy, and photothermal therapy.

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

    PubMed

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

    2015-06-01

    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.

  14. [Video-assisted Thoracoscopic Segmentectomy Using Infrared Thoracoscopy with Indocyanine Green].

    PubMed

    Tarumi, Shintaro; Yokomise, Hiroyasu

    2016-07-01

    The maintenance of a good surgical view is mandatory in video-assisted thoracoscopic surgery (VATS). For routine segmentectomy, it is necessary to re-inflate the lung in order to identify the intersegmental borders. However, such re-inflation can occasionally obstruct the surgical view and can lead to prolongation of operation time, particularly in the context of VATS. Infrared thoracoscopy( IRT) with indocyanine green (ICG) is a new method of evaluating lung perfusion. There are 2 methods in IRT. One is based on ICG absorption, and the other is based on ICG fluorescence. In our experience, both of them were useful for identification of segmental borders. However, the former method was superior for the clarity of images. No complications attributable to IRT with ICG were observed. IRT with ICG is based on blood flow rather than on ventilation and can thus achieve anatomical segmentectomy without lung re-inflation. This method will be especially useful for VATS segmentectomy. PMID:27440031

  15. In Vivo Photoacoustic and Fluorescence Cystography Using Clinically Relevant Dual Modal Indocyanine Green

    PubMed Central

    Park, Sungjo; Kim, Jeesu; Jeon, Mansik; Song, Jaewon; Kim, Chulhong

    2014-01-01

    Conventional X-ray-based cystography uses radio-opaque materials, but this method uses harmful ionizing radiation and is not sensitive. In this study, we demonstrate nonionizing and noninvasive photoacoustic (PA) and fluorescence (FL) cystography using clinically relevant indocyanine green (ICG) in vivo. After transurethral injection of ICG into rats through a catheter, their bladders were photoacoustically and fluorescently visualized. A deeply positioned bladder below the skin surface (i.e., ∼1.5–5 mm) was clearly visible in the PA and FL image using a laser pulse energy of less than 2 mJ/cm2 (1/15 of the safety limit). Then, the in vivo imaging results were validated through in situ studies. Our results suggest that dual modal cystography can provide a nonionizing and noninvasive imaging tool for bladder mapping. PMID:25337743

  16. 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

  17. Segmental analysis of indocyanine green pharmacokinetics for the reliable diagnosis of functional vascular insufficiency

    NASA Astrophysics Data System (ADS)

    Kang, Yujung; Lee, Jungsul; An, Yuri; Jeon, Jongwook; Choi, Chulhee

    2011-03-01

    Accurate and reliable diagnosis of functional insufficiency of peripheral vasculature is essential since Raynaud phenomenon (RP), most common form of peripheral vascular insufficiency, is commonly associated with systemic vascular disorders. We have previously demonstrated that dynamic imaging of near-infrared fluorophore indocyanine green (ICG) can be a noninvasive and sensitive tool to measure tissue perfusion. In the present study, we demonstrated that combined analysis of multiple parameters, especially onset time and modified Tmax which means the time from onset of ICG fluorescence to Tmax, can be used as a reliable diagnostic tool for RP. To validate the method, we performed the conventional thermographic analysis combined with cold challenge and rewarming along with ICG dynamic imaging and segmental analysis. A case-control analysis demonstrated that segmental pattern of ICG dynamics in both hands was significantly different between normal and RP case, suggesting the possibility of clinical application of this novel method for the convenient and reliable diagnosis of RP.

  18. 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.

  19. 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

  20. 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.

  1. Near infrared fluorescence-guided real-time endoscopic detection of peritoneal ovarian cancer nodules using intravenously injected indocyanine green.

    PubMed

    Kosaka, Nobuyuki; Mitsunaga, Makoto; Longmire, Michelle R; Choyke, Peter L; Kobayashi, Hisataka

    2011-10-01

    Near infrared fluorescence-guidance can be used for the detection of small cancer metastases and can aid in the endoscopic management of cancer. Indocyanine green (ICG) is a Food and Drug Administration (FDA)-approved fluorescence agent. Through non-specific interactions with serum proteins, ICG achieves enhanced permeability and retention (EPR) effects. Yet, ICG demonstrates rapid clearance from the circulation. Therefore, ICG may be an ideal contrast agent for real-time fluorescence imaging of tumors. To evaluate the usefulness of real-time dual fluorescence and white light endoscopic optical imaging to detect tumor implants using the contrast agent ICG, fluorescence-guided laparoscopic procedures were performed in mouse models of peritoneally disseminated ovarian cancers. Animals were administered intravenous ICG or a control contrast agent, IR800-conjugated to albumin. The ability to detect small ovarian cancer implants was then compared. Using the dual view microendoscope, ICG clearly enabled visualization of peritoneal ovarian cancer metastatic nodules derived from SHIN3 and OVCAR5 cells at 6 and 24 hr after injection with significantly higher tumor-to-background ratio than the control agent, IR800-albumin (p < 0.001). In conclusion, ICG has the desirable properties of having both EPR effects and rapid clearance for the real-time endoscopic detection of tiny ovarian cancer peritoneal implants compared to a control macromolecular agent with theoretically better EPR effects but longer circulatory retention. Given that ICG is already FDA-approved and has a long track record of human use, this method could be easily translated to the clinic as a robust tool for fluorescence-guided endoscopic procedures for the management and treatment of cancer.

  2. 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.

  3. 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.

  4. Indocyanine green loaded SPIO nanoparticles with phospholipid-PEG coating for dual-modal imaging and photothermal therapy.

    PubMed

    Ma, Yan; Tong, Sheng; Bao, Gang; Gao, Chuang; Dai, Zhifei

    2013-10-01

    A biodegradable nanotheranostic agent has been successfully constructed for fluorescence/magnetic resonance dual-modal imaging guided photothermal therapy by loading indocyanine green (ICG) molecules into 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy (polyethylene glycol)] (DSPE-PEG) coated superparamagnetic iron oxide (SPIO) nanoparticles (NPs). It was proved that the obtained SPIO@DSPE-PEG/ICG NPs with an average diameter around 27.4 nm could serve as an efficient probe to simultaneously enhance fluorescence imaging and magnetic resonance imaging greatly in vivo. After tail vein injection, the SPIO@DSPE-PEG/ICG NPs were found selectively accumulate at the tumor site. Encapsulation of ICG into the lipid coating of SPIO NPs results in higher photostability than free ICG due to the protection from degradation. SPIO@DSPE-PEG/ICG NPs exhibited significant photothermal cytotoxicity. Cancer cells could be killed in vitro and tumors could be ablated in vivo efficiently through photothermal effects of SPIO@DSPE-PEG/ICG NPs under laser irradiation. In summary, SPIO@DSPE-PEG/ICG NPs integrate multiple capabilities for effective tumor imaging and therapy. This is very helpful for accurately interpreting the obtained images, identifying the size and location of the tumor, as well as guiding and monitoring the photothermal therapy through a single agent.

  5. Dual-Modal Imaging-Guided Theranostic Nanocarriers Based on Indocyanine Green and mTOR Inhibitor Rapamycin.

    PubMed

    Pang, Xiaojuan; Wang, Jinping; Tan, Xiaoxiao; Guo, Fang; Lei, Mingzhu; Ma, Man; Yu, Meng; Tan, Fengping; Li, Nan

    2016-06-01

    The development of treatment protocols that resulted in a complete response to photothermal therapy (PTT) was usually hampered by uneven heat distribution and low effectiveness. Here, we reported an NIR fluorescence and photoacoustic dual-modal imaging-guided active targeted thermal sensitive liposomes (TSLs) based on the photothermal therapy agent Indocyanine green (ICG) and antiangiogenesis agent Rapamycin (RAPA) to realize enhanced therapeutic and diagnostic functions. As expected, the in vitro drug release studies exhibited the satisfactory result of drug released from the TSLs under hyperthermia conditions induced by NIR stimulation. The in vitro cellular studies confirmed that the FA-ICG/RAPA-TSLs plus NIR laser exhibited efficient drug accumulation and cytotoxicity in tumor cells and epithelial cells. After 24 h intravenous injection of FA-ICG/RAPA-TSLs, the margins of tumor and normal tissue were accurately identified via the in vivo NIR fluorescence and photoacoustic dual-modal imaging. In addition, FA-ICG/RAPA-TSLs combined with NIR irradiation treated tumor-bearing nude mice inhibited tumor growth to a great extent and possessed much lower side effects to normal organs. All detailed evidence suggested that the theranostic TSLs which were capable of enhancing the therapeutic index might be a suitable drug delivery system for dual-modal imaging-guided therapeutic tools for diagnostics as well as the treatment of tumors.

  6. Dynamic imaging of PEGylated indocyanine green (ICG) liposomes within the tumor microenvironment using multi-spectral optoacoustic tomography (MSOT).

    PubMed

    Beziere, Nicolas; Lozano, Neus; Nunes, Antonio; Salichs, Juan; Queiros, Daniel; Kostarelos, Kostas; Ntziachristos, Vasilis

    2015-01-01

    Multispectral optoacoustic tomography (MSOT) is a powerful modality that allows high-resolution imaging of photo-absorbers deep within tissue, beyond the classical depth and resolution limitations of conventional optical imaging. Imaging of intrinsic tissue contrast can be complemented by extrinsically administered gold nanoparticles or fluorescent molecular probes. Instead, we investigated herein generation of re-engineered clinically-used PEGylated liposomes incorporating indocyanine green (LipoICG) as a contrast strategy that combines materials already approved for clinical use, with strong photo-absorbing signal generation available today only from some metallic nanoparticles (e.g. gold nanorods). Using MSOT we confirmed LipoICG as a highly potent optoacoustic agent and resolved tissue accumulation in tumor-bearing animals over time with high-sensitivity and resolution using two tumor models of different vascularisation. We further showcase a paradigm shift in pharmacology studies and nanoparticle investigation, by enabling detailed volumetric optical imaging in vivo through the entire tumor tissue non-invasively, elucidating never before seen spatiotemporal features of optical agent distribution. These results point to LipoICG as a particle with significant advantageous characteristics over gold nanoparticles and organic dyes.

  7. 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.

  8. Short PEG-linkers improve the performance of targeted, activatable monoclonal antibody-indocyanine green optical imaging probes.

    PubMed

    Sano, Kohei; Nakajima, Takahito; Miyazaki, Kiminori; Ohuchi, Yuya; Ikegami, Takashi; Choyke, Peter L; Kobayashi, Hisataka

    2013-05-15

    The ability to switch optical imaging probes from the quenched (off) to the active state (on) has greatly improved target to background ratios. The optimal activation efficiency of an optical probe depends on complete quenching before activation and complete dequenching after activation. For instance, monoclonal antibody-indocyanine green (mAb-ICG) conjugates, which are promising agents for clinical translation, are normally quenched, but can be activated when bound to a cell surface receptor and internalized. However, the small fraction of commonly used ICG derivative (ICG-Sulfo-OSu) can bind noncovalently to its mAb and is, thus, gradually released from the mAb leading to relatively high background signal especially in the liver and the abdomen. In this study, we re-engineered a mAb-ICG conjugate, (Panitumumab-ICG) using bifunctional ICG derivatives (ICG-PEG4-Sulfo-OSu and ICG-PEG8-Sulfo-OSu) with short polyethylene glycol (PEG) linkers. Higher covalent binding (70-86%) was observed using the bifunctional ICG with short PEG linkers resulting in less in vivo noncovalent dissociation. Panitumumab-ICG conjugates with short PEG linkers were able to detect human epidermal growth factor receptor 1 (EGFR)-positive tumors with high tumor-to-background ratios (15.8 and 6.9 for EGFR positive tumor-to-negative tumor and tumor-to-liver ratios, respectively, at 3 d postinjection).

  9. Enhanced photo-stability, thermal-stability and aqueous-stability of indocyanine green in polymeric nanoparticulate systems.

    PubMed

    Saxena, Vishal; Sadoqi, Mostafa; Shao, Jun

    2004-03-19

    Photo-degradation, thermal-degradation and aqueous-instability of indocyanine green (ICG) limits its application as a fluorescence contrast agent for imaging purposes. Thus, the objective of this study is to develop polymeric nanoparticles entrapping ICG and to establish its effectiveness in providing photo-stability, thermal stability and aqueous stability to ICG. Nanoparticles entrapping ICG were engineered, characterized and the degradation kinetics of ICG in the nanoparticles was investigated in aqueous media. The entrapment of ICG in the nanoparticles causes a shift in its wavelength of peak fluorescence and a decrease in its peak fluorescence intensity. The degradation of ICG in aqueous nanoparticle suspension followed first-order kinetics for the time period studied. ICG entrapment in the nanoparticles enhanced aqueous-stability of ICG (half-life, t(1/2) was 72.2+/-6.1 h for ICG in the nanoparticles as compared to 16.8+/-1.5 h for free ICG solution), photo-stability of ICG (t(1/2) was 73.7+/-7.5 h for ICG in the nanoparticles as compared to 14.4+/-2.4 h for free ICG solution when exposed to room light from two 32 W normal fluorescent tubes) and thermal-stability of ICG (t(1/2) of ICG at 42 degrees C was 62.4+/-1.7 h for ICG in the nanoparticles as compared to 10.1+/-0.6 h for free ICG solution).

  10. 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.

  11. 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

    2016-01-01

    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. PMID:26861313

  12. 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.

  13. Indocyanine Green Fluorescence Imaging in the Surgical Management of an Iatrogenic Lymphatic Fistula: Description of a Surgical Technique.

    PubMed

    Papadia, Andrea; Imboden, Sara; Mohr, Stefan; Lanz, Susanne; Nirgianakis, Konstantinos; Mueller, Michael D

    2015-01-01

    We present a case of laparoscopic surgical management of an iatrogenic lymphorrhea using indocyanine green (ICG). A case of a patient who developed recurrent symptomatic lymphorrhea after laparoscopic radical hysterectomy and bilateral pelvic lymphadenectomy for an early stage cervical cancer is presented. Intraoperative bipedal interdigital subcutaneous injection of ICG exactly localized the disrupted lymphatic duct on fluorescence imaging performed with a near-infrared laparoscopic fluorescent optic device, thus allowing a successful surgical repair.

  14. Mesoporous silica-coated gold nanorods with embedded indocyanine green for dual mode X-ray CT and NIR fluorescence imaging.

    PubMed

    Luo, Teng; Huang, Peng; Gao, Guo; Shen, Guangxia; Fu, Shen; Cui, Daxiang; Zhou, Chuanqing; Ren, Qiushi

    2011-08-29

    Indocyanine green-loaded mesoporous silica-coated gold nanorods (ICG-loaded Au@SiO2) were prepared for the dual capability of X-ray computed tomography (CT) and fluorescence imaging. X-ray CT scanning showed that ICG-loaded Au@SiO2 could provide significant contrast enhancement; Near-infrared fluorescence generated by the nanomaterial was present up to 12 h post intratumoral injection, thus enabling ICG-loaded Au@SiO2 to be used as a promising dual mode imaging contrast agent. Multiplexed images can be more easily obtained with this novel type of multimodal nanostructure compared with traditional contrast agents. The dual mode imaging probe has great potential for use in applications such as cancer targeting, molecular imaging in combination with radiotherapy, and photothermolysis.

  15. 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

  16. An Activatable Theranostic Nanomedicine Platform Based on Self-Quenchable Indocyanine Green-Encapsulated Polymeric Micelles.

    PubMed

    Liu, Lanxia; Ma, Guilei; Zhang, Chao; Wang, Hai; Sun, Hongfan; Wang, Chun; Song, Cunxian; Kong, Deling

    2016-06-01

    Self-quenchable indocyanine green (ICG)-encapsulated micelles with folic acid (FA)-targeting specificity (FA-ICG-micelles) were developed for biologically activatable photodynamic theranostics. FA-ICG-micelles were successfully prepared using the thin-film hydration method, which allows ICG to be encapsulated with a high drug loading that induces an efficient ICG-based quenched state. FA-ICG-micelles are initially in the "OFF" state with no fluorescence signal or phototoxicity, but they become highly fluorescent and phototoxic in cellular degradative environments. Importantly, via folate receptor-mediated endocytosis, the FA targeting of FA-ICG-micelles enhanced intracellular uptake and photodynamic therapy (PDT) efficacy. Systematic administration of FA-ICG-micelles to folate receptor-positive tumor-bearing mice elicited prolonged blood circulation, enhanced tumor accumulation and improved therapeutic efficiency compared to free ICG. Therefore, based on the FA-targeted specificity and switchable photoactivity, FA-ICG-micelles have potential for photodynamic theranostics in cancer. PMID:27319216

  17. Targeted imaging of ovarian cancer cells using viral nanoparticles doped with indocyanine green

    NASA Astrophysics Data System (ADS)

    Guerrero, Yadir; Bahmani, Baharak; Jung, Bonsu; Vullev, Valentine; Kundra, Vikas; Anvari, Bahman

    2013-03-01

    Our group has constructed a new type of viral nanoparticles (VNPs) from genome-depleted plant infecting brome mosaic virus (BMV) that encapsulates the FDA-approved near infrared (NIR) indocyanine green (ICG)[1]. We refer to these VNPs as optical viral ghosts (OVGs) since the constructs lack the genomic content of wild-type BMV. One of our areas of interest is the application of OVGs for real-time intraoperative NIR fluorescence imaging of small peritoneal ovarian tumor nodules. We target human epidermal growth factor receptor-2 (HER-2) expression in ovarian cancer as a biomarker associated with ovarian cancer, since its over-expression is linked to the disease's progression to death. We functionalize the OVGs with anti-HER-2 monoclonal antibodies using reductive amination methods. We used fluorescence imaging to visualize the SKOV-3 cells (high HER-2 expression) after incubation with free ICG, OVGs, and functionalized OVGs. Our results suggest the possibility of using anti-HER2 conjugated OVGs in conjunction with cytoreductive surgery to detect small tumor nodules (<5cm) which currently are not excised during surgery.

  18. Current use and perspective of indocyanine green clearance in liver diseases.

    PubMed

    Levesque, Eric; Martin, Eléonore; Dudau, Daniela; Lim, Chetana; Dhonneur, Gilles; Azoulay, Daniel

    2016-02-01

    Indocyanine green (ICG) is a water-soluble anionic compound that binds to plasma proteins after intravenous administration. It is selectively taken up at the first pass by hepatocytes and excreted unchanged into the bile. With the development of ICG elimination measurement by spectrophotometry, the ICG retention test has become a safe, rapid, reproducible, inexpensive and noninvasive tool for the assessment of liver function. Clinical evidence suggests that the ICG retention test can enable the establishment of tailored management strategies by providing prognostic information. In particular, this method has been evaluated as a prognostic marker in patients with advanced cirrhosis or awaiting liver transplantation. In addition, it is used as a marker of portal hypertension in cirrhotic patients, as a prognostic factor in intensive care units and for the assessment of liver function in patients undergoing liver surgery. Since recent technology enables ICG-PDR to be measured noninvasively at the bedside, this parameter is an attractive addition to liver function and regional haemodynamic monitoring. However, the current state-of-the-art as concerns this technology remains at a low level of evidence and thorough assessment is required. PMID:26477363

  19. 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.

  20. [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.

  1. 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.

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

    PubMed Central

    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. PMID:26877776

  3. 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). PMID:21895342

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

    PubMed

    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.

  5. 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.

  6. 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.

  7. In vivo observing x-ray attenuation of intratumor injection of indocyanine green

    NASA Astrophysics Data System (ADS)

    Ye, Chang; Luo, Qingming; Liang, Wenxi; Lu, Jinling

    2003-12-01

    We report our experimental results of in vivo observing x-ray attenuation of intra-tumor injection of indocyanine green (ICG). An eight- to nine-week-old male BALB/c mouse weighting between 15 and 20 g is used in the experiments, which has been implanted with myeloma cell line (SP2/0) two week before. The system used to monitor the intratumor diffusion of ICG is a digital x-ray imaging system. It works at 33kVp, 0.3mAs, 4 seconds and 1.5×magnification. The objective of this research is to study the x-ray attenuation at different area, which represented by gray-scale value. Compare to the ROI in the tissue without ICG and ROI of black background in the image, there is an obvious change before and after injecting ICG in the tumor, which is the area ICG can diffuse to. It shows the feasibility of using digital x-ray imaging system to dynamically, effectively and noninterventionly monitor the diffusion of the ICG.

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

    PubMed

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

    2013-06-01

    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.

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

    NASA Astrophysics Data System (ADS)

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

    2013-06-01

    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.

  10. Indocyanine green enhanced near infrared laser treatment of SCK tumors in a mouse model pilot study

    NASA Astrophysics Data System (ADS)

    Shafirstein, Gal; Bäumler, Wolfgang; Friedman, Ran; Hennings, Leah; Webber, Jessica; Suen, James; Griffin, Robert J.

    2011-03-01

    Background and Purpose. Determine the efficacy of indocyanine green (ICG) dye in enhancing near infrared (NIR) laser ablation of tumors in a mouse model. Methods. Mammary carcinoma cells of A/J mice were injected subcutaneously in the lower back of female A/J mice (n=6). Five to seven days post inoculation the tumors (7-9 mm) were treated with 755-nm laser using 70 J/cm2 radiant exposures and 3-ms pulse time. Epidermal cooling was accomplished by cryogen spray cooling. Two minutes prior to laser irradiation mice were injected, intravenously, with 4 mg/kg body weight of ICG solution. Results. Complete tumor ablation was observed in the tumor region and minor damage was seen in the healthy skin. No major skin damage was observed post treatment. Substantial damage (up to 100% coagulative necrosis) was observed in tissue collected from tumors that were treated with laser/ICG. Conclusions. Intravenous administration of 4 mg/kg ICG significantly enhanced thermal ablation of tumors during NIR laser irradiation while sparing healthy skin.

  11. Hybrid polypeptide micelles loading indocyanine green for tumor imaging and photothermal effect study.

    PubMed

    Wu, Lei; Fang, Shengtao; Shi, Shuai; Deng, Jizhe; Liu, Bin; Cai, Lintao

    2013-09-01

    Indocyanine green (ICG) is a near-infrared (NIR) fluorescence dye for extensive applications; however, it is limited for further biological application due to its poor aqueous stability in vitro, concentration-dependent aggregation, rapid elimination from the body, and lack of target specificity. To overcome its limitations, ICG was encapsulated in the core of a polymeric micelle, which self-assembled from amphiphilic PEG-polypeptide hybrid triblock copolymers of poly(ethylene glycol)-b-poly(l-lysine)-b-poly(l-leucine) (PEG-PLL-PLLeu), with PLLeu as the hydrophobic core and PEG as the hydrophilic shell. The ICG was associated with the hydrophobic core via hydrophobic interaction and also the hydrophilic heads through electrostatic attractive interaction. Compared with free ICG, PEG-PLL-PLLeu-ICG micelles significantly improved quantum yield and fluorescent stability. The cellular uptake experiments showed that PEG-PLL-PLLeu-ICG micelles have a high cellular uptake rate. And the in vivo experiments revealed the excellent passive tumor targeting ability and long circulation time of PEG-PLL-PLLeu-ICG. The above results indicated the broad prospects of PEG-PLL-PLLeu-ICG application in the fields of tumor diagnosis and imaging. In addition, temperature measurements under NIR laser irradiation and in vitro photothermal ablation studies proved the potential application of PEG-PLL-PLLeu-ICG in tumor photothermal therapy.

  12. Minibody-indocyanine green based activatable optical imaging probes: the role of short polyethylene glycol linkers.

    PubMed

    Watanabe, Rira; Sato, Kazuhide; Hanaoka, Hirofumi; Harada, Toshiko; Nakajima, Takahito; Kim, Insook; Paik, Chang H; Wu, Anna M; Choyke, Peter L; Kobayashi, Hisataka

    2014-04-10

    Minibodies show rapider blood clearance than IgGs due to smaller size that improves target-to-background ratio (TBR) in in vivo imaging. Additionally, the ability to activate an optical probe after binding to the target greatly improves the TBR. An optical imaging probe based on a minibody against prostate-specific membrane antigen (PSMA-MB) and conjugated with an activatable fluorophore, indocyanine green (ICG), was designed to fluoresce only after binding to cell-surface PSMA. To further reduce background signal, short polyethylene glycol (PEG) linkers were employed to improve the covalent bonding ratio of ICG. New PSMA-MBs conjugated with bifunctional ICG derivatives specifically visualized PSMA-positive tumor xenografts in mice bearing both PSMA-positive and -negative tumors within 6 h postinjection. The addition of short PEG linkers significantly improved TBRs; however, it did not significantly alter the biodistribution. Thus, minibody-ICG conjugates could be a good alternative to IgG-ICG in the optical cancer imaging for further clinical applications.

  13. Indocyanine green-loaded nanoparticles for image-guided tumor surgery.

    PubMed

    Hill, Tanner K; Abdulahad, Asem; Kelkar, Sneha S; Marini, Frank C; Long, Timothy E; Provenzale, James M; Mohs, Aaron M

    2015-02-18

    Detecting positive tumor margins and local malignant masses during surgery is critical for long-term patient survival. The use of image-guided surgery for tumor removal, particularly with near-infrared fluorescent imaging, is a potential method to facilitate removing all neoplastic tissue at the surgical site. In this study we demonstrate a series of hyaluronic acid (HLA)-derived nanoparticles that entrap the near-infrared dye indocyanine green, termed NanoICG, for improved delivery of the dye to tumors. Self-assembly of the nanoparticles was driven by conjugation of one of three hydrophobic moieties: aminopropyl-1-pyrenebutanamide (PBA), aminopropyl-5β-cholanamide (5βCA), or octadecylamine (ODA). Nanoparticle self-assembly, dye loading, and optical properties were characterized. NanoICG exhibited quenched fluorescence that could be activated by disassembly in a mixed solvent. NanoICG was found to be nontoxic at physiologically relevant concentrations and exposure was not found to inhibit cell growth. Using an MDA-MB-231 tumor xenograft model in mice, strong fluorescence enhancement in tumors was observed with NanoICG using a fluorescence image-guided surgery system and a whole-animal imaging system. Tumor contrast with NanoICG was significantly higher than with ICG alone.

  14. Noninvasive optical measurement of cerebral blood flow in mice using molecular dynamics analysis of indocyanine green.

    PubMed

    Ku, Taeyun; Choi, Chulhee

    2012-01-01

    In preclinical studies of ischemic brain disorders, it is crucial to measure cerebral blood flow (CBF); however, this requires radiological techniques with heavy instrumentation or invasive procedures. Here, we propose a noninvasive and easy-to-use optical imaging technique for measuring CBF in experimental small animals. Mice were injected with indocyanine green (ICG) via tail-vein catheterization. Time-series near-infrared fluorescence signals excited by 760 nm light-emitting diodes were imaged overhead by a charge-coupled device coupled with an 830 nm bandpass-filter. We calculated four CBF parameters including arrival time, rising time and mean transit time of a bolus and blood flow index based on time and intensity information of ICG fluorescence dynamics. CBF maps were generated using the parameters to estimate the status of CBF, and they dominantly represented intracerebral blood flows in mice even in the presence of an intact skull and scalp. We demonstrated that this noninvasive optical imaging technique successfully detected reduced local CBF during middle cerebral artery occlusion. We further showed that the proposed method is sufficiently sensitive to detect the differences between CBF status in mice anesthetized with either isoflurane or ketamine-xylazine, and monitor the dynamic changes in CBF after reperfusion during transient middle cerebral artery occlusion. The near-infrared optical imaging of ICG fluorescence combined with a time-series analysis of the molecular dynamics can be a useful noninvasive tool for preclinical studies of brain ischemia.

  15. Multidrug resistance p-glycoprotein 2 is essential for the biliary excretion of indocyanine green.

    PubMed

    Huang, L; Vore, M

    2001-05-01

    Multidrug resistance P-glycoprotein 2 (Mdr2) is a phospholipid translocator in the canalicular membrane that is essential for the formation of biliary phospholipid vesicles and mixed lipid/bile salt micelles. Incorporation into biliary vesicles and micelles is thought to contribute to the hepatobiliary excretion of certain hydrophobic organic anions, such as indocyanine green (ICG). The present studies characterized the biliary excretion of two hydrophobic organic anions, ICG and estradiol-17beta(beta-D-glucuronide) (E(2)17G), in the single-pass isolated perfused liver and the biliary excretion of glutathione (GSH) in vivo in wild-type and Mdr2-/- female mice. The biliary excretion of ICG (0.4 micromol) was reduced by 90%, while the biliary excretion of total GSH was decreased by 65% in Mdr2-/- mice relative to wild-type mice. In contrast, the biliary excretion of E(2)17G (0.1 micromol) was increased by 30% in Mdr2-/- mice. These data indicate that the absence of Mdr2 differentially influences the biliary excretion of these organic anions and suggest that phospholipid vesicles and mixed micelles in bile are essential for the biliary excretion of ICG.

  16. Changes in susceptibility to acetaminophen-induced liver injury by the organic anion indocyanine green.

    PubMed

    Silva, V M; Chen, C; Hennig, G E; Whiteley, H E; Manautou, J E

    2001-03-01

    The non-metabolizable organic anion indocyanine green (ICG) has been shown previously to reduce markedly the biliary secretion of acetaminophen, particularly the glutathione conjugate of APAP (APAP-GSH), suggesting that this APAP metabolite may compete with other xenobiotics for excretion into the bile via a canalicular organic anion transport process. This study was conducted to determine whether changes in the biliary disposition of APAP induced by ICG could lead to alterations in susceptibility to APAP hepatotoxicity. To investigate this, groups of overnight-fasted male CD-1 mice received 30 micromol ICG/kg, intravenously, immediately prior to APAP dosing (500 mg/kg, ip). Controls were given propylene glycol vehicle. Mice were killed at 4 h after APAP challenge for immunochemical analysis of cytosolic protein arylation and determination of non-protein sulfhydryl (NPSH) depletion, or at 12 and 24 h for biochemical and histological assessment of liver injury. Elevated plasma sorbitol dehydrogenase activity and centrilobular hepatocellular necrosis was present in control mice receiving APAP at 12 and 24 h. Treatment with ICG did not alter susceptibility to APAP toxicity when measured at 12 h after challenge. However, the severity of histologic lesions in the ICG-APAP group was significantly lower at 24 h after challenge. Furthermore, treatment with ICG did not alter APAP-induced glutathione depletion or cytosolic protein arylation. These data suggest that the organic anion ICG has a protective effect on APAP toxicity that promotes a faster recovery from liver injury.

  17. Effect of penicillic acid on biliary excretion of indocyanine green in the mouse and rat.

    PubMed

    Chan, P K; Hayes, A W

    1981-02-01

    Penicillic acid (PA), a mycotoxin, is hepatotoxic. A study was undertaken to investigate its effects on hepatobiliary excretory function, using the anionic compounds indocyanine green (ICG), in mice and rats. Pretreatment with a single dose of PA (90 mg/kg, ip, an LD50 dose in both species) resulted in depression of ICG excretion in both species. This depression was dose- and time-dependent. Decreases of 42 and 57% in biliary excretion of ICG were observed in rats and mice 48 and 72 h after PA pretreatment, respectively. Although bile flow was depressed significantly when expressed in terms of body weight, it was not altered in mice when expressed in terms of liver weight. Bile flow was not affected in rats. While the serum ICG concentration was increased after PA treatment in both species, the liver ICG concentration was not affected. The liver-to-serum, bile-to-serum, and bile-to-liver ICG concentration ratios decreased in PA-treated animals. These data suggest that the PA-induced hepatobiliary excretory dysfunction may result from depression of both uptake of ICG into the liver and bile canlicular transport of ICG.

  18. Noninvasive Optical Measurement of Cerebral Blood Flow in Mice Using Molecular Dynamics Analysis of Indocyanine Green

    PubMed Central

    Ku, Taeyun; Choi, Chulhee

    2012-01-01

    In preclinical studies of ischemic brain disorders, it is crucial to measure cerebral blood flow (CBF); however, this requires radiological techniques with heavy instrumentation or invasive procedures. Here, we propose a noninvasive and easy-to-use optical imaging technique for measuring CBF in experimental small animals. Mice were injected with indocyanine green (ICG) via tail-vein catheterization. Time-series near-infrared fluorescence signals excited by 760 nm light-emitting diodes were imaged overhead by a charge-coupled device coupled with an 830 nm bandpass-filter. We calculated four CBF parameters including arrival time, rising time and mean transit time of a bolus and blood flow index based on time and intensity information of ICG fluorescence dynamics. CBF maps were generated using the parameters to estimate the status of CBF, and they dominantly represented intracerebral blood flows in mice even in the presence of an intact skull and scalp. We demonstrated that this noninvasive optical imaging technique successfully detected reduced local CBF during middle cerebral artery occlusion. We further showed that the proposed method is sufficiently sensitive to detect the differences between CBF status in mice anesthetized with either isoflurane or ketamine–xylazine, and monitor the dynamic changes in CBF after reperfusion during transient middle cerebral artery occlusion. The near-infrared optical imaging of ICG fluorescence combined with a time-series analysis of the molecular dynamics can be a useful noninvasive tool for preclinical studies of brain ischemia. PMID:23119000

  19. 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.

  20. Diode laser anastemoses of medium-size arteries with indocyanine green dye-enhanced albumine

    NASA Astrophysics Data System (ADS)

    Weng, Guo-Xing; Williamson, Warren; Aretz, H. Thomas

    1998-11-01

    In order to achieve a better long-term patency result and solve the problem of tensile strength in laser artery anastomoses, diode laser and Indocyanine Green (ICG) enhanced albumin were applied to medium-size artery anastomoses with three different methods, that is, direct laser vascular anastomoses, direct method enforced with ICG albumin, and laser welding with ICG albumin as 'solder'. Internal mammary artery (IMA) harvested from patients undergoing coronary bypass procedures, in vivo rat abdominal artery, and in vitro swine heart and IMA were chosen as the experimental materials. The results revealed that only 3.15 +/- 0.36 minutes were required for each anastomosis; the bursting pressure and tensile strength were greater in the groups enforced with ICG albumin and laser welding than that with direct laser anastomoses. In the laser soldering group, the thermal damage was limited in the adventitial layer, only at a depth of 200 micrometers . There was also a satisfied result in the in vivo laser welding rat's abdominal adventitial layer, only at a depth of 200 micrometers . There was also a satisfied result in the in vivo laser welding rat's abdominal arteries. However, end-to-side laser welding of IMA soronary artery with ICG albumin needs further investigation about its tensile strength in an in vivo model.

  1. 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.

  2. Indocyanine green fluorescence and three-dimensional imaging of right gastroepiploic artery in gastric tube cancer.

    PubMed

    Nakano, Toru; Sakurai, Tadashi; Maruyama, Shota; Ozawa, Yohei; Kamei, Takashi; Miyata, Go; Ohuchi, Noriaki

    2015-01-01

    A 79-year-old male was admitted to our hospital for the treatment of cancer of the gastric tube. Gastrointestinal examination revealed a T1b Union for International Cancer Control (UICC) tumor at the pyloric region of the gastric tube. Laparotomy did not reveal infiltration into the serosa, peritoneal dissemination, regional lymph node swelling, or distant metastasis. We performed a distal gastrectomy preserving the right gastroepiploic artery by referencing the preoperative three-dimensional computed tomoangiography. We also evaluated the blood flow of the right gastroepiploic artery and in the proximal gastric tube by using indocyanine green fluorescence imaging intra-operatively and then followed with a gastrojejunal anastomosis with Roux-en-Y reconstruction. The definitive diagnosis was moderately differentiated adenocarcinoma of the gastric tube, pT1bN0M0, pStage IA (UICC). His postoperative course was uneventful. Three-dimensional computed tomographic imaging is effective for assessing the course of blood vessels and the relationship with the surrounding structures. Intraoperative evaluation of blood flow of the right gastroepiploic artery and of the gastric tube in the anastomotic portion is very valuable information and could contribute to a safe gastrointestinal reconstruction. PMID:25574113

  3. Intraoperative indocyanine green fluorescence angiography--an objective evaluation of anastomotic perfusion in colorectal surgery.

    PubMed

    Protyniak, Bogdan; Dinallo, Anthony M; Boyan, William P; Dressner, Roy M; Arvanitis, Michael L

    2015-06-01

    The essentials for any bowel anastomosis are: adequate perfusion, tension free, accurate tissue apposition, and minimal local spillage. Traditionally, perfusion is measured by assessing palpable pulses in the mesentery, active bleeding at cut edges, and lack of tissue discoloration. However, subjective methods lack predictive accuracy for an anastomotic leak. We used intraoperative indocyanine green (ICG) fluorescence angiography to objectively assess colon perfusion before a bowel anastomosis. Seventy-seven laparoscopic colorectal operations, between June 2013 and June 2014, were retrospectively reviewed. The perfusion to the colon and ileum was clinically assessed, and then measured using the SPY Elite Imaging System. The absolute value provided an objective number on a 0-256 gray-scale to represent differences in ICG fluorescence intensity. The lowest absolute value was used in data analysis for each anastomosis (including small bowel) to represent the theoretical least perfused/weakest anastomotic area. The lowest absolute value recorded was 20 in a patient who underwent a laparoscopic right hemicolectomy for an adenoma, with no postoperative complications. Four low anterior resection patients had additional segments of descending colon resected. There was one mortality in a patient who underwent a laparoscopic right hemicolectomy. This study illustrates an initial experience with the SPY system in colorectal surgery. The SPY provides an objective, numerical value of bowel perfusion. However, evidence is scant as to the significance of these numbers. Large-scale randomized controlled trials are required to determine specific cutoff values correlated with surgical outcomes, specifically anastomotic leak rates. PMID:26031270

  4. Sentinel Lymph Node Detection Using Laser-Assisted Indocyanine Green Dye Lymphangiography in Patients with Melanoma

    PubMed Central

    Jain, Vikalp; Phillips, Brett T.

    2013-01-01

    Introduction. Sentinel lymph node (SLN) biopsy is a vital component of staging and management of multiple cancers. The current gold standard utilizes technetium 99 (tech99) and a blue dye to detect regional nodes. While the success rate is typically over 90%, these two methods can be inconclusive or inconvenient for both patient and surgeon. We evaluated a new technique using laser-assisted ICG dye lymphangiography to identify SLN. Methods. In this retrospective analysis, we identified patients with melanoma who were candidates for SLN biopsy. In addition to tech99 and methylene blue, patients received a dermal injection of indocyanine green (ICG). The infrared signal was detected with the SPY machine (Novadaq), and nodes positive by any method were excised. Results. A total of 15 patients were evaluated, with 40 SLNs removed. Four patients were found to have nodal metastases on final pathology. 100% of these 4 nodes were identified by ICG, while only 75% (3/4) were positive for tech99 and/or methylene blue. Furthermore, none of the nodes missed by ICG (4/40) had malignant cells. Conclusion. ICG dye lymphangiography is a reasonable alternative for locating SLNs in patients with melanoma. Prospective studies are needed to better ascertain the full functionality of this technique. PMID:24382997

  5. 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.

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

    PubMed

    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

    2016-02-11

    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.

  7. Application of femtosecond ultrashort pulse laser to photodynamic therapy mediated by indocyanine green

    PubMed Central

    Sawa, M; Awazu, K; Takahashi, T; Sakaguchi, H; Horiike, H; Ohji, M; Tano, Y

    2004-01-01

    Backgrounds/aims: To evaluate treatment with high peak power pulse energy by femtosecond ultrashort pulse laser (titanium sapphire laser) delivered at an 800 nm wavelength for corneal neovascularisation using photodynamic therapy (PDT) mediated by indocyanine green (ICG). Methods: Using a gelatin solid as an in vitro corneal model, the safety of laser power was studied to determine if it degenerated gelatin with or without ICG. The authors then induced corneal neovascularisation in rabbit eyes by an intracorneal suturing technique. Fluorescein angiography was used to evaluate occlusion before PDT and 0, 1, 3, and 10 days after PDT. The authors performed light microscopy with haematoxylin eosin staining and transmission electron microscopy to determine thrombosis formation in the neovascular regions. Results: The threshold of peak laser power density ranged from 39 to 53 W/cm2. Laser irradiation was started 30 seconds after a 10 mg/kg ICG injection, and all irradiated segments were occluded at 0, 1, 3, and 10 days at 3.8 J/cm2. Light and electron microscopy documented thrombosis formation in the neovascular region. Conclusion: Femtosecond pulse laser enhanced by ICG can be used for PDT. Because of effective closure of corneal neovascularisation at a low energy level, the high peak power pulse energy of the femtosecond pulse laser might be more efficacious than continuous wave laser for use with PDT. PMID:15148220

  8. Advantage of microscope integrated for both indocyanine green and fluorescein videoangiography on aneurysmal surgery: case report.

    PubMed

    Yoshioka, Hideyuki; Kinouchi, Hiroyuki; Nishiyama, Yoshihisa; Kanemaru, Kazuya; Yagi, Takashi; Hanihara, Mitsuto; Horikoshi, Toru

    2014-01-01

    Neck clipping of a large middle cerebral artery aneurysm was performed using a newly developed surgical microscope integrated with modules for both indocyanine green (ICG) and fluorescein videoangiography. During surgery, ICG and fluorescein videoangiography by intra-arterial or intravenous injection were safely carried out without interrupting the surgical procedure. Based on the findings obtained from the case, we evaluated the differences between the dyes and the injection routes. With intra-arterial injection, fluorescein offered sharper contrast images and was better at depicting fine arteries than ICG. Patchy staining of vessel walls was observed in intravenous fluorescein videoangiography, while it was not evident in ICG. Intra-arterial injection method had a great advantage in the rapid clearance of the dyes, which allowed us to perform repeated videoangiography within a short period, and was useful in detecting incomplete clipping in this case; however, catheter insertion requires additional work and carries a potential risk. Use of a microscope integrated for both ICG and fluorescein videoangiography would be another method for repeated evaluation. Namely, alternate use of the dyes enables us to perform videoangiography in a short time even via intravenous injection.

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

    PubMed

    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

  10. An Activatable Theranostic Nanomedicine Platform Based on Self-Quenchable Indocyanine Green-Encapsulated Polymeric Micelles.

    PubMed

    Liu, Lanxia; Ma, Guilei; Zhang, Chao; Wang, Hai; Sun, Hongfan; Wang, Chun; Song, Cunxian; Kong, Deling

    2016-06-01

    Self-quenchable indocyanine green (ICG)-encapsulated micelles with folic acid (FA)-targeting specificity (FA-ICG-micelles) were developed for biologically activatable photodynamic theranostics. FA-ICG-micelles were successfully prepared using the thin-film hydration method, which allows ICG to be encapsulated with a high drug loading that induces an efficient ICG-based quenched state. FA-ICG-micelles are initially in the "OFF" state with no fluorescence signal or phototoxicity, but they become highly fluorescent and phototoxic in cellular degradative environments. Importantly, via folate receptor-mediated endocytosis, the FA targeting of FA-ICG-micelles enhanced intracellular uptake and photodynamic therapy (PDT) efficacy. Systematic administration of FA-ICG-micelles to folate receptor-positive tumor-bearing mice elicited prolonged blood circulation, enhanced tumor accumulation and improved therapeutic efficiency compared to free ICG. Therefore, based on the FA-targeted specificity and switchable photoactivity, FA-ICG-micelles have potential for photodynamic theranostics in cancer.

  11. Estimation of indocyanine green concentration in blood from fluorescence emission: application to hemodynamic assessment during hemodialysis

    NASA Astrophysics Data System (ADS)

    Maarek, Jean-Michel I.; Holschneider, Daniel P.

    2009-09-01

    There is considerable interest in assessing cardiovascular function noninvasively in patients receiving hemodialysis. A possible approach is to measure the blood concentration of bolus-injected indocyanine green dye and to apply the dye-dilution method for estimating cardiac output and blood volume. Blood ICG concentration can be derived from a measurement of the ICG fluorescence through the dialysis tubing if a simple and unique calibration relationship can be established between transmural fluorescence intensity and blood ICG concentration. We investigated this relationship using Monte Carlo simulations of light transport in blood with varying hematocrit and ICG concentrations and performed empiric measurements of optical absorption and ICG fluorescence emission to confirm our findings. The ICG fluorescence intensity measured at the blood surface, as well as the light intensity remitted by the blood, varied as hematocrit changes modified the absorption and scattering characteristics of the blood. Calibration relationships were developed between fluorescence intensity and ICG concentration that accounted for hematocrit changes. Combining the backreflected fluorescence and the reflected light measured near the point of illumination provided optimal signal intensity, linearity, and robustness to hematocrit changes. These results provide a basis for developing a noninvasive approach to derive optically circulating blood ICG concentration in hemodialysis circuits.

  12. Establishment of an indocyanine green test using an automatic chemistry analyzer.

    PubMed

    Seong, Moon-Woo; Song, Sang-Hoon; Oh, Joo-Young; Park, Joong-Won; Lee, Do-Hoon

    2006-01-01

    The indocyanine green (ICG) clearance test has been used to assess the reserve of hepatic function. This method is based on the spectrometric measurement of its plasma concentration at maximum wavelength of 805 nm, which requires a spectrophotometer and associated maintenance. We established an ICG clearance test using a Toshiba 200FR automatic chemistry analyzer that can be tuned to a wavelength of approximately 805 nm. Five pooled sera spiked from 0 to 4.0 mg/dL were analyzed for linearity test and precision was determined at five levels in the range 0.1-2.0 mg/dL. The ICG retention rate at 15 min (R15) was determined for 38 patients using a conventional method and our method. The ICG clearance test using the automatic chemistry analyzer showed good linearity, and precision ranged from 0.3% to 1.0% for within-run CVs and from 0.6% to 4.7% for total CVs. The degree of agreement between the two methods was also acceptable (mean difference of 1.5%). It is expected that the ICG test using the automatic chemistry analyzer can replace the conventional ICG clearance test, considering the excellent agreement, good precision and linearity over a clinically relevant range.

  13. Combined use of intraoperative indocyanine green and dynamic angiography in rotational vertebral artery occlusion.

    PubMed

    Chaudhry, Nauman S; Ambekar, Sudheer; Elhammady, Mohamed Samy; Riley, Jonathan P; Pradilla, Gustavo; Nogueira, Raul G; Ahmad, Faiz U

    2016-08-01

    Rotational vertebral artery occlusion, also known as bow hunter's syndrome, is a well-documented surgically amenable cause of vertebrobasilar insufficiency. Traditionally, patients have been imaged using dynamic rotational angiography. The authors sought to determine whether intraoperative indocyanine green (ICG) angiography could reliably assess the adequacy of surgical decompression of the vertebral artery (VA). The authors report two patients who presented with multiple transient episodes of syncope provoked by turning their head to the right. Rotational dynamic angiography revealed a dominant VA that became occluded with head rotation to the right side. The patients underwent successful surgical decompression of the VA via an anterior cervical approach. Intraoperative ICG angiography demonstrated patency of the VA with head rotation. This was further confirmed by intraoperative dynamic catheter angiography. To our knowledge, we present the first two cases of the use of ICG combined with intraoperative dynamic rotational angiography to document the adequacy of surgical decompression of the VA in a patient with rotational vertebral artery occlusion. Intraoperative ICG angiography is a useful adjunct and may potentially supplant the need for intraoperative catheter angiography. PMID:27041076

  14. Free DOX and chitosan-N-arginine conjugate stabilized indocyanine green nanoparticles for combined chemophotothermal therapy.

    PubMed

    Jheng, Pei-Ru; Lu, Kun-Ying; Yu, Shu-Huei; Mi, Fwu-Long

    2015-12-01

    Indocyanine green (ICG) is a FDA-approved near-infrared (NIR) cyanine dye used in medical diagnostics. However, the utility of ICG remains limited by its unstable optical property, and concentration-dependent aggregation and precipitation. A chitosan-arginine conjugate (CS-N-Arg) was developed to increase the stability of ICG in physiological buffer saline via formation of strong electrostatic interactions between ICG and CS-N-Arg. The CS-N-Arg/ICG complex prevented ICG from aggregation and precipitation, thus it could serve as a theranostic nanomaterial for image-guided photothermal cancer therapy. The CS-N-Arg/ICG NPs showed excellent photostability, clear fluorescent images, and rapid temperature rise under laser irradiation. Cell viability assay indicated that CS-N-Arg/ICG NPs could efficiently suppress the growth of doxorubicin (DOX) resistant breast cancer cell (MCF-7/ADR cells) under NIR photothermal treatments. In combination of DOX with CS-N-Arg/ICG NPs, a combined effect was observed in MCF-7/ADR breast cancer cells due to dual hyperthermia and chemical therapeutic effects. The present observations suggest that CS-N-Arg/ICG NPs can effectively deliver ICG molecules to MCF-7/ADR breast cancer cells and overcome DOX resistance in the cells by hyperthermia.

  15. Clinical application of near-infrared thoracoscope with indocyanine green in video-assisted thoracoscopic bullectomy

    PubMed Central

    Li, Hao; Zhou, Jian; Chi, Chongwei; Mao, Yamin; Yang, Fan; Tian, Jie

    2016-01-01

    Failure to identify all the possible bullous lesions was considered an important reason for the higher recurrence rate after the VATS bullectomy. We applied the latest near-infrared (NIR) thoracoscope with indocyanine green (ICG) to detect bullous lesions for patients with spontaneous pneumothorax. Two male patients with spontaneous pneumothorax and poorly identified bullae intraoperatively were included in this pilot study. An NIR thoracoscope with two different doses of ICG injection (0.2 and 0.6 mg/kg) was used to detect bullous lesions during VATS bullectomy. Partial lung resections of the bullous lesions were performed under syncretic mode. Data was managed with ImageJ software. No procedure-related complications were observed. The fluorescent signal was detected in normal lung tissue 10.5 seconds (mean, 10–11 seconds) after the ICG bolus, and lasted up to 525 seconds (mean, 480–570 seconds). The bullous lesions showed an obviously decreased fluorescent densities comparing to adjacent normal tissue. At the dosage of 0.6 mg/kg, ICG emits sufficient fluorescence to demonstrate the precise border of bullae, with the max SBR of 6.32. All resected specimens were confirmed as bullous lesions microscopically. NIR thoracoscope with intravenous ICG is a safe, accurate and real-time method to detect bullous lesions of lung tissue difficult to be found under normal light in human subjects. Trial registration NCT02611245 (https://register.clinicaltrials.gov/). PMID:27499979

  16. Cerebral blood flow imaging using time-series analysis of indocyanine green molecular dynamics in mice

    NASA Astrophysics Data System (ADS)

    Ku, Taeyun; Lee, Jungsul; Choi, Chulhee

    2010-02-01

    Measurement of cerebral perfusion is important for study of various brain disorders such as stroke, epilepsy, and vascular dementia; however, efficient and convenient methods which can provide quantitative information about cerebral blood flow are not developed. Here we propose an optical imaging method using time-series analysis of dynamics of indocyanine green (ICG) fluorescence to generate cerebral blood flow maps. In scalp-removed mice, ICG was injected intravenously, and 740nm LED light was illuminated for fluorescence emission signals around 820nm acquired by cooled-CCD. Time-lapse 2-dimensional images were analyzed by custom-built software, and the maximal time point of fluorescent influx in each pixel was processed as a blood flow-related parameter. The generated map exactly reflected the shape of the brain without any interference of the skull, the dura mater, and other soft tissues. This method may be further applicable for study of other disease models in which the cerebral hemodynamics is changed either acutely or chronically.

  17. Polyoxazoline multivalently conjugated with indocyanine green for sensitive in vivo photoacoustic imaging of tumors

    PubMed Central

    Kanazaki, Kengo; Sano, Kohei; Makino, Akira; Homma, Tsutomu; Ono, Masahiro; Saji, Hideo

    2016-01-01

    Photoacoustic imaging, which enables high-resolution imaging in deep tissues, has lately attracted considerable attention. For tumor imaging, photoacoustic probes have been proposed to enhance the photoacoustic effect to improve detection sensitivity. Here, we evaluated the feasibility of using a biocompatible hydrophilic polymer, polyoxazoline, conjugated with indocyanine green (ICG) as a tumor-targeted photoacoustic probe via enhanced permeability and retention effect. ICG molecules were multivalently conjugated to partially hydrolyzed polyoxazoline, thereby serving as highly sensitive photoacoustic probes. Interestingly, loading multiple ICG molecules to polyoxazoline significantly enhanced photoacoustic signal intensity under the same ICG concentration. In vivo biodistribution studies using tumor bearing mice demonstrated that 5% hydrolyzed polyoxazoline (50 kDa) conjugated with ICG (ICG/polyoxazoline = 7.8), P14-ICG7.8, showed relatively high tumor accumulation (9.4%ID/g), resulting in delivery of the highest dose of ICG among the probes tested. P14-ICG7.8 enabled clear visualization of the tumor regions by photoacoustic imaging 24 h after administration; the photoacoustic signal increased in proportion with the injected dose. In addition, the signal intensity in blood vessels in the photoacoustic images did not show much change, which was attributed to the high tumor-to-blood ratios of P14-ICG7.8. These results suggest that polyoxazoline-ICG would serve as a robust probe for sensitive photoacoustic tumor imaging. PMID:27667374

  18. 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.

  19. [Indocyanine green infrared fluorescence angiography and histopathological correlation in experimental choroidal circulatory disturbance. Report 2].

    PubMed

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

    1997-02-01

    We performed an experimental study on choroidal circulatory disturbance to clarify basic problems about interpretation of retino-choroidal lesions in indocyanine green fluorescence angiography (ICG angiography). We severed the posterior ciliary arteries to produce choroidal circulatory disturbance. Fluorescein angiography and ICG angiography were performed at one week, and one month after occlusion. These findings were compared with histopathological findings. One week after occlusion, the area of choroidal infarct showed occlusion of choriocapillaris and proliferation of the retinal pigment epithelial (RPE) cells, this area showed hypofluorescence in the early phase ICG angiography. The hypofluorescence area increased in the late phase. One month after occlusion, the lesion showed loss of choriocapillaris at the center and proliferation of fibroblast-like cells at the edge of the lesion. The subretinal strand showed hyperfluorescence in late phase ICG angiography. Proliferated RPE cells masked ICG fluorescence in the late phase. Fibroblast-like cells showed tissue staining. When reading ICG angiography, we have to take into account that the ICG angiogram is greatly modified by condition of the RPE.

  20. Polymeric nanoparticulate delivery system for Indocyanine green: biodistribution in healthy mice.

    PubMed

    Saxena, Vishal; Sadoqi, Mostafa; Shao, Jun

    2006-02-01

    The objective of this study is to investigate the biodistribution of Indocyanine green (ICG) in healthy mice, when delivered through polymeric nanoparticles. The poly(DL-lactic-co-glycolic acid) (PLGA) nanoparticles entrapping ICG were engineered and characterized. The extraction method for ICG recovery from biological samples was developed. The biodistribution of ICG was determined in healthy C57BL/6 mice (female, 10-week old) when delivered through PLGA nanoparticles in comparison to free ICG solution, using a fluorometric assay method. The extraction method for ICG shows efficiency above 80% for various organs and plasma. When nanoparticles were used to deliver ICG, 2-8 times higher concentrations of ICG was deposited in various organs, with 5-10 times higher plasma levels till 4 h, after an i.v. dose as compared to free ICG solution. In conclusion, the nanoparticle formulation significantly increased the ICG concentration and circulation time in plasma as well as the ICG uptake, accumulation and retention in various organs. Overall, this study represents the first step in exploring and establishing the potential of nanoparticles as an ICG-delivery system for use in tumor-diagnosis and photodynamic therapy.

  1. 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

  2. [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. PMID:26946971

  3. Stability assessment of indocyanine green within dextran-coated mesocapsules by absorbance spectroscopy.

    PubMed

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

    2007-01-01

    The biocompatibility and high absorption in the near IR range of indocyanine green (ICG) have made it a suitable candidate chromophore for optical imaging and laser-mediated therapy of superficial tumors. However, its clinical efficacy remains limited by factors such as rapid circulation kinetics, lack of target specificity, and molecular instability. Such drawbacks motivated us to encapsulate ICG into carrier particles to improve target specificity and retention time. We use absorbance spectroscopy to investigate the effects of encapsulating ICG within dextran-coated capsules. The mesocapsules (MCs) containing ICG are synthesized using a previously reported charge-assembly technique. Both freely dissolved ICG and ICG-MCs are prepared with ICG concentrations of either 50 or 10 microg/ml. Samples are exposed either to a broadband light source or incubated at 3, 23, or 40 degrees C. Absorbance spectra are recorded at various time points up to 96 h. At the lower concentration of 10 microg/ml, ICG within MCs experiences less light-induced degradation. The MC system also protects ICG from thermal degradation at all tested temperatures. The polymer-salt aggregate core of the MCs hinders the mobility of ICG molecules. The MC system shields ICG from vibrational and translational agitation as well as molecular changes such as fragmentation.

  4. 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.

  5. 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

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

    PubMed Central

    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

    2016-01-01

    Aim: 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. Methods: 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. Results: 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. Conclusion: SIPNs show temperature-sensitive drug release following NIR laser irradiation, which can inhibit the growth and metastasis of breast cancer cells in vitro. PMID:27133295

  7. 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

    2015-09-01

    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.

  8. Enhanced tumor treatment using biofunctional indocyanine green-containing nanostructure by intratumoral or intravenous injection.

    PubMed

    Zheng, Xiaohui; Zhou, Feifan; Wu, Baoyan; Chen, Wei R; Xing, Da

    2012-03-01

    Indocyanine green (ICG) is a conventional dye that can be used in clinical near-infrared (NIR) imaging, and it is also an effective light absorber for laser-mediated photothermal therapy. However, applications of ICG were limited due to its fast degradation in aqueous media and quick clearance from the body. Herein, an ICG-containing nanostructure, ICG-PL-PEG, was developed for photothermal therapy, which was self-assembled by ICG and phospholipid-polyethylene glycol (PL-PEG). Our in vitro and in vivo experiments demonstrated that ICG-PL-PEG suspension was more efficient in producing a NIR-dependent temperature increase than ICG alone, due to the increase of ICG monomers from the addition of PL-PEG to match the central wavelength of the 808 nm laser. When conjugated with integrin α(v)β(3) monoclonal antibody (mAb), ICG-PL-PEG could be selectively internalized and retained in target tumor cells. Irradiation of an 808 nm laser after intravenous administration of ICG-PL-PEG-mAb resulted in tumor suppression in mice, while ICG alone had only limited effect. This is the first time an ICG-containing nanostructure has been used through systemic administration to achieve an efficient in vivo photothermal effect for cancer treatment. Therefore, ICG-PL-PEG could be used as a fluorescent marker as well as a light-absorber for imaging-guided photothermal therapy. All the components of ICG-PL-PEG have been approved for human use. Therefore, this unique ICG-containing nanostructure has great potential in clinical applications.

  9. Targeted indocyanine-green-loaded calcium phosphosilicate nanoparticles for in vivo photodynamic therapy of leukemia.

    PubMed

    Barth, Brian M; I Altinoğlu, Erhan; Shanmugavelandy, Sriram S; Kaiser, James M; Crespo-Gonzalez, Daniza; DiVittore, Nicole A; McGovern, Christopher; Goff, Trevor M; Keasey, Nicole R; Adair, James H; Loughran, Thomas P; Claxton, David F; Kester, Mark

    2011-07-26

    Leukemia is one of the most common and aggressive adult cancers, as well as the most prevalent childhood cancer. Leukemia is a cancer of the hematological system and can be divided into a diversity of unique malignancies based on the onset of the disease as well as the specific cell lineages involved. Cancer stem cells, including recently identified leukemia stem cells (LSCs), are hypothesized to be responsible for cancer development, relapse, and resistance to treatment, and new therapeutics targeting these cellular populations are urgently needed. Nontoxic and nonaggregating calcium phosphosilicate nanoparticles (CPSNPs) encapsulating the near-infrared fluoroprobe indocyanine green (ICG) were recently developed for diagnostic imaging and drug delivery as well as for photodynamic therapy (PDT) of solid tumors. Prior studies revealed that specific targeting of CPSNPs allowed for enhanced accumulation within breast cancer tumors, via CD71 targeting, or pancreatic cancer tumors, via gastrin receptor targeting. In the present study, ICG-loaded CPSNPs were evaluated as photosensitizers for PDT of leukemia. Using a novel bioconjugation approach to specifically target CD117 or CD96, surface features enhanced on leukemia stem cells, in vitro ICG-CPSNP PDT of a murine leukemia cell line and human leukemia samples were dramatically improved. Furthermore, the in vivo efficacy of PDT was dramatically enhanced in a murine leukemia model by utilizing CD117-targeted ICG-CPSNPs, resulting in 29% disease-free survival. Altogether, this study demonstrates that leukemia-targeted ICG-loaded CPSNPs offer the promise to effectively treat relapsing and multidrug-resistant leukemia and to improve the life of leukemia patients.

  10. Indocyanine green enhanced near-infrared laser treatment of murine mammary carcinoma.

    PubMed

    Shafirstein, Gal; Bäumler, Wolfgang; Hennings, Leah J; Siegel, Eric R; Friedman, Ran; Moreno, Mauricio A; Webber, Jessica; Jackson, Cassie; Griffin, Robert J

    2012-03-01

    It is well accepted that near-infrared (NIR) lasers are appropriate to ablate benign lesions and induce irreversible thermal injury in deeply seated blood vessels. At this wavelength, the laser light penetrates deep (3-5 mm) into the skin. However, many researchers have reported noticeable pain, extending from mild to severe, during and immediately after NIR laser treatment. Intravenous administration of an exogenous chromophore [indocyanine green (ICG), dye] can effectively convert NIR laser light into heat. In this approach, the presence of ICG has shown to enhance thermal injury of blood vessels in the treatment of healthy tissues. However, the effectiveness of thermal injury on the regression of cutaneous carcinomas during ICG/NIR laser therapy has not been assessed. The purpose of our study was to evaluate the potential benefit of using ICG/NIR laser therapy to regress superficial carcinoma with thermal injury. Two groups of A/J mice with subcutaneous mammary adenocarcinoma tumors (7-9 mm) were irradiated with a 808-nm NIR laser preceded by tail vein injection of ICG dye or sterile saline. Histological evaluation of the subcutaneous tissue revealed minor thermal damage and necrosis in the laser/saline group and substantial damage (up to 100% necrosis) in the laser/ICG group. The laser/ICG-treated group showed a steady reduction in tumor volume compared to the laser/saline group: 48% by day 5 (p = 0.045) and 69-70% by days 8, 9 and 10 (p values 0.0005 or less). The vascular-targeted ICG-NIR laser therapy appears to have potential for treating superficial tumors.

  11. The effects of ultrasound and light on indocyanine-green-treated tumour cells and tissues.

    PubMed

    Nomikou, Nikolitsa; Sterrett, Christine; Arthur, Ciara; McCaughan, Bridgeen; Callan, John F; McHale, Anthony P

    2012-08-01

    Photodynamic therapy (PDT) is emerging as a treatment modality for the management of neoplastic disease. Despite considerable clinical success, its application for the treatment of deep-seated lesions is constrained by the inability of visible light to penetrate deeply into tissues. An emerging alternative approach exploits the fact that many photosensitisers respond to ultrasound, eliciting cytotoxic effects on target cells and tissues; this has become known as sonodynamic therapy (SDT). The objectives of this study were 1) to determine whether the IR-absorbing dye, indocyanine green (ICG), can be employed as a sonosensitiser and 2) to determine whether ultrasound can be used to enhance ICG-mediated PDT. Exposing ICG-treated mouse fibrosarcoma cells to ultrasound at an energy density of 30 J cm(-2) decreased cell viability by 65 %. Prior exposure of ICG-treated cells to light (λ 830 nm) and subsequent treatment with ultrasound led to a 90 % decrease in cell viability. In combination treatments a synergistic effect was observed at lower doses of ultrasound. Microscopic examination of cell populations treated with light or ultrasound demonstrated the production of intracellular reactive oxygen species (ROS). Using a mouse tumour model, treatment with light, ultrasound, or a combination thereof led to respective decreases in tumour growth of 42, 67, and 98 % at day 27 post-treatment. These results could provide a means of circumventing light-penetration issues that currently challenge the widespread use of PDT in the treatment of cancer.

  12. 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.

  13. Laser-induced heating of dextran-coated mesocapsules containing indocyanine green.

    PubMed

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

    2007-01-01

    Indocyanine green (ICG) is a photosensitive reagent with clinically relevant diagnostic and therapeutic applications. Recently, ICG has been investigated for its utility as an exogenous chromophore during laser-induced heating. However, ICG's effectiveness remains hindered by its molecular instability, rapid circulation kinetics, and nonspecific systemic distribution. To overcome these limitations, we have encapsulated ICG within dextran-coated mesocapsules (MCs). Our objective in this study was to explore the ability of MCs to induce thermal damage in response to laser irradiation. To simulate tumorous tissue targeted with MCs, cylindrical phantoms were prepared consisting of gelatin, intralipid emulsion, and various concentrations of MCs. The phantoms were embedded within fresh chicken breast tissue representing surrounding normal tissue. The tissue models were irradiated at lambda = 808 nm for 10 min at constant power (P = 4.2 W). Five hypodermic thermocouples were used to record the temperature at various depths below the tissue surface and transverse distances from the laser beam central axis during irradiation. Temperature profiles were processed to remove the baseline temperature and influence of light absorption by the thermocouple and subsequently used to calculate a damage index based on the Arrhenius damage integral. Tissue models containing MCs experienced a maximum temperature change of 18.5 degrees C. Damage index calculations showed that the heat generation from MCs at these parameters is sufficient to induce thermal damage, while no damage was predicted in the absence of MCs. ICG maintains its heat-generating capabilities in response to NIR laser irradiation when encapsulated within MCs. Such encapsulation provides a potentially useful methodology for laser-induced therapeutic strategies. PMID:17914861

  14. 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

  15. Intraoperative indocyanine green angiography for the objective measurement of blood flow

    PubMed Central

    Park, Ho-Chul; Han, Sang-Ah; Ahn, Hyung Joon

    2016-01-01

    Purpose Intraoperative assessment of tissue perfusion is important to predict wound healing or improvement of symptoms in patients with peripheral arterial disease (PAD) or vascular trauma. There is no widely accepted standard for intraoperative measurement of tissue perfusion. Here, we report the use of indocyanine green (ICG)-based angiography to determine the blood flow in patients with PAD and vascular trauma. Methods The SPY fluorescent imaging system was utilized. A dose of 3–5 mL of ICG (2.5 mg/mL) was injected intravenously followed by a 10 mL normal saline flush. The SPY imaging system was used to quantitatively assess perfusion. During the study period, the SPY imaging system was applied in 4 patients with PAD and one patient with vascular trauma. Results In 3 patients with PAD associated with an ischemic wound, complete wound healing was achieved with the indication of viable tissue by the SPY system. In one patient with severe claudication in both lower extremities, the ICG angiography was used to determine the increased blood flow after revascularization. In the case of vascular trauma, this imaging system enabled the delineation of viability of the injured tissue. Conclusion ICG angiography can determine the surface tissue viability in PAD patients. In cases of severe vascular trauma,the SPY system can be used to determine tissue perfusion. Further study is warranted to define the definite utility of this technology to assess perfusion, response to revascularization, and potentially, to predict the likelihood of wound healing. PMID:27186573

  16. 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

  17. 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.

  18. Fat tissue histological study at indocyanine green-mediated photothermal/photodynamic treatment of the skin in vivo

    NASA Astrophysics Data System (ADS)

    Yanina, Irina Yu.; Tuchin, Valery V.; Navolokin, Nikita A.; Matveeva, Olga V.; Bucharskaya, Alla B.; Maslyakova, Galina N.; Altshuler, Gregory B.

    2012-05-01

    Histological slices of skin samples with the subcutaneous adipose tissue after photothermal/photodynamic treatment are analyzed. In the case of subcutaneous indocyanine green injection and 808-nm diode laser exposure of the rat skin site in vivo, the greatest changes in tissue condition were observed. Processes were characterized by dystrophy, necrosis, and desquamation of the epithelial cells, swelling and necrosis of the connective tissue, and widespread necrosis of the subcutaneous adipose tissue. The obtained data are useful for safe layer-by-layer dosimetry of laser illumination of ICG-stained adipose tissue for treatment of obesity and cellulite.

  19. Predictive lymphatic mapping: a method for mapping lymphatic channels in patients with advanced unilateral lymphedema using indocyanine green lymphography.

    PubMed

    Mihara, Makoto; Seki, Yukio; Hara, Hisako; Iida, Takuya; Oka, Aiko; Kikuchi, Kazuki; Narushima, Mitsunaga; Haragi, Makiko; Furniss, Dominic; Hin-Lun, Lawrence; Mitsui, Kito; Murai, Noriyuki; Koshima, Isao

    2014-01-01

    In severe lymphedema, indocyanine green lymphography cannot be used to map lymphatic channels before lymphaticovenular anastomosis (LVA) because linear lymphatics cannot be detected in a severely affected leg. Here, we describe a new method, which we refer to as predictive lymphatic mapping, to predict the location of lymphatics for anastomosis in unilateral lymphedema, thereby improving surgical accuracy and efficiency. The approach consists of marking anatomical landmarks and joining selected landmarks with fixed lines. The distance from these fixed lines to lymphatic channels mapped by indocyanine green lymphography in the unaffected leg is then measured, scaled up based on the difference in circumference between the legs, and transposed to the affected leg. To date, we have used this method in 5 cases of unilateral or asymmetric lymphedema of the lower extremities. In no cases have we failed to find a lymphatic channel suitable for LVA within a 2-cm incision. These results suggest that predictive lymphatic mapping is a useful additional tool for surgeons performing LVA under local anesthesia, which will help to improve the accuracy of incisions and the efficiency of surgery.

  20. 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.

  1. Pilot study: intravenous use of indocyanine green as an enhancer for 808-nm diode laser application in the equine

    NASA Astrophysics Data System (ADS)

    Tate, Lloyd P.; Blikslager, Anthony T.; Papich, Mark G.

    2000-05-01

    The 808-nm diode laser, delivering 20 - 40 watts of power, has been produced for medical applications by several manufacturers over the past 10 years. This laser's power output is less than most Neodymium:yttrium aluminum garnet (Nd:YAG) lasers and other high power cutting lasers that use fiberoptic delivery systems. The 808-nm diode laser has not gained popularity in equine transendoscopic laser surgery. Indocyanine green (ICG) is absorbed at 810-nm of light which when concentrated in tissue should be an excellent absorber for the energy produced by the 808-nm diode laser. This study compares the depths and widths of penetration achieved with the 808-nm diode laser after intravenous injection of ICG in equine respiratory tissue. Indocyanine green was administered at two doses: 1.5 mg/kg and 3 mg/kg. The 808-nm diode laser was set to deliver 200 joules of energy. The depths and widths of penetration were also compared to the Nd:YAG laser applied at the same energy setting.

  2. 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

  3. [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.

  4. Evaluation of the near infrared compound indocyanine green as a probe substrate of p-glycoprotein.

    PubMed

    Portnoy, Emma; Gurina, Marina; Magdassi, Shlomo; Eyal, Sara

    2012-12-01

    The efflux transporter P-glycoprotein (P-gp) affects the pharmacokinetics of many drugs. Currently used methods for characterization of P-gp's functional activity in vivo involve the use of radiolabeled substrates, are costly, and are technically demanding. Our objective was to evaluate whether the FDA-approved near-infrared compound indocyanine green (ICG) can be used as a probe substrate of P-gp. We also characterized the interaction of ICG with another efflux transporter, the breast cancer resistance protein (BCRP). We evaluated ICG accumulation and transport in MDCK cells overexpressing P-gp or BCRP (MDCK-MDR1 and MDCK-BCRP, respectively) compared to control MDCK cells, in the presence or the absence of transporter inhibitors. In vivo imaging of ICG biodistribution in mice was conducted over 3.5 h using valspodar as the P-gp inhibitor. The EC50 values for ICG accumulation in control MDCK and MDCK-MDR1 cells were 9.0 × 10(-6) ± 5.7 × 10(-7) M and 1.5 × 10(-5) ± 1.1 × 10(-6) M, respectively. The efflux ratio for ICG in MDCK-MDR1 cells was 6.8-fold greater than in control cells. P-gp inhibition attenuated ICG efflux from MDR1-MDCK cells, and their effects in those cells were greater than in control MDCK cells. In contrast, BCRP level of expression or pharmacological inhibition did not significantly affect ICG cellular accumulation. In vivo imaging indicated enhanced cerebral ICG distribution with valspodar (brain - foot area under the concentration-time curves of 3.0 × 10(10), 5.6 × 10(10) and 3.7 × 10(10) h·[p/s/sr]/μW in valspodar-treated mice vs 9.0 × 10(9) and 5.3 × 10(9) h·[p/s/sr]/μW in controls). The findings from this pilot study suggest that near-infrared imaging using ICG as the probe substrate should be further characterized as a methodology for in vivo evaluation of P-gp activity.

  5. Dynamic fluorescent imaging with indocyanine green for monitoring the therapeutic effects of photoimmunotherapy.

    PubMed

    Ali, Towhid; Nakajima, Takahito; Sano, Kohei; Sato, Kazuhide; Choyke, Peter L; Kobayashi, Hisataka

    2014-01-01

    A new type of monoclonal antibody (mAb)-based, highly specific phototherapy (photoimmunotherapy; PIT) that uses a near-infrared (NIR) phthalocyanine dye, IRDye700DX (IR700) conjugated with an mAb, has recently been described. NIR light exposure leads to immediate, target-selective necrotic cell death. However, tumor shrinkage takes several days to occur, making it difficult to detect earlier changes in the tumor. In this study, Panitumumab targeting the epidermal growth factor receptor (EGFR1) conjugated to IR700 was used to treat EGFR-expressing A431 tumor cells and in vivo xenografts. PIT was performed at varying doses of NIR light (10, 30, 50 and 100 J cm(-2)) in xenograft tumors in mice. Indocyanine green (ICG) dynamic imaging was evaluated for monitoring cytotoxic effects for the first hour after PIT. Our results demonstrated a statistical difference (p < 0.05) in ICG intensity between control and PIT treated tumors in the higher light exposure groups (50 J cm(-2): 2.94 ± 0.35 vs 5.22 ± 0.92, p = 0.02; and 100 J cm(-2) : 3.56 ± 0.96 vs 5.71 ± 1.43, p = 0.008) as early as 20 min post ICG injection. However, no significant difference (p > 0.05) in ICG intensity between control and PIT treated tumors was evident in the lower light exposure group at any time points up to 60 min (10 J cm(-2) : 1.92 ± 0.49 vs 1.71 ± 0.3, p = 0.44; and 30 J cm(-2): 1.57 ± 0.35 vs 2.75 ± 0.59, p = 0.07). Similarly, the retention index (background to corrected uptake ratio of ICG) varied with light exposure. In conclusion, ICG may serve as a potential indicator of acute cytotoxic effects of mAb-IR700-induced PIT even before morphological changes can be seen in targeted tumors.

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

    PubMed

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

    2016-03-01

    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

  7. 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

  8. Hepatic function in rats with dietary-induced fatty liver, as measured by the uptake of indocyanine green.

    PubMed

    Jahoor, F; Jackson, A A

    1982-05-01

    1. The hepatic uptake of indocyanine green (ICG) has been measured in rats receiving a 50 g protein/kg diet for 6, 12 or 20 d or a choline-deficient diet for 2 or 6 d. 2. There was no effect on ICG uptake on the choline-deficient diet, although all the rats developed an intense fatty infiltration of the liver by 6 d. 3. The rats on the 50 g protein/kg diet showed impaired uptake of ICG at 6, 12 and 20 d, which appeared to be related to the extent of fatty infiltration. 4. It is concluded that ICG uptake is predominantly a function of the periportal zone of the liver lobule, and therefore likely to be sensitive to insults that exert their predominant effect in this zone.

  9. Time-resolved fluorescence for breast cancer detection using an octreotate-indocyanine green derivative dye conjugate

    NASA Astrophysics Data System (ADS)

    Sordillo, Laura A.; Das, B. B.; Pu, Yang; Liang, Kexian; Milione, Giovanni; Sordillo, Peter P.; Achilefu, Sam; Alfano, R. R.

    2013-03-01

    Time-resolved fluorescence was used to investigate malignant and normal adjacent breast tissues stained with a conjugate of indocyanine green and octreotate. A marked increase in fluorescence lifetime intensity was seen in the breast cancer sample compared to the normal sample. The fluorescent lifetimes were also investigated and showed similar fluorescence decay curves in stained malignant and normal breast tissue. These results confirm that somatostatin receptors occur on human breast carcinomas, suggest that the presence of somatostatin receptors should be investigated as a marker of breast cancer aggressiveness, and suggest that this conjugate might be used to detect the presence of residual breast cancer after surgery, allowing better assessment of tumor margins and reducing the need for second or repeat biopsies in selected patients. These results may also provide clues for designing future treatment options for breast cancer patients.

  10. Role of Indocyanine Green in Sentinel Node Mapping in Gynecologic Cancer: Is Fluorescence Imaging the New Standard?

    PubMed

    Darin, María Cecilia; Gómez-Hidalgo, Natalia Rodriguez; Westin, Shannon N; Soliman, Pamela T; Escobar, Pedro F; Frumovitz, Michael; Ramirez, Pedro T

    2016-02-01

    Sentinel lymph node biopsy has proven safe and feasible in a number of gynecologic cancers such as vulvar cancer, cervical cancer, and endometrial cancer. The proposed aim of lymphatic mapping and sentinel node identification is to decrease the associated morbidity of a complete lymphadenectomy, particularly the rate of lymphedema, while also increasing the detection of small tumor deposits in the node. Different tracers have been shown to be useful, including technetium-99 and blue dye, with a detection reported in 66% to 86%. Recently, there has been increasing interest in the use of fluorescent dies such as indocyanine green (ICG). In this report we provide a review of the existing literature regarding the use of ICG in cervical or endometrial cancer with the goal to provide details on its utility and compare it with other tracers.

  11. Improved technique for evaluating oral free flaps by pinprick testing assisted by indocyanine green near-infrared fluorescence angiography.

    PubMed

    Nagata, Tetsuji; Masumoto, Kazuma; Uchiyama, Yoshiyuki; Watanabe, Yoshiko; Azuma, Ryuichi; Morimoto, Yuji; Katou, Fuminori

    2014-10-01

    In head and neck surgery, free-flap reconstruction using a microvascular anastomosis is an indispensable option after tumor ablation. Because the success of free-flap reconstruction is enhanced by rapid identification and salvage of failing flaps, postoperative monitoring of free flaps is essential. We describe a new technique using indocyanine green (ICG) near-infrared angiography and pinprick testing to monitor intraoral free flaps. A solution of ICG (Diagnogreen, 5 ml) was intravenously injected, and scanning was performed with a near-infrared video camera system. Thirty seconds after ICG injection, a pinprick test was performed by placing a 24-gage needle through the dermis to the subcutaneous fat of the flap. Pinprick testing during ICG fluorescence imaging was performed in 30 patients. Flap perfusion was confirmed in all patients, and all flaps survived postoperatively. ICG fluorescence imaging demonstrated that flap perfusion was maintained.

  12. Assessment of Preoperative Liver Function in Patients with Hepatocellular Carcinoma – The Albumin-Indocyanine Green Evaluation (ALICE) Grade

    PubMed Central

    Kokudo, Takashi; Hasegawa, Kiyoshi; Amikura, Katsumi; Uldry, Emilie; Shirata, Chikara; Yamaguchi, Takamune; Arita, Junichi; Kaneko, Junichi; Akamatsu, Nobuhisa; Sakamoto, Yoshihiro; Takahashi, Amane; Sakamoto, Hirohiko; Makuuchi, Masatoshi; Matsuyama, Yutaka; Demartines, Nicolas; Malagó, Massimo; Kokudo, Norihiro; Halkic, Nermin

    2016-01-01

    Background Most patients with hepatocellular carcinoma (HCC) have underlying liver disease, therefore, precise preoperative evaluation of the patient’s liver function is essential for surgical decision making. Methods We developed a grading system incorporating only two variables, namely, the serum albumin level and the indocyanine green retention rate at 15 minutes (ICG R15), to assess the preoperative liver function, based on the overall survival of 1868 patients with HCC who underwent liver resection. We then tested the model in a European cohort (n = 70) and analyzed the predictive power for the postoperative short-term outcome. Results The Albumin-Indocyanine Green Evaluation (ALICE) grading system was developed in a randomly assigned training cohort: linear predictor = 0.663 × log10ICG R15 (%)−0.0718 × albumin (g/L) (cut-off value: -2.20 and -1.39). This new grading system showed a predictive power for the overall survival similar to the Child-Pugh grading system in the validation cohort. Determination of the ALICE grade in Child-Pugh A patients allowed further stratification of the postoperative prognosis. This result was reproducible in the European cohort. Determination of the ALICE grade allowed better prediction of the risk of postoperative liver failure and mortality (ascites: grade 1, 2.1%; grade 2, 6.5%; grade 3, 16.0%; mortality: grade 1, 0%; grade 2, 1.3%; grade 3, 5.3%) than the previously reported model based on the presence/absence of portal hypertension. Conclusions This new grading system is a simple method for prediction of the postoperative long-term and short-term outcomes. PMID:27434062

  13. Encapsulation and stabilization of indocyanine green within poly(styrene-alt-maleic anhydride) block-poly(styrene) micelles for near-infrared imaging.

    PubMed

    Rodriguez, Victoria B; Henry, Scott M; Hoffman, Allan S; Stayton, Patrick S; Li, Xingde; Pun, Suzie H

    2008-01-01

    Indocyanine green (ICG) is a Federal Drug Administration-approved near-infrared imaging agent susceptible to chemical degradation, nonspecific binding to blood proteins, and rapid clearance from the body. In this study, we describe the encapsulation of ICG within polymeric micelles formed from poly(styrene-alt-maleic anhydride)-block-poly(styrene) (PSMA-b-PSTY) diblock copolymers to stabilize ICG for applications in near-infrared diagnostic imaging. In aqueous solution, the diblock copolymers self-assemble to form highly stable micelles approximately 55 nm in diameter with a critical micelle concentration (CMC) of approximately 1 mg/L. Hydrophobic ICG salts readily partition into the PSTY core of these micelles with high efficiency, and produce no change in micelle morphology or CMC. Once loaded in the micelle core, ICG is protected from aqueous and thermal degradation, with no significant decrease in fluorescence emission over 14 days at room temperature and retaining 63% of its original emission at 37 degrees C. Free ICG does not release rapidly from the micelle core, with only 11% release over 24 h. The ICG-loaded micelles do not exhibit significant cell toxicity. This system has the potential to greatly improve near-infrared imaging in breast cancer detection by increasing the stability of ICG for formulation/administration, and by providing a means to target ICG to tumor tissue.

  14. 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.

  15. Interactions of indocyanine green and lipid in enhancing near-infrared fluorescence properties: the basis for near-infrared imaging in vivo.

    PubMed

    Kraft, John C; Ho, Rodney J Y

    2014-03-01

    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.

  16. Noninvasive Optical Imaging and In Vivo Cell Tracking of Indocyanine Green Labeled Human Stem Cells Transplanted at Superficial or In-Depth Tissue of SCID Mice.

    PubMed

    Sabapathy, Vikram; Mentam, Jyothsna; Jacob, Paul Mazhuvanchary; Kumar, Sanjay

    2015-01-01

    Stem cell based therapies hold great promise for the treatment of human diseases; however results from several recent clinical studies have not shown a level of efficacy required for their use as a first-line therapy, because more often in these studies fate of the transplanted cells is unknown. Thus monitoring the real-time fate of in vivo transplanted cells is essential to validate the full potential of stem cells based therapy. Recent studies have shown how real-time in vivo molecular imaging has helped in identifying hurdles towards clinical translation and designing potential strategies that may contribute to successful transplantation of stem cells and improved outcomes. At present, there are no cost effective and efficient labeling techniques for tracking the cells under in vivo conditions. Indocyanine green (ICG) is a safer, economical, and superior labelling technique for in vivo optical imaging. ICG is a FDA-approved agent and decades of usage have clearly established the effectiveness of ICG for human clinical applications. In this study, we have optimized the ICG labelling conditions that is optimal for noninvasive optical imaging and demonstrated that ICG labelled cells can be successfully used for in vivo cell tracking applications in SCID mice injury models.

  17. 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.

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

    PubMed

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

    2016-12-01

    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.

  19. Indocyanine green in-situ administration and photothermal destruction of tumor cells using an 808-nm diode laser

    NASA Astrophysics Data System (ADS)

    Chen, Wei R.; Phillips, Claudia S.; Bartels, Kenneth E.; Adams, Robert L.; Nordquist, Robert E.

    1996-05-01

    Laser tumor tissue photothermal interaction was studied using an 808 nm diode laser and indocyanine green as the photosensitizer. This in vitro study employed laser power in the range of 3 to 5 watts and an aqueous ICG solution that was administered to murine mammary tumor tissue by intralesional injection. Histology revealed a highly selective photothermal tumor tissue destruction at the center of the ICG injection, while the tumor cells not in the ICG area were spared. Also studied was the retention of photosensitizer in tissue following different methods of administration. The absorption spectra of tissue in the range of 400 to 900 nm were obtained at different time intervals after ICG injections for liver and kidney tissue, as well as tumor tissue. Our results showed, shortly after intracardiac injection, a rapid increase of ICG concentration in liver and virtually no accumulation of ICG in the subcutaneous tumor tissue. In contrast, the intratumoral-injected ICG remained in the tumor with sufficient concentration for a duration up to 48 hours, particularly in the case of well- circumscribed tumors. The combination of the in situ ICG administration and the 808-nm diode laser provided selective and controllable cancer tissue destruction when appropriate laser powers and dosage of ICG were employed.

  20. 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. PMID:27217837

  1. Diagnostic Performance of Indocyanine Green-Guided Sentinel Lymph Node Biopsy in Breast Cancer: A Meta-Analysis

    PubMed Central

    Zhou, Yidong; Mao, Feng; Lin, Yan; Guan, Jinghong; Sun, Qiang

    2016-01-01

    Background The diagnostic performance of indocyanine green (ICG) fluorescence-guided sentinel lymph node biopsy (SLNB) for the presence of metastases in breast cancer remains unclear. Objective We performed a meta-analysis to investigate the diagnostic performance of ICG-guided SLNB. Methods Eligible studies were identified from searches of the databases PubMed and EMBASE up to September 2015. Studies that reported the detection rate of ICG fluorescence-guided SLNB with full axillary lymph node dissection and histological or immunohistochemical examinations were included. A meta-analysis was performed to generate pooled detection rate, sensitivity, specificity, false negative rate, diagnostic odds ratio (DOR) and a summary receiver operator characteristic curve (SROC). Results Nineteen published studies were included to generate a pooled detection rate, comprising 2594 patients. The pooled detection rate was 0.98 (95% confidence interval [CI], 0.96–0.99). Six studies finally met the criteria for meta-analysis, which yielded a pooled sensitivity of 0.92 (95% CI, 0.85–0.96), specificity 1 (95% CI, 0.97–1), and DOR 311.47 (95% CI, 84.11–1153.39). The area under the SROC was 0.9758. No publication bias was found. Conclusion ICG fluorescence-guided SLNB is viable for detection of lymph node metastases in breast cancer. Large-scale randomized multi-center trials are necessary to confirm our results. PMID:27280407

  2. Double sentinel lymph node mapping with indocyanine green and 99m-technetium-tin colloid in oral squamous cell carcinoma.

    PubMed

    Murase, R; Tanaka, H; Hamakawa, T; Goda, H; Tano, T; Ishikawa, A; Hino, S; Sumida, T; Nakashiro, K; Hamakawa, H

    2015-10-01

    Oral squamous cell carcinoma (OSCC) frequently metastasizes to cervical lymph nodes, which is the most known prognostic factor. Screening methods to identify sentinel lymph nodes (SLNs) are therefore of great interest for the management of potential neck metastasis. The purpose of this study was to evaluate the clinical benefit of double SLN mapping with indocyanine green (ICG) and 99m-technetium-tin colloid ((99m)Tc-tin colloid) for sentinel node navigation surgery (SNNS). Between 2007 and 2010, 16 patients diagnosed with OSCC were investigated by SLN biopsy using the double mapping method. (99m)Tc-tin colloid was injected into the peri-tumoural region on the preoperative day, and ICG was administered intraoperatively in the same position to assist in detecting nodes during surgery. Based on the gamma-ray signal and near-infrared (NIR) fluorescence of ICG, SLNs were identified and thereafter assessed pathologically and genetically for cancer involvement. Radio-guided detection was successful for all patients. ICG mapping identified a relatively larger number of nodes, suggesting that several non-SLNs were potentially involved. The double mapping method assisted surgeons to explore SLNs. Since the ICG fluorescence was shielded by the subcutaneous fatty tissue and the muscle layer including platysma and sternocleidomastoid, it was necessary to retract the tissue away from nodes.

  3. Morphological study in B16F10 murine melanoma cells after photodynamic hyperthermal therapy with indocyanine green (ICG).

    PubMed

    Radzi, Rozanaliza; Osaki, Tomohiro; Tsuka, Takeshi; Imagawa, Tomohiro; Minami, Saburo; Okamoto, Yoshiharu

    2012-04-01

    Photodynamic hyperthermal therapy (PHT) with indocyanine green (ICG) is a combination of photodynamic therapy (PDT) and hyperthermia (HT). The low toxicity of ICG with an absorption wavelength of 700-800 nm is thought to make it a good candidate as a photosensitizer for PHT. Upon irradiation, ICG produces oxygen radicals and generates heat. The optimal concentration of ICG and the PHT post-irradiation time effects were evaluated by the cytotoxicity of the treatment on B16F10 murine melanoma. The cytotoxicity of PHT was determined based on the morphology of apoptotic and necrotic cells under phase-contrast microscope, confocal laser scanning microscope (CLSM) with DAPI and Annexin V-FITC/PI double staining, and cell surface structure evaluation by scanning electron microscopy (SEM). The use of ICG at a concentration of 150 µM was selected, as cell proliferation was inhibited from 0 to 24 hr post-PHT with a 3-fold decrease in cell viability (P<0.001) compared to the control group. A morphological observation revealed apoptotic and some degree of necrotic features in the PHT-treated cells. PMID:22134111

  4. 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.

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

    PubMed

    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.

  6. Indocyanine green-loaded biodegradable tumor targeting nanoprobes for in vitro and in vivo imaging.

    PubMed

    Zheng, Cuifang; Zheng, Mingbin; Gong, Ping; Jia, Dongxue; Zhang, Pengfei; Shi, Bihua; Sheng, Zonghai; Ma, Yifan; Cai, Lintao

    2012-08-01

    Indocyanine green (ICG) is a near-infrared (NIR) fluorescence dye for extensive biological application, but limited by its poor aqueous stability in vitro, concentration-dependent aggregation, rapid elimination from the body, and lack of target specificity. In this paper, to overcome these limitations, folate receptor-targeted, ICG dye-doped poly(d,l-lactide-co-glycolide) (PLGA) lipid nanoparticles (FA-ICG-PLGA-lipid NPs) were constructed by a single-step self-assemble and nanoprecipitation method. The prepared FA-ICG-PLGA-lipid NPs exhibited good biocompatibility, monodispersity, excellent NIR penetration ability, significant stability against photobleaching and long circulation time. The intracellular uptake experiment proved the targeting efficacy of the FA-ICG-PLGA-lipid NPs was more effective in folate receptor over-expressing MCF-7 cells than folate receptor negative A549 cells. Furthermore, the in vivo experiments showed the FA-ICG-PLGA-lipid NPs were specifically targeted to the tumor, and its circulation time was much longer than free ICG. These biocompatible and biodegradable NIR-NPs prove a potential application in tumor diagnosis and targeted imaging due to its high aqueous stability, excellent NIR optical properties and significantly targeting property in vivo.

  7. Morphological study in B16F10 murine melanoma cells after photodynamic hyperthermal therapy with indocyanine green (ICG).

    PubMed

    Radzi, Rozanaliza; Osaki, Tomohiro; Tsuka, Takeshi; Imagawa, Tomohiro; Minami, Saburo; Okamoto, Yoshiharu

    2012-04-01

    Photodynamic hyperthermal therapy (PHT) with indocyanine green (ICG) is a combination of photodynamic therapy (PDT) and hyperthermia (HT). The low toxicity of ICG with an absorption wavelength of 700-800 nm is thought to make it a good candidate as a photosensitizer for PHT. Upon irradiation, ICG produces oxygen radicals and generates heat. The optimal concentration of ICG and the PHT post-irradiation time effects were evaluated by the cytotoxicity of the treatment on B16F10 murine melanoma. The cytotoxicity of PHT was determined based on the morphology of apoptotic and necrotic cells under phase-contrast microscope, confocal laser scanning microscope (CLSM) with DAPI and Annexin V-FITC/PI double staining, and cell surface structure evaluation by scanning electron microscopy (SEM). The use of ICG at a concentration of 150 µM was selected, as cell proliferation was inhibited from 0 to 24 hr post-PHT with a 3-fold decrease in cell viability (P<0.001) compared to the control group. A morphological observation revealed apoptotic and some degree of necrotic features in the PHT-treated cells.

  8. Use of indocyanine green for detecting the sentinel lymph node in breast cancer patients: from preclinical evaluation to clinical validation.

    PubMed

    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.

  9. 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.

  10. Activatable fluorescent cys-diabody conjugated with indocyanine green derivative: consideration of fluorescent catabolite kinetics on molecular imaging.

    PubMed

    Sano, Kohei; Nakajima, Takahito; Ali, Towhid; Bartlett, Derek W; Wu, Anna M; Kim, Insook; Paik, Chang H; Choyke, Peter L; Kobayashi, Hisataka

    2013-10-01

    Antibody fragments including diabodies have more desirable pharmacokinetic characteristics than whole antibodies. An activatable optical imaging probe based on a cys-diabody targeting prostate-specific membrane antigen conjugated with the near-infrared fluorophore, indocyanine green (ICG), was designed such that it can only be activated when bound to the tumor, leading to high signal-to-background ratios. We employed short polyethylene glycol (PEG) linkers between the ICG and the reactive functional group (Sulfo-OSu group), resulting in covalent conjugation of ICG to the cys-diabody, which led to lower dissociation of ICG from cys-diabody early after injection, reducing hepatic uptake. However, unexpectedly, high and long-term fluorescence was observed in the kidneys, liver, and blood pool more than 1 h after injection of the cys-diabody PEG-ICG conjugate. A biodistribution study using I125-labeled cys-diabody-ICG showed immediate uptake in the kidneys followed by a rapid decrease, while gastric activity increased due to released radioiodine during rapid cys-diabody-ICG catabolism in the kidneys. To avoid this catabolic pathway, it would be preferable to use antibody fragments large enough not to be filtered through glomerulus or to conjugate the fragments with fluorescent dyes that are readily excreted into urine when cleaved from the cys-diabody to achieve high tumor-specific detection.

  11. False-negative indocyanine green videoangiography among complex unruptured middle cerebral artery aneurysms: the importance of further aneurysm inspection.

    PubMed

    Kulwin, Charles; Cohen-Gadol, Aaron A

    2014-10-01

    Successful surgical treatment of cerebral aneurysms requires complete occlusion of the aneurysm lumen while maintaining patency of the adjacent branching and perforating arteries. Intraoperative flow assessment allows aneurysm clip repositioning in the event these requirements are not met, avoiding the risk of postoperative rehemorrhage or infarction. A number of modalities have been proposed for primarily intraoperative qualitative blood flow assessment, including microdoppler ultrasonography, intraoperative digital subtraction angiography (DSA), and more recently noninvasive fluorescent angiography including indocyanine green (ICG) fluorescent imaging. Puncture of the aneurysm dome to exclude aneurysm sac filling may also assess the efficacy of clip placement. Although a high concordance between ICG and DSA has been reported, there remains an important subset of aneurysms for which negative ICG study may erroneously suggest aneurysm occlusion. A high-risk situation for such a false-negative study is an atherosclerotic middle cerebral artery (MCA) aneurysm in which vessel wall plaque interferes with the ICG signal. Furthermore, a decreased flow within the aneurysm may not allow enough emission light for detection under the current technology. In this report, we describe our experience with cases of MCA aneurysms with false-negative ICG-VA studies requiring clip adjustment for optimal surgical treatment and discuss two illustrative cases of MCA aneurysms with intraoperative fluorescence studies that were falsely negative, requiring puncture of the aneurysm to correctly identify incomplete aneurysm occlusion. PMID:24552255

  12. [A study of serum protein fraction binding to indocyanine green (ICG) by combined method of immunoelectrophoresis and ICG fundus videosystem].

    PubMed

    Saito, T; Komatsu, Y; Mori, S; Deguchi, T; Koyama, I; Yoneya, S

    1996-08-01

    Binding characteristics of indocyanine green (ICG) to human serum were investigated, with a combination of immunoelectrophoresis and an ICG fundus video system. Serum samples were obtained from three healthy volunteers, 1 minute after intravenous administration of 50 mg/2 ml ICG, and then fractionated immunoelectrophoretically on agarose plates. Electrophoretic patterns on these plates could be observed with an ICG fundus video system as well as an immunoviewer. Using anti-human sera, only one infrared fluorescent line showing the ICG binding immunoprecipitate was recognized near the area of beta fraction, which was also identified by the use of anti-beta-lipoprotein (Lp) antibody. We also studied the affinity of ICG for apolipoproteins (Apo) AI, B, and CIII, which were the main protein components of serum Lps. Electrophoresis showed that ICG bound only to Apo-B, but not to the others. These results indicated that ICG mainly bound to beta-Lp in the blood, and that ICG angiographic patterns were directly reflecting the dynamics of serum Lps, especially for LDL. The high affinity of ICG for only Apo-B could explain the reason why ICG mainly bound to beta-Lp among several serum Lps, because large amounts of Apo-B are included in beta-Lp but a little in other serum Lps.

  13. Intraoperative Combined Use of Somatosensory Evoked Potential, Microvascular Doppler Sonography, and Indocyanine Green Angiography in Clipping of Intracranial Aneurysm

    PubMed Central

    Li, Zhili; Zhang, Guanni; Huang, Guangfu; Wang, Zhengyu; Tan, Haibin; Liu, Jinping; Li, Aiguo

    2016-01-01

    Background The aim of this study was to evaluate the effect of combining application of somatosensory evoked potential (SEP), microvascular Doppler sonography (MDS), and indocyanine green angiography (ICGA) in intracranial aneurysm clipping surgery. Material/Methods A total of 158 patients undergoing an intracranial aneurysm clipping operation were recruited. All patients were evaluated with intraoperative SEP and MDS monitoring, and 28 of them were evaluated with intraoperative combined monitoring of SEP, MDS, and ICGA. Results The SEP waves dropped during temporary occlusion of arteries in 19 cases (12.0%), and returned to normal after the clips were repositioned. After aneurysms were clipped, the vortex flow signals were detected by MDS in 6 cases. The aneurysm neck remnants were detected by ICGA in 2 cases of olfactory artery (OA) and in 1 case of middle cerebral artery (MCA), which disappeared after the clips were repositioned. Postoperative CTA or DSA showed that aneurysms were clipped completely and parent arteries and perforating vessels were patent. GOS at 1 month after the surgery was good in 111 cases (70.3%), mild disability in 22 cases (13.9%), severe disability in 14 cases (8.9%), vegetative state in 5 cases (3.2%), and death in 6 cases (3.8%). Conclusions Intraoperative combining application of SEP, MDS, and ICGA can reduce brain tissue ischemia and damage and disability and mortality rate after effective clipping of intracranial aneurysms, thereby improving surgical outcomes. PMID:26845425

  14. Intraoperative Near-infrared Fluorescence Imaging with Novel Indocyanine Green-Loaded Nanocarrier for Spinal Metastasis: A Preliminary Animal Study

    PubMed Central

    Funayama, Toru; Sakane, Masataka; Abe, Tetsuya; Hara, Isao; Ozeki, Eiichi; Ochiai, Naoyuki

    2012-01-01

    Marginal resection during resection of a spinal metastasis is frequently difficult because of the presence of important tissues such as the aorta, vena cava, and dura mater, including the spinal cord adjacent to the vertebral body. Thus, there is an urgent need for novel intraoperative imaging modalities with the ability to clearly identify bone metastasis. We have proposed a novel nanocarrier loaded with indocyanine green (ICG) (ICG-lactosome) with tumor selectivity attributable to its enhanced permeation and retention (EPR) effect. We studied its feasibility in intraoperative near-infrared (NIR) fluorescence diagnosis with ICG-lactosome for imaging spinal metastasis. A rat model of subcutaneous mammary tumor and a rat model of spinal metastasis of breast cancer were used. Fluorescence emitted by the subcutaneous tumors and the spinal metastasis were clearly detected for at least 24 h. Moreover, imaging of the dissected spine revealed clear fluorescence emitted by the metastatic lesion in the L6 vertebra while the normal bone lacked fluorescence. This study was the first report on NIR fluorescence imaging of spinal metastasis in vivo. NIR fluorescence imaging with ICG-lactosome could be an effective intraoperative imaging modality for detecting spinal metastasis. PMID:22787518

  15. 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.

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

    PubMed Central

    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

    2015-01-01

    ABSTRACT 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. PMID:26398933

  17. Effect of near-infrared diode laser and indocyanine green to treat infections on different wound models

    NASA Astrophysics Data System (ADS)

    Topaloglu, Nermin; Yuksel, Sahru; Gulsoy, Murat

    2014-05-01

    The emergence of antibiotic resistant bacteria causes significant increase in deaths due to wound infections around the world. Nowadays, it could be impossible to find appropriate antibiotics to treat some bacterial strains, especially multidrug resistant types. The aim of this study is to use photodynamic therapy that destroys these kinds of bacteria with the interaction of Indocyanine green (ICG) and 808-nm diode laser. In this study, antibacterial Photodynamic Therapy technique that we call ICG-IR Laser PDT was applied on antibiotic-resistant strains of Staphylococcus aureus that infected two different types of wound model (excisional and abrasion wound model) in vivo. Wistar albino rats were used to create animal wound models. Excisional or abrasion wounds were formed on the dorsal skin of the rats. They were infected with Staphylococcus aureus. 300 mW and 500 mW of 808-nm diode laser were applied on the wounds for 30 minutes and 15 minutes of exposure duration, respectively. ICG concentrations applied topically were 500, 1000, 1500 and 2000 μg/ml. Then the tissue was dissected properly and homogenized in buffer solution. From this solution, bacterial cell count was determined by serial dilution method. 1-2 log reduction in viable cell count was observed after these applications. The temperature increase in the tissue was between 6-8°C during these applications. From these findings, it was understood that this method with 808-nm and ICG is promising but it must be improved by further dosimetry studies.

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

    PubMed Central

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

    2014-01-01

    Introduction 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. Material and methods PubMed and Medline databases were searched for ICG and MB use in urological settings, along with data published in abstracts of urological conferences. Results 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. Conclusions 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. PMID:25247093

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

    PubMed Central

    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. PMID:27217837

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

    PubMed

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

    2010-02-17

    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 are difficult to carry out. We report the three-step room-temperature synthesis of approximately 120-nm capsules loaded with ICG within salt-cross-linked polyallylamine aggregates, and coated with antiepidermal 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/cm(2). These results illustrate the ability to design a colloidal material with cell targeting and heat generating capabilities using noncovalent chemistry.

  1. Activatable fluorescent cys-diabody conjugated with indocyanine green derivative: consideration of fluorescent catabolite kinetics on molecular imaging

    PubMed Central

    Sano, Kohei; Nakajima, Takahito; Ali, Towhid; Bartlett, Derek W.; Wu, Anna M.; Kim, Insook; Paik, Chang H.; Choyke, Peter L.

    2013-01-01

    Abstract. Antibody fragments including diabodies have more desirable pharmacokinetic characteristics than whole antibodies. An activatable optical imaging probe based on a cys-diabody targeting prostate-specific membrane antigen conjugated with the near-infrared fluorophore, indocyanine green (ICG), was designed such that it can only be activated when bound to the tumor, leading to high signal-to-background ratios. We employed short polyethylene glycol (PEG) linkers between the ICG and the reactive functional group (Sulfo-OSu group), resulting in covalent conjugation of ICG to the cys-diabody, which led to lower dissociation of ICG from cys-diabody early after injection, reducing hepatic uptake. However, unexpectedly, high and long-term fluorescence was observed in the kidneys, liver, and blood pool more than 1 h after injection of the cys-diabody PEG-ICG conjugate. A biodistribution study using I125-labeled cys-diabody-ICG showed immediate uptake in the kidneys followed by a rapid decrease, while gastric activity increased due to released radioiodine during rapid cys-diabody-ICG catabolism in the kidneys. To avoid this catabolic pathway, it would be preferable to use antibody fragments large enough not to be filtered through glomerulus or to conjugate the fragments with fluorescent dyes that are readily excreted into urine when cleaved from the cys-diabody to achieve high tumor-specific detection. PMID:23752742

  2. 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.

  3. 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

  4. 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.

  5. Laparoscopic sentinel lymph node mapping after cervical injection of indocyanine green for endometrial cancer – preliminary report

    PubMed Central

    Reinholz-Jaskolska, Malgorzata; Bidzinski, Mariusz

    2015-01-01

    Introduction Endometrial cancer (EC) has an increasing incidence worldwide, with lymph node metastases as the main prognostic factor. Systemic lymphadenectomy is connected with elevated morbidity. Sentinel lymph node (SLN) biopsy is intended to avoid extensive lymphadenectomy and provide significant oncologic information. Aim To evaluate the accuracy of laparoscopic SLN biopsy guided by indocyanine green (ICG) injection into the cervix in EC patients and to develop ideas to improve this method. The optimal time from dye injection to lymph node visualization was assessed. Material and methods This retrospective study was conducted between July 2014 and March 2015 in a group of 9 women with EC, at low and intermediate risk of recurrence, scheduled for total laparoscopic hysterectomy and pelvic lymphadenectomy. All patients underwent cervical ICG injection and SLN biopsy, followed by surgery. Pelvic lymph nodes were located using an ICG endoscopic camera. Results The following data were collected: There were 9 patients with endometrial cancer at low and intermediate risk of recurrence. Median patient age was 59 years, median body mass index (BMI) 28 kg/m2, endometrioid adenocarcinoma in 9 cases, grading: G1 – 1 patient, G2 – 8 patients. No intraoperative or postoperative complications were noted. Median time from ICG injection and SLN detection during surgery was 25 min. There were no lymph nodes metastasis, all identified by the SLN protocol using ICG injection. Conclusions Sentinel lymph node mapping can play a significant role in lymph node assessment and staging in early-stage EC patients with low risk of recurrence according to the ESMO classification. The use of SLN mapping in EC is much needed and the therapeutic benefit is high. PMID:26649087

  6. Blood flow speed of the gastric conduit assessed by indocyanine green fluorescence: New predictive evaluation of anastomotic leakage after esophagectomy.

    PubMed

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

    2016-07-01

    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

  7. Enhancement of the photostability and retention time of indocyanine green in sentinel lymph node mapping by anionic polyelectrolytes.

    PubMed

    Noh, Young-Woock; Park, Hye Sun; Sung, Moon-Hee; Lim, Yong Taik

    2011-09-01

    Sentinel lymph node (SLN) biopsy techniques have been widely used in the diagnosis of cancer metastasis because lymph node metastasis is one of the most important prognostic signs. Indocyanine green (ICG) has potential application as a molecular imaging probe for SLN mapping due to its fluorescent properties emitting in the near-infrared (NIR) region, where light transmission through biological tissue is maximized. However, its low photostability in an aqueous solution at the physiological temperature and its rapid diffusion behavior through SLN into the second lymph node have limited its wide use in real clinical fields. In this study, we developed a new NIR imaging contrast system consisting of ICG and poly (γ-glutamic acid) (γ-PGA) polymers for efficient sentinel lymph node mapping. By a combination of clinically used ICG and the biocompatible anionic polyelectrolyte, γ-PGA, the photostabilities of aqueous ICG solutions at room and body temperatures were drastically enhanced. When the ICG/γ-PGA complex was injected subcutaneously into the front paw of a mouse, it entered the lymphatics and migrated to the axillary sentinel lymph node (SLN) within 2 min. Furthermore, the NIR fluorescent signal intensity and retention time of ICG/γ-PGA complex in lymph node were superior to those of ICG only. In addition, a histofluorescentstudy of the SLN resected under NIR imaging revealed that ICG and γ-PGA were co-localized in the lymph node.Taken together, the experimental results on the enhanced photostability and retention time of the ICG/γ-PGA complex provide strong evidence that it has promising potential for improved sentinel lymph node mapping.

  8. Indocyanine green clearance varies as a function of N-acetylcysteine treatment in a murine model of acetaminophen toxicity.

    PubMed

    Milesi-Hallé, Alessandra; Abdel-Rahman, Susan M; Brown, Aliza; McCullough, Sandra S; Letzig, Lynda; Hinson, Jack A; James, Laura P

    2011-02-01

    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 (Cl(T)) 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 Cl(T) 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.

  9. 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

  10. Optimization of the enhanced permeability and retention effect for near-infrared imaging of solid tumors with indocyanine green

    PubMed Central

    Jiang, Jack X; Keating, Jane J; Jesus, Elizabeth M De; Judy, Ryan P; Madajewski, Brian; Venegas, Ollin; Okusanya, Olugbenga T; Singhal, Sunil

    2015-01-01

    Surgery is the most effective method to cure patients with solid tumors. New techniques in near-infrared (NIR) cancer imaging are being used to identify surgical margins and residual tumor cells in the wound. Our goal was to determine the optimal time and dose for imaging solid tumors using Indocyanine Green. Syngeneic murine flank tumor models were used to test NIR imaging of ICG at various doses ranging from 0 to 10 mg/kg. Imaging was performed immediately after injection and up to 72 hours later. Biodistribution in the blood and murine organs were quantified by spectroscopy and fluorescence microscopy. Based on these results, a six patient dose titration study was performed. In murine flank tumors, the tumor-to-background ratio (TBR) for ICG at doses less than 5 mg/kg were less than 2 fold at all time points, and the surgeons could not subjectively identify tissue contrast. However, for doses ranging from 5 mg/kg to 10 mg/kg, the TBR ranged from 2.1 to 8.0. The tumor signal was best appreciated at 24 hours and the background was least pronounced after 24 hours. Biodistribution studies in the blood and murine organs revealed excretion through the biliary tree and gastrointestinal tract, with minimal blood fluorescence at the higher doses. A follow up pilot study confirmed that these findings were applicable to lung cancer patients, and tumor was clearly delineated from surrounding normal tissue by NIR imaging. For non-hepatic solid tumors, we found ICG was optimal when dosed at 5 mg/kg and 24 hours before surgery. PMID:26269776

  11. 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

  12. Photothermal ablation of human lung cancer by low-power near-infrared laser and topical injection of indocyanine green.

    PubMed

    Hirohashi, Kentaro; Anayama, Takashi; Wada, Hironobu; Nakajima, Takahiro; Kato, Tatsuya; Keshavjee, Shaf; Orihashi, Kazumasa; Yasufuku, Kazuhiro

    2015-04-01

    The present study was designed to evaluate the efficacy of photothermal ablation therapy for lung cancer by low-power near-infrared laser and topical injection of indocyanine green (ICG). In vitro study 1: an 808 nm laser with 250 mW was irradiated for 10 minutes using different dilutions of ICG and the temporal thermal effect was monitored. ICG (1 mL of 0.5 g/L) was heated to a temperature of >30°C from the base temperature by laser irradiation. In vitro study 2: the cytotoxic effect of hyperthermia on human lung cancer cells was examined in different temperature and time settings. Cell viability was quantified by both an MTS assay and reculturing. Fatal conditions evaluated by reculturing were as follows: thermal treatment at 55°C for 5 minutes, 53°C for 10 minutes, and 51°C for 15 minutes. The MTS assay study suggested that thermal treatment at 59°C for 5 minutes and 57°C for 20 minutes showed a severe cytotoxic effect. In vivo study: nude mouse subcutaneous NCI-H460 human lung cancer xenograft models were used for the study. Saline or 0.5 g/L of ICG was injected topically into the tumor (n=3/group). Tumors were irradiated with a laser at 500 mW for 10 minutes. Although the tumor diameter reached 1 cm within 24 days after treatment in all 3 mice using saline/laser, tumor sizes were gradually reduced in all 3 mice using the ICG/laser. In 2 of the 3 mice using ICG/laser, tumors had disappeared macroscopically. The efficacy of the photothermal ablation therapy by low-power near-infrared laser and a topical injection of ICG was clarified using a mouse subcutaneous a lung cancer xenograft model.

  13. Influence of different output powers on the efficacy of photodynamic therapy with 809-nm diode laser and indocyanine green

    NASA Astrophysics Data System (ADS)

    Topaloglu, Nermin; Yuksel, Sahru; Gulsoy, Murat

    2013-02-01

    Photodynamic therapy (PDT) is an alternative antimicrobial treatment method. Different wavelengths of light sources mostly in the visible spectrum have been investigated for antimicrobial Photodynamic Therapy. Even though the wavelengths in near infrared spectrum have the advantage of higher penetration capability in biological tissue, they have not been preferred for PDT because of their possible photothermal effect in biological tissues. In our previous studies, the desired PDT effect was achieved with 809-nm diode laser and indocyanine green (ICG) on drug resistant pathogens. In this study, it was aimed to investigate the influence of different output powers during PDT applications with 809-nm diode laser to clarify whether there is a photothermal effect to kill the pathogens or only the photochemical effect of photodynamic therapy. 4 different output powers (500 mW, 745 mW, 1000 mW, 1500 mW) were examined in Laseronly and PDT groups of P. aeruginosa ATCC 27853 in vitro. In the PDT groups, a non-phototoxic ICG concentration (50 μl/ml) has been chosen to eliminate the toxic effect of ICG and evaluate only the thermal effect of laser. Applied energy dose (252 J/cm2) was kept constant by increasing the exposure duration (300, 240, 180 and 120 seconds respectively). These output powers in Laser-only or PDT groups did not seem to cause photothermal effect. There was not any significant decrease or increase on bacterial load after the applications with different output powers. Higher output powers in PDT groups with the same ICG concentration did not cause any higher killing effect.

  14. Near-infrared spectroscopy extended with indocyanine green dye dilution for cerebral blood flow measurement: Median values in healthy volunteers

    NASA Astrophysics Data System (ADS)

    Mudra, R.; Muroi, C.; Niederer, P.; Keller, E.

    2008-09-01

    The cerebral blood flow (CBF) is an important vital parameter in neurointensive care. Currently, there is no non-invasive method for its measurement that can easily be applied at the bedside. A new tool to determine CBF is based on near-infrared spectroscopy (NIRS) applied together with indocyanine green (ICG) dye dilution. From a bilateral measurement on selected regions on the head of infrared (IR) absorption at various wavelengths during the dilution maneuver, the vascular perfusion characteristics of the two brain hemispheres can be determined in terms of mean transit time (mtt) of ICG, cerebral blood volume (CBV) and CBF. So far, on nine healthy volunteers, NIRS ICG dye dilution bihemispheric measurements were performed, which yielded to mtt given as median (range) of 9.3 s (5.1-16.3 s), CBV of 3.5 ml/100 g (1.7-4.1 ml/100 g), and CBF of 18.2 ml/(100 g×min) [11.1-48.6 ml/(100 g×min)]. Additionally, the blood flow index (BFI) was calculated with BFI= 13.8 mg/(100 g×s) [6.6-15.2 mg/(100 g×s)]. The Spearman rank correlation coefficient between CBF and BFI was RS = 0.76. However, as the Bland & Altman plot between CBFNIRS and the CBFBFI documents, the limits of agreement are rather wide (21.9±6.7). Under physiological conditions in healthy volunteers, no differences could be detected between the hemispheres.

  15. 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.

  16. Effects of indocyanine green in treatment of murine mammary tumor by an 808-nm diode laser: an in-vivo study

    NASA Astrophysics Data System (ADS)

    Chen, Wei R.; Wichert, Kelly G.; Higgins, Aaron K.; Bartels, Kenneth E.; Adams, Robert L.; Nordquist, Robert E.

    1996-04-01

    Indocyanine green was used to enhance laser-induced photothermal destruction of murine mammary tumor cells. The 808-nm diode laser used in these experiments matches the absorption peak of the indocyanine green. The combination of the laser and in situ administration of aqueous ICG provided a highly selective photothermal destruction pattern of the tumor tissue. Histology showed that within the power range of 3 to 5 watts. The ICG- targeted tumor tissues were fatally injured, while the peripheral tissues such as skin and other interdicting tissue not containing ICG were spared. Higher powers (10 to 15 watts) could inflict severe surface damage but only resulted in limited tissue penetration. Post-treatment observation also revealed surviving tumor cells, the cause of which might be the non-uniform distribution of ICG as well as the random scattering of photons inside tissue. After laser-ICG treatment, the tumor continued to grow, but at a slower rate, and to metastasize, leading to the death of the rats. The findings of our experiments question the long-term efficacy of the photothermal effect of a single treatment using the ICG and diode laser. However, the controlled killing of tumor cells on a large scale may be proven crucial when the treatment is applied repeatedly and/or in an earlier stage so that tumor growth could be stopped and metastases prevented. This photothermal interaction may also be effective when used in conjunction with other modalities.

  17. 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.

  18. Photodynamic hyperthermal therapy with indocyanine green (ICG) induces apoptosis and cell cycle arrest in B16F10 murine melanoma cells.

    PubMed

    Radzi, Rozanaliza; Osaki, Tomohiro; Tsuka, Takeshi; Imagawa, Tomohiro; Minami, Saburo; Nakayama, Yuji; Okamoto, Yoshiharu

    2012-05-01

    We examined the effects of photodynamic hyperthemal therapy (PHT), which is a combination of photodynamic therapy (PDT) and hyperthermia (HT), on the apoptosis and cell cycle progression of murine melanoma B16F10 cells. The percentage of apoptotic cell was determined by flow cytometry using fluorescein isothiocyanate (FITC)-conjugated Annexin V and propidium iodide (PI) double staining. The cell cycle analysis was performed by PI staining with flow cytometry. The expression of cyclins and heat shock protein 70 (Hsp70) were examined by a Western blotting analysis. PHT induces death in B16F10 cells, and PHT-mediated apoptosis occurred acutely and persistently in vitro. Our study demonstrated that PHT using indocyanine green (ICG) and near infrared (NIR) light source induces apoptosis and G0/G1 cell cycle arrest in the B16F10 cells. PMID:22146339

  19. 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.

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

    NASA Astrophysics Data System (ADS)

    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.

  1. Photodynamic hyperthermal therapy with indocyanine green (ICG) induces apoptosis and cell cycle arrest in B16F10 murine melanoma cells.

    PubMed

    Radzi, Rozanaliza; Osaki, Tomohiro; Tsuka, Takeshi; Imagawa, Tomohiro; Minami, Saburo; Nakayama, Yuji; Okamoto, Yoshiharu

    2012-05-01

    We examined the effects of photodynamic hyperthemal therapy (PHT), which is a combination of photodynamic therapy (PDT) and hyperthermia (HT), on the apoptosis and cell cycle progression of murine melanoma B16F10 cells. The percentage of apoptotic cell was determined by flow cytometry using fluorescein isothiocyanate (FITC)-conjugated Annexin V and propidium iodide (PI) double staining. The cell cycle analysis was performed by PI staining with flow cytometry. The expression of cyclins and heat shock protein 70 (Hsp70) were examined by a Western blotting analysis. PHT induces death in B16F10 cells, and PHT-mediated apoptosis occurred acutely and persistently in vitro. Our study demonstrated that PHT using indocyanine green (ICG) and near infrared (NIR) light source induces apoptosis and G0/G1 cell cycle arrest in the B16F10 cells.

  2. 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.

  3. In vivo dual-modality imaging of lymphatic systems using indocyanine green in rats: three-dimensional photoacoustic imaging and planar fluorescence imaging

    NASA Astrophysics Data System (ADS)

    Kim, Chulhong; Song, Kwang Hyun; Wang, Lihong V.

    2010-02-01

    The purpose of this study is to map non-invasively sentinel lymph nodes (SLNs) and lymphatic vessels of rats in vivo using FDA-approved indocyanine green (ICG) and two non-ionizing imaging modalities: volumetric spectroscopic photoacoustic (PA) imaging, which measures optical absorption, and planar fluorescence imaging, which measures fluorescent emission. SLNs and lymphatic vessels were clearly visible after a 0.2 ml-intradermal-injection of 1 mM ICG in both imaging systems. We also imaged deeply positioned lymph nodes in vivo by layering biological tissues on top of rats. These two modalities, when used together with ICG, have the potential to map SLNs in axillary staging and to study tumor metastasis in breast cancer patients.

  4. Usage of invisible near infrared light (NIR) fluorescence with indocyanine green (ICG) and methylene blue (MB) in urological oncology. Part 1

    PubMed Central

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

    2014-01-01

    Introduction Near infrared (NIR) technology has recently garnered much interest as a tool for intraoperative image–guided surgery in various surgical sub–disciplines. In urology, although nascent, NIR technology is also fostering much enthusiasm. This review discusses the two major fluorophores, indocyanine green (ICG) and methlyene blue (MB), with NIR guidance in experimental and clinical urology. The authors aim to illustrate and analyze the currently available initial studies to better understand the potential and practicability of NIR–guided imaging in the diagnosis and surgical outcome improvement. In the first part of the study we analyzed problems associated with sentinel lymph node biopsy, NIR–guided detection and imaging of tumors. Material and methods PubMed and Medline databases were searched for ICG and MB use in urological settings, along with data published in abstracts of urological conferences. Results Although NIR–guided ICG and MB are still in their initial phases, there have been significant developments in major domains of urology, including uro–oncological surgery: 1) sentinel lymph node biopsy, 2) detection and imaging of tumors Conclusions Much like in other fields of surgical medicine, the application of NIR technology in urology is at its early stages. Therefore, more studies are needed to assess the true potential and limitations of the technology. However, initial developments hint towards a pioneering tool that may influence various aspects of urology. PMID:25140227

  5. A Near-Infrared Photothermal Effect-Responsive Drug Delivery System Based on Indocyanine Green and Doxorubicin-Loaded Polymeric Micelles Mediated by Reversible Diels-Alder Reaction.

    PubMed

    Li, Hui; Li, Junjie; Ke, Wendong; Ge, Zhishen

    2015-10-01

    Near-infrared light (NIR) possesses great advantages for light-responsive controllable drug release, such as deep tissue penetration and low damage to healthy tissues. Herein, a NIR-responsive drug delivery system is developed based on a NIR dye, indocyanine green (ICG), and anticancer drug, doxorubicin (DOX)-loaded thermoresponsive block copolymer micelles, in which the drug release can be controlled via NIR irradiation. First, block copolymers, poly(oligo(ethylene glycol) methacrylate)-block-poly(furfuryl methacrylate) (POEGMA-b-PFMA), are synthesized by sequential reversible addition-fragmentation chain-transfer (RAFT) polymerization, followed by modification with N-octyl maleimide through Diels-Alder (DA) reaction to produce POEGMA-b-POMFMA. The self-assembly of POEGMA-b-POMFMA by nano-precipitation in aqueous solution affords the polymeric micelles which are used to simultaneously encapsulate ICG and DOX. Upon irradiation by NIR light (805 nm), the loaded DOX is released rapidly from the micelles due to partial retro DA reaction and local temperature increase-induced faster drug diffusion by the photothermal effect. Cytotoxicity evaluation and intracellular distribution observation demonstrate significant synergistic effects of NIR-triggered drug release, photothermal, and chemotherapy toward cancer cells under NIR irradiation.

  6. 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.

  7. 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.

  8. Near-Infrared Sentinel Lymph Node Mapping With Indocyanine Green Using the VITOM II ICG Exoscope for Open Surgery for Gynecologic Malignancies.

    PubMed

    Buda, Alessandro; Dell'Anna, Tiziana; Vecchione, Francesca; Verri, Debora; Di Martino, Giampaolo; Milani, Rodolfo

    2016-01-01

    Sentinel lymph node (SLN) mapping is emerging as an effective method for surgical staging of different gynecologic malignancies. Near-infrared (NIR) technology using a fluorescent dye such as indocyanine green (ICG) represents an interesting and feasible method for SLN mapping even in traditional open surgeries by applying video telescope operating microscope (VITOM) system technology. We report our preliminary experience in 12 women who underwent surgical nodal staging for early-stage vulvar and uterine or cervical cancer. Surgical and pathological outcomes are described, and the VITOM II ICG system's intraoperative image quality, handling and docking, and teaching value are assessed. The general impression of the surgical staff was that the VITOM II system is easy to use, and that the image quality of the anatomic structures is impressive. Traditional open SLN mapping with ICG appears to be easy to perform and reproducible, providing a new tool in the management of patients with gynecologic malignancies. Moreover, we believe that this technology has great potential as an operative teaching and learning modality for trainers for open surgical cases. Additional studies involving the VITOM system with a large sample size of patients are needed to confirm these promising results. PMID:26921484

  9. Preliminary report: comparison of 980-nm, 808-nm diode laser enhanced with indocyanine green to the Nd:YAG laser applied to equine respiratory tissue

    NASA Astrophysics Data System (ADS)

    Tate, Lloyd P.; Blikslager, Anthony T.; Campbell, Nigel B.

    2001-05-01

    The Neodynium: Yttrium Aluminum Garnet (Nd:YAG) laser has been the mainstay of performing upper respiratory laser surgery in the equine since 1984. The 808-nm diode laser has also been applied transendoscopically as well as the 980-nm diode laser over recent years. It has been shown that Indocyanine Green (ICG) enhances the performance of the 808- nm laser because it is absorbed at 810 nm of light. The 808- nm laser's tissue interaction combined with ICG is equivalent to or greater than the Nd:YAG laser's cutting ability. The 980-nm diode laser performance was similar to that of the Nd:YAG as determined by the parameters of this study. This study compared the depths and widths of penetration achieved with the 808-nm diode laser after intravenous injection of ICG on equine respiratory tissue. It also compared depths and widths of penetration achieved by the non-contact application of the 980-nm diode laser delivering the same energy of 200 joules. The depths and widths of penetration of both diode lasers were compared to themselves and to the Nd:YAG laser with all factors remaining constant.

  10. Analysis of near-infrared spectroscopy and indocyanine green dye dilution with Monte Carlo simulation of light propagation in the adult brain

    NASA Astrophysics Data System (ADS)

    Mudra, Regina M.; Nadler, Andreas; Keller, Emanuela; Niederer, Peter F.

    2006-07-01

    Near-infrared spectroscopy (NIRS) combined with indocyanine green (ICG) dilution is applied externally on the head to determine the cerebral hemodynamics of neurointensive care patients. We applied Monte Carlo simulation for the analysis of a number of problems associated with this method. First, the contamination of the optical density (OD) signal due to the extracerebral tissue was assessed. Second, the measured OD signal depends essentially on the relative blood content (with respect to its absorption) in the various transilluminated tissues. To take this into account, we weighted the calculated densities of the photon distribution under baseline conditions within the different tissues with the changes and aberration of the relative blood volumes that are typically observed under healthy and pathologic conditions. Third, in case of NIRS ICG dye dilution, an ICG bolus replaces part of the blood such that a transient change of absorption in the brain tissues occurs that can be recorded in the OD signal. Our results indicate that for an exchange fraction of Δ=30% of the relative blood volume within the intracerebral tissue, the OD signal is determined from 64 to 74% by the gray matter and between 8 to 16% by the white matter maximally for a distance of d=4.5 cm.

  11. Biodegradable polymer thin film for enhancement of laser-assisted incision closure with an indocyanine-green-doped liquid albumin solder

    NASA Astrophysics Data System (ADS)

    Sorg, Brian S.; McNally-Heintzelman, Karen M.; Welch, Ashley J.

    2000-05-01

    The purpose of this study was to determine if solid material reinforcement of a liquid albumin solder coagulum could improve the cohesive strength of the solder and thus the ultimate breaking strength of the incision repair in vitro. A 50%(w/v) bovine serum albumin solder with 0.5 mg/mL Indocyanine Green (ICG) dye was used to repair an incision in bovine aorta. The solder was coagulated with an 806 nm CW diode laser. A 50 micrometer thick poly(DL-lactic-co-glycolic acid) film was used to reinforce the solder (the controls had no reinforcement). Acute breaking strengths were measured and the data were analyzed by one-way ANOVA (P less than 0.05). Multiple comparisons of means were performed using the Newman- Keuls test. Observations of the failure modes indicated cohesive strength reinforcement of the test specimens versus the controls. At the higher laser powers used in this study (400 and 450 mW), the reinforced solder was consistently stronger than the controls. Reinforcement of liquid albumin solders in laser-assisted incision repair may have mechanical advantages in terms of acute breaking strength over conventional methods that do not reinforce the cohesive strength of the solder.

  12. Impact of Indocyanine Green Concentration, Exposure Time, and Degree of Dissolution in Creating Toxic Anterior Segment Syndrome: Evaluation in a Rabbit Model

    PubMed Central

    Khoramnia, Ramin; Uwe Auffarth, Gerd

    2016-01-01

    Purpose. To investigate the role of indocyanine green (ICG) dye as a causative material of toxic anterior segment syndrome (TASS) in an experimental rabbit model. Method. Eight eyes of four rabbits were allocated to this study. Capsular staining was performed using ICG dye, after which the anterior chamber was irrigated with a balanced salt solution. The effects of different concentrations (control, 0.25, 0.5, and 1.0%), exposure times (10 and 60 seconds), and the degree of dissolution (differently vortexed) were investigated. The analysis involved anterior segment photography, ultrasound pachymetry, prostaglandin assay (PGE2 Parameter Assay, R&D systems, Inc.), and scanning electron microscopy of each iris. Result. There was no reaction in the control eye. A higher aqueous level of PGE2 and more severe inflammatory reaction were observed in cases of eyes with higher concentration, longer exposure time, and poorly dissolved dye. Additionally, scanning electron microscopy revealed larger and coarser ICG particles. Conclusion. TASS occurrence may be associated with the concentration, exposure time, and degree of dissolution of ICG dye during cataract surgery. PMID:27478634

  13. Sentinel Lymph Node Mapping With Near-Infrared Fluorescent Imaging Using Indocyanine Green: A New Tool for Laparoscopic Platform in Patients With Endometrial and Cervical Cancer.

    PubMed

    Buda, Alessandro; Bussi, Beatrice; Di Martino, Giampaolo; Di Lorenzo, Paolo; Palazzi, Sharon; Grassi, Tommaso; Milani, Rodolfo

    2016-02-01

    Indocyanine green (ICG) represents a feasible alternative to the more traditional methods of sentinel lymph node (SLN) mapping, and interest in this promising tracer is growing. This report outlines our experience with ICG in a minimally invasive laparoscopic approach in women with endometrial cancer and cervical cancer using the Storz SPIES ICG near-infrared fluorescence imaging technology. A total of 49 patients with clinical stage I endometrial cancer (n = 40) or stage I cervical cancer (n = 9) were retrospectively reviewed. All patients had undergone simple or radical laparoscopic hysterectomy with pelvic and/or aortic lymphadenectomy and SLN mapping by means of an intracervical injection of ICG dye at the 3 o'clock and 9 o'clock locations after the induction of general anesthesia. The detection rate of ICG was 100% (49 of 49). The rate of bilateral SLN detection was 86% (42 of 49). Positive lymph nodes were found in 6 patients (12%), with at least 1 positive SLN. The sensitivity and negative predictive value of SLN detection were 100%. All procedures were successfully completed without conversion to open laparotomy, and no intraoperative or postoperative complications occurred. In our preliminary experience, ICG showed a high overall detection rate, and bilateral mapping appears to be a feasible alternative to the more traditional methods of SLN mapping in patients with endometrial cancer and cervical cancer. Laparoscopic SLN mapping with ICG appears to be safe, easy, and reproducible, with a positive impact on patient management.

  14. A Near-Infrared Photothermal Effect-Responsive Drug Delivery System Based on Indocyanine Green and Doxorubicin-Loaded Polymeric Micelles Mediated by Reversible Diels-Alder Reaction.

    PubMed

    Li, Hui; Li, Junjie; Ke, Wendong; Ge, Zhishen

    2015-10-01

    Near-infrared light (NIR) possesses great advantages for light-responsive controllable drug release, such as deep tissue penetration and low damage to healthy tissues. Herein, a NIR-responsive drug delivery system is developed based on a NIR dye, indocyanine green (ICG), and anticancer drug, doxorubicin (DOX)-loaded thermoresponsive block copolymer micelles, in which the drug release can be controlled via NIR irradiation. First, block copolymers, poly(oligo(ethylene glycol) methacrylate)-block-poly(furfuryl methacrylate) (POEGMA-b-PFMA), are synthesized by sequential reversible addition-fragmentation chain-transfer (RAFT) polymerization, followed by modification with N-octyl maleimide through Diels-Alder (DA) reaction to produce POEGMA-b-POMFMA. The self-assembly of POEGMA-b-POMFMA by nano-precipitation in aqueous solution affords the polymeric micelles which are used to simultaneously encapsulate ICG and DOX. Upon irradiation by NIR light (805 nm), the loaded DOX is released rapidly from the micelles due to partial retro DA reaction and local temperature increase-induced faster drug diffusion by the photothermal effect. Cytotoxicity evaluation and intracellular distribution observation demonstrate significant synergistic effects of NIR-triggered drug release, photothermal, and chemotherapy toward cancer cells under NIR irradiation. PMID:26274805

  15. Impact of Indocyanine Green Concentration, Exposure Time, and Degree of Dissolution in Creating Toxic Anterior Segment Syndrome: Evaluation in a Rabbit Model.

    PubMed

    Tandogan, Tamer; Khoramnia, Ramin; Uwe Auffarth, Gerd; Janusz Koss, Michael; Young Choi, Chul

    2016-01-01

    Purpose. To investigate the role of indocyanine green (ICG) dye as a causative material of toxic anterior segment syndrome (TASS) in an experimental rabbit model. Method. Eight eyes of four rabbits were allocated to this study. Capsular staining was performed using ICG dye, after which the anterior chamber was irrigated with a balanced salt solution. The effects of different concentrations (control, 0.25, 0.5, and 1.0%), exposure times (10 and 60 seconds), and the degree of dissolution (differently vortexed) were investigated. The analysis involved anterior segment photography, ultrasound pachymetry, prostaglandin assay (PGE2 Parameter Assay, R&D systems, Inc.), and scanning electron microscopy of each iris. Result. There was no reaction in the control eye. A higher aqueous level of PGE2 and more severe inflammatory reaction were observed in cases of eyes with higher concentration, longer exposure time, and poorly dissolved dye. Additionally, scanning electron microscopy revealed larger and coarser ICG particles. Conclusion. TASS occurrence may be associated with the concentration, exposure time, and degree of dissolution of ICG dye during cataract surgery. PMID:27478634

  16. Synthesis and Characterization of Chitosan-Coated Near-Infrared (NIR) Layered Double Hydroxide-Indocyanine Green Nanocomposites for Potential Applications in Photodynamic Therapy

    PubMed Central

    Wei, Pei-Ru; Kuthati, Yaswanth; Kankala, Ranjith Kumar; Lee, Chia-Hung

    2015-01-01

    We designed a study for photodynamic therapy (PDT) using chitosan coated Mg–Al layered double hydroxide (LDH) nanoparticles as the delivery system. A Food and Drug Administration (FDA) approved near-infrared (NIR) fluorescent dye, indocyanine green (ICG) with photoactive properties was intercalated into amine modified LDH interlayers by ion-exchange. The efficient positively charged polymer (chitosan (CS)) coating was achieved by the cross linkage using surface amine groups modified on the LDH nanoparticle surface with glutaraldehyde as a spacer. The unique hybridization of organic-inorganic nanocomposites rendered more effective and successful photodynamic therapy due to the photosensitizer stabilization in the interlayer of LDH, which prevents the leaching and metabolization of the photosensitizer in the physiological conditions. The results indicated that the polymer coating and the number of polymer coats have a significant impact on the photo-toxicity of the nano-composites. The double layer chitosan coated LDH–NH2–ICG nanoparticles exhibited enhanced photo therapeutic effect compared with uncoated LDH–NH2–ICG and single layer chitosan-coated LDH–NH2–ICG due to the enhanced protection to photosensitizers against photo and thermal degradations. This new class of organic-inorganic hybrid nanocomposites can potentially serve as a platform for future non-invasive cancer diagnosis and therapy. PMID:26340627

  17. Synthesis and Characterization of Chitosan-Coated Near-Infrared (NIR) Layered Double Hydroxide-Indocyanine Green Nanocomposites for Potential Applications in Photodynamic Therapy.

    PubMed

    Wei, Pei-Ru; Kuthati, Yaswanth; Kankala, Ranjith Kumar; Lee, Chia-Hung

    2015-09-01

    We designed a study for photodynamic therapy (PDT) using chitosan coated Mg-Al layered double hydroxide (LDH) nanoparticles as the delivery system. A Food and Drug Administration (FDA) approved near-infrared (NIR) fluorescent dye, indocyanine green (ICG) with photoactive properties was intercalated into amine modified LDH interlayers by ion-exchange. The efficient positively charged polymer (chitosan (CS)) coating was achieved by the cross linkage using surface amine groups modified on the LDH nanoparticle surface with glutaraldehyde as a spacer. The unique hybridization of organic-inorganic nanocomposites rendered more effective and successful photodynamic therapy due to the photosensitizer stabilization in the interlayer of LDH, which prevents the leaching and metabolization of the photosensitizer in the physiological conditions. The results indicated that the polymer coating and the number of polymer coats have a significant impact on the photo-toxicity of the nano-composites. The double layer chitosan coated LDH-NH₂-ICG nanoparticles exhibited enhanced photo therapeutic effect compared with uncoated LDH-NH₂-ICG and single layer chitosan-coated LDH-NH₂-ICG due to the enhanced protection to photosensitizers against photo and thermal degradations. This new class of organic-inorganic hybrid nanocomposites can potentially serve as a platform for future non-invasive cancer diagnosis and therapy.

  18. 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.

  19. 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. PMID:27257484

  20. 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. PMID:26005762

  1. Intraoperative near-infrared indocyanine green-videoangiography (ICG-VA) and graphic analysis of fluorescence intensity in cerebral aneurysm surgery.

    PubMed

    Oda, Jumpei; Kato, Yoko; Chen, S F; Sodhiya, Paresh; Watabe, T; Imizu, S; Oguri, D; Sano, H; Hirose, Y

    2011-08-01

    We present our preliminary experience with intraoperative near-infrared indocyanine green-videoangiography (ICG-VA) and analysis of blood flow dynamics using fluorescence intensity assessment in cerebral aneurysm clipping surgery. Thirty-nine patients with 43 intracranial aneurysms underwent microsurgical clipping. Intraoperative ICG-VA was performed before and after clip application. An infrared fluorescence module integrated into a surgical microscope was used to visualize fluorescence in the surgical field and we recorded the emitted fluorescent light. An integrated analytical visualization tool simultaneously analyzed the video sequence and converted it into an intensity diagram, which allowed an objective evaluation of the results rather than the subjective assessment of fluorescence using ICG-VA. Overall, ICG-VA was performed 137 times. Incomplete clipping was detected in four patients, which allowed suitable adjustment to completely obliterate the aneurysm. In 12 patients, perforators arising close to, or from, the aneurysmal neck were identified in the surgical field. In three patients, the ICG-VA intensity diagram provided valuable information leading to modification of the primary surgical maneuver. ICG-VA provides high resolution images allowing real-time assessment of the blood flow in the parent artery and arterial branches, including the perforators. The intensity diagram is useful for providing a more objective record of the hemodynamics than the traditional ICG-VA, which relies more on subjective assessment and may allow interobserver variability. We conclude that ICG-VA, combined with the intensity diagram, can reduce the morbidity and complications associated with aneurysm clipping and improve patient outcomes.

  2. A new LigaSure technique for the formation of segmental plane by intravenous indocyanine green fluorescence during thoracoscopic anatomical segmentectomy

    PubMed Central

    Dejima, Hitoshi; Mizumo, Tetsuya; Sakakura, Noriaki; Sakao, Yukinori

    2016-01-01

    Background The purpose of this study was to present a new approach to the formation of a segmental plane by LigaSure (Covidien, Mansfield, MA, USA) with indocyanine green (ICG) fluorescence system during thoracoscopic segmentectomy. Methods This was a consecutive study that compared 12 patients who underwent a new LigaSure technique (LT) for segmental plane formation during thoracoscopic anatomical segmentectomy with 38 patients who underwent conventional methods using the staple technique (ST). Eleven patients were followed up more than 3 months after discharge. Results The mean age of the patients was 66 years in the LT group and 67 years in ST. The mean duration for the formation of segmental plane and the mean number of staples was 22.8 min and 1.8 per surgery, respectively, in the LT group; and 16.2 min and 3.4 per surgery, respectively, in ST. No patient had a prolonged air leak (PAL) of more than 7 days. Minor air leak was identified early in two and was delayed in one. Two-thirds of patients with early minor air leak had low index of prolonged air leak (IPAL) score. There was no air leak in the patients with high IPAL score. Eventually, we deduced that the cause of the minor air leak was a technical problem. Conclusions In the formation of segmental plane during thoracoscopic segmentectomy, a combination of ICG fluorescence and LigaSure may be beneficial for patients. As a new operative instrument, LT constitutes, in our opinion, a feasible and easy alternative to other thoracoscopic techniques. PMID:27293839

  3. Left paraaortic, inframesenteric lymphadenectomy preserving the superior hypogastric plexus supported by indocyanine green (ICG) labeling of the lymphatic compartment in cervical cancer.

    PubMed

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

    2016-11-01

    Superior hypogastric plexus (SHG) contains mainly sympathetic and most probably also postganglionic parasympathetic fibers. Thus, surgical damage of SHG may cause autonomic pelvic organ dysfunction (Kraima et al., 2015). As already shown for rectal cancer, preservation of the autonomic nerves is facilitated by robotic surgery and may avoid sexual dysfunctions and voiding disorders (Kim et al., 2015). In this educational video, we demonstrate left lower paraaortic lymph node dissection preserving the SHG using ICG fluorescence to label the lymphatic compartment. Prior to total mesometrial resection (TMMR) with therapeutic lymphadenectomy for cervical cancer (Höckel et al., 2009, Kimmig et al., 2013) 4 × 0.5 ml of a 1.66 mg/ml Indocyanine green solution (ICG Pulsion®, PMS SE, Feldkirchen, Germany) was injected into the uterine cervix at all four quadrants, 0.5 cm in depth (Kimmig et al., 2016). The lymphatic network of the downstream common iliac and inferior paraaortic lymph compartments of the uterine cervix is visualized (ICG fluorescence) including the individual connecting vessels between the different compartments. As can be demonstrated, the medial upper common iliac (subaortic) compartment drains preferentially into the anterior (mesenteric) compartment, whereas lateral common iliac lymphatic vessels mainly drain to the posterior (lumbar) paraaortic compartment. The autonomic nerve fibers of the SHP may easily be identified and preserved due to the excellent image resolution and the discrimination from fluorescent lymphatic structures. The video shows the preparation of left lower paraaortic nodes in cervical cancer following ICG labeling using a da Vinci Xi system®. This technique seems not only advantageous for preserving SHP, but even more highly educational to learn surgical anatomy for trainees.

  4. Enhanced fluorescence diffuse optical tomography with indocyanine green-encapsulating liposomes targeted to receptors for vascular endothelial growth factor in tumor vasculature

    NASA Astrophysics Data System (ADS)

    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 t 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 t 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 t 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.

  5. In vivo photoacoustic imaging of cancer using indocyanine green-labeled monoclonal antibody targeting the epidermal growth factor receptor.

    PubMed

    Sano, Kohei; Ohashi, Manami; Kanazaki, Kengo; Ding, Ning; Deguchi, Jun; Kanada, Yuko; Ono, Masahiro; Saji, Hideo

    2015-08-28

    Photoacoustic (PA) imaging is an attractive imaging modality for sensitive and depth imaging of biomolecules with high resolution in vivo. The aim of this study was to evaluate the effectiveness of an anti-epidermal growth factor receptor (EGFR) monoclonal antibody (panitumumab; Pan) labeled with indocyanine green derivative (ICG-EG4-Sulfo-OSu), Pan-EG4-ICG, as a PA imaging probe to target cancer-associated EGFR. In vitro PA imaging studies demonstrated that Pan-EG4-ICG yielded high EGFR-specific PA signals in EGFR-positive cells. To determine the optimal injection dose and scan timing, we investigated the biodistribution of radiolabeled Pan-EG4-ICG (200-400 μg) in A431 tumor (EGFR++)-bearing mice. The highest tumor accumulation (29.4% injected dose/g) and high tumor-to-blood ratio (2.1) was observed 7 days after injection of Pan-EG4-ICG (400 μg). In in vivo PA imaging studies using Pan-EG4-ICG (400 μg), the increase in PA signal (114%) was observed in A431 tumors inoculated in the mammary glands 7 days post-injection. Co-injection of excess Pan resulted in a 35% inhibition of this PA signal, indicating the EGFR-specific accumulation. In conclusion, the ICG-labeled monoclonal antibody (i.e., panitumumab) has the potential to enhance target-specific PA signal, leading to the discrimination of aggressiveness and metastatic potential of tumors and the selection of effective therapeutic strategies.

  6. 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.

  7. Detecting abnormalities in choroidal vasculature in a mouse model of age-related macular degeneration by time-course indocyanine green angiography.

    PubMed

    Kumar, Sandeep; Berriochoa, Zachary; Jones, Alex D; Fu, Yingbin

    2014-02-19

    Indocyanine Green Angiography (or ICGA) is a technique performed by ophthalmologists to diagnose abnormalities of the choroidal and retinal vasculature of various eye diseases such as age-related macular degeneration (AMD). ICGA is especially useful to image the posterior choroidal vasculature of the eye due to its capability of penetrating through the pigmented layer with its infrared spectrum. ICGA time course can be divided into early, middle, and late phases. The three phases provide valuable information on the pathology of eye problems. Although time-course ICGA by intravenous (IV) injection is widely used in the clinic for the diagnosis and management of choroid problems, ICGA by intraperitoneal injection (IP) is commonly used in animal research. Here we demonstrated the technique to obtain high-resolution ICGA time-course images in mice by tail-vein injection and confocal scanning laser ophthalmoscopy. We used this technique to image the choroidal lesions in a mouse model of age-related macular degeneration. Although it is much easier to introduce ICG to the mouse vasculature by IP, our data indicate that it is difficult to obtain reproducible ICGA time course images by IP-ICGA. In contrast, ICGA via tail vein injection provides high quality ICGA time-course images comparable to human studies. In addition, we showed that ICGA performed on albino mice gives clearer pictures of choroidal vessels than that performed on pigmented mice. We suggest that time-course IV-ICGA should become a standard practice in AMD research based on animal models.

  8. 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.

  9. 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

  10. Left paraaortic, inframesenteric lymphadenectomy preserving the superior hypogastric plexus supported by indocyanine green (ICG) labeling of the lymphatic compartment in cervical cancer.

    PubMed

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

    2016-11-01

    Superior hypogastric plexus (SHG) contains mainly sympathetic and most probably also postganglionic parasympathetic fibers. Thus, surgical damage of SHG may cause autonomic pelvic organ dysfunction (Kraima et al., 2015). As already shown for rectal cancer, preservation of the autonomic nerves is facilitated by robotic surgery and may avoid sexual dysfunctions and voiding disorders (Kim et al., 2015). In this educational video, we demonstrate left lower paraaortic lymph node dissection preserving the SHG using ICG fluorescence to label the lymphatic compartment. Prior to total mesometrial resection (TMMR) with therapeutic lymphadenectomy for cervical cancer (Höckel et al., 2009, Kimmig et al., 2013) 4 × 0.5 ml of a 1.66 mg/ml Indocyanine green solution (ICG Pulsion®, PMS SE, Feldkirchen, Germany) was injected into the uterine cervix at all four quadrants, 0.5 cm in depth (Kimmig et al., 2016). The lymphatic network of the downstream common iliac and inferior paraaortic lymph compartments of the uterine cervix is visualized (ICG fluorescence) including the individual connecting vessels between the different compartments. As can be demonstrated, the medial upper common iliac (subaortic) compartment drains preferentially into the anterior (mesenteric) compartment, whereas lateral common iliac lymphatic vessels mainly drain to the posterior (lumbar) paraaortic compartment. The autonomic nerve fibers of the SHP may easily be identified and preserved due to the excellent image resolution and the discrimination from fluorescent lymphatic structures. The video shows the preparation of left lower paraaortic nodes in cervical cancer following ICG labeling using a da Vinci Xi system®. This technique seems not only advantageous for preserving SHP, but even more highly educational to learn surgical anatomy for trainees. PMID:27672677

  11. 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. PMID:24034538

  12. Biostimulative effect of 809-nm diode laser and indocyanine green on p. aeruginosa instead of photodynamic therapy

    NASA Astrophysics Data System (ADS)

    Aysan, Nuray; Topaloglu, Nermin; Yuksel, Sahru; Gulsoy, Murat

    2013-03-01

    Photodynamic therapy (PDT) is a safe and alternative antimicrobial treatment that consists of a chemical agent, called photosensitizer, which can be activated by light of an appropriate wavelength to produce reactive oxygen species (ROS). PDT can be used for photoinactivation of bacteria in an attempt to overcome the problem of bacterial multidrug resistance. In particular, it is an effective antimicrobial treatment against infected wounds that have antibiotic resistance and wound infections would otherwise lead to mortality and morbidity. The main purpose of this study was to demonstrate the importance of PDT dosimetry (light dose and concentration of photosensitizer). If the dosimetry of PDT was not optimized properly, photoinactivation of bacteria cannot be achieved and even worse biostimulation on pathogens could be observed. This study investigated whether there is a biostimulative effect due to free oxygen radicals of PDT when light dose and photosensitizer concentration are too low. In this study, the biostimulative effect on P. aeruginosa strain was observed instead of the PDT effect, when 84 J/cm2 of energy dose (809-nm diode laser) was applied with 20, 50, 100 and 150 μg/ml of ICG concentrations. The killing effect of PDT was observed with higher ICG concentrations, such as 200, 250 μg/ml of ICG. However the killing effect was not enough to destroy pathogen efficiently with these high concentrations of ICG.

  13. 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…

  14. The challenge of developing green tea polyphenols as therapeutic agents.

    PubMed

    Huo, C; Wan, S B; Lam, W H; Li, L; Wang, Z; Landis-Piwowar, K R; Chen, D; Dou, Q P; Chan, T H

    2008-10-01

    The health benefits of green tea and its main constituent (-)-epigallocatechin gallate [(-)-EGCG] have been widely supported by results from epidemiological, cell culture, animal and clinical studies. On the other hand, there are a number of issues, such as stability, bioavailability and metabolic transformations under physiological conditions, facing the development of green tea polyphenols into therapeutic agents. We previously reported that the synthetic peracetate of (-)-EGCG has improved stability and better bioavailability than (-)-EGCG itself and can act as pro-drug under both in vitro and in vivo conditions. Analogs of catechins have been synthesized and their structure activity relationship provides an understanding to the mechanism of proteasome inhibition. Metabolic methylation of catechins leading to methylated (-)-EGCG may alter the biological activities of these compounds. PMID:18815735

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

    PubMed

    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.

  16. 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. PMID:26616992

  17. 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.

  18. 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.

  19. 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.

  20. The role of indocyanine green angiography imaging in further differential diagnosis of patients with nAMD who are morphologically poor responders to ranibizumab in a real-life setting.

    PubMed

    Ozkaya, A; Alagoz, C; Garip, R; Alkin, Z; Perente, I; Yazici, A T; Taskapili, M

    2016-07-01

    PurposeTo evaluate the neovascular age-related macular degeneration (nAMD) in patients who were morphologically poor responders to intravitreal ranibizumab (IVR) treatment using indocyanine green angiography (ICGA) for further investigation.MethodsThis was a cross-sectional, retrospective study. The patients with an initial diagnosis of nAMD who made through the clinical examination, optical coherence tomography, and fluorescein angiography imaging, and were treated with at least three monthly IVR injections that resulted with a morphological poor response, were included. ICGA was obtained from the patients and evaluated in regard to differential diagnosis of other macular diseases, which might mimic nAMD.ResultsThe study included 132 eyes of 117 patients. The mean age was 67.4±9.4 years. After ICGA imaging, 13 eyes (9.8%) were diagnosed as true nAMD, 74 eyes (56.1%) as polypoidal choroidal vasculopathy (PCV), 35 eyes (26.5%) as chronic central serous chorioretinopathy (CSC), 3 eyes (2.3%) as retinal angiomatous proliferation (RAP), 3 eyes (2.3%) as choroidal neovascularization secondary to CSC, 2 eyes (1.5%) as adult-onset vitelliform macular dystrophy, and 2 eyes (1.5%) as drusenoid pigment epithelial detachment with vitelliform material, respectively. The duration between the initial diagnosis and the revised diagnosis was 15.6±10.5 months in the non-AMD group, and the mean injection number of these patients was 6.6±4.4.ConclusionsMost of the nAMD patients who were thought to be morphologically poor responders to IVR were diagnosed as having non-AMD diseases via ICGA. A detailed differential diagnostic work-up is needed before considering these patients as poor responders. PMID:27080484

  1. Fluorescence Identification of Head and Neck Squamous Cell Carcinoma and High-Risk Oral Dysplasia With BLZ-100, a Chlorotoxin-Indocyanine Green Conjugate

    PubMed Central

    Baik, FM; Hansen, S; Knoblaugh, SE; Sahetya, D; Mitchell, RM; Xu, C; Olson, JM; Parrish-Novak, J; Méndez, E

    2016-01-01

    Importance Surgical cure of head and neck squamous cell carcinoma (HNSCC) remains hampered by inadequately resected tumors and poor recognition of lesions with malignant potential. BLZ-100 is chlorotoxin-based tumor targeting agent which has not yet been studied in HNSCC. Objective To evaluate BLZ-100 uptake in models of HNSCC and oral dysplasia. Design Observational study (including sensitivity/specificity analysis) of BLZ-100 uptake in an orthotopic xenograft mouse model of HNSCC and a carcinogen-induced dysplasia model of hamster cheek pouches. Setting Research laboratory Participants NSG mice, Golden Syrian hamsters Interventions Various HNSCC xenografts were established in the tongues of NSG mice. BLZ-100 was intravenously injected and fluorescence uptake was measured. To induce dysplasia, the carcinogen DMBA was applied to the cheek pouch of Golden Syrian hamsters for 9–16 weeks. BLZ-100 was subcutaneously injected and fluorescence uptake was measured. Main Outcomes and Measures The signal-to-background ratio (SBR) of BLZ-100 was measured in tumor xenografts. To calculate the sensitivity and specificity of BLZ-100 uptake, a digital grid was placed over tissue sections and correlative histologic sections to discretely measure fluorescence intensity and presence of tumor; a receiver operating characteristic (ROC) curve was then plotted. In the hamster dysplasia model, cheeks were graded according to dysplasia severity. The SBR of BLZ-100 was compared among dysplasia grades. Results In HNSCC xenografts, BLZ-100 demonstrated an overall signal-to-background ratio (SBR) of 2.51 +/− 0.47 SD. The ROC curve demonstrated an area under the curve (AUC) of 0.889; a SBR of 2.5 corresponded to 92% sensitivity and 74% specificity. When this analysis was focused on the tumor and non-tumor interface, the AUC increased to 0.971; a SBR of 2.5 corresponded to 95% sensitivity and 91% specificity. DMBA treatment of hamster cheek pouches generated lesions representing all grades

  2. In vivo photoacoustic flow cytometry for monitoring of circulating single cancer cells and contrast agents

    NASA Astrophysics Data System (ADS)

    Zharov, Vladimir P.; Galanzha, Ekaterina I.; Shashkov, Evgeny V.; Khlebtsov, Nicolai G.; Tuchin, Valery V.

    2006-12-01

    A new photoacoustic flow cytometry was developed for real-time detection of circulating cells, nanoparticles, and contrast agents in vivo. Its capability, integrated with photothermal and optical clearing methods, was demonstrated using a near-infrared tunable laser to characterize the in vivo kinetics of Indocyanine Green alone and single cancer cells labeled with gold nanorods and Indocyanine Green in the vasculature of the mouse ear. In vivo applications are discussed, including selective nanophotothermolysis of metastatic squamous cells, label-free detection of melanoma cells, study of pharmokinetics, and immune response to apoptotic and necrotic cells, with potential translation to humans. The threshold sensitivity is estimated as one cancer cell in the background of 107 normal blood cells.

  3. Effect of chitosan and its derivatives as antifungal and preservative agents on postharvest green asparagus.

    PubMed

    Qiu, Miao; Wu, Chu; Ren, Gerui; Liang, Xinle; Wang, Xiangyang; Huang, Jianying

    2014-07-15

    The antifungal activity and effect of high-molecular weight chitosan (H-chitosan), low-molecular weight chitosan (L-chitosan) and carboxymethyl chitosan (C-chitosan) coatings on postharvest green asparagus were evaluated. L-chitosan and H-chitosan efficiently inhibited the radial growth of Fusarium concentricum separated from postharvest green asparagus at 4 mg/ml, which appeared to be more effective in inhibiting spore germination and germ tube elongation than that of C-chitosan. Notably, spore germination was totally inhibited by L-chitosan and H-chitosan at 0.05 mg/ml. Coated asparagus did not show any apparent sign of phytotoxicity and maintained good quality over 28 days of cold storage, according to the weight loss and general quality aspects. Present results inferred that chitosan could act as an attractive preservative agent for postharvest green asparagus owing to its antifungal activity and its ability to stimulate some defense responses during storage.

  4. Concentration Effect of Reducing Agents on Green Synthesis of Gold Nanoparticles: Size, Morphology, and Growth Mechanism

    NASA Astrophysics Data System (ADS)

    Kim, Hyun-seok; Seo, Yu Seon; Kim, Kyeounghak; Han, Jeong Woo; Park, Youmie; Cho, Seonho

    2016-04-01

    Under various concentration conditions of reducing agents during the green synthesis of gold nanoparticles (AuNPs), we obtain the various geometry (morphology and size) of AuNPs that play a crucial role in their catalytic properties. Through both theoretical and experimental approaches, we studied the relationship between the concentration of reducing agent (caffeic acid) and the geometry of AuNPs. As the concentration of caffeic acid increases, the sizes of AuNPs were decreased due to the adsorption and stabilizing effect of oxidized caffeic acids (OXCAs). Thus, it turns out that optimal concentration exists for the desired geometry of AuNPs. Furthermore, we investigated the growth mechanism for the green synthesis of AuNPs. As the caffeic acid is added and adsorbed on the surface of AuNPs, the aggregation mechanism and surface free energy are changed and consequently resulted in the AuNPs of various geometry.

  5. Two-photon excitation microscopy using the second singlet state of fluorescent agents within the ``tissue optical window''

    NASA Astrophysics Data System (ADS)

    Pu, Yang; Shi, Lingyan; Pratavieira, Sebastião; Alfano, R. R.

    2013-10-01

    Two-photon (2P) excitation of the second singlet (S2) state of a group of fluorescent agents with near infrared emission was used to extend the optical excitation and imaging regime of 2P microscope into "tissue optical window" (650-1100 nm). As the first step to achieve deeper optical imaging, Chlorophyll a and Indocyanine green are investigated and demonstrated as imaging agents using 2P S2 excitation at 800 nm for microscope imaging at 685 nm. The salient feature is to drive both the 2P excitation and emission wavelengths of the imaging agents to fall into the "tissue optical window."

  6. Intradermal administration of fluorescent contrast agents for delivery to axillary lymph nodes

    NASA Astrophysics Data System (ADS)

    Rasmussen, John C.; Meric-Berstam, Funda; Krishnamurthy, Savitri; Tan, I.-Chih; Zhu, Banghe; Wagner, Jamie L.; Babiera, Gildy V.; Mittendorf, Elizabeth A.; Sevick-Muraca, Eva M.

    2014-05-01

    In this proof-of-concept study we seek to demonstrate the delivery of fluorescent contrast agent to the tumor-draining lymph node basin following intraparenchymal breast injections and intradermal arm injection of micrograms of indocyanine green in 20 breast cancer patients undergoing complete axillary lymph node dissection. Individual lymph nodes were assessed ex vivo for presence of fluorescent signal. In all, 88% of tumor-negative lymph nodes and 81% of tumor-positive lymph nodes were fluorescent. These results indicate that future studies utilizing targeted fluorescent contrast agents may demonstrate improved surgical and therapeutic intervention.

  7. Cariostatic Effect of Green Tea in Comparison with Common Anticariogenic Agents: An in Vitro Study

    PubMed Central

    Jazaeri, Mina; Pakdek, Farzaneh; Rezaei-Soufi, Loghman; Abdolsamadi, Hamidreza; Rafieian, Nasrin

    2015-01-01

    Background and aims. Anticariogenic effects of different mouthrinses have been shown previously. In this in vitro study the anticariogenic effects of polyphenol extract of green tea with 0.05% fluoride, 0.2% chlorhexidine and fluoride-chlorhexidine were compared. Materials and methods. This in vitro study was performed on 50 maxillary premolars in 5 groups: 1) normal saline; 2) a 10% solution of green tea polyphenol extract; 3) 0.05% fluoride; 4) 0.2% chlorhexidine; and 5) fluoride-chlorhexidine. Each tooth was placed in a tube which contained a cariogenic solution. Every day the teeth were washed (depending on the experimental groups) with 5 mL of mouthrinse solution. The depth of the caries was measured under a polarized light microscope. Data were analyzed using SPSS 13.0 with Kolmogorov-Smirnov, one-way ANOVA and Tukey tests. Results. The mean and standard deviation (in µm) of caries depth were 194±16.43, 175±17.94, 142±9.34, 155±13.27, and 144±8.57 in groups 1 to 5, respectively, with significant differences between the groups (P<0.001). Tukey test showed that although there was no significant difference in the depth of caries in groups 1 and 2 (P>0.001), they were significantlyless than those in groups 3 to 5 (P<0.001). There was no significant difference between decay depth of groups 3, 4 and 5 (P>0.001). Conclusion. The anticariogenic effect of fluoride-chlorhexidine was the highest among the groups. Although green tea showed higher cariostatic effects than normal saline, in comparison with other mouthrinses, it is less effective. More re-search is strongly recommended for clinical use of green tea as an anticariogenic agent. PMID:25973154

  8. Cariostatic effect of green tea in comparison with common anticariogenic agents: an in vitro study.

    PubMed

    Jazaeri, Mina; Pakdek, Farzaneh; Rezaei-Soufi, Loghman; Abdolsamadi, Hamidreza; Rafieian, Nasrin

    2015-01-01

    Background and aims. Anticariogenic effects of different mouthrinses have been shown previously. In this in vitro study the anticariogenic effects of polyphenol extract of green tea with 0.05% fluoride, 0.2% chlorhexidine and fluoride-chlorhexidine were compared. Materials and methods. This in vitro study was performed on 50 maxillary premolars in 5 groups: 1) normal saline; 2) a 10% solution of green tea polyphenol extract; 3) 0.05% fluoride; 4) 0.2% chlorhexidine; and 5) fluoride-chlorhexidine. Each tooth was placed in a tube which contained a cariogenic solution. Every day the teeth were washed (depending on the experimental groups) with 5 mL of mouthrinse solution. The depth of the caries was measured under a polarized light microscope. Data were analyzed using SPSS 13.0 with Kolmogorov-Smirnov, one-way ANOVA and Tukey tests. Results. The mean and standard deviation (in µm) of caries depth were 194±16.43, 175±17.94, 142±9.34, 155±13.27, and 144±8.57 in groups 1 to 5, respectively, with significant differences between the groups (P<0.001). Tukey test showed that although there was no significant difference in the depth of caries in groups 1 and 2 (P>0.001), they were significantlyless than those in groups 3 to 5 (P<0.001). There was no significant difference between decay depth of groups 3, 4 and 5 (P>0.001). Conclusion. The anticariogenic effect of fluoride-chlorhexidine was the highest among the groups. Although green tea showed higher cariostatic effects than normal saline, in comparison with other mouthrinses, it is less effective. More re-search is strongly recommended for clinical use of green tea as an anticariogenic agent. PMID:25973154

  9. 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.

  10. 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. PMID:23270888

  11. Green Synthesis of Silver Nanoparticles: Effect of Dextran Molecular Weight Used as Stabilizing-Reducing Agent.

    PubMed

    Carré-Rangel, Luceldi; Alonso-Nuñez, Gabriel; Espinoza-Gómez, Heriberto; Flores-López, Lucía Z

    2015-12-01

    This paper describes an easy green chemistry method for the synthesis of silver nanoparticles (AgNPs). The AgNPs were obtained through the use of an aqueous silver nitrate solution (AgNO3), with dextrans aqueous solutions of different molecular weights acting as stabilizing and reducing agent, employing the chemical reduction method. We made a comparative study to determine which molecular weight dextran was the best stabilizing and reducing agent, and it was found that the molecular size of the stabilizing agent is inversely proportional to the size of the nanoparticle synthesized. The formation of the AgNPs was demonstrated by UV-Vis spectroscopy, atomic force microscopy (AFM), scanning electron microscopy-energy dispersive spectroscopy (SEM-EDS) and transmission electron microscopy (TEM). SEM-EDS analysis shows the formation of particles with dendritic structure. TEM shows nanoparticles which are spherical in shape and 1-10 nm in size; also, the clear lattice fringes show highly crystalline AgNPs (FCC). PMID:26682423

  12. 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.

  13. 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

  14. 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. PMID:22103574

  15. 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.

  16. Green synthesis of gold nanoparticles using aqueous ethanol extract of Curcuma mangga rhizomes as reducing agent

    NASA Astrophysics Data System (ADS)

    Yee, Foo Yiing; Periasamy, Vengadesh; Malek, Sri Nurestri Abd

    2015-04-01

    Green synthesis of gold nanoparticles (AuNPs) had been developed as an alternative to chemical and physical methods due to its simplicity, cost effectiveness and eco-friendliness. The high biocompatibility and biostability features of AuNPs have found importance in biomedical applications in recent years. In this study, aqueous ethanol extract of Curcuma mangga rhizomes which acts as reducing and stabilizing agent was used to synthesize stable AuNPs by bioreduction of chloroauric acid. The formation of AuNPs was highlighted by the color change of the suspension from light yellow to reddish purple. Time-evolution was monitored by UV-visible spectroscopy, while surface plasmon (SP) absorption band of the AuNPs suspension was observed at a maximum absorption of 540 nm. Hydrodynamic radii and size distribution of the AuNPs in the suspension were evaluated using dynamic light scattering (DLS) and zeta potential measurement demonstrated negative surface charge. The particle size was calculated in the range of 2-30 nm using High Resolution Transmission Electron Microscopy (HRTEM). The morphology and elemental composition were further determined by Field Effect Scanning Electron Microscopy (FESEM) and Energy Dispersive X-ray (EDX) spectroscopy. Fourier transform infrared (FTIR) spectroscopy meanwhile was used to confirm the presence of AuNPs and functional groups involved in the gold bio-reduction process. Influence of the volume of extract and concentration of gold (III) chloride trihydrate (HAuCl4.3H2O) on the synthesis of AuNPs were also investigated. The results obtained indicate potential optimization and functionalization of AuNPs for future applications in bionanotechnology especially in the field of medicine.

  17. Green synthesis of gold nanoparticles using aqueous ethanol extract of Curcuma mangga rhizomes as reducing agent

    SciTech Connect

    Yee, Foo Yiing; Malek, Sri Nurestri Abd; Periasamy, Vengadesh

    2015-04-24

    Green synthesis of gold nanoparticles (AuNPs) had been developed as an alternative to chemical and physical methods due to its simplicity, cost effectiveness and eco-friendliness. The high biocompatibility and biostability features of AuNPs have found importance in biomedical applications in recent years. In this study, aqueous ethanol extract of Curcuma mangga rhizomes which acts as reducing and stabilizing agent was used to synthesize stable AuNPs by bioreduction of chloroauric acid. The formation of AuNPs was highlighted by the color change of the suspension from light yellow to reddish purple. Time-evolution was monitored by UV-visible spectroscopy, while surface plasmon (SP) absorption band of the AuNPs suspension was observed at a maximum absorption of 540 nm. Hydrodynamic radii and size distribution of the AuNPs in the suspension were evaluated using dynamic light scattering (DLS) and zeta potential measurement demonstrated negative surface charge. The particle size was calculated in the range of 2-30 nm using High Resolution Transmission Electron Microscopy (HRTEM). The morphology and elemental composition were further determined by Field Effect Scanning Electron Microscopy (FESEM) and Energy Dispersive X-ray (EDX) spectroscopy. Fourier transform infrared (FTIR) spectroscopy meanwhile was used to confirm the presence of AuNPs and functional groups involved in the gold bio-reduction process. Influence of the volume of extract and concentration of gold (III) chloride trihydrate (HAuCl{sub 4}.3H{sub 2}O) on the synthesis of AuNPs were also investigated. The results obtained indicate potential optimization and functionalization of AuNPs for future applications in bionanotechnology especially in the field of medicine.

  18. Virus-mimicking nano-constructs as a contrast agent for near infrared photoacoustic imaging

    NASA Astrophysics Data System (ADS)

    Gupta, Sharad; Chatni, Muhammad R.; Rao, Ayala L. N.; Vullev, Valentine I.; Wang, Lihong V.; Anvari, Bahman

    2013-02-01

    We report the first proof-of-principle demonstration of photoacoustic imaging using a contrast agent composed of a plant virus protein shell, which encapsulates indocyanine green (ICG), the only FDA-approved near infrared chromophore. These nano-constructs can provide higher photoacoustic signals than blood in tissue phantoms, and display superior photostability compared to non-encapsulated ICG. Our preliminary results suggest that the constructs do not elicit an acute immunogenic response in healthy mice.We report the first proof-of-principle demonstration of photoacoustic imaging using a contrast agent composed of a plant virus protein shell, which encapsulates indocyanine green (ICG), the only FDA-approved near infrared chromophore. These nano-constructs can provide higher photoacoustic signals than blood in tissue phantoms, and display superior photostability compared to non-encapsulated ICG. Our preliminary results suggest that the constructs do not elicit an acute immunogenic response in healthy mice. Electronic supplemental information (ESI) available: Information on experimental procedure for fabrication of the nano-constructs, photoacoustic imaging, and immunogenic studies. See DOI: 10.1039/c3nr34124k

  19. Study of anti-angiogenic drugs by fluorescence imaging and spectroscopy of a contrast agent in mice

    NASA Astrophysics Data System (ADS)

    Valentini, G.; D'Andrea, C.; Ferrari, R.; Pifferi, A.; Cubeddu, R.; Caronia, D.; Martinelli, M.; Giavazzi, R.

    2007-07-01

    We used two fluorescence techniques based on the Indocyanine Green contrast agent to study the effectiveness of antiangionenic drugs in mice. To this purpose, the volume of the active vasculature in different tumor models implanted in mice was assessed by means of a low noise fluorescence imaging setup and by a photon counting system working in transmittance geometry. Using a first tumor model (carcinoma MDA-MB-435) we observed that mice treated with a Vascular Disrupting Agent (ZD6126) showed a reduction in fluorescence emission of the contrast agent with respect to control mice. This was a clear indication of the vascular shutdown that took place in tumors. The effectiveness of the treatment was also confirmed by histological sections. Then, in a second experiment we considered a second tumor model (carcinoma 1A9-VS1) overexpressing the Vascular Endotelial Growth Factor (VEGF121), which is used by tumor cells to promote angiogenesis. We measured the Indocyanine Green fluorescence in mice treated with an antioangiogenic drug (Avastin TM) and in control mice. In tumors of treated mice we observed an ICG emission lower than the one detected in control mice. This demonstrated that VEGF activity was effectively blocked by the treatment with Avastin. In conclusion, ICG fluorescence provides a simple and reliable way to assess the effectiveness of vascular targeting therapies. Measurements of the fluorescence signal can be repeated every 24 hours, thus allowing oncologists to perform longitudinal studies on the same animals.

  20. Simple and rapid green synthesis of micrometer scale single crystalline gold nanoplates using chitosan as the reducing agent

    NASA Astrophysics Data System (ADS)

    Alex, Saji; Tian, Kun; Teng, Shiang; Siegel, Gene; Tiwari, Ashutosh

    2014-11-01

    A simple, rapid and green chemical method for the synthesis of single crystalline gold nanoplates of several micrometeres in size has been demonstrated. The synthesis involved the reduction of HAuCl4 in aqueous solution using low molecular weight chitosan at boiling temperature for 25 min. The [Au3+]:[chitosan] molar ratio plays an important role in the formation of gold nanoplates and found that an optimized molar ratio in the range of 80 to 125 was suitable for the formation of nanoplates. The size and morphology of the nanoplates can be tuned by adjusting the molar ratio. In this process, the chitosan functions both as a reducing as well as a stabilizing agent and no other special agents were added to induce the nanoplate formation. The obtained nanoplates were single crystals with (1 1 1) planes as the basal planes with shapes of hexagonal, triangular, or truncated triangular plates.

  1. In vivo characterization of cyanine dyes as contrast agents for near-infrared imaging

    NASA Astrophysics Data System (ADS)

    Riefke, Bjoern; Licha, Kai; Semmler, Wolfhard; Nolte, Dirk; Ebert, Bernd; Rinneberg, Herbert H.

    1996-12-01

    In this study indotricarbocyanines were investigated in vivo as near-infrared contrast agents. The known dye indocyanine green (ICG) has several disadvantages regarding its use in near-infrared imaging. ICG has a very short plasma half- life, limited tolerability and is unstable in aqueous solutions. Therefore, several indotricarbocyanine dyes, structurally related to ICG but with different hydrophilicities and physicochemical properties, were synthesized. The tolerability of synthesized dyes was tested in mice. The pharmacokinetic behavior and elimination characteristics were studied in a rat model. The in vivo imaging properties of synthesized dyes were investigated using a tunable, pulsed, solid state laser system for excitation and an intensified CCD camera for fluorescence imaging of different tumor-bearing nude mice models and mamma-carcinoma-bearing rat models. The dye-specific fluorescence exitance was followed at different times after dye administration. The results are demonstrated in comparison to indocyanine green. Synthesized hydrophilic indotricarbocyanine dyes had longer plasma half-lives and increasing renal elimination, corresponding to higher hydrophilicity. Tolerability in mice was increased up to 60- fold compared to ICG. Increased fluorescence exitance in tumors was observed for several dyes 24 h p.i. in the tumor models studied, whereas ICG showed no tumor fluorescence signal under the same conditions.

  2. Enhancing the depth of tissue microscope imaging using two-photon excitation of the second singlet state of fluorescent agents

    NASA Astrophysics Data System (ADS)

    Pu, Yang; Shi, Lingyan; Pratavieira, Sebastião.; Alfano, R. R.

    2014-03-01

    Increasing the depth to image inside tissue is critical in biomedicine. Two-photon (2P) excitation of the second singlet (S2) state of a group of fluorescent agents with near infrared emission, Chlorophyll a (Chl a) and Indocyanine green (ICG), is used to extend the optical imaging regime of 2PM into "tissue optical window" for deep tissue penetration. The fast nonradiative from S2 to S1 yields both emission and absorption wavelengths in the therapeutic window. The salient feature is to place both the 2P excitation and emission wavelengths of the imaging agents falling into the "tissue optical window". As a first step to achieve deeper optical imaging, Chl a and ICG are investigated and demonstrated as imaging agents for 2P S2 excitation microscope image.

  3. 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.

  4. 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. PMID:26644164

  5. An efficient green synthesis of 2-arylbenzothiazole analogues as potent antibacterial and anticancer agents.

    PubMed

    Chhabra, Mohit; Sinha, Sohini; Banerjee, Swagata; Paira, Priyankar

    2016-01-01

    We have demonstrated a novel and green approach for the synthesis of 2-substituted benzothiazole analogues. A number of 2-aryl and heteroaryl benzothiazole scaffolds were synthesized using Amberlite IR-120 resin under microwave irradiation. The catalytic role and reusability of the resin was well established here. 2-Substituted benzothiazole analogues (3a-l) were also tested against several bacterial strains (Staphylococcus aureus, Escherichia coli, Bacillus subtilis, Salmonella) and cancer cell lines (MCF-7 and HeLa). The stability of compound 2-phenyl benzothiazole (3a) and 2-pyridin-2-yl-benzothiazole (3k) in GSH (0.01mM dissolved in DMSO) was measured by UV-Vis spectroscopy. Compound 3k also shows remarkable fluorescence in MeOH.

  6. Application of glucose as a green capping agent and reductant to fabricate CuI micro/nanostructures

    SciTech Connect

    Tavakoli, Farnosh; Salavati-Niasari, Masoud; Ghanbari, Davood; Saberyan, Kamal; Hosseinpour-Mashkani, S. Mostafa

    2014-01-01

    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{sub 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.

  7. Targeting tumor hypoxia: a third generation 2-nitroimidazole-indocyanine dye-conjugate with improved fluorescent yield.

    PubMed

    Zhou, Feifei; Zanganeh, Saeid; Mohammad, Innus; Dietz, Christopher; Abuteen, Akram; Smith, Michael B; Zhu, Quing

    2015-12-14

    Tumor hypoxia is associated with the rapid proliferation and growth of malignant tumors, and the ability to detect tumor hypoxia is important for predicting tumor response to anti-cancer treatments. We have developed a class of dye-conjugates that are related to indocyanine green (ICG, ) to target tumor hypoxia, based on in vivo infrared fluorescence imaging using nitroimidazole moieties linked to indocyanine fluorescent dyes. We previously reported that linking 2-nitroimidazole to an indocyanine dicarboxylic acid dye derivative () using an ethanolamine linker (ethanolamine-2-nitroimidazole-ICG, ), led to a dye-conjugate that gave promising results for targeting cancer hypoxia in vivo. Structural modification of the dye conjugate replaced the ethanolamine unit with a piperazineacetyl unit and led a second generation dye conjugate, piperzine-2-nitroimidazole-ICG (). This second generation dye-conjugate showed improved targeting of tumor hypoxia when compared with . Based on the hypothesis that molecules with more planar and rigid structures have a higher fluorescence yield, as they could release less absorbed energy through molecular vibration or collision, we have developed a new 2-nitroimidazole ICG conjugate, , with two carbon atoms less in the polyene linker. Dye-conjugate was prepared from our new dye (), and coupled to 2-nitroimidazole using a piperazine linker to produce this third-generation dye-conjugate. Spectral measurements showed that the absorption/emission wavelengths of 657/670 were shifted ∼100 nm from the second-generation hypoxia dye of 755/780 nm. Its fluorescence quantum yield was measured to be 0.467, which is about 5 times higher than that of (0.083). In vivo experiments were conducted with balb/c mice and showed more than twice the average in vivo fluorescence intensity in the tumor beyond two hours post retro-orbital injection as compared with . These initial results suggest that may significantly improve in vivo tumor hypoxia targeting.

  8. Green synthesis of gold nanoparticles using plant extracts as reducing agents.

    PubMed

    Elia, Paz; Zach, Raya; Hazan, Sharon; Kolusheva, Sofiya; Porat, Ze'ev; Zeiri, Yehuda

    2014-01-01

    Gold nanoparticles (GNPs) were prepared using four different plant extracts as reducing and stabilizing agents. The extracts were obtained from the following plants: Salvia officinalis, Lippia citriodora, Pelargonium graveolens and Punica granatum. The size distributions of the GNPs were measured using three different methods: dynamic light scattering, nanoparticle-tracking analysis and analysis of scanning electron microscopy images. The three methods yielded similar size distributions. Biocompatibility was examined by correlation of L-cell growth in the presence of different amounts of GNPs. All GNPs showed good biocompatibility and good stability for over 3 weeks. Therefore, they can be used for imaging and drug-delivery applications in the human body. High-resolution transmission electron microscopy was used to view the shapes of the larger GNPs, while infrared spectroscopy was employed to characterize the various functional groups in the organic layer that stabilize the particles. Finally, active ingredients in the plant extract that might be involved in the formation of GNPs are proposed, based on experiments with pure antioxidants that are known to exist in that plant.

  9. Green synthesis of silver nanoparticles as antibacterial agent using Rhodomyrtus tomentosa acetone extract

    NASA Astrophysics Data System (ADS)

    Voravuthikunchai, Supayang P.; Chorachoo, Julalak; Jaiswal, Lily; Shankar, Shiv

    2013-12-01

    The capability of Rhodomyrtus tomentosa acetone extract (RAE) for the production of silver nanoparticles (AgNPs) has been explored for the first time. Silver nanoparticles with a surface plasmon resonance band centered at 420-430 nm were synthesized by reacting RAE with AgNO3. Reaction time, temperature, concentration of AgNO3 and RAE could accelerate the reduction rate of Ag+ and affect AgNPs size. The nanoparticles were found to be 10-30 nm in size and spherical in shape. XRD data demonstrated crystalline nature of AgNPs dominated by (200) facets. FTIR results showed decrease in intensity of peaks at 3394, 1716 and 1618 cm-1 indicating the involvement of O-H, carbonyl group and C=C stretching with the formation of AgNPs with RAE, respectively. The C-O-C and C-N stretching suggested the presence of many phytochemicals on the surface of the nanoparticles. High negative zeta potential values confirmed the stability of AgNPs in water. In vitro antibacterial activity of AgNPs was tested against Staphylococcus aureus using broth microdilution method. AgNPs capped with RAE demonstrated profound antibacterial activity against the organisms with minimum inhibitory concentration and minimum bactericidal concentration in the range between 3.1-6.2 and 6.2-50 μgmL-1, respectively. The synthesized nanoparticles could be applied as an effective antimicrobial agent against staphylococcal infections.

  10. Green synthesis of gold nanoparticles using plant extracts as reducing agents.

    PubMed

    Elia, Paz; Zach, Raya; Hazan, Sharon; Kolusheva, Sofiya; Porat, Ze'ev; Zeiri, Yehuda

    2014-01-01

    Gold nanoparticles (GNPs) were prepared using four different plant extracts as reducing and stabilizing agents. The extracts were obtained from the following plants: Salvia officinalis, Lippia citriodora, Pelargonium graveolens and Punica granatum. The size distributions of the GNPs were measured using three different methods: dynamic light scattering, nanoparticle-tracking analysis and analysis of scanning electron microscopy images. The three methods yielded similar size distributions. Biocompatibility was examined by correlation of L-cell growth in the presence of different amounts of GNPs. All GNPs showed good biocompatibility and good stability for over 3 weeks. Therefore, they can be used for imaging and drug-delivery applications in the human body. High-resolution transmission electron microscopy was used to view the shapes of the larger GNPs, while infrared spectroscopy was employed to characterize the various functional groups in the organic layer that stabilize the particles. Finally, active ingredients in the plant extract that might be involved in the formation of GNPs are proposed, based on experiments with pure antioxidants that are known to exist in that plant. PMID:25187704

  11. Green synthesis of gold nanoparticles using plant extracts as reducing agents

    PubMed Central

    Elia, Paz; Zach, Raya; Hazan, Sharon; Kolusheva, Sofiya; Porat, Ze’ev; Zeiri, Yehuda

    2014-01-01

    Gold nanoparticles (GNPs) were prepared using four different plant extracts as reducing and stabilizing agents. The extracts were obtained from the following plants: Salvia officinalis, Lippia citriodora, Pelargonium graveolens and Punica granatum. The size distributions of the GNPs were measured using three different methods: dynamic light scattering, nanoparticle-tracking analysis and analysis of scanning electron microscopy images. The three methods yielded similar size distributions. Biocompatibility was examined by correlation of L-cell growth in the presence of different amounts of GNPs. All GNPs showed good biocompatibility and good stability for over 3 weeks. Therefore, they can be used for imaging and drug-delivery applications in the human body. High-resolution transmission electron microscopy was used to view the shapes of the larger GNPs, while infrared spectroscopy was employed to characterize the various functional groups in the organic layer that stabilize the particles. Finally, active ingredients in the plant extract that might be involved in the formation of GNPs are proposed, based on experiments with pure antioxidants that are known to exist in that plant. PMID:25187704

  12. Bacterial cellulose of Gluconoacetobacter hansenii as a potential bioadsorption agent for its green environment applications.

    PubMed

    Mohite, Bhavna V; Patil, Satish V

    2014-01-01

    Bacterial cellulose (BC) is an interesting biopolymer produced by bacteria having superior properties. BC produced by Gluconoacetobacter hansenii (strain NCIM 2529) under shaking condition and explored for its applications in dye removal and bioadsorption of protein and heavy metals. Purity of BC was confirmed by Fourier transform infrared spectroscopy and scanning electron microscopy (SEM) analysis. BC removed azo dye and Aniline blue (400 mg/L) with 80% efficiency within 60 min. The adsorption and elution of Bovine serum albumin (BSA) and heavy metals like lead, cadmium and nickel (Pb(2+), Cd(2+) and Ni(2+)) was achieved with BC which confirms the exclusion ability with reusability. The BSA adsorption quantity was increased with increase in protein concentration with more than 90% adsorption and elution ratio. The effect of pH and temperature on BSA adsorption has been investigated. Bioadsorption (82%) and elution ratio (92%) of BC for Pb(2+) was more when compared with Cd(2+) (41 and 67%) and Ni(2+) (33 and 85%), respectively. BC was also explored as soil conditioner to increase the water-holding capacity and porosity of soil. The results elucidated the significance of BC as renewable effective ecofriendly bioadsorption agent.

  13. Crystalline Silver Nanoparticles by Using Polygala tenuifolia Root Extract as a Green Reducing Agent.

    PubMed

    Jun, Sang Hui; Cha, Song-Hyun; Kim, Jinwoong; Cho, Seonho; Park, Youmie

    2015-02-01

    Due to the emergence of multidrug-resistant bacteria, silver nanoparticles (AgNPs) have found interest as a new category of antibacterial agents. The toxicity of the chemicals involved in the commonly employed chemical methods for synthesizing AgNPs present limitations for subsequent pharmaceutical and biomedical applications. In this report, 70% aqueous ethanol extracts of Polygala tenuifolia root were used to reduce Ag+1 ions for AgNPs synthesis. The as-synthesized AgNPs were characterized via UV-Visible spectrophotometry, high resolution transmission electron microscopy, atomic force microscopy, X-ray diffraction, and Fourier transform infrared spectroscopy. A strong surface plasmon resonance band was observed at 414 nm. Images from the high resolution transmission electron microscopy and atomic force microscopy demonstrated the spherical and irregular shapes of the AgNPs were synthesized. The AgNP crystalline structure was confirmed by the strong diffraction peaks in the X-ray diffraction results and by the bright circular spots observed in selected-area electron diffraction, whose average diameter was measured to be 17.97 8.63 nm or 15.12 nm via high resolution transmission electron microscopy images or X-ray diffraction analysis, respectively. The as-synthesized AgNPs exerted the highest antibacterial activity against Escherichia coli among the tested Gram-positive and Gram-negative bacteria. The current method is eco-friendly, straightforward, cost-effective, biocompatible, and easily scaled up to produce of AgNPs for applications in the treatment of bacterial infections. PMID:26353692

  14. Enhanced sensitivity carbon nanotubes as targeted photoacoustic molecular imaging agents

    NASA Astrophysics Data System (ADS)

    de la Zerda, Adam; Liu, Zhuang; Zavaleta, Cristina; Bodapati, Sunil; Teed, Robert; Vaithilingam, Srikant; Ma, Te-Jen; Oralkan, Omer; Chen, Xiaoyuan; Khuri-Yakub, Butrus T.; Dai, Hongjie; Gambhir, Sanjiv S.

    2009-02-01

    Photoacoustic imaging of living subjects offers high spatial resolution at increased tissue depths compared to purely optical imaging techniques. We have recently shown that intravenously injected single walled carbon nanotubes (SWNTs) can be used as targeted photoacoustic imaging agents in living mice using RGD peptides to target αvβ3 integrins. We have now developed a new targeted photoacoustic imaging agent based on SWNTs and Indocyanine Green (SWNT-ICG) with absorption peak at 780nm. The photoacoustic signal of the new imaging agent is enhanced by ~20 times as compared to plain SWNTs. The particles are synthesized from SWNT-RGD that noncovalently attach to multiple ICG molecules through pi-pi stacking interactions. Negative control particles had RAD peptide instead of RGD. We measured the serum stability of the particles and verified that the RGD/RAD conjugation did not alter the particle's absorbance spectrum. Finally, through cell uptake studies with U87MG cells we verified that the particles bind selectively to αvβ3 integrin. In conclusion, the extremely high absorption of the SWNT-ICG particles shows great promise for high sensitivity photoacoustic imaging of molecular targets in-vivo. This work lays the foundations for future in-vivo studies that will use the SWNT-ICG particles as imaging agents administered systemically.

  15. Multi-channel LED light source for fluorescent agent aided minimally invasive surgery.

    PubMed

    Ren, Jiacheng; Venugopalan, Janani; Xu, Jian; Kairdolf, Brad; Durfee, Robert; Wang, May D

    2014-01-01

    Cancer is one of the most common and deadly diseases around the world. Amongst all the different treatments of cancer such as surgery, chemotherapy and radiation therapy, surgical resection is the most effective. Successful surgeries greatly rely on the detection of the accurate tumor size and location, which can be enhanced by contrast agents. Commercial endoscope light sources, however, offer only white light illumination. In this paper, we present the development of a LED endoscope light source that provides 2 light channels plus white light to help surgeons to detect a clear tumor margin during minimally invasive surgeries. By exciting indocyanine green (ICG) and 5-Aminolaevulinic acid (ALA)-induced protoporphyrin IX (PPIX), the light source is intended to give the user a visible image of the tumor margin. This light source is also portable, easy to use and costs less than $300 to build. PMID:25571589

  16. Multi-Channel LED Light Source for Fluorescent Agent Aided Minimally Invasive Surgery

    PubMed Central

    Ren, Jiacheng; Venugopalan, Janani; Xu, Jian; Kairdolf, Brad; Durfee, Robert; Wang, May D.

    2016-01-01

    Cancer is one of the most common and deadly diseases around the world. Amongst all the different treatments of cancer such as surgery, chemotherapy and radiation therapy, surgical resection is the most effective. Successful surgeries greatly rely on the detection of the accurate tumor size and location, which can be enhanced by contrast agents. Commercial endoscope light sources, however, offer only white light illumination. In this paper, we present the development of a LED endoscope light source that provides 2 light channels plus white light to help surgeons to detect a clear tumor margin during minimally invasive surgeries. By exciting indocyanine green (ICG) and 5-Aminolaevulinic acid (ALA)-induced protoporphyrin IX (PPIX), the light source is intended to give the user a visible image of the tumor margin. This light source is also portable, easy to use and costs less than $300 to build. PMID:25571589

  17. Green synthesis of silver nanoparticles using Ganoderma neo-japonicum Imazeki: a potential cytotoxic agent against breast cancer cells

    PubMed Central

    Gurunathan, Sangiliyandi; Raman, Jegadeesh; Malek, Sri Nurestri Abd; John, Priscilla A; Vikineswary, Sabaratnam

    2013-01-01

    Background Silver nanoparticles (AgNPs) are an important class of nanomaterial for a wide range of industrial and biomedical applications. AgNPs have been used as antimicrobial and disinfectant agents due their detrimental effect on target cells. The aim of our study was to determine the cytotoxic effects of biologically synthesized AgNPs using hot aqueous extracts of the mycelia of Ganoderma neo-japonicum Imazeki on MDA-MB-231 human breast cancer cells. Methods We developed a green method for the synthesis of water-soluble AgNPs by treating silver ions with hot aqueous extract of the mycelia of G. neo-japonicum. The formation of AgNPs was characterized by ultraviolet-visible absorption spectroscopy, X-ray diffraction, dynamic light scattering, and transmission electron microscopy. Furthermore, the toxicity of synthesized AgNPs was evaluated using a series of assays: such as cell viability, lactate dehydrogenase leakage, reactive oxygen species generation, caspase 3, DNA laddering, and terminal deoxynucleotidyl transferase deoxyuridine triphosphate nick-end labeling in human breast cancer cells (MDA-MB-231). Results The ultraviolet-visible absorption spectroscopy results showed a strong resonance centered on the surface of AgNPs at 420 nm. The X-ray diffraction analysis confirmed that the synthesized AgNPs were single-crystalline, corresponding with the result of transmission electron microscopy. Treatment of MDA-MB-231 breast cancer cells with various concentrations of AgNPs (1–10 μg/mL) for 24 hours revealed that AgNPs could inhibit cell viability and induce membrane leakage in a dose-dependent manner. Cells exposed to AgNPs showed increased reactive oxygen species and hydroxyl radical production. Furthermore, the apoptotic effects of AgNPs were confirmed by activation of caspase 3 and DNA nuclear fragmentation. Conclusion The results indicate that AgNPs possess cytotoxic effects with apoptotic features and suggest that the reactive oxygen species generated by

  18. 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.

  19. Description of a new species of Anagyrus Howard (Hymenoptera: Chalcidoidea: Encyrtidae), a promising biological control agent of the invasive Madeira mealybug, Phenacoccus madeirensis Green (Hemiptera: Sternorrhyncha: Pseudococcidae).

    PubMed

    Rameshkumar, A; Noyes, J S; Poorani, J; Chong, J H

    2013-01-01

    Anagyrus amnestos sp. n. (Hymenoptera: Encyrtidae), a promising parasitoid of the invasive Madeira mealybug, Phenacoccus madeirensis Green (Hemiptera: Pseudococcidae), is described based on material collected from India. This parasitoid was identified as Anagyrus sp. nov. nr. sinope Noyes & Menezes in recent literature, and was initially collected in Georgia, USA. It was found to be a specific parasitoid of the Madeira mealybug and its biological attributes and potential as a biological control agent of this pest were studied. In what appears to be a case of fortuitous introduction, we detected this parasitoid in large numbers on Madeira mealybugs from the southern Indian state of Karnataka, where the mealybug is a recently introduced invasive pest. In view of its economic importance as a potential biological control agent of the Madeira mealybug, it is formally described and illustrated here. Comparative accounts of the new species vis-a-vis its close relatives in India and the Americas are provided.

  20. Description of a new species of Anagyrus Howard (Hymenoptera: Chalcidoidea: Encyrtidae), a promising biological control agent of the invasive Madeira mealybug, Phenacoccus madeirensis Green (Hemiptera: Sternorrhyncha: Pseudococcidae).

    PubMed

    Rameshkumar, A; Noyes, J S; Poorani, J; Chong, J H

    2013-01-01

    Anagyrus amnestos sp. n. (Hymenoptera: Encyrtidae), a promising parasitoid of the invasive Madeira mealybug, Phenacoccus madeirensis Green (Hemiptera: Pseudococcidae), is described based on material collected from India. This parasitoid was identified as Anagyrus sp. nov. nr. sinope Noyes & Menezes in recent literature, and was initially collected in Georgia, USA. It was found to be a specific parasitoid of the Madeira mealybug and its biological attributes and potential as a biological control agent of this pest were studied. In what appears to be a case of fortuitous introduction, we detected this parasitoid in large numbers on Madeira mealybugs from the southern Indian state of Karnataka, where the mealybug is a recently introduced invasive pest. In view of its economic importance as a potential biological control agent of the Madeira mealybug, it is formally described and illustrated here. Comparative accounts of the new species vis-a-vis its close relatives in India and the Americas are provided. PMID:26176096

  1. Characterization of the effects of heat stress on the DNA-intercalating dye EvaGreen for potential use with the joint biological agent identification and diagnostic system.

    PubMed

    Nowadly, Craig D; David, Jason W; Grogger, Melanie L M; Demkowicz, Erik R; Atchley, Daniel H; Veverka, Donald V

    2014-06-01

    Although advances in real-time polymerase chain reaction (PCR) technology and equipment have facilitated field research, only a limited selection of reagents do not require cold storage. This study explored the temperature stability of the commercially available DNA-intercalating dye EvaGreen after exposure to a spectrum of temperatures for 176 days by analyzing quantification cycle (Cq) and end fluorescence levels during amplification of the invA gene of Salmonella typhimurium. To further characterize potential dye stability, the effects of small differences in dye volume were examined and dye samples were subjected to an Air Force deployment to the Middle East. Significant differences in Cq and end fluorescence were found; however, the magnitude of mean Cq differences was less than one cycle and the magnitude of mean fluorescence differences was less than that attributable to a difference of 0.25 μL of dye per 25 μL reaction. Liquid EvaGreen dye may thus be stable at temperatures as high as 65°C for up to 6 months for use in real-time PCR. These results warrant further investigation by using liquid EvaGreen dye to adapt traditional lab-based real-time PCR assays for Joint Biological Agent Identification and Diagnostic System use and testing the assays in the field.

  2. Characterization of the effects of heat stress on the DNA-intercalating dye EvaGreen for potential use with the joint biological agent identification and diagnostic system.

    PubMed

    Nowadly, Craig D; David, Jason W; Grogger, Melanie L M; Demkowicz, Erik R; Atchley, Daniel H; Veverka, Donald V

    2014-06-01

    Although advances in real-time polymerase chain reaction (PCR) technology and equipment have facilitated field research, only a limited selection of reagents do not require cold storage. This study explored the temperature stability of the commercially available DNA-intercalating dye EvaGreen after exposure to a spectrum of temperatures for 176 days by analyzing quantification cycle (Cq) and end fluorescence levels during amplification of the invA gene of Salmonella typhimurium. To further characterize potential dye stability, the effects of small differences in dye volume were examined and dye samples were subjected to an Air Force deployment to the Middle East. Significant differences in Cq and end fluorescence were found; however, the magnitude of mean Cq differences was less than one cycle and the magnitude of mean fluorescence differences was less than that attributable to a difference of 0.25 μL of dye per 25 μL reaction. Liquid EvaGreen dye may thus be stable at temperatures as high as 65°C for up to 6 months for use in real-time PCR. These results warrant further investigation by using liquid EvaGreen dye to adapt traditional lab-based real-time PCR assays for Joint Biological Agent Identification and Diagnostic System use and testing the assays in the field. PMID:24902129

  3. Reducing-Agent-Free Instant Synthesis of Carbon-Supported Pd Catalysts in a Green Leidenfrost Droplet Reactor and Catalytic Activity in Formic Acid Dehydrogenation

    NASA Astrophysics Data System (ADS)

    Lee, Dong-Wook; Jin, Min-Ho; Lee, Young-Joo; Park, Ju-Hyoung; Lee, Chun-Boo; Park, Jong-Soo

    2016-05-01

    The development of green synthesis methods for supported noble metal catalysts remains important challenges to improve their sustainability. Here we first synthesized carbon-supported Pd catalysts in a green Leidenfrost droplet reactor without reducing agents, high-temperature calcination and reduction procedures. When the aqueous solution containing Pd nitrate precursor, carbon support, and water is dripped on a hot plate, vapor layer is formed between a solution droplet and hot surface, which allow the solution droplet to be levitated on the hot surface (Leidenfrost phenomena). Subsequently, Pd nanoparticles can be prepared without reducing agents in a weakly basic droplet reactor created by the Leidenfrost phenomena, and then the as-prepared Pd nanoparticles are loaded on carbon supports during boiling down the droplet on hot surface. Compared to conventional incipient wetness and chemical synthetic methods, the Leidenfrost droplet reactor does not need energy-consuming, time-consuming, and environmentally unfriendly procedures, which leads to much shorter synthesis time, lower carbon dioxide emission, and more ecofriendly process in comparison with conventional synthesis methods. Moreover, the catalysts synthesized in the Leidenfrost droplet reactor provided much better catalytic activity for room-temperature formic acid decomposition than those prepared by the incipient wetness method.

  4. Reducing-Agent-Free Instant Synthesis of Carbon-Supported Pd Catalysts in a Green Leidenfrost Droplet Reactor and Catalytic Activity in Formic Acid Dehydrogenation.

    PubMed

    Lee, Dong-Wook; Jin, Min-Ho; Lee, Young-Joo; Park, Ju-Hyoung; Lee, Chun-Boo; Park, Jong-Soo

    2016-05-20

    The development of green synthesis methods for supported noble metal catalysts remains important challenges to improve their sustainability. Here we first synthesized carbon-supported Pd catalysts in a green Leidenfrost droplet reactor without reducing agents, high-temperature calcination and reduction procedures. When the aqueous solution containing Pd nitrate precursor, carbon support, and water is dripped on a hot plate, vapor layer is formed between a solution droplet and hot surface, which allow the solution droplet to be levitated on the hot surface (Leidenfrost phenomena). Subsequently, Pd nanoparticles can be prepared without reducing agents in a weakly basic droplet reactor created by the Leidenfrost phenomena, and then the as-prepared Pd nanoparticles are loaded on carbon supports during boiling down the droplet on hot surface. Compared to conventional incipient wetness and chemical synthetic methods, the Leidenfrost droplet reactor does not need energy-consuming, time-consuming, and environmentally unfriendly procedures, which leads to much shorter synthesis time, lower carbon dioxide emission, and more ecofriendly process in comparison with conventional synthesis methods. Moreover, the catalysts synthesized in the Leidenfrost droplet reactor provided much better catalytic activity for room-temperature formic acid decomposition than those prepared by the incipient wetness method.

  5. Reducing-Agent-Free Instant Synthesis of Carbon-Supported Pd Catalysts in a Green Leidenfrost Droplet Reactor and Catalytic Activity in Formic Acid Dehydrogenation

    PubMed Central

    Lee, Dong-Wook; Jin, Min-Ho; Lee, Young-Joo; Park, Ju-Hyoung; Lee, Chun-Boo; Park, Jong-Soo

    2016-01-01

    The development of green synthesis methods for supported noble metal catalysts remains important challenges to improve their sustainability. Here we first synthesized carbon-supported Pd catalysts in a green Leidenfrost droplet reactor without reducing agents, high-temperature calcination and reduction procedures. When the aqueous solution containing Pd nitrate precursor, carbon support, and water is dripped on a hot plate, vapor layer is formed between a solution droplet and hot surface, which allow the solution droplet to be levitated on the hot surface (Leidenfrost phenomena). Subsequently, Pd nanoparticles can be prepared without reducing agents in a weakly basic droplet reactor created by the Leidenfrost phenomena, and then the as-prepared Pd nanoparticles are loaded on carbon supports during boiling down the droplet on hot surface. Compared to conventional incipient wetness and chemical synthetic methods, the Leidenfrost droplet reactor does not need energy-consuming, time-consuming, and environmentally unfriendly procedures, which leads to much shorter synthesis time, lower carbon dioxide emission, and more ecofriendly process in comparison with conventional synthesis methods. Moreover, the catalysts synthesized in the Leidenfrost droplet reactor provided much better catalytic activity for room-temperature formic acid decomposition than those prepared by the incipient wetness method. PMID:27198855

  6. Reducing-Agent-Free Instant Synthesis of Carbon-Supported Pd Catalysts in a Green Leidenfrost Droplet Reactor and Catalytic Activity in Formic Acid Dehydrogenation.

    PubMed

    Lee, Dong-Wook; Jin, Min-Ho; Lee, Young-Joo; Park, Ju-Hyoung; Lee, Chun-Boo; Park, Jong-Soo

    2016-01-01

    The development of green synthesis methods for supported noble metal catalysts remains important challenges to improve their sustainability. Here we first synthesized carbon-supported Pd catalysts in a green Leidenfrost droplet reactor without reducing agents, high-temperature calcination and reduction procedures. When the aqueous solution containing Pd nitrate precursor, carbon support, and water is dripped on a hot plate, vapor layer is formed between a solution droplet and hot surface, which allow the solution droplet to be levitated on the hot surface (Leidenfrost phenomena). Subsequently, Pd nanoparticles can be prepared without reducing agents in a weakly basic droplet reactor created by the Leidenfrost phenomena, and then the as-prepared Pd nanoparticles are loaded on carbon supports during boiling down the droplet on hot surface. Compared to conventional incipient wetness and chemical synthetic methods, the Leidenfrost droplet reactor does not need energy-consuming, time-consuming, and environmentally unfriendly procedures, which leads to much shorter synthesis time, lower carbon dioxide emission, and more ecofriendly process in comparison with conventional synthesis methods. Moreover, the catalysts synthesized in the Leidenfrost droplet reactor provided much better catalytic activity for room-temperature formic acid decomposition than those prepared by the incipient wetness method. PMID:27198855

  7. 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.

  8. Contrast agents for diagnostic ultrasound: development and evaluation of polymer-coated microbubbles.

    PubMed

    Wheatley, M A; Schrope, B; Shen, P

    1990-11-01

    Although the concept of an ultrasound contrast agent dates from Gramiak's work in 1968 in which indocyanine green was injected into the ascending aorta and heart, no universally accepted contrast agent for ultrasound now exists. This is primarily due to problems with stability, size and/or toxicity of the agents which have been investigated. Development of an effective ultrasound contrast agent would be highly significant for the health care industry, since it would greatly expand the scope of ultrasound (a noninvasive and safe procedure) as a diagnostic technique. While encapsulated gas bubbles offer particular advantages in stability over hand-agitated systems, they frequently present problems with size. Capsules larger than 10 microns in diameter become entrapped in the capillary bed of the lung. This paper describes the use of ionotropic gelation of the naturally occurring polysaccharide, alginate, for microencapsulation of air. Two procedures have been investigated. A novel jet head has been developed which allows co-extrusion of a solution of sodium alginate and air to produce nascent microencapsulated air bubbles which fall into a hardening solution of calcium ions. A second method employs ultrasound to introduce cavitation-induced bubbles into the alginate before capsule formation by spraying. Power spectra of these preparations demonstrate echogenicity (that is strong scatter of the incident ultrasound wave back to the emitting transducer, which also acts as a receiver), with resonant peaks that are a function of capsule size and wall characteristics. PMID:2090309

  9. Hypoxia targeted carbon nanotubes as a sensitive contrast agent for photoacoustic imaging of tumors

    NASA Astrophysics Data System (ADS)

    Zanganeh, Saeid; Aguirre, Andres; Biswal, Nrusingh C.; Pavlik, Christopher; Smith, Michael B.; Alqasemi, Umar; Li, Hai; Zhu, Quing

    2011-03-01

    Development of new and efficient contrast agents is of fundamental importance to improve detection sensitivity of smaller lesions. Within the family of nanomaterials, carbon nanotubes (CNT) not only have emerged as a new alternative and efficient transporter and translocater of therapeutic molecules but also as a photoacoustic molecular imaging agent owing to its strong optical absorption in the near-infrared region. Drugs, Antibodies and nucleic acids could functionalize the CNT and prepare an appropriate system for delivering the cargos to cells and organs. In this work, we present a novel photoacoustic contrast agent which is based on a unique hypoxic marker in the near infrared region, 2-nitroimidazole -bis carboxylic acid derivative of Indocyanine Green conjugated to single walled carbon nanotube (SWCNT-2nitroimidazole-ICG). The 2-nitroimidazole-ICG has an absorption peak at 755 nm and an extinction coefficient of 20,5222 M-1cm-1. The conjugation of this marker with SWCNT shows more than 25 times enhancement of optical absorption of carbon nanotubes in the near infrared region. This new conjugate has been optically evaluated and shows promising results for high contrast photoacoustic imaging of deeply located tumors. The conjugate specifically targets tumor hypoxia, an important indicator of tumor metabolism and tumor therapeutic response. The detection sensitivity of the new contrast agent has been evaluated in-vitro cell lines and with in-vivo tumors in mice.

  10. A comparative study of the effect of α-, β-, and γ-cyclodextrins as stabilizing agents in the synthesis of silver nanoparticles using a green chemistry method.

    PubMed

    Suárez-Cerda, Javier; Nuñez, Gabriel Alonso; Espinoza-Gómez, Heriberto; Flores-López, Lucía Z

    2014-10-01

    This paper describes the effect of different types of cyclodextrins (CDs) in the synthesis of silver nanoparticles (Ag-NPs), using an easy green chemistry method. The Ag-NPs were obtained using an aqueous silver nitrate solution (AgNO3) with α-, β-, or γ-CDs (aqueous solutions) as stabilizing agents, employing the chemical reduction method with citric acid as a reducing agent. A comparative study was done to determine which cyclodextrin (CD) was the best stabilizing agent, and we found out that β-CD was the best due to the number of glucopyranose units in its structure. The formation of the Ag-NPs was demonstrated by analysis of UV-vis spectroscopy, atomic force microscopy (AFM), scanning electron microscopy-energy dispersive spectroscopy (SEM-EDS) and transmission electron microscopy (TEM). SEM-EDS showed the formation of a cluster with a significant amount of silver, for β-CD-Ag-NPs, spherical agglomerates can be observed. However, for α-, γ-CD, the agglomerates do not have a specific form, but their appearance is porous. TEM analysis shows spherical nanoparticles in shape and size between ~0.5 to 7 nm. The clear lattice fringes in TEM images and the typical selected area electron diffraction (SAED) pattern, showed that the Ag-NPs obtained were highly crystalline with a face cubic center structure (FCC). PMID:25175183

  11. Construction and characterization of stable, constitutively expressed, chromosomal green and red fluorescent transcriptional fusions in the select agents, Bacillus anthracis, Yersinia pestis, Burkholderia mallei, and Burkholderia pseudomallei

    PubMed Central

    Su, Shengchang; Bangar, Hansraj; Saldanha, Roland; Pemberton, Adin; Aronow, Bruce; Dean, Gary E; Lamkin, Thomas J; Hassett, Daniel J

    2014-01-01

    Here, we constructed stable, chromosomal, constitutively expressed, green and red fluorescent protein (GFP and RFP) as reporters in the select agents, Bacillus anthracis, Yersinia pestis, Burkholderia mallei, and Burkholderia pseudomallei. Using bioinformatic approaches and other experimental analyses, we identified P0253 and P1 as potent promoters that drive the optimal expression of fluorescent reporters in single copy in B. anthracis and Burkholderia spp. as well as their surrogate strains, respectively. In comparison, Y. pestis and its surrogate strain need two chromosomal copies of cysZK promoter (P2cysZK) for optimal fluorescence. The P0253-, P2cysZK-, and P1-driven GFP and RFP fusions were first cloned into the vectors pRP1028, pUC18R6KT-mini-Tn7T-Km, pmini-Tn7-gat, or their derivatives. The resultant constructs were delivered into the respective surrogates and subsequently into the select agent strains. The chromosomal GFP- and RFP-tagged strains exhibited bright fluorescence at an exposure time of less than 200 msec and displayed the same virulence traits as their wild-type parental strains. The utility of the tagged strains was proven by the macrophage infection assays and lactate dehydrogenase release analysis. Such strains will be extremely useful in high-throughput screens for novel compounds that could either kill these organisms, or interfere with critical virulence processes in these important bioweapon agents and during infection of alveolar macrophages. PMID:25044501

  12. A comparative study of the effect of α-, β-, and γ-cyclodextrins as stabilizing agents in the synthesis of silver nanoparticles using a green chemistry method.

    PubMed

    Suárez-Cerda, Javier; Nuñez, Gabriel Alonso; Espinoza-Gómez, Heriberto; Flores-López, Lucía Z

    2014-10-01

    This paper describes the effect of different types of cyclodextrins (CDs) in the synthesis of silver nanoparticles (Ag-NPs), using an easy green chemistry method. The Ag-NPs were obtained using an aqueous silver nitrate solution (AgNO3) with α-, β-, or γ-CDs (aqueous solutions) as stabilizing agents, employing the chemical reduction method with citric acid as a reducing agent. A comparative study was done to determine which cyclodextrin (CD) was the best stabilizing agent, and we found out that β-CD was the best due to the number of glucopyranose units in its structure. The formation of the Ag-NPs was demonstrated by analysis of UV-vis spectroscopy, atomic force microscopy (AFM), scanning electron microscopy-energy dispersive spectroscopy (SEM-EDS) and transmission electron microscopy (TEM). SEM-EDS showed the formation of a cluster with a significant amount of silver, for β-CD-Ag-NPs, spherical agglomerates can be observed. However, for α-, γ-CD, the agglomerates do not have a specific form, but their appearance is porous. TEM analysis shows spherical nanoparticles in shape and size between ~0.5 to 7 nm. The clear lattice fringes in TEM images and the typical selected area electron diffraction (SAED) pattern, showed that the Ag-NPs obtained were highly crystalline with a face cubic center structure (FCC).

  13. Construction and characterization of stable, constitutively expressed, chromosomal green and red fluorescent transcriptional fusions in the select agents, Bacillus anthracis, Yersinia pestis, Burkholderia mallei, and Burkholderia pseudomallei.

    PubMed

    Su, Shengchang; Bangar, Hansraj; Saldanha, Roland; Pemberton, Adin; Aronow, Bruce; Dean, Gary E; Lamkin, Thomas J; Hassett, Daniel J

    2014-10-01

    Here, we constructed stable, chromosomal, constitutively expressed, green and red fluorescent protein (GFP and RFP) as reporters in the select agents, Bacillus anthracis, Yersinia pestis, Burkholderia mallei, and Burkholderia pseudomallei. Using bioinformatic approaches and other experimental analyses, we identified P0253 and P1 as potent promoters that drive the optimal expression of fluorescent reporters in single copy in B. anthracis and Burkholderia spp. as well as their surrogate strains, respectively. In comparison, Y. pestis and its surrogate strain need two chromosomal copies of cysZK promoter (P2cysZK) for optimal fluorescence. The P0253-, P2cysZK-, and P1-driven GFP and RFP fusions were first cloned into the vectors pRP1028, pUC18R6KT-mini-Tn7T-Km, pmini-Tn7-gat, or their derivatives. The resultant constructs were delivered into the respective surrogates and subsequently into the select agent strains. The chromosomal GFP- and RFP-tagged strains exhibited bright fluorescence at an exposure time of less than 200 msec and displayed the same virulence traits as their wild-type parental strains. The utility of the tagged strains was proven by the macrophage infection assays and lactate dehydrogenase release analysis. Such strains will be extremely useful in high-throughput screens for novel compounds that could either kill these organisms, or interfere with critical virulence processes in these important bioweapon agents and during infection of alveolar macrophages.

  14. Targeted Delivery of Chemotherapeutic Agents Using Improved Radiosensitive Liquid Core Microcapsules and Assessment of Their Antitumor Effect

    SciTech Connect

    Harada, Satoshi Ehara, Shigeru; Ishii, Keizo; Yamazaki, Hiromichi; Matsuyama, Shigeo; Sato, Takahiro; Oikawa, Shyoichi; Kamiya, Tomihiro; Arakawa, Kazuo; Yokota, Wataru; Sera, Koichiro; Ito, Jyun

    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. 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.

  15. Assessment of Bioautography and Spot Screening of TLC of Green Tea (Camellia) Plant Extracts as Antibacterial and Antioxidant Agents

    PubMed Central

    Bashir, S.; Khan, B. M.; Babar, M.; Andleeb, S.; Hafeez, M.; Ali, S.; Khan, M. F.

    2014-01-01

    This study was carried out as a prerequisite to evaluate the therapeutic potential of Camellia varieties. The crude extracts of six different plants of green tea Camellia assamica and Camellia sinensis were tested against three Gram-positive and four Gram-negative bacteria using agar disk diffusion method at 50 mg/ml concentration. 2,2’-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) and diphenyl-(2,4,6-trinitrophenyl)iminoazanium free radical scavenging methods were performed to evaluate the antioxidant potential. Phytochemical constituents and trace metals were detected through thin layer chromatography and Inductively Coupled Plasma Atomic Emission Spectrophotometer, respectively. The maximum inhibition of Staphylococcus aureus was recorded by dimethyl sulphoxide extracts of green tea varieties. The measured zone of inhibition of dimethyl sulphoxide extracts by Qimen was (10.00±0.0 mm), Japanese (10.00±0.0 mm), Turkish (10.00±0.0 mm), Indonesian (8.33±1.0 mm), P3 clone (10.00±0.0 mm) and Sri Lankan (10.00±0.0 mm). Maximum scavenging potential activity was found with ethanol, methanol and dimethyl sulphoxide extracts. Spot screening of TLC-developed plates indicated that the presence of active biological compounds such as flavonoids, proteins, phenols, alkaloids and glycosides also exhibited strong activity against tested bacterial strains. This study reveals the potential biological activities of Camellia assamica and Camellia sinensis having massive phytochemical constituents and trace elements. PMID:25284935

  16. 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

  17. Near-infrared dye-loaded magnetic nanoparticles as photoacoustic contrast agent for enhanced tumor imaging

    PubMed Central

    Gao, Chuang; Deng, Zi-Jian; Peng, Dong; Jin, Yu-Shen; Ma, Yan; Li, Yan-Yan; Zhu, Yu-Kun; Xi, Jian-Zhong; Tian, Jie; Dai, Zhi-Fei; Li, Chang-Hui; Liang, Xiao-Long

    2016-01-01

    Objective: Photoacoustic (PA) tomography (PAT) has attracted extensive interest because of its optical absorption contrast and ultrasonic detection. This study aims to develop a biocompatible and biodegradable PA contrast agent particularly promising for clinical applications in human body. Methods: In this study, we presented a PA contrast agent: 1, 2-distearoyl-sn-glycero-3-phosphoethanolamine- N-[methoxy (polyethylene glycol)] (DSPE-PEG)-coated superparamagnetic iron oxide (SPIO) nanoparticles (NPs) loaded with indocyanine green (ICG). We used ICG and SPIO NPs because both drugs are approved by the U.S. Food and Drug Administration. Given the strong absorption of near-infrared laser pulses, SPIO@DSPE-PEG/ICG NPs with a uniform diameter of ~28 nm could significantly enhance PA signals. Results: We demonstrated the contrast enhancement of these NPs in phantom and animal experiments, in which the in vivo circulation time of SPIO@DSPE-PEG/ICG NPs was considerably longer than that of free ICG. These novel NPs also displayed a high efficiency of tumor targeting. Conclusions: SPIO@DSPE-PEG/ICG NPs are promising PAT contrast agents for clinical applications. PMID:27807502

  18. Fluorescent property of indocyanine green (ICG) rubber ring using LED and laser light sources.

    PubMed

    Hong, Nha Young; Kim, Hong Rae; Lee, Hyun Min; Sohn, Dae Kyung; Kim, Kwang Gi

    2016-05-01

    Fluorescent properties of ICG depends on solvent. Fluorescent characteristics of ICG rubber rings and optimized detection system condition were identified. The fluorescent rubber rings are produced by drying mixture of ICG solution and liquid rubber. LED and laser light sources were used to test differences between them. Other variables are ICG molar concentration (100, 80, 60, 40, 20, 10μM), excitation light spectrum (740, 760, 785nm) and angle of view (0~80°). We observed that ICG ring emitted fluorescence at longer wavelength than in blood and aqueous state. Observation angle between 0 and 50 provided similar brightness of images, while others are significantly less luminous. Excitation light between 740~760nm ensured non-overlapping spectrums of excitation light and fluorescence emission. PMID:27280060

  19. Indocyanine green: A test of hepatic function and a measure of plasma volume in the duck

    USGS Publications Warehouse

    Patton, J.F.

    1978-01-01

    1. 1. The exponential removal of ICG from the plasma by the mallard duck liver made possible the measurement of fractional dye clearance (K), plasma volume (PV) and plasma clearance (PC). 2. 2. Values obtained for K (14.9%/min), PV (39.2 ml/kg) and PC (5.8 ml/min per kg) agreed with those obtained by other techniques used in a number of species. 3. 3. Sex did not affect the removal of ICG by the liver. However, increases in K, PV and PC were noted in hen mallards in laying condition. 4. 4. The data should prove useful as baseline values for physiological and pathological studies on the avian liver

  20. Electron beam induced water-soluble silk fibroin nanoparticles as a natural antioxidant and reducing agent for a green synthesis of gold nanocolloid

    NASA Astrophysics Data System (ADS)

    Wongkrongsak, Soraya; Tangthong, Theeranan; Pasanphan, Wanvimol

    2016-01-01

    The research proposes a novel water-soluble silk fibroin nanoparticles (WSSF-NPs) created by electron beam irradiation. In this report, we demonstrate the effects of electron beam irradiation doses ranging from 1 to 30 kGy on the molecular weight (MW), nanostructure formation, antioxidant activity and reducing power of the WSSF-NPs. Electron beam-induced degradation of SF causing MW reduction from 250 to 37 kDa. Chemical characteristic functions of SF still remained after exposing to electron beam. The WSSF-NPs with the MW of 37 kDa exhibited spherical morphology with a nanoscaled size of 40 nm. Antioxidant activities and reducing powers were investigated using 2,2-diphenyl-1-picrylhryl free radical (DPPH•) scavenging activity and ferric reducing antioxidant power (FRAP) assays, respectively. The WSSF-NPs showed greater antioxidant activity and reducing power than non-irradiated SF. By increasing their antioxidant and reducing power efficiencies, WSSF-NPs potentially created gold nanocolloid. WSSF-NPs produced by electron beam irradiation would be a great merit for the uses as a natural antioxidant additive and a green reducing agent in biomedical, cosmetic and food applications.

  1. 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.

  2. Near-infrared Au nanorods in photodynamic therapy, hyperthermia agents, and near-infrared optical imaging

    NASA Astrophysics Data System (ADS)

    Kuo, Wen-Shuo; Chang, Chich-Neng; Chang, Yi-Ting; Yang, Meng-Heng; Chien, Yi-Hsin; Chen, Shean-Jen; Yeh, Chen-Sheng

    2011-03-01

    The development of multifunctional nanomaterials is currently a topic of interest in the field of nanotechnology. Integrated systems that incorporate therapeutics, molecular targeting, and diagnostic imaging capabilities are considered to be the next generation of multifunctional nanomedicine. In this work, we present the first example of using Au nanorods simultaneously serving not only as photodynamic and photothermal agents to destroy A549 malignant cells but also as optical contrast agents simultaneously to monitor cellular image. Au nanorods were successfully conjugated with hydrophilic photosensitizer, indocyanine green (ICG), to achieve photodynamic therapy (PDT) and hyperthermia. With the combination of PDT and hyperthermia proved to be efficiently killing cancer cells as compared to PDT or hyperthermia treatment alone and enhanced the effectiveness of photodestruction. Moreover, Au nanorods conjugated with ICG displayed high chemical stability and simultaneously acted as a promising cellular image probe. As a result, the preparation of Au nanorods conjugated with photosensitizers as well as their use in biomedical applications is valuable developments in multifunctional nanomaterials.

  3. Cyanine dyes as contrast agents for near-infrared imaging in vivo: acute tolerance, pharmacokinetics, and fluorescence imaging

    NASA Astrophysics Data System (ADS)

    Ebert, Bernd; Riefke, Björn; Sukowski, Uwe; Licha, Kai

    2011-06-01

    We compare pharmacokinetic, tolerance, and imaging properties of two near-IR contrast agents, indocyanine green (ICG) and 1,1'-bis-(4-sulfobutyl) indotricarbocyanine-5,5'-dicarboxylic acid diglucamide monosodium salt (SIDAG). ICG is a clinically approved imaging agent, and its derivative SIDAG is a more hydrophilic counterpart that has recently shown promising imaging properties in preclinical studies. The rather lipophilic ICG has a very short plasma half-life, thus limiting the time available to image body regions during its vascular circulation (e.g., the breast in optical mammography where scanning over several minutes is required). In order to change the physicochemical properties of the indotricarbocyanine dye backbone, several derivatives were synthesized with increasing hydrophilicity. The most hydrophilic dye SIDAG is selected for further biological characterization. The acute tolerance of SIDAG in mice is increased up to 60-fold compared to ICG. Contrary to ICG, the pharmacokinetic properties of SIDAG are shifted toward renal elimination, caused by the high hydrophilicity of the molecule. N-Nitrosomethylurea (NMU)-induced rat breast carcinomas are clearly demarcated, both immediately and 24 h after intravenous administration of SIDAG, whereas ICG shows a weak tumor contrast under the same conditions. Our findings demonstrate that SIDAG is a high potential contrast agent for optical imaging, which could increase the sensitivity for detection of inflamed regions and tumors.

  4. A novel near-infrared indocyanine dye-polyethylenimine conjugate allows DNA delivery imaging in vivo.

    PubMed

    Masotti, Andrea; Vicennati, Paola; Boschi, Federico; Calderan, Laura; Sbarbati, Andrea; Ortaggi, Giancarlo

    2008-05-01

    Near-infrared (NIR) fluorescence light has been applied to monitor several biological events in vivo since it penetrates tissues more efficiently than visible light. Dyes exhibiting NIR fluorescence and having large Stokes shift are key elements for this promising optical imaging technology. Here, we report the synthesis of a novel conjugate between a near-infrared indocyanine dye and an organic polyamine polymer (polyethylenimine, PEI) (IR820-PEI) with high chemical stability and good optical properties. IR820-PEI absorbs at 665 nm, emits at 780 nm, and displays a large Stokes shift (115 nm). Moreover, the reported conjugate is able to bind DNA, and the delivery process can be monitored in vivo with noninvasive optical imaging techniques. These characteristics make IR820-PEI one of the most effective and versatile indocyanine dye polymeric-conjugate reported so far.

  5. Thiadiazole molecules and poly(ethylene glycol)-block-polylactide self-assembled nanoparticles as effective photothermal agents.

    PubMed

    Sun, Tingting; Qi, Ji; Zheng, Min; Xie, Zhigang; Wang, Zhiyuan; Jing, Xiabin

    2015-12-01

    A new photothermal nano-agent was obtained by the coprecipitation of 2,5-Bis(2,5-bis(2-thienyl)-N-dodecyl pyrrole) thieno[3,4-b][1,2,5] thiadiazole (TPT-TT) and a biodegradable amphiphilic block copolymer, methoxypoly(ethylene glycol)2K-block-poly(D,L-lactide)2K (mPEG2K-PDLLA2K). TPT-TT, a donor-acceptor-donor (D-A-D) type small molecule, with bis(2-thienyl)-N-alkylpyrrole (TPT) as the donor and thieno[3,4-b]thiadiazole (TT) as the acceptor was a strong near infrared (NIR) absorber, which could convert the absorbed light energy into heat. The formation of TPT-TT nanoparticles (TPT-NPs), which possessed high stability in water, was confirmed by dynamic light scattering (DLS) and transmission electron microscopy (TEM). TPT-NPs showed high photothermal conversion efficiency (32%) and excellent photostability and heating reproducibility. The photostability of TPT-TT NPs was much better than that of indocyanine green (ICG), a federal drug administration (FDA) approved NIR dye. Besides, TPT-TT NPs exhibited significant photothermal therapeutic effect toward human cervical carcinoma (HeLa) and human liver hepatocellular carcinoma (HepG2) cells, while no appreciable dark cytotoxicity was observed. These results highlight the potential of TPT-TT NPs as an effective photothermal agent for cancer therapy. PMID:26398145

  6. 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

  7. Gold nanorods/mesoporous silica-based nanocomposite as theranostic agents for targeting near-infrared imaging and photothermal therapy induced with laser.

    PubMed

    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

  8. 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.

  9. A biomimetic hybrid nanoplatform for encapsulation and precisely controlled delivery of therasnostic agents

    PubMed Central

    Wang, Hai; Agarwal, Pranay; Zhao, Shuting; Yu, Jianhua; Lu, Xiongbin; He, Xiaoming

    2015-01-01

    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. PMID:26621191

  10. 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.

  11. A biomimetic hybrid nanoplatform for encapsulation and precisely controlled delivery of theranostic agents. [Corrected].

    PubMed

    Wang, Hai; Agarwal, Pranay; Zhao, Shuting; Yu, Jianhua; Lu, Xiongbin; He, Xiaoming

    2015-01-01

    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. PMID:26621191

  12. Single wall carbon nanotube/bis carboxylic acid-ICG as a sensitive contrast agent for in vivo tumor imaging in photoacoustic tomography

    NASA Astrophysics Data System (ADS)

    Zanganeh, Saeid; Li, Hai; Kumavor, Patrick; Alqasemi, Umar; Aguirre, Andres; Mohammad, Innus; Stanford, Courtney; Smith, Michael B.; Zhu, Quing

    2013-03-01

    In this study, we present a novel photoacoustic contrast agent which is based on bis-carboxylic acid derivative of Indocyanine green (ICG) covalently conjugated to single-wall carbon nanotubes (ICG/SWCNT). Covalently attaching ICG to the functionalized SWCNT provides a more robust system that delivers much more ICG to the tumor site. The detection sensitivity of the new contrast agent in mouse tumor model is demonstrated in vivo by our custom built photoacoustic imaging system. PAT summation signal is defined to show the long-term light absorption of tumor areas in ICG injected mice and ICG/SWCNT injected mice. It is shown that ICG is able to provide 33% enhancement at approximately 20 minutes peak response time referred to pre-injection PAT summation level, while ICG/SWCNT provides 128% enhancement at 80 minutes and even higher enhancement of 196% at the end point of experiments (120 minutes on average). Additionally, the ICG/SWCNT enhancement was mainly observed at the tumor periphery as confirmed by fluorescence images of the tumor samples. This feature is highly valuable in guiding surgeons to assess tumor boundaries and dimensions in vivo and improve surgical resection of tumors for achieving clean tumor margins.

  13. 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

  14. 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).

  15. Transformation with green fluorescent protein of Trichoderma harzianum 1051, a strain with biocontrol activity against Crinipellis perniciosa, the agent of witches'-broom disease of cocoa.

    PubMed

    Inglis, Peter W.; Queiroz, Paulo R.; Valadares-Inglis, M. Cléria

    1999-04-01

    A plasmid vector for fungal expression of an enhanced, red-shifted variant of the Aequoria victoriae green fluorescent protein was constructed by fusion of the EGFP gene to the highly expressed Aspergillus nidulans gpd promoter and the A. nidulans trpC terminator. This construction was introduced by cotransformation, using benomyl selection, into Trichoderma harzianum strain 1051, a strain being evaluated for the biological control of witches'-broom disease of cocoa caused by Crinipellis perniciosa. Epifluorescence microscopy was used to monitor germination and attachment of stable transformant conidia on the surface of C. perniciosa hyphae.

  16. Brooklyn Green, North Green, South Green, & West Green, parts ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    Brooklyn Green, North Green, South Green, & West Green, parts of Brown Road, Canterbury Road (Route 169), Hartford Road (Route 6), Hyde Road, Pomfret Road (Route 169), Prince Hill Road, Providence Road (Route 6), Wauregan Road (Routes 169 & 205), & Wolf Den Road, Brooklyn, Windham County, CT

  17. Filamentous, mixed micelles of triblock copolymers enhance tumor localization of indocyanine green in a murine xenograft model

    PubMed Central

    Kim, Tae Hee; Mount, Christopher W; Dulken, Benjamin W; Ramos, Jenelyn; Fu, Caroline J; Khant, Htet A; Chiu, Wah; Gombotz, Wayne R; Pun, Suzie H

    2012-01-01

    Polymeric micelles formed by the self-assembly of amphiphilic block copolymers can be used to encapsulate hydrophobic drugs for tumor-delivery applications. Filamentous carriers with high aspect ratios offer potential advantages over spherical carriers, including prolonged circulation times. In this work, mixed micelles comprised of poly (ethylene oxide)-poly-[(R)-3-hydroxybutyrate]-poly (ethylene oxide) (PEO-PHB-PEO) and Pluronic F-127 (PF-127) were used to encapsulate a near-infrared fluorophore. The micelle formulations were assessed for tumor accumulation after tail vein injection to xenograft tumor-bearing mice by non-invasive optical imaging. The mixed micelle formulation that facilitated the highest tumor accumulation was shown by cryo-electron microscopy to be filamentous in structure compared to spherical structures of pure PF-127 micelles. In addition, increased dye loading efficiency and dye stability was attained in this mixed micelle formulation compared to pure PEO-PHB-PEO micelles. Therefore, the optimized PEO-PHB-PEO/PF-127 mixed micelle formulation offers advantages for cancer delivery over micelles formed from the individual copolymer components. PMID:22118658

  18. Filamentous, mixed micelles of triblock copolymers enhance tumor localization of indocyanine green in a murine xenograft model.

    PubMed

    Kim, Tae Hee; Mount, Christopher W; Dulken, Benjamin W; Ramos, Jenelyn; Fu, Caroline J; Khant, Htet A; Chiu, Wah; Gombotz, Wayne R; Pun, Suzie H

    2012-01-01

    Polymeric micelles formed by the self-assembly of amphiphilic block copolymers can be used to encapsulate hydrophobic drugs for tumor-delivery applications. Filamentous carriers with high aspect ratios offer potential advantages over spherical carriers, including prolonged circulation times. In this work, mixed micelles composed of poly(ethylene oxide)-poly[(R)-3-hydroxybutyrate]-poly(ethylene oxide) (PEO-PHB-PEO) and Pluronic F-127 (PF-127) were used to encapsulate a near-infrared fluorophore. The micelle formulations were assessed for tumor accumulation after tail vein injection to xenograft tumor-bearing mice by noninvasive optical imaging. The mixed micelle formulation that facilitated the highest tumor accumulation was shown by cryo-electron microscopy to be filamentous in structure compared to spherical structures of pure PF-127 micelles. In addition, increased dye loading efficiency and dye stability were attained in this mixed micelle formulation compared to pure PEO-PHB-PEO micelles. Therefore, the optimized PEO-PHB-PEO/PF-127 mixed micelle formulation offers advantages for cancer delivery over micelles formed from the individual copolymer components.

  19. Monoclonal antibody-targeted PEGylated liposome-ICG encapsulating doxorubicin as a potential theranostic agent.

    PubMed

    Lozano, Neus; Al-Ahmady, Zahraa S; Beziere, Nicolas S; Ntziachristos, Vasilis; Kostarelos, Kostas

    2015-03-30

    Indocyanine green (ICG) is an FDA-approved, strongly photo-absorbent/fluorescent probe that has been incorporated into a clinically-relevant PEGylated liposome as a flexible optoacoustic contrast agent platform. This study describes the engineering of targeted PEGylated liposome-ICG using the anti-MUC-1 "humanized" monoclonal antibody (MoAb) hCTM01 as a tumour-specific theranostic system. We aimed to visualise non-invasively the tumour accumulation of these MoAb-targeted liposomes over time in tumour-bearing mice using multispectral optoacoustic tomography (MSOT). Preferential accumulation of targeted PEGylated liposome-ICG was studied after intravenous administration in comparison to non-targeted PEGylated liposome-ICG using both fast growing (4T1) and slow growing (HT-29) MUC-1 positive tumour models. Monitoring liposomal ICG in the tumour showed that both targeted and non-targeted liposome-ICG formulations preferentially accumulated into the tumour models studied. Rapid accumulation was observed for targeted liposomes at early time points mainly in the periphery of the tumour volume suggesting binding to available MUC-1 receptors. In contrast, non-targeted PEGylated liposomes showed accumulation at the centre of the tumour at later time points. In an attempt to take this a step further, we successfully encapsulated the anticancer drug, doxorubicin (DOX) into both targeted and non-targeted PEGylated liposome-ICG. The engineering of DOX-loaded targeted ICG liposome systems present a novel platform for combined tumour-specific therapy and diagnosis. This can open new possibilities in the design of advanced image-guided cancer therapeutics.

  20. Image-guided synergistic photothermal therapy using photoresponsive imaging agent-loaded graphene-based nanosheets.

    PubMed

    Miao, Wenjun; Shim, Gayong; Kim, Gunwoo; Lee, Soondong; Lee, Hee-Jung; Kim, Young Bong; Byun, Youngro; Oh, Yu-Kyoung

    2015-08-10

    We report the image-guided synergistic photothermal antitumor effects of photoresponsive near-infrared (NIR) imaging agent, indocyanine green (ICG), by loading onto hyaluronic acid-anchored, reduced graphene oxide (HArGO) nanosheets. Loading of ICG onto either rGO (ICG/rGO) or HArGO (ICG/HArGO) substantially improved the photostability of photoresponsive ICG upon NIR irradiation. After 1min of irradiation, the NIR absorption peak of ICG almost disappeared whereas the peak of ICG on rGO or HArGO was retained even after 5min of irradiation. Compared with plain rGO, HArGO provided greater cellular delivery of ICG and photothermal tumor cell-killing effects upon laser irradiation in CD44-positive KB cells. The temperature of cell suspensions treated with ICG/HArGO was 2.4-fold higher than that of cells treated with free ICG. Molecular imaging revealed that intravenously administered ICG/HArGO accumulated in KB tumor tissues higher than ICG/rGO or free ICG. Local temperatures in tumor tissues of laser-irradiated KB cell-bearing nude mice were highest in those intravenously administered ICG/HArGO, and were sufficient to trigger thermal-induced complete tumor ablation. Immunohistologically stained tumors also showed the highest percentages of apoptotic cells in the group treated with ICG/HArGO. These results suggest that photoresponsive ICG-loaded HArGO nanosheets could serve as a potential theranostic nano-platform for image-guided and synergistic photothermal antitumor therapy.

  1. Monoclonal antibody-targeted PEGylated liposome-ICG encapsulating doxorubicin as a potential theranostic agent.

    PubMed

    Lozano, Neus; Al-Ahmady, Zahraa S; Beziere, Nicolas S; Ntziachristos, Vasilis; Kostarelos, Kostas

    2015-03-30

    Indocyanine green (ICG) is an FDA-approved, strongly photo-absorbent/fluorescent probe that has been incorporated into a clinically-relevant PEGylated liposome as a flexible optoacoustic contrast agent platform. This study describes the engineering of targeted PEGylated liposome-ICG using the anti-MUC-1 "humanized" monoclonal antibody (MoAb) hCTM01 as a tumour-specific theranostic system. We aimed to visualise non-invasively the tumour accumulation of these MoAb-targeted liposomes over time in tumour-bearing mice using multispectral optoacoustic tomography (MSOT). Preferential accumulation of targeted PEGylated liposome-ICG was studied after intravenous administration in comparison to non-targeted PEGylated liposome-ICG using both fast growing (4T1) and slow growing (HT-29) MUC-1 positive tumour models. Monitoring liposomal ICG in the tumour showed that both targeted and non-targeted liposome-ICG formulations preferentially accumulated into the tumour models studied. Rapid accumulation was observed for targeted liposomes at early time points mainly in the periphery of the tumour volume suggesting binding to available MUC-1 receptors. In contrast, non-targeted PEGylated liposomes showed accumulation at the centre of the tumour at later time points. In an attempt to take this a step further, we successfully encapsulated the anticancer drug, doxorubicin (DOX) into both targeted and non-targeted PEGylated liposome-ICG. The engineering of DOX-loaded targeted ICG liposome systems present a novel platform for combined tumour-specific therapy and diagnosis. This can open new possibilities in the design of advanced image-guided cancer therapeutics. PMID:25445515

  2. Green Architecture

    NASA Astrophysics Data System (ADS)

    Lee, Seung-Ho

    Today, the environment has become a main subject in lots of science disciplines and the industrial development due to the global warming. This paper presents the analysis of the tendency of Green Architecture in France on the threes axes: Regulations and Approach for the Sustainable Architecture (Certificate and Standard), Renewable Materials (Green Materials) and Strategies (Equipments) of Sustainable Technology. The definition of 'Green Architecture' will be cited in the introduction and the question of the interdisciplinary for the technological development in 'Green Architecture' will be raised up in the conclusion.

  3. Microfluidic platform for photodynamic therapy cytotoxicity analysis of nanoencapsulated indocyanine-type photosensitizers.

    PubMed

    Jastrzębska, Elżbieta; Bazylińska, Urszula; Bułka, Magdalena; Tokarska, Katarzyna; Chudy, Michał; Dybko, Artur; Wilk, Kazimiera Anna; Brzózka, Zbigniew

    2016-01-01

    The application of nanotechnology is important to improve research and development of alternative anticancer therapies. In order to accelerate research related to cancer diagnosis and to improve the effectiveness of cancer treatment, various nanomaterials are being tested. The main objective of this work was basic research focused on examination of the mechanism and effectiveness of the introduction of nanoencapsulated photosensitizers to human carcinoma (A549) and normal cells (MRC-5). Newly encapsulated hydrophobic indocyanine-type photosensitizer (i.e., IR-780) was subjected to in vitro studies to determine its release characteristics on a molecular level. The photosensitizers were delivered to carcinoma and normal cells cultured under model conditions using multiwell plates and with the use of the specially designed hybrid (poly(dimethylsiloxane) (PDMS)/glass) microfluidic system. The specific geometry of our microsystem allows for the examination of intercellular interactions between cells cultured in the microchambers connected with microchannels of precisely defined length. Our microsystem allows investigating various therapeutic procedures (e.g., photodynamic therapy) on monoculture, coculture, and mixed culture, simultaneously, which is very difficult to perform using standard multiwell plates. In addition, we tested the cellular internalization of nanoparticles (differing in size, surface properties) in carcinoma and normal lung cells. We proved that cellular uptake of nanocapsules loaded with cyanine IR-780 in carcinoma cells was more significant than in normal cells. We demonstrated non cytotoxic effect of newly synthesized nanocapsules built with polyelectrolytes (PEs) of opposite surface charges: polyanion-polysodium-4-styrenesulphonate and polycation-poly(diallyldimethyl-ammonium) chloride loaded with cyanine IR-780 on human lung carcinoma and normal cell lines. However, the differences observed in the photocytotoxic effect between two types of

  4. Doppler photoacoustic and Doppler ultrasound in blood with optical contrast agent

    NASA Astrophysics Data System (ADS)

    Sheinfeld, Adi; Eyal, Avishay

    2013-03-01

    Photoacoustic Doppler flowmetry as well as Doppler ultrasound were performed in acoustic resolution regime on tubes filled with flowing blood with indocyanine green (ICG) at different concentrations. The photoacoustic excitation utilized a pair of directly-modulated fiber-coupled 830nm laser-diodes, modulated with either CW or tone-bursts for depthresolved measurements. The amplitude of the Doppler peak in photoacoustic Doppler measurements was found to be proportional to the ICG concentration. Photoacoustic Doppler was measured in ICG at human safe concentrations, but not in whole blood. Comparing the results between the two modalities implied that using a wavelength with higher optical absorption may improve the photoacoustic signal in blood.

  5. Agent Orange

    MedlinePlus

    ... Index Agent Orange Agent Orange Home Facts about Herbicides Veterans' Diseases Birth Defects Benefits Exposure Locations Provider ... millions of gallons of Agent Orange and other herbicides on trees and vegetation during the Vietnam War. ...

  6. Code Green.

    ERIC Educational Resources Information Center

    McMinn, John

    2002-01-01

    Assesses the integrated approach to green design in the new Computer Science Building at Toronto's York University. The building design fulfills the university's demand to combine an energy efficient design with sustainability. Floor and site plans are included. (GR)

  7. Green Infrastructure

    EPA Science Inventory

    Large paved surfaces keep rain from infiltrating the soil and recharging groundwater supplies. Alternatively, Green infrastructure uses natural processes to reduce and treat stormwater in place by soaking up and storing water. These systems provide many environmental, social, an...

  8. Green Roofs

    SciTech Connect

    2004-08-01

    A New Technology Demonstration Publication Green roofs can improve the energy performance of federal buildings, help manage stormwater, reduce airborne emissions, and mitigate the effects of urban heat islands.

  9. Green Coffee

    MedlinePlus

    ... orange in combination with caffeine or caffeine-containing herbs can increase blood pressure and heart rate in ... serious heart problems. Avoid this combination.Caffeine-containing herbs and supplementsUsing green coffee along with other caffeine- ...

  10. Plant mediated green synthesis: modified approaches

    NASA Astrophysics Data System (ADS)

    Das, Ratul Kumar; Brar, Satinder Kaur

    2013-10-01

    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.

  11. Plant mediated green synthesis: modified approaches.

    PubMed

    Das, Ratul Kumar; Brar, Satinder Kaur

    2013-11-01

    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. PMID:24056951

  12. Green foot.

    PubMed

    LeFeber, W P; Golitz, L E

    1984-07-01

    Pseudomonas aeruginosa may infect the skin surface, nails, hair follicles, or deeper tissues. We report a 13-year-old male with an asymptomatic green discoloration of the toenails and sole of the right foot. Pseudomonas aeruginosa was cultured from the shoe, but not from the discolored skin. We suspect that constant wearing of occlusive, rubber-soled, basketball shoes associated with hyperhidrosis allowed colonization of his shoe with pseudomonas. This case is unique in that colonization resulted in a green color of the foot not associated with infection of the skin.

  13. Going Green.

    ERIC Educational Resources Information Center

    Kennedy, Mike

    2001-01-01

    Discusses the benefits that schools and universities can gain by adopting environmentally sensitive practices in their design and operations. Includes resources for locating additional information about green schools and a list of 11 features that represent a comprehensive, sustainable school. (GR)

  14. Green Schools.

    ERIC Educational Resources Information Center

    Kozlowski, David, Ed.

    1998-01-01

    Discusses "going green" concept in school-building design, its cost-savings benefits through more efficient energy use, and its use by the State University of New York at Buffalo as solution to an energy retrofit program. Examples are provided of how this concept can be used, even for small colleges without large capital budgets, and how it can…

  15. Green Power

    ERIC Educational Resources Information Center

    Schaffhauser, Dian

    2009-01-01

    In the world of higher education, even the most ambitious sustainability plans often begin with tiny steps taken by individual departments. Michael Crowley, a program manager for Environmental Health & Engineering (EH&E) and former assistant director of the Harvard (Massachusetts) Green Campus Initiative, explains that going for small wins through…

  16. Buying Green

    ERIC Educational Resources Information Center

    Layng, T. V. Joe

    2010-01-01

    In "Buying Green," Joe Layng recognizes that, like all choices we make, our decisions as consumers are more likely to be influenced by their short-term consequences for us as individuals (price, quality) than they are by their long-term consequences for society (environmental impact). He believes that the equation can be tilted in favor of greener…

  17. Green pioneers.

    PubMed

    Trueland, Jennifer

    The government has set tough targets for the NHS in England to reduce its carbon footprint. In this article, nurses and managers at Nottinghamshire Healthcare NHS Trust explain how a programme of 'greening' initiatives - including a trial of electric cars for community staff - have slashed the trust's CO2 output.

  18. Think green.

    PubMed

    Serb, Chris

    2008-08-01

    Hospitals typically don't come to mind when you think about cutting-edge environmental programs, but that's changing. Rising energy costs, the need to replace older facilities, and a growing environmental consciousness have spurred hospitals nationwide to embrace a green ideology. The executive suite is a vocal and active player in these efforts. PMID:19062433

  19. Green pioneers.

    PubMed

    Trueland, Jennifer

    The government has set tough targets for the NHS in England to reduce its carbon footprint. In this article, nurses and managers at Nottinghamshire Healthcare NHS Trust explain how a programme of 'greening' initiatives - including a trial of electric cars for community staff - have slashed the trust's CO2 output. PMID:23763098

  20. Going Green

    ERIC Educational Resources Information Center

    Witkowsky, Kathy

    2009-01-01

    Going green saves money and can even make money. Sustainable practices promote better health, less absenteeism, and more productivity. They also attract students, who are paying increasing attention to schools' environmental policies. Beyond being the smart thing to do, administrators at the University of Washington say repeatedly, it's the right…

  1. Green Leaders

    ERIC Educational Resources Information Center

    Kennedy, Mike

    2008-01-01

    More and more people are viewing the world through green-tinted glasses, and those ideas about making school and university facilities more environmentally friendly suddenly are appearing to be prudent and responsible. Among the groups that have been advocating for environmentally friendly school design for years are the Collaborative for High…

  2. Think green.

    PubMed

    Serb, Chris

    2008-08-01

    Hospitals typically don't come to mind when you think about cutting-edge environmental programs, but that's changing. Rising energy costs, the need to replace older facilities, and a growing environmental consciousness have spurred hospitals nationwide to embrace a green ideology. The executive suite is a vocal and active player in these efforts.

  3. Biological Agents

    MedlinePlus

    ... to Z Index Contact Us FAQs What's New Biological Agents This page requires that javascript be enabled ... and Health Topics A-Z Index What's New Biological agents include bacteria, viruses, fungi, other microorganisms and ...

  4. First In-human Intraoperative Imaging of HCC using Fluorescence Goggle System and Transarterial Delivery of Near-infrared Fluorescent Imaging Agent: a Pilot Study

    PubMed Central

    Akers, Walter; Tang, Zhao-You; Fan, Jia; Sun, Hui-Chuan; Ye, Qing-Hai; Wang, Lu; Achilefu, Samuel

    2013-01-01

    Surgical resections remain the primary curative interventions for hepatocellular carcinoma (HCC). However, lack of real-time intraoperative image guidance confines surgeons to subjective visual assessment of the surgical bed, leading to poor visualization of small positive nodules and the extension of diffuse HCC. To address this problem, we developed a wearable fluorescence imaging and display system (fluorescence goggle) for intraoperative imaging of HCCs in human patients. In this pilot study, both intravenous (i.v.) and transarterial hepatic (TAH) delivery of indocyanine green (ICG) were explored to facilitate fluorescence goggle-mediated HCC imaging. The results show that all primary tumors in patients (n=4) who received TAH delivery of ICG were successfully identified by the fluorescence goggle. In addition, 6 satellite tumors were also detected by the goggle, 5 of which were neither identifiable in pre-operative MRI and CT images nor by visual inspection and palpation. In the group (n=5) that received ICG by i.v., only 2 out of 6 tumors visible in the pre-operative MRI or CT images were identified with the fluorescence goggle, demonstrating the limitation of this delivery route for a non-tumor selective imaging agent. Comparative analysis shows that the HCC-to-liver florescence contrast detected by the goggle was significantly higher in patients that received TAH than i.v. delivery of ICG (P=0.013). This pilot study demonstrates the feasibility of using the fluorescence goggle to identify multifocal lesions and small tumor deposits using TAH ICG delivery in HCC patients. PMID:23747795

  5. Green toxicology.

    PubMed

    Maertens, Alexandra; Anastas, Nicholas; Spencer, Pamela J; Stephens, Martin; Goldberg, Alan; Hartung, Thomas

    2014-01-01

    Historically, early identification and characterization of adverse effects of industrial chemicals was difficult because conventional toxicological test methods did not meet R&D needs for rapid, relatively inexpensive methods amenable to small amounts of test material. The pharmaceutical industry now front-loads toxicity testing, using in silico, in vitro, and less demanding animal tests at earlier stages of product development to identify and anticipate undesirable toxicological effects and optimize product development. The Green Chemistry movement embraces similar ideas for development of less toxic products, safer processes, and less waste and exposure. Further, the concept of benign design suggests ways to consider possible toxicities before the actual synthesis and to apply some structure/activity rules (SAR) and in silico methods. This requires not only scientific development but also a change in corporate culture in which synthetic chemists work with toxicologists. An emerging discipline called Green Toxicology (Anastas, 2012) provides a framework for integrating the principles of toxicology into the enterprise of designing safer chemicals, thereby minimizing potential toxicity as early in production as possible. Green Toxicology`s novel utility lies in driving innovation by moving safety considerations to the earliest stage in a chemical`s lifecycle, i.e., to molecular design. In principle, this field is no different than other subdisciplines of toxicology that endeavor to focus on a specific area - for example, clinical, environmental or forensic toxicology. We use the same principles and tools to evaluate an existing substance or to design a new one. The unique emphasis is in using 21st century toxicology tools as a preventative strategy to "design out" undesired human health and environmental effects, thereby increasing the likelihood of launching a successful, sustainable product. Starting with the formation of a steering group and a series of workshops

  6. 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.

  7. Green Manufacturing

    SciTech Connect

    Patten, John

    2013-12-31

    Green Manufacturing Initiative (GMI): The initiative provides a conduit between the university and industry to facilitate cooperative research programs of mutual interest to support green (sustainable) goals and efforts. In addition to the operational savings that greener practices can bring, emerging market demands and governmental regulations are making the move to sustainable manufacturing a necessity for success. The funding supports collaborative activities among universities such as the University of Michigan, Michigan State University and Purdue University and among 40 companies to enhance economic and workforce development and provide the potential of technology transfer. WMU participants in the GMI activities included 20 faculty, over 25 students and many staff from across the College of Engineering and Applied Sciences; the College of Arts and Sciences' departments of Chemistry, Physics, Biology and Geology; the College of Business; the Environmental Research Institute; and the Environmental Studies Program. Many outside organizations also contribute to the GMI's success, including Southwest Michigan First; The Right Place of Grand Rapids, MI; Michigan Department of Environmental Quality; the Michigan Department of Energy, Labor and Economic Growth; and the Michigan Manufacturers Technical Center.

  8. A difunctional squarylium indocyanine dye distinguishes dead cells through diverse staining of the cell nuclei/membranes.

    PubMed

    Li, Jie; Guo, Kunru; Shen, Jie; Yang, Wantai; Yin, Meizhen

    2014-04-01

    Functionalized fluorescent dyes have attracted great interest for the specific staining of subcellular organelles in multicellular organisms. A novel nanometer-sized water-soluble multi-functional squarylium indocyanine dye (D1) that contains four primary amines is synthesized. The dye exhibits good photostability, non-toxicity and biocompatibility. Isothermal titration calorimetry demonstrates that an affinity between D1 and DNA is higher than that between D1 and analogue of phospholipids. Analysis of circular dichroism spectra indicates that D1 targets to the DNA minor groove and aggregates to a helix. Because of the distinct affinity between the dye and subcellular organelles, the dye exhibits difunctional abilities to label the cell nuclei in fixed cells/tissue and the cell membranes in live cells/tissue. By combination of the two staining capabilities, the dye is further explored as a specific marker to distinguish apoptotic cells in live cells/tissue. The research opens a new way to design novel multifunctional dyes for life science applications.

  9. Green Phosphors

    NASA Astrophysics Data System (ADS)

    Singh, Vijay; Chakradhar, R. P. S.; Rao, J. L.; Dhoble, S. J.; Kim, S. H.

    2014-11-01

    Manganese-doped LaMgAl11O19 powder has been prepared by an easy combustion method. Powder x-ray diffraction and scanning electron microscopy have been used to characterize the as-prepared phosphor. The electron paramagnetic resonance (EPR) spectrum of LaMgAl11O19:Mn2+ phosphor exhibits six-line hyperfine structure centered at g ≈ 1.973. The number of spins participating in resonance ( N) and the paramagnetic susceptibility ( χ) for the resonance signal at g ≈ 1.973 have been calculated as a function of temperature. The photoluminescence spectrum exhibits green emission at 516 nm, which is attributed to 4T1 → 6A1 transition of Mn2+ ions. From EPR and luminescence studies, it is observed that Mn2+ ions occupy Mg2+ sites and Mn2+ ions are located at tetrahedral sites in the prepared phosphors.

  10. 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.

  11. Green nanotechnology

    NASA Astrophysics Data System (ADS)

    Smith, Geoff B.

    2011-10-01

    Nanotechnology, in particular nanophotonics, is proving essential to achieving green outcomes of sustainability and renewable energy at the scales needed. Coatings, composites and polymeric structures used in windows, roof and wall coatings, energy storage, insulation and other components in energy efficient buildings will increasingly involve nanostructure, as will solar cells. Nanostructures have the potential to revolutionize thermoelectric power and may one day provide efficient refrigerant free cooling. Nanomaterials enable optimization of optical, opto-electrical and thermal responses to this urgent task. Optical harmonization of material responses to environmental energy flows involves (i) large changes in spectral response over limited wavelength bands (ii) tailoring to environmental dynamics. The latter includes engineering angle of incidence dependencies and switchable (or chromogenic) responses. Nanomaterials can be made at sufficient scale and low enough cost to be both economic and to have a high impact on a short time scale. Issues to be addressed include human safety and property changes induced during manufacture, handling and outdoor use. Unexpected bonuses have arisen in this work, for example the savings and environmental benefits of cool roofs extend beyond the more obvious benefit of reduced heat flows from the roof into the building.

  12. Sunscreening Agents

    PubMed Central

    Martis, Jacintha; Shobha, V; Sham Shinde, Rutuja; Bangera, Sudhakar; Krishnankutty, Binny; Bellary, Shantala; Varughese, Sunoj; Rao, Prabhakar; Naveen Kumar, B.R.

    2013-01-01

    The increasing incidence of skin cancers and photodamaging effects caused by ultraviolet radiation has increased the use of sunscreening agents, which have shown beneficial effects in reducing the symptoms and reoccurrence of these problems. Many sunscreen compounds are in use, but their safety and efficacy are still in question. Efficacy is measured through indices, such as sun protection factor, persistent pigment darkening protection factor, and COLIPA guidelines. The United States Food and Drug Administration and European Union have incorporated changes in their guidelines to help consumers select products based on their sun protection factor and protection against ultraviolet radiation, whereas the Indian regulatory agency has not yet issued any special guidance on sunscreening agents, as they are classified under cosmetics. In this article, the authors discuss the pharmacological actions of sunscreening agents as well as the available formulations, their benefits, possible health hazards, safety, challenges, and proper application technique. New technologies and scope for the development of sunscreening agents are also discussed as well as the role of the physician in patient education about the use of these agents. PMID:23320122

  13. Can "the voices in the car" persuade drivers to go green?: effects of benefit appeals from in-vehicle voice agents and the role of drivers' affective states on eco-driving.

    PubMed

    Joo, Yeon Kyoung; Lee, Jong-Eun Roselyn

    2014-04-01

    The present research investigated the possibility of using an in-vehicle voice agent to promote eco-driving. Considering that both types of benefit appeals--egoistic (emphasizing benefits to the self) and altruistic (emphasizing benefits to others)--could be employed to promote eco-driving behavior, we explored the effects of benefit appeals delivered by an in-vehicle voice agent on driving performance. In particular, we tested whether and how the valence (positive vs. negative) of drivers' affective states moderates the effects, drawing on the functionalist affect-cognition framework, which has theorized that positive affect leads people to focus more on self-interest, whereas negative affect leads people to become more sensitive to social norms. An experiment was conducted in which participants, after undergoing affect (happy vs. sad) elicitation, received messages (egoistic vs. altruistic) promoting eco-driving from an in-vehicle voice agent while performing a simulated driving task. Results were partially consistent with the functionalist affect-cognition framework. Happy participants performed better on eco-driving when they were exposed to egoistic appeals than to altruistic appeals. On the other hand, the driving performance data from sad participants did not yield a significant difference between the egoistic condition and the altruistic condition. Participants' driving performance data further revealed that the joint effects of benefit appeals and affective states on safe driving performance mirrored the joint effects on eco-driving performance, confirming a close relationship between the two driving behaviors. Theoretical and practical implications for the use of in-vehicle voice agents and benefit appeals in promoting eco-driving and safe driving are discussed. PMID:24479527

  14. 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…

  15. Pseudo-first-order reaction of chemically and biologically formed green rusts with HgII and C₁₅H₁₅N₃O₂: effects of pH and stabilizing agents (phosphate, silicate, polyacrylic acid, and bacterial cells).

    PubMed

    Remy, P-Ph; Etique, M; Hazotte, A A; Sergent, A-S; Estrade, N; Cloquet, C; Hanna, K; Jorand, F P A

    2015-03-01

    The kinetics of Hg(II) and methyl red (MR) reduction by hydroxycarbonate green rust (GR1) and by hydroxysulfate green rust (GR2) were studied in the presence of naturally occurring organic and inorganic ligands (phosphate, polyacrylic acid, bacterial cells, silicate). The reducing ability of biogenic hydroxycarbonate green rust (GR1bio), obtained after microbial reduction of lepidocrocite by Shewanella putrefaciens, was also investigated and compared to those of chemically synthesized GR1 and GR2 (GR1ab and GR2ab). Pseudo first-order rate constants (kobs) of Hg(II) reduction (at pH 7.0, 8.2, and 9.5) and MR reduction (at pH 7.0) were determined and were normalized to the structural Fe(II) content of GRs (kFeII) and to the estimated concentration of surface Fe(II) sites (kS). The kS values ranged from 0.3 L mmol(-1) min(-1) to 43 L mmol(-1) min(-1) for the Hg reduction, and from 0.007 L mmol(-1) min(-1) to 3.4 L mmol(-1) min(-1) for the MR reduction. No significant discrepancy between GRab and GRbio was observed in term of reactivity. However, the reduction kinetics of MR was generally slower than the Hg(II) reduction kinetics for all tested GRs. While a slight difference in Hg(II) reduction rate was noted whatever the pH values (7.0, 8.2, or 9.5), the reduction of MR was significantly affected in the presence of ligands. A decrease by a factor of 2-200, depending on the type of ligand used, was observed. These data give new insights into the reactivity of GRs in the presence of co-occurring organic and inorganic ligands, and have major implications in the characterization of contaminated systems as well as water treatment processes. PMID:25543237

  16. Pseudo-first-order reaction of chemically and biologically formed green rusts with HgII and C₁₅H₁₅N₃O₂: effects of pH and stabilizing agents (phosphate, silicate, polyacrylic acid, and bacterial cells).

    PubMed

    Remy, P-Ph; Etique, M; Hazotte, A A; Sergent, A-S; Estrade, N; Cloquet, C; Hanna, K; Jorand, F P A

    2015-03-01

    The kinetics of Hg(II) and methyl red (MR) reduction by hydroxycarbonate green rust (GR1) and by hydroxysulfate green rust (GR2) were studied in the presence of naturally occurring organic and inorganic ligands (phosphate, polyacrylic acid, bacterial cells, silicate). The reducing ability of biogenic hydroxycarbonate green rust (GR1bio), obtained after microbial reduction of lepidocrocite by Shewanella putrefaciens, was also investigated and compared to those of chemically synthesized GR1 and GR2 (GR1ab and GR2ab). Pseudo first-order rate constants (kobs) of Hg(II) reduction (at pH 7.0, 8.2, and 9.5) and MR reduction (at pH 7.0) were determined and were normalized to the structural Fe(II) content of GRs (kFeII) and to the estimated concentration of surface Fe(II) sites (kS). The kS values ranged from 0.3 L mmol(-1) min(-1) to 43 L mmol(-1) min(-1) for the Hg reduction, and from 0.007 L mmol(-1) min(-1) to 3.4 L mmol(-1) min(-1) for the MR reduction. No significant discrepancy between GRab and GRbio was observed in term of reactivity. However, the reduction kinetics of MR was generally slower than the Hg(II) reduction kinetics for all tested GRs. While a slight difference in Hg(II) reduction rate was noted whatever the pH values (7.0, 8.2, or 9.5), the reduction of MR was significantly affected in the presence of ligands. A decrease by a factor of 2-200, depending on the type of ligand used, was observed. These data give new insights into the reactivity of GRs in the presence of co-occurring organic and inorganic ligands, and have major implications in the characterization of contaminated systems as well as water treatment processes.

  17. Antiparasitic agents.

    PubMed

    Rosenblatt, J E

    1992-03-01

    In recent years, introduction of new and more effective agents has improved the overall therapy for parasitic infections. This field, however, is still plagued by numerous problems, including the development of resistance to antimicrobial agents (especially with malaria), unavailability of agents in the United States or lack of approval by the Food and Drug Administration, and major toxicities or lack of experience in pregnant women and children, which limits use in these groups of patients. Widespread resistance of Plasmodium falciparum to chloroquine and other agents has complicated the treatment and prophylaxis of this type of malaria. A combination of quinine and Fansidar is usually effective oral therapy for falciparum malaria; quinidine may be administered if intravenous therapy is needed. Mefloquine, which is currently recommended for prophylaxis against chloroquine-resistant P. falciparum, is also effective for single-dose oral treatment, although this regimen has not yet been approved by the Food and Drug Administration. Metronidazole has been widely used for treatment of gastroenteritis due to Entamoeba histolytica and Giardia lamblia (not approved by the Food and Drug Administration for the latter) and is considered safe and effective. A new macrolide, azithromycin, has been reported to be effective for cryptosporidiosis in experimental animals; currently, no effective therapy is available for human infections. Combinations of sulfonamides with other antifolates, trimethoprim or pyrimethamine, are recommended therapy for Pneumocystis carinii pneumonia or toxoplasmosis, respectively. Therapies for the various types of leishmaniasis and trypanosomiasis are complex, often toxic, and often of limited efficacy. The benzimidazoles are effective for roundworm infections, although thiabendazole has severe toxic effects. The recent introduction of ivermectin has revolutionized the treatment and control of onchocerciasis. Another relatively new agent, praziquantel

  18. Antidiabetic Agents.

    ERIC Educational Resources Information Center

    Plummer, Nancy; Michael, Nancy, Ed.

    This module on antidiabetic agents is intended for use in inservice or continuing education programs for persons who administer medications in long-term care facilities. Instructor information, including teaching suggestions, and a listing of recommended audiovisual materials and their sources appear first. The module goal and objectives are then…

  19. 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. PMID:25615873

  20. 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.

  1. The effects of different polymerization agents on structural and optical properties of (K0.5Na0.5)NbO3 nanopowders synthesized by a facile green route

    NASA Astrophysics Data System (ADS)

    Khorrami, Gh. H.; Kompany, A.; Zak, A. Khorsand

    2014-11-01

    (K0.5N0.5)NbO3 lead-free nanopowders were synthesized by a modified sol-gel method in different media: gelatin, starch and chitosan, as polymerization and stabilizer agents. The proper temperature needed for calcinating the prepared gel was obtained using thermogravometric analysis (TGA). Structural and optical properties of the prepared powders were investigated and compared using X-ray diffraction (XRD), transmission electron microscopy (TEM) and UV-Vis diffused reflectance spectroscopy. The XRD patterns of the synthesized samples confirmed the formation of the orthorhombic structure at 600°C calcination temperature with no remarkable extra peaks. TEM images showed that the morphologies of the particles prepared in the three different media are cubic with the average size of about 69, 34 and 49 nm for gelatin, starch and chitosan, respectively. The value of the energy band gap of the samples was calculated by diffused reflectance spectroscopy, using Kubelka-Munk method. Our results showed that the type of the polymerization agent is important in preparing KNN nanoparticles and affects the structural and optical properties of the synthesized samples.

  2. A Nano-MgO and Ionic Liquid-Catalyzed 'Green' Synthesis Protocol for the Development of Adamantyl-Imidazolo-Thiadiazoles as Anti-Tuberculosis Agents Targeting Sterol 14α-Demethylase (CYP51).

    PubMed

    Anusha, Sebastian; Cp, Baburajeev; Mohan, Chakrabhavi Dhananjaya; Mathai, Jessin; Rangappa, Shobith; Mohan, Surender; Chandra; Paricharak, Shardul; Mervin, Lewis; Fuchs, Julian E; M, Mahedra; Bender, Andreas; Basappa; Rangappa, Kanchugarakoppal S

    2015-01-01

    In this work, we describe the 'green' synthesis of novel 6-(adamantan-1-yl)-2-substituted-imidazo[2,1-b][1,3,4]thiadiazoles (AITs) by ring formation reactions using 1-(adamantan-1-yl)-2-bromoethanone and 5-alkyl/aryl-2-amino1,3,4-thiadiazoles on a nano material base in ionic liquid media. Given the established activity of imidazothiadiazoles against M. tuberculosis, we next examined the anti-TB activity of AITs against the H37Rv strain using Alamar blue assay. Among the tested compounds 6-(adamantan-1-yl)-2-(4-methoxyphenyl)imidazo[2,1-b][1,3,4]thiadiazole (3f) showed potent inhibitory activity towards M. tuberculosis with an MIC value of 8.5 μM. The inhibitory effect of this molecule against M. tuberculosis was comparable to the standard drugs such as Pyrazinamide, Streptomycin, and Ciprofloxacin drugs. Mechanistically, an in silico analysis predicted sterol 14α-demethylase (CYP51) as the likely target and experimental activity of 3f in this system corroborated the in silico target prediction. In summary, we herein report the synthesis and biological evaluation of novel AITs against M. tuberculosis that likely target CYP51 to induce their antimycobacterial activity.

  3. Green Flight Challenge

    NASA Video Gallery

    The CAFE Green Flight Challenge sponsored by Google will be held at the CAFE Foundation Flight Test Center at Charles M. Schulz Sonoma County Airport in Santa Rosa, Calif. The Green Flight Challeng...

  4. Blue-green algae

    MedlinePlus

    “Blue-green algae” describes a large and diverse group of simple, plant-like organisms found in salt water and some large fresh water lakes. Blue-green algae products are used for many conditions, but so ...

  5. KGB agents

    NASA Astrophysics Data System (ADS)

    Gaina, Alex

    A short story is reported in which the activity of Communist Party of the USSR and secret KGB agents, which were payed by the State, in view of controlling of the conscience of population. The story reffers to the Physics Department of the Moscow University, Planing Institute of the Gosplan of Moldavian S.S.R. and Chishinau Technical University (actually: Technical University of Moldova), where the author has worked during Soviet times. Almost every 6-th citizen in the USSR was engaged in this activity, while actually the former communists rule in the Republic of Moldova.

  6. What Is Green?

    ERIC Educational Resources Information Center

    Pokrandt, Rachel

    2010-01-01

    Green is a question with varying answers and sometimes no answer at all. It is a question of location, resources, people, environment, and money. As green really has no end point, a teacher's goal should be to teach students to question and consider green. In this article, the author provides several useful metrics to help technology teachers…

  7. Public Libraries Going Green

    ERIC Educational Resources Information Center

    Miller, Kathryn

    2010-01-01

    Going green is now a national issue, and patrons expect their library to respond in the same way many corporations have. Libraries are going green with logos on their Web sites, programs for the public, and a host of other initiatives. This is the first book to focus strictly on the library's role in going green, helping you with: (1) Collection…

  8. Show Me the Green

    ERIC Educational Resources Information Center

    Norbury, Keith

    2013-01-01

    Gone are the days when green campus initiatives were a balm to the soul and a drain on the wallet. Today's environmental initiatives are all about saving lots of green--in every sense of the word. The environmental benefits of green campus projects--whether wind turbines or better insulation--are pretty clear. Unfortunately, in today's…

  9. The Green Man

    ERIC Educational Resources Information Center

    Watson-Newlin, Karen

    2010-01-01

    The Jolly Green Giant. Robin Hood. The Bamberg Cathedral. Tales of King Arthur. Ecology. What do they have in common? What legends and ancient myths are shrouded in the tales of the Green Man? Most often perceived as an ancient Celtic symbol as the god of spring and summer, the Green Man disappears and returns year after year, century after…

  10. In the Green

    ERIC Educational Resources Information Center

    Kennedy, Mike

    2011-01-01

    Education officials used to debate whether they could afford to pursue green design and construction. Now the green movement has gained a foothold not just in education, but in society at large, and the prevailing attitude seems to have shifted. Can schools afford "not" to go green? As budgets are slashed repeatedly, education administrators must…

  11. EPA's Green Roof Research

    EPA Science Inventory

    This is a presentation on the basics of green roof technology. The presentation highlights some of the recent ORD research projects on green roofs and provices insight for the end user as to the benefits for green roof technology. It provides links to currently available EPA re...

  12. Promoting green engineering through green chemistry.

    PubMed

    Kirchhoff, Mary M

    2003-12-01

    The decisions made by chemists in designing chemical products and processes directly impactthe options available to engineers. The physical and chemical properties of a material, for example, dictate the type of reactor that must be used in a given process. The task of the engineer is simplified when chemists design products and processes that reduce or eliminate the use and generation of hazardous substances. Green chemistry provides a foundation on which to build green engineering. This paper highlights green chemistry technologies that minimize the need for engineering safeguards in the areas of feedstocks, reagents, solvents, and syntheses. PMID:14700319

  13. Filling agents.

    PubMed

    Glavas, Ioannis P

    2005-06-01

    Injectable fillers have become an important component of minimally invasive facial rejuvenation modalities. Their ease of use, effectiveness, low morbidity, and fast results with minimal downtime are factors that have made them popular among patients. Soft tissue augmentation has evolved to a unique combination of medicine and art. A wide selection of available agents and new products, each one with unique properties, may be used alone or in combination. The physician acquires the tools to rebalance facial characteristics not only by filling wrinkles but also by having the ability to shape the face and restore bony contours and lines. Careful selection of candidates, realistic expectations, and an understanding of the limitations of fillers are crucial for a successful result.

  14. Health care agents

    MedlinePlus

    Durable power of attorney for health care; Health care proxy; End-of-life - health care agent; Life support treatment - ... Respirator - health care agent; Ventilator - health care agent; Power of attorney - health care agent; POA - health care ...

  15. Detecting agents.

    PubMed Central

    Johnson, Susan C

    2003-01-01

    This paper reviews a recent set of behavioural studies that examine the scope and nature of the representational system underlying theory-of-mind development. Studies with typically developing infants, adults and children with autism all converge on the claim that there is a specialized input system that uses not only morphological cues, but also behavioural cues to categorize novel objects as agents. Evidence is reviewed in which 12- to 15-month-old infants treat certain non-human objects as if they have perceptual/attentional abilities, communicative abilities and goal-directed behaviour. They will follow the attentional orientation of an amorphously shaped novel object if it interacts contingently with them or with another person. They also seem to use a novel object's environmentally directed behaviour to determine its perceptual/attentional orientation and object-oriented goals. Results from adults and children with autism are strikingly similar, despite adults' contradictory beliefs about the objects in question and the failure of children with autism to ultimately develop more advanced theory-of-mind reasoning. The implications for a general theory-of-mind development are discussed. PMID:12689380

  16. Green tea: nature's defense against malignancies.

    PubMed

    Butt, Masood Sadiq; Sultan, Muhammad Tauseef

    2009-05-01

    The current practice of introducing phytochemicals to support the immune system or fight against diseases is based on centuries old traditions. Nutritional support is a recent advancement in the domain of diet-based therapies; green tea and its constituents are one of the important components of these strategies to prevent and cure various malignancies. The anti-carcinogenic and anti-mutagenic activities of green tea were highlighted some years ago suggesting that it could reduce the prevalence of cancer and even provide protection. The pharmacological actions of green tea are mainly attributed to polyphenols that includes epigallocatechin-3-gallate (EGCG), epicatechin, epicatechin-3-gallate, epigallocatechin. Green tea and its components effectively mitigate cellular damage arising due to oxidative stress. Green tea is supposed to enhance humoral and cell-mediated immunity, decreasing the risk of certain cancers, and may have certain advantage in treating inflammatory disorders. Much of the cancer chemopreventive properties of green tea are mediated by EGCG that induces apoptosis and promotes cell growth arrest, by altering the expression of cell cycle regulatory proteins, activating killer caspases, and suppressing nuclear factor kappa-B activation. Besides, it regulates and promotes IL-23 dependent DNA repair and stimulates cytotoxic T cells activities in a tumor microenvironment. It also blocks carcinogenesis by modulating the signal transduction pathways involved in cell proliferation, transformation, inflammation and metastasis. The review is intended to highlight the chemistry of green tea, its antioxidant potential, its immunopotentiating properties and mode of action against various cancer cell lines that showed its potential as a chemopreventive agent against colon, skin, lung, prostate, and breast cancer.

  17. Green tea catechins for treatment of external genital warts.

    PubMed

    Meltzer, Sara M; Monk, Bradley J; Tewari, Krishnansu S

    2009-03-01

    This review evaluates the antiviral, antioxidant, and immunostimulatory properties of green tea catechins. Two randomized trials evaluating the activity and efficacy of green tea catechins in the management of external genital warts are presented, and the reported side effects associated with this topical treatment modality are outlined. Finally, the mechanism of action, percent of wart clearance, time to clearance, and toxicity profile of green tea catechins are compared with those of podofilox and imiquimod, 2 other patient-administered topical agents approved for treatment of anogenital warts.

  18. Green Cleaning Label Power

    ERIC Educational Resources Information Center

    Balek, Bill

    2012-01-01

    Green cleaning plays a significant and supportive role in helping education institutions meet their sustainability goals. However, identifying cleaning products, supplies and equipment that truly are environmentally preferable can be daunting. The marketplace is inundated with products and services purporting to be "green" or environmentally…

  19. Lighting: Green Light.

    ERIC Educational Resources Information Center

    Maniccia, Dorine

    2003-01-01

    Explains that by using sustainable (green) building practices, schools and universities can make their lighting systems more efficient, noting that embracing green design principles can help schools attract students. Discusses lighting-control technologies (occupancy sensing technology, daylighting technology, and scheduling based technologies),…

  20. Greening the Future

    ERIC Educational Resources Information Center

    Williamson, Norma Velia

    2011-01-01

    Because educators vicariously touch the future through their students, the author believes that they sometimes have the uncanny ability to see the future. One common future forecast is the phenomenal growth of green jobs in the emerging green economy, leading to the creation of the "Reach of the Sun" Solar Energy Academy at La Mirada High School…

  1. Green Buildings and Health.

    PubMed

    Allen, Joseph G; MacNaughton, Piers; Laurent, Jose Guillermo Cedeno; Flanigan, Skye S; Eitland, Erika Sita; Spengler, John D

    2015-09-01

    Green building design is becoming broadly adopted, with one green building standard reporting over 3.5 billion square feet certified to date. By definition, green buildings focus on minimizing impacts to the environment through reductions in energy usage, water usage, and minimizing environmental disturbances from the building site. Also by definition, but perhaps less widely recognized, green buildings aim to improve human health through design of healthy indoor environments. The benefits related to reduced energy and water consumption are well-documented, but the potential human health benefits of green buildings are only recently being investigated. The objective of our review was to examine the state of evidence on green building design as it specifically relates to indoor environmental quality and human health. Overall, the initial scientific evidence indicates better indoor environmental quality in green buildings versus non-green buildings, with direct benefits to human health for occupants of those buildings. A limitation of much of the research to date is the reliance on indirect, lagging and subjective measures of health. To address this, we propose a framework for identifying direct, objective and leading "Health Performance Indicators" for use in future studies of buildings and health. PMID:26231502

  2. Green Infrastructure 101

    EPA Science Inventory

    Green Infrastructure 101 • What is it? What does it do? What doesn’t it do? • Green Infrastructure as a stormwater and combined sewer control • GI Controls and Best Management Practices that make sense for Yonkers o (Include operations and maintenance requirements for each)

  3. 10 Paths to Green

    ERIC Educational Resources Information Center

    Kennedy, Mike

    2008-01-01

    Some institutions may feel comfortable with a few baby steps into the green world, while others may be ready to commit totally to environmental consciousness. Here, the author discusses 10 areas in which educators and administrators can beef up their green portfolio. These areas are in: alternative fuel, bikes/walking, water, education tools,…

  4. Custodial Operations: Green & Sustainable

    ERIC Educational Resources Information Center

    Campbell, J. Kirk

    2008-01-01

    Custodial Operations can have a significant impact on institutional green and sustainable goals if given the proper support and challenge. This article describes the green and sustainable custodial operations in place at Carleton College in Northfield, Minnesota. The article reviews the college's sustainable efforts on biodegradables, packaging,…

  5. Green Building Research Laboratory

    SciTech Connect

    Sailor, David Jean

    2013-12-29

    This project provided support to the Green Building Research Laboratory at Portland State University (PSU) so it could work with researchers and industry to solve technical problems for the benefit of the green building industry. It also helped to facilitate the development of PSU’s undergraduate and graduate-level training in building science across the curriculum.

  6. Sowing Green Seeds

    ERIC Educational Resources Information Center

    Yingjun, Chen; Jianzhuang, Rong

    2004-01-01

    This article deals with the development of environmental education Hunan Yueyang Middle School Number One. Famous for its beautiful environment and lush green trees, the school has won titles such as "park" unit, "garden" school, "green school" and "National Advanced Unit for Environmental Education." In order to popularize scientific knowledge of…

  7. Green Buildings and Health.

    PubMed

    Allen, Joseph G; MacNaughton, Piers; Laurent, Jose Guillermo Cedeno; Flanigan, Skye S; Eitland, Erika Sita; Spengler, John D

    2015-09-01

    Green building design is becoming broadly adopted, with one green building standard reporting over 3.5 billion square feet certified to date. By definition, green buildings focus on minimizing impacts to the environment through reductions in energy usage, water usage, and minimizing environmental disturbances from the building site. Also by definition, but perhaps less widely recognized, green buildings aim to improve human health through design of healthy indoor environments. The benefits related to reduced energy and water consumption are well-documented, but the potential human health benefits of green buildings are only recently being investigated. The objective of our review was to examine the state of evidence on green building design as it specifically relates to indoor environmental quality and human health. Overall, the initial scientific evidence indicates better indoor environmental quality in green buildings versus non-green buildings, with direct benefits to human health for occupants of those buildings. A limitation of much of the research to date is the reliance on indirect, lagging and subjective measures of health. To address this, we propose a framework for identifying direct, objective and leading "Health Performance Indicators" for use in future studies of buildings and health.

  8. Green Chemistry and Education.

    ERIC Educational Resources Information Center

    Hjeresen, Dennis L.; Schutt, David L.; Boese, Janet M.

    2000-01-01

    Many students today are profoundly interested in the sustainability of their world. Introduces Green Chemistry and its principles with teaching materials. Green Chemistry is the use of chemistry for pollution prevention and the design of chemical products and processes that are environmentally benign. (ASK)

  9. The Green Revolution.

    ERIC Educational Resources Information Center

    Huke, Robert E.

    1985-01-01

    Modern agriculture's green revolution refers to a complex package that includes improved seeds and a wide range of efficient management practices. The genetic history of and technological developments that led to the green revolution are described, and its impact discussed. (RM)

  10. A Green Clean

    ERIC Educational Resources Information Center

    Kravitz, Robert

    2006-01-01

    In the professional cleaning industry, green cleaning has been much discussed in the past few years. Usually, the information pertains to the many reasons why a green cleaning program should be started, the steps involved to get the program off the ground, and the potential benefits. However, although many facility managers and school…

  11. Green tea in dermatology.

    PubMed

    Pazyar, Nader; Feily, Amir; Kazerouni, Afshin

    2012-01-01

    The purpose of this brief review is to summarize all in vitro, in vivo, and controlled clinical trials on green tea preparations and their uses in dermatology. An extensive literature search was carried out to identify in vivo and in vitro studies as well as clinical trials. Twenty studies were assessed and the results suggest that oral administration of green tea can be effective in the scavenging of free radicals, cancer prevention, hair loss, and skin aging plus protection against the adverse effects associated with psoralen-UV-A therapy. Topical application of green tea extract should be potentially effective for atopic dermatitis, acne vulgaris, rosacea, androgenetic alopecia, hirsutism, keloids, genital warts, cutaneous leishmaniasis, and candidiosis. There are promising results with the use of green tea for several dermatologic conditions; however, the efficacy of oral and topical green tea has not always been confirmed. PMID:23346663

  12. Green tea in dermatology.

    PubMed

    Pazyar, Nader; Feily, Amir; Kazerouni, Afshin

    2012-01-01

    The purpose of this brief review is to summarize all in vitro, in vivo, and controlled clinical trials on green tea preparations and their uses in dermatology. An extensive literature search was carried out to identify in vivo and in vitro studies as well as clinical trials. Twenty studies were assessed and the results suggest that oral administration of green tea can be effective in the scavenging of free radicals, cancer prevention, hair loss, and skin aging plus protection against the adverse effects associated with psoralen-UV-A therapy. Topical application of green tea extract should be potentially effective for atopic dermatitis, acne vulgaris, rosacea, androgenetic alopecia, hirsutism, keloids, genital warts, cutaneous leishmaniasis, and candidiosis. There are promising results with the use of green tea for several dermatologic conditions; however, the efficacy of oral and topical green tea has not always been confirmed.

  13. Preparing Change Agents for Change Agent Roles.

    ERIC Educational Resources Information Center

    Sedlacek, James R.

    Seventy-seven Spanish- and Portuguese-speaking agricultural change agents from developing Central and South American countries responded to a questionnaire which sought perceptions of the roles in which the change agents felt they were involved and the roles for which they felt they were being trained. The agents were participating in training…

  14. Building the green way.

    PubMed

    Lockwood, Charles

    2006-06-01

    Just five or six years ago, the term "green building" evoked visions of barefoot, tie-dyed, granola-munching denizens. There's been a large shift in perception. Of course, green buildings are still known for conserving natural resources by, for example, minimizing on-site grading, using alternative materials, and recycling construction waste. But people now see the financial advantages as well. Well-designed green buildings yield lower utility costs, greater employee productivity, less absenteeism, and stronger attraction and retention of workers than standard buildings do. Green materials, mechanical systems, and furnishings have become more widely available and considerably less expensive than they used to be-often cheaper than their standard counterparts. So building green is no longer a pricey experiment; just about any company can do it on a standard budget by following the ten rules outlined by the author. Reliable building-rating systems like the U.S. Green Building Council's rigorous Leadership in Energy and Environmental Design (LEED) program have done much to underscore the benefits of green construction. LEED evaluates buildings and awards points in several areas, such as water efficiency and indoor environmental quality. Other rating programs include the UK's BREEAM (Building Research Establishment's Environmental Assessment Method) and Australia's Green Star. Green construction is not simply getting more respect; it is rapidly becoming a necessity as corporations push it fully into the mainstream over the next five to ten years. In fact, the author says, the owners of standard buildings face massive obsolescence. To avoid this problem, they should carry out green renovations. Corporations no longer have an excuse for eschewing environmental and economic sustainability. They have at their disposal tools proven to lower overhead costs, improve productivity, and strengthen the bottom line.

  15. Going Green: Greening Your Marketing Efforts

    ERIC Educational Resources Information Center

    Germain, Carol Anne

    2009-01-01

    There is no doubt that the "Going Green" movement is in full swing. With global warming and other ecological concerns, people are paying closer attention to environmental issues and striving to live in a more sustainable world. For libraries, this is a perfect opportunity to be active in a campus-wide program and simultaneously promote library…

  16. Collection Development "Green Business": The Green Capitalist

    ERIC Educational Resources Information Center

    Eagan, Robert

    2009-01-01

    The "greening" of corporate behemoths like Wal-Mart, DuPont, and Toyota has received much media attention in recent years. But consider small businesses: according to the U.S. Small Business Administration, of the estimated 27 million firms in the United States, 99.7 percent have fewer than 500 employees, 97.5 percent have fewer than 20, and more…

  17. Remote Agent Demonstration

    NASA Technical Reports Server (NTRS)

    Dorais, Gregory A.; Kurien, James; Rajan, Kanna

    1999-01-01

    We describe the computer demonstration of the Remote Agent Experiment (RAX). The Remote Agent is a high-level, model-based, autonomous control agent being validated on the NASA Deep Space 1 spacecraft.

  18. White is green

    NASA Astrophysics Data System (ADS)

    Glicksman, Hal

    1998-12-01

    Green is the center of the visible spectrum and the hue to which we are most sensitive. In RGB color, green is 60 percent of white. When we look through a prism at a white square, as Goethe did, we see white between yellow and cyan, just where green appears in the spectrum of Newton. Additional arguments were published previously and appear at www.csulb.edu/-percept, along with the Percept color chart of the hue/value relationships. A new argument, derived from the perception of leaves, is presented here. The Percept color chart transformed into a color wheel is also presented.

  19. Green Light Pulse Oximeter

    DOEpatents

    Scharf, John Edward

    1998-11-03

    A reflectance pulse oximeter that determines oxygen saturation of hemoglobin using two sources of electromagnetic radiation in the green optical region, which provides the maximum reflectance pulsation spectrum. The use of green light allows placement of an oximetry probe at central body sites (e.g., wrist, thigh, abdomen, forehead, scalp, and back). Preferably, the two green light sources alternately emit light at 560 nm and 577 nm, respectively, which gives the biggest difference in hemoglobin extinction coefficients between deoxyhemoglobin, RHb, and oxyhemoglobin, HbO.sub.2.

  20. 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...

  1. Green Supercomputing at Argonne

    SciTech Connect

    Pete Beckman

    2009-11-18

    Pete Beckman, head of Argonne's Leadership Computing Facility (ALCF) talks about Argonne National Laboratory's green supercomputing—everything from designing algorithms to use fewer kilowatts per operation to using cold Chicago winter air to cool the machine more efficiently.

  2. The Green Revolution Game.

    ERIC Educational Resources Information Center

    Corbridge, Stuart

    1985-01-01

    The Green Revolution game helps college students learn about agrarian change in which people use science to transform nature. The rational and basic objectives of the game are discussed, and the game's strengths and weaknesses are examined. (RM)

  3. No More Green Thumbs!

    ERIC Educational Resources Information Center

    Bland, Judith A.

    1977-01-01

    An alternative method of bacterial spore staining using malachite green is described. This technique is designed to save time and expense by a less messy procedure. Advantages and adaptations of the technique are also given. (MR)

  4. Expanding the Green Revolution.

    ERIC Educational Resources Information Center

    Mellor, John W.; Riely, Frank Z.

    1989-01-01

    Described are some of the successes of the Green Revolution in third-world nations. Discussed are research priorities; misconceptions; and improvements in management skills, training and education, infrastructure, and international trade. (CW)

  5. 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.

  6. 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. PMID:25902988

  7. Biological warfare agents.

    PubMed

    Pohanka, Miroslav; Kuca, Kamil

    2010-01-01

    Biological warfare agents are a group of pathogens and toxins of biological origin that can be potentially misused for military or criminal purposes. The present review attempts to summarize necessary knowledge about biological warfare agents. The historical aspects, examples of applications of these agents such as anthrax letters, biological weapons impact, a summary of biological warfare agents and epidemiology of infections are described. The last section tries to estimate future trends in research on biological warfare agents.

  8. Spacecraft sanitation agent development

    NASA Technical Reports Server (NTRS)

    1972-01-01

    The development of an effective sanitizing agent that is compatible with the spacecraft environment and the human occupant is discussed. Experimental results show that two sanitation agents must be used to satisfy mission requirements: one agent for personal hygiene and one for equipment maintenance. It was also recommended that a water rinse be used with the agents for best results, and that consideration be given to using the agents pressure packed or in aerosol formulations.

  9. 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.

  10. A Green Solvent Induced DNA Package

    NASA Astrophysics Data System (ADS)

    Satpathi, Sagar; Sengupta, Abhigyan; Hridya, V. M.; Gavvala, Krishna; Koninti, Raj Kumar; Roy, Bibhisan; Hazra, Partha

    2015-03-01

    Mechanistic details of DNA compaction is essential blue print for gene regulation in living organisms. Many in vitro studies have been implemented using several compaction agents. However, these compacting agents may have some kinds of cytotoxic effects to the cells. To minimize this aspect, several research works had been performed, but people have never focused green solvent, i.e. room temperature ionic liquid as DNA compaction agent. To the best of our knowledge, this is the first ever report where we have shown that guanidinium tris(pentafluoroethyl)trifluorophosphate (Gua-IL) acts as a DNA compacting agent. The compaction ability of Gua-IL has been verified by different spectroscopic techniques, like steady state emission, circular dichroism, dynamic light scattering and UV melting. Notably, we have extensively probed this compaction by Gua-IL through field emission scanning electron microscopy (FE-SEM) and fluorescence microscopy images. We also have discussed the plausible compaction mechanism process of DNA by Gua-IL. Our results suggest that Gua-IL forms a micellar kind of self aggregation above a certain concentration (>=1 mM), which instigates this compaction process. This study divulges the specific details of DNA compaction mechanism by a new class of compaction agent, which is highly biodegradable and eco friendly in nature.

  11. Green Clay Minerals

    NASA Astrophysics Data System (ADS)

    Velde, B.

    2003-12-01

    Color is a problem for scientific study. One aspect is the vocabulary one used to describe color. Mint green, bottle green, and Kelly green are nice names but not of great utility in that people's physical perception of color is not always the same. In some industries, such as colored fabric manufacture, current use is to send a set of standard colors which are matched by the producer. This is similar to the use of the Munsell color charts in geology. None of these processes makes use of physical optical spectral studies. The reason is that they are difficult to obtain and interpret. For a geologist, color is very important but we rarely have the possibility to standardize the method of our color perception. One reason is that color is both a reflective and transmission phenomenon. The thickness of the sample is critical to any transmission characteristics. Hence, a field color determination is different from one made by using a petrographic microscope. Green glauconite in a hand specimen is not the same color in 30 μm thick thin section seen with a microscope using transmitted light.A second problem is that color in a spectral identification is the result of several absorption emissions,with overlapping signal, forming a complicated spectrum. Interpretation depends very greatly on the spectrum of the light source and the conditions of transmission-reflection of the sample. As a result, for this text, we will not attempt to analyze the physical aspect of green in green clays. In the discussion which follows, reference is made concerning color, to thin section microscopic perception.Very briefly, green clay minerals are green, because they contain iron. This is perhaps not a great revelation to mineralogists, but it is the key to understanding the origin and stability of green clay minerals. In fact, iron can color minerals either red or green or in various shades of orange and brown. The color most likely depends upon the relative abundance of the iron ion valence

  12. On being green: can flow chemistry help?

    PubMed

    Ley, Steven V

    2012-08-01

    The principles of Green Chemistry are important but challenging drivers for most modern synthesis programs. To meet these challenges new flow chemistry tools are proving to be very effective by providing improved heat/mass transfer opportunities, lower solvent usage, less waste generation, hazardous compound containment, and the possibility of a 24/7 working regime. This machine-assisted approach can be used to effect repetitive or routine scale-up steps or when combined with reagent and scavenger cartridges, to achieve multi-step synthesis of complex natural products and pharmaceutical agents. PMID:22711555

  13. On being green: can flow chemistry help?

    PubMed

    Ley, Steven V

    2012-08-01

    The principles of Green Chemistry are important but challenging drivers for most modern synthesis programs. To meet these challenges new flow chemistry tools are proving to be very effective by providing improved heat/mass transfer opportunities, lower solvent usage, less waste generation, hazardous compound containment, and the possibility of a 24/7 working regime. This machine-assisted approach can be used to effect repetitive or routine scale-up steps or when combined with reagent and scavenger cartridges, to achieve multi-step synthesis of complex natural products and pharmaceutical agents.

  14. Green Logistics Management

    NASA Astrophysics Data System (ADS)

    Chang, Yoon S.; Oh, Chang H.

    Nowadays, environmental management becomes a critical business consideration for companies to survive from many regulations and tough business requirements. Most of world-leading companies are now aware that environment friendly technology and management are critical to the sustainable growth of the company. The environment market has seen continuous growth marking 532B in 2000, and 590B in 2004. This growth rate is expected to grow to 700B in 2010. It is not hard to see the environment-friendly efforts in almost all aspects of business operations. Such trends can be easily found in logistics area. Green logistics aims to make environmental friendly decisions throughout a product lifecycle. Therefore for the success of green logistics, it is critical to have real time tracking capability on the product throughout the product lifecycle and smart solution service architecture. In this chapter, we introduce an RFID based green logistics solution and service.

  15. Chemical warfare agents.

    PubMed

    Chauhan, S; Chauhan, S; D'Cruz, R; Faruqi, S; Singh, K K; Varma, S; Singh, M; Karthik, V

    2008-09-01

    Chemical warfare agents (CWA's) are defined as any chemical substance whose toxic properties are utilised to kill, injure or incapacitate an enemy in warfare and associated military operations. Chemical agents have been used in war since times immemorial, but their use reached a peak during World War I. During World War II only the Germans used them in the infamous gas chambers. Since then these have been intermittently used both in war and acts of terrorisms. Many countries have stockpiles of these agents. There has been a legislative effort worldwide to ban the use of CWA's under the chemical weapons convention which came into force in 1997. However the manufacture of these agents cannot be completely prohibited as some of them have potential industrial uses. Moreover despite the remedial measures taken so far and worldwide condemnation, the ease of manufacturing these agents and effectiveness during combat or small scale terrorist operations still make them a powerful weapon to reckon with. These agents are classified according to mechanism of toxicity in humans into blister agents, nerve agents, asphyxiants, choking agents and incapacitating/behavior altering agents. Some of these agents can be as devastating as a nuclear bomb. In addition to immediate injuries caused by chemical agents, some of them are associated with long term morbidities and psychological problems. In this review we will discuss briefly about the historical background, properties, manufacture techniques and industrial uses, mechanism of toxicity, clinical features of exposure and pharmacological management of casualties caused by chemical agents. PMID:21783898

  16. Green Supercomputing at Argonne

    ScienceCinema

    Beckman, Pete

    2016-07-12

    Pete Beckman, head of Argonne's Leadership Computing Facility (ALCF) talks about Argonne National Laboratory's green supercomputing—everything from designing algorithms to use fewer kilowatts per operation to using cold Chicago winter air to cool the machine more efficiently. Argonne was recognized for green computing in the 2009 HPCwire Readers Choice Awards. More at http://www.anl.gov/Media_Center/News/2009/news091117.html Read more about the Argonne Leadership Computing Facility at http://www.alcf.anl.gov/

  17. Apollo 15 green glasses.

    NASA Technical Reports Server (NTRS)

    Ridley, W. I.; Reid, A. M.; Warner, J. L.; Brown, R. W.

    1973-01-01

    The samples analyzed include 28 spheres, portions of spheres, and angular fragments from soil 15101. Emerald green glasses from other soils are identical to those from 15101. The composition of the green glass is unlike that of any other major lunar glass group. The Fe content is comparable to that in mare basalts, but Ti is much lower. The Mg content is much higher than in most lunar materials analyzed to date, and the Cr content is also high. The low Al content is comparable to that of mare basalt glasses.

  18. 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

  19. Mobile Agents Applications.

    ERIC Educational Resources Information Center

    Martins, Rosane Maria; Chaves, Magali Ribeiro; Pirmez, Luci; Rust da Costa Carmo, Luiz Fernando

    2001-01-01

    Discussion of the need to filter and retrieval relevant information from the Internet focuses on the use of mobile agents, specific software components which are based on distributed artificial intelligence and integrated systems. Surveys agent technology and discusses the agent building package used to develop two applications using IBM's Aglet…

  20. Hydroxypyridonate chelating agents

    DOEpatents

    Raymond, Kenneth N.; Scarrow, Robert C.; White, David L.

    1987-01-01

    Chelating agents having 1-hydroxy-2-pyridinone (HOPO) and related moieties incorporated within their structures, including polydentate HOPO-substituted polyamines such as spermidine and spermine, and HOPO-substituted desferrioxamine. The chelating agents are useful in selectively removing certain cations from solution, and are particularly useful as ferric ion and actinide chelators. Novel syntheses of the chelating agents are provided.

  1. Raising a "Green Generation"

    ERIC Educational Resources Information Center

    Leger-Ferraro, Susan

    2010-01-01

    These days, "going green" is at the forefront of conversation in political, entertainment, and corporate circles. Yet to truly impact change, future generations must carry the torch of transformation. To ensure success, adults need to begin the practices with the fertile minds of young children in early education. Practicing sustainability is not…

  2. A Green Role Model

    ERIC Educational Resources Information Center

    Hoffman, Paul J.

    2008-01-01

    Building a new green campus and adopting a philosophy of sustainability is exciting, but if not done properly, it is not always the wisest decision. As one considers the education, health, and safety of a campus community, along with its business objectives, one may discover that there are numerous ways to make the campus more sustainable without…

  3. News: Green Chemistry & Technology

    EPA Science Inventory

    A series of 21 articles focused on different features of green chemistry in a recent issue of Chemical Reviews. Topics extended over a wide range to include the design of sustainable synthetic processes to biocatalysis. A selection of perspectives follows as part of this colu

  4. The Green Team

    ERIC Educational Resources Information Center

    Jahnigen, Charlie

    2006-01-01

    As interest in green building grows, much discussion has focused on aligning a project with the principles of Leadership in Energy and Environmental Design (LEED) certification: (1) cost savings through energy and water conservation; (2) improved worker productivity; (3) health, insurance and risk-management benefits; and (4) enhanced building…

  5. The Green Obligation

    ERIC Educational Resources Information Center

    Adams, Cameron

    2007-01-01

    As the green movement grows, studies provide conclusive evidence about the benefits of environmentally conscious practices indoors and outdoors. Schools are no exception. Many of these studies demonstrate how poor indoor air quality (IAQ) in schools adversely affects many of the nation's 55 million students with health problems such as asthma and…

  6. The Green Hunter.

    ERIC Educational Resources Information Center

    Reid, Ed

    1991-01-01

    Environmentalists who oppose hunting have little understanding of the sport, its ethics and regulations, and its immense role in wildlife conservation. "Green" hunting involves not only the hunter's methods but also his perceptions of the hunt as a cultural or spiritual experience. (SV)

  7. Putting on the green

    EPA Science Inventory

    The green chemistry movement is scrutinized for marks of tangible success in this short perspective. Beginning with the easily identified harm of the Union Carbide Bhopal, India disaster and the concerns of Love Canal site in Niagara Falls, NY the public can begin to more easily ...

  8. Brassica greens herbicide screening

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The objective of this study was to screen herbicides for potential use in brassica greens. Plots were in a RBD with 4 replications. The study was direct seeded on May 19, 2009 with a seeding rate of 272,000 seeds/acre (‘Savanna’ mustard). Treatments included trifluralin PPI + DCPA pre-emergence ap...

  9. Toward Green Challenge Courses.

    ERIC Educational Resources Information Center

    Johnson, Karl E.

    1999-01-01

    Designing environmentally friendly challenge courses involves considering factors such as clearing, trees versus poles, soil erosion and compaction, toilet design, waste disposal, and carrying capacity. Strategies used in "green development" such as systems thinking, solution multipliers, and brainstorming with stakeholders could promote challenge…

  10. Green Schools: Electric Youth

    ERIC Educational Resources Information Center

    Demski, Jennifer

    2008-01-01

    A student committee whose main duty is changing light bulbs may sound like the punch line to a bad joke, but as the students and faculty at Montgomery County Public Schools (MCPS) in Rockville, MD, know, changing a light bulb is no laughing matter. As part of the district's green initiative, all standard incandescent and fluorescent light bulbs…

  11. Green Supercomputing at Argonne

    ScienceCinema

    Pete Beckman

    2016-07-12

    Pete Beckman, head of Argonne's Leadership Computing Facility (ALCF) talks about Argonne National Laboratory's green supercomputing—everything from designing algorithms to use fewer kilowatts per operation to using cold Chicago winter air to cool the machine more efficiently.

  12. The Green Bank Telescope

    NASA Astrophysics Data System (ADS)

    Prestage, R. M.; Constantikes, K. T.; Hunter, T. R.; King, L. J.; Lacasse, R. J.; Lockman, F. J.; Norrod, R. D.

    2009-08-01

    The Robert C. Byrd Green Bank Telescope of the National Radio Astronomy Observatory is the world's premiere single-dish radio telescope operating at centimeter to long millimeter wavelengths. This paper describes the history, construction, and main technical features of the telescope.

  13. Green chemistry metrics

    EPA Science Inventory

    Synthetic chemists have always had an objective to achieve reliable and high-yielding routes to the syntheses of targeted molecules. The importance of minimal waste generation has emphasized the use of green chemistry principles and sustainable development. These directions lead ...

  14. Elements of Green.

    ERIC Educational Resources Information Center

    Turckes, Steven; Engelbrecht, Kathie

    2002-01-01

    Discusses incorporating green design into school construction, asserting that schools can improve their impact on the environment and reduce their operating costs while educating people about the value of sustainable design. Addresses energy reduction (including daylighting), site design for low environmental impact, flexible design, indoor air…

  15. Lean Green Machines

    ERIC Educational Resources Information Center

    Villano, Matt

    2011-01-01

    Colleges and universities have been among the leaders nationwide in adopting green initiatives, partly due to their demographics, but also because they are facing their own budget pressures. Virtualization has become the poster child of many schools' efforts, because it provides significant bang for the buck. However, more and more higher…

  16. EPA NRMRL green Infrastructure research

    EPA Science Inventory

    Green Infrastructure is an engineering approach to wet weather flow management that uses infiltration, evapotranspiration, capture and reuse to better mimic the natural drainage processes than traditional gray systems. Green technologies supplement gray infrastructure to red...

  17. Green tea: potential health benefits.

    PubMed

    Schneider, Craig; Segre, Tiffany

    2009-04-01

    Green tea has been used widely and in high doses for centuries as a health tonic in many societies. Evidence suggests that green tea is effective for treating genital warts. There is some supportive evidence for the use of green tea in cancer prevention. Drinking green tea is associated with a decrease in all-cause mortality, but not in cancer-related mortality. Small clinical studies have found that green tea may also be helpful in losing and managing weight, and lowering cholesterol. Epidemiologic evidence suggests that green tea may prevent stroke and cardiovascular disease. Green tea appears to be safe, although there have been case reports of hepatotoxicity possibly related to a specific extract in pill or beverage form. Green tea seems to be a low-risk complementary therapy for a number of conditions, but more studies are needed.

  18. Green tea polyphenols for prostate cancer chemoprevention: A translational perspective

    PubMed Central

    Johnson, J.J.; Bailey, H.H.; Mukhtar, H.

    2009-01-01

    Every year nearly 200,000 men in the United States are diagnosed with prostate cancer (PCa), and another 29,000 men succumb to the disease. Within certain regions of the world population based studies have identified a possible role for green tea in the prevention of certain cancers, especially PCa. One constituent in particular, epigallocatechin-3-gallate also known as EGCG has been shown in cell culture models to decrease cell viability and promote apoptosis in multiple cancer cell lines including PCa with no effect on non-cancerous cell lines. In addition, animal models have consistently shown that standardized green tea polyphenols when administered in drinking water delay the development and progression of PCa. Altogether, three clinical trials have been performed in PCa patients and suggest that green tea may have a distinct role as a chemopreventive agent. This review will present the available data for standardized green tea polyphenols in regard to PCa chemoprevention that will include epidemiological, mechanism based studies, safety, pharmacokinetics, and applicable clinical trials. The data that has been collected so far suggests that green tea may be a promising agent for PCa chemoprevention and further clinical trials of participants at risk of PCa or early stage PCa are warranted. PMID:19959000

  19. Standard Agent Framework 1

    SciTech Connect

    Goldsmith, Steven Y.

    1999-04-06

    The Standard Agent framework provides an extensible object-oriented development environment suitable for use in both research and applications projects. The SAF provides a means for constructing and customizing multi-agent systems through specialization of standard base classes (architecture-driven framework) and by composition of component classes (data driven framework). The standard agent system is implemented as an extensible object-centerd framework. Four concrete base classes are developed: (1) Standard Agency; (2) Standard Agent; (3) Human Factor, and (4) Resources. The object-centered framework developed and utilized provides the best comprimise between generality and flexibility available in agent development systems today.

  20. The green highway forum

    SciTech Connect

    2006-07-01

    In late 2004, as part of American Coal Ash Association's (ACAA) strategic planning process, a plan was approved by its Board of Directors implementing a 'green highways' concept which emphasized use of coal combustion products (CCPs) in highways in a variety of ways including being used alone, in combination with other forms of CCPs, and combined with non ash materials. The incentives behind the developed concept were the derived advantages from beneficial technical economic and environmental impacts. Although the primary use of fly ash is concrete, other forms of CCPs could be considered for more non-traditional highway applications. For example, these might include soils stabilization, binders for in-place pavement recycling, use in flowable fills, aggregates, source materials for structural fills and embankments, components in manufactured soils, and for granular base courses beneath pavements. At this same time, unknown to ACCA, EPA Region 3 in Philadelphia was working with the Wetlands and Watershed Work Group, a non-profit organization involved in wetlands policy and management along with the Federal Highway Administration (FHWA) on their own Green Highways initiative. These groups were planning a conference, the 'Green Highway Forum'. This was held in College Park, Maryland at the University of Maryland, Nov 8-10 2005. At the conference a draft 'roadmap' was presented as a guide to executive level participants bringing the diverse viewpoints of many agencies and interest groups together. Ten guiding principals were considered. The 'Green Highways' is a new effort to recognize the 'greenness' of many projects already completed and those to be initiated. 2 photos.

  1. "Green" School Programs. Research Brief

    ERIC Educational Resources Information Center

    Johnston, J. Howard

    2009-01-01

    What are "Green School" programs and how do they benefit students, teachers and the community? Green School programs seek to weave concepts of sustainability and environmental awareness into the social and academic culture of the school community. Green schools are high performance facilities that have been designed, built, renovated operated or…

  2. It's Not Easy Building Green.

    ERIC Educational Resources Information Center

    Higgins, Joseph

    2003-01-01

    Discusses green buildings, facilities designed, constructed, and operated in an environmentally friendly and resource-efficient way. Discusses reasons for campuses to "go green," the "shades of green" or variations in environmental-friendliness, certification through the Leadership in Energy and Environmental Design (LEED) rating system, financial…

  3. Green Roofs for Stormwater Management

    EPA Science Inventory

    This project evaluated green roofs as a stormwater management tool. Results indicate that the green roofs are capable of removing 40% of the annual rainfall volume from a roof through retention and evapotranspiration. Rainfall not retained by green roofs is detained, effectively...

  4. Greening from the Top Down.

    ERIC Educational Resources Information Center

    Oberndorfer, Erica

    2002-01-01

    Green roofs, with their topsoil and plants, improve insulation, filter air, reduce water runoff, and provide habitat for urban wildlife. They are compatible with schools because they save energy; schools' flat roofs are conducive to greening; and green roofs can be outdoor classrooms for botany, ecology, and energy efficiency. Although scarce in…

  5. Green Schools on Ordinary Budgets

    ERIC Educational Resources Information Center

    Hanson, Mark E.

    2010-01-01

    Some in the green building industry have spoken for some time now of green buildings not needing to cost more. Jason McLennan in his 2004 book "The Philosophy of Sustainable Design" discusses not falling into the "green is always more" syndrome. He goes on to explain the concept of tunneling through the cost barrier. A 2007 cost study by the…

  6. 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.

  7. Green tea polyphenols: DNA photodamage and photoimmunology.

    PubMed

    Katiyar, S K; Bergamo, B M; Vyalil, P K; Elmets, C A

    2001-12-31

    Green tea is a popular beverage consumed worldwide. The epicatechin derivatives, which are commonly called 'polyphenols', are the active ingredients in green tea and possess antioxidant, anti-inflammatory and anti-carcinogenic properties. Studies conducted by our group on human skin have demonstrated that green tea polyphenols (GTP) prevent ultraviolet (UV)-B-induced cyclobutane pyrimidine dimers (CPD), which are considered to be mediators of UVB-induced immune suppression and skin cancer induction. GTP treated human skin prevented penetration of UV radiation, which was demonstrated by the absence of immunostaining for CPD in the reticular dermis. The topical application of GTP or its most potent chemopreventive constituent (-)-epigallocatechin-3-gallate (EGCG) prior to exposure to UVB protects against UVB-induced local as well as systemic immune suppression in laboratory animals. Additionally, studies have shown that EGCG treatment of mouse skin inhibits UVB-induced infiltration of CD11b+ cells. CD11b is a cell surface marker for activated macrophages and neutrophils, which are associated with induction of UVB-induced suppression of contact hypersensitivity responses. EGCG treatment also results in reduction of the UVB-induced immunoregulatory cytokine interleukin (IL)-10 in skin as well as in draining lymph nodes, and an elevated amount of IL-12 in draining lymph nodes. These in vivo observations suggest that GTPs are photoprotective, and can be used as pharmacological agents for the prevention of solar UVB light-induced skin disorders associated with immune suppression and DNA damage.

  8. Biogenic synthesis of metallic nanoparticles and prospects toward green chemistry.

    PubMed

    Adil, Syed Farooq; Assal, Mohamed E; Khan, Mujeeb; Al-Warthan, Abdulrahman; Siddiqui, Mohammed Rafiq H; Liz-Marzán, Luis M

    2015-06-01

    The immense importance of nanoparticles and their applications is a strong motivation for exploring new synthetic techniques. However, due to strict regulations that manage the potential environmental impacts greener alternatives for conventional synthesis are the focus of intense research. In the scope of this perspective, a concise discussion about the use of green reducing and stabilizing agents toward the preparation of metal nanoparticles is presented. Reports on the synthesis of noble metal nanoparticles using plant extracts, ascorbic acid and sodium citrate as green reagents are summarized and discussed, pointing toward an urgent need of understanding the mechanistic aspects of the involved reactions. PMID:25633046

  9. 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.

  10. Biogenic synthesis of metallic nanoparticles and prospects toward green chemistry.

    PubMed

    Adil, Syed Farooq; Assal, Mohamed E; Khan, Mujeeb; Al-Warthan, Abdulrahman; Siddiqui, Mohammed Rafiq H; Liz-Marzán, Luis M

    2015-06-01

    The immense importance of nanoparticles and their applications is a strong motivation for exploring new synthetic techniques. However, due to strict regulations that manage the potential environmental impacts greener alternatives for conventional synthesis are the focus of intense research. In the scope of this perspective, a concise discussion about the use of green reducing and stabilizing agents toward the preparation of metal nanoparticles is presented. Reports on the synthesis of noble metal nanoparticles using plant extracts, ascorbic acid and sodium citrate as green reagents are summarized and discussed, pointing toward an urgent need of understanding the mechanistic aspects of the involved reactions.

  11. 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. PMID:27074852

  12. Magnetic fields of green.

    PubMed

    Branton, Scott; Lile, Lawrence

    2011-01-01

    By incorporating even the basic elements of a more environmentally friendly, "green"construction and design in an MRI setting can create a safer, more pleasant space for the patients and staff, better images, and operational cost savings. Using building systems that have reduced amounts of steel can decrease construction time, increase thermal insulation, and reduce the weight of the structure meaning less energy required to transport and install. HVAC systems and lighting design can also play a major role in creating a "green"MRI suite. LEED certification places a focus on quality of the built environment, life cycle cost, and a productive indoor environment, as well as impact on the exterior environment. An LEED certified building considers costs and benefits for the lifetime of the building. PMID:22043731

  13. Green biorefinery - Industrial implementation.

    PubMed

    Kamm, B; Schönicke, P; Hille, Ch

    2016-04-15

    Oil refineries currently generate a multitude of products for almost every sphere of life at very high efficiency. However, fossil raw materials are just available in limited quantities. The development of comparable BIOREFINERIES is necessary to make a variety of competitive biological products regarding their equivalent products based on fossil raw materials. The product range of a biorefinery comprises products that can be manufactured on the basis of crude oil, as well as such products that cannot be produced on the basis of crude oil (Kamm, Gruber, & Kamm, 2011). GREEN BIOREFINERIES [GBR's] are complex systems of sustainable, environment- and resource-friendly technologies for a comprehensive material and energy use or recovery of renewable raw materials in form of green and waste biomasses from a sustainable land use as target (Kamm et al., 2009; Digman, Runge, Shinners, & Hatfield, 2013). PMID:26675876

  14. Magnetic fields of green.

    PubMed

    Branton, Scott; Lile, Lawrence

    2011-01-01

    By incorporating even the basic elements of a more environmentally friendly, "green"construction and design in an MRI setting can create a safer, more pleasant space for the patients and staff, better images, and operational cost savings. Using building systems that have reduced amounts of steel can decrease construction time, increase thermal insulation, and reduce the weight of the structure meaning less energy required to transport and install. HVAC systems and lighting design can also play a major role in creating a "green"MRI suite. LEED certification places a focus on quality of the built environment, life cycle cost, and a productive indoor environment, as well as impact on the exterior environment. An LEED certified building considers costs and benefits for the lifetime of the building.

  15. Green biorefinery - Industrial implementation.

    PubMed

    Kamm, B; Schönicke, P; Hille, Ch

    2016-04-15

    Oil refineries currently generate a multitude of products for almost every sphere of life at very high efficiency. However, fossil raw materials are just available in limited quantities. The development of comparable BIOREFINERIES is necessary to make a variety of competitive biological products regarding their equivalent products based on fossil raw materials. The product range of a biorefinery comprises products that can be manufactured on the basis of crude oil, as well as such products that cannot be produced on the basis of crude oil (Kamm, Gruber, & Kamm, 2011). GREEN BIOREFINERIES [GBR's] are complex systems of sustainable, environment- and resource-friendly technologies for a comprehensive material and energy use or recovery of renewable raw materials in form of green and waste biomasses from a sustainable land use as target (Kamm et al., 2009; Digman, Runge, Shinners, & Hatfield, 2013).

  16. Agent Architectures for Compliance

    NASA Astrophysics Data System (ADS)

    Burgemeestre, Brigitte; Hulstijn, Joris; Tan, Yao-Hua

    A Normative Multi-Agent System consists of autonomous agents who must comply with social norms. Different kinds of norms make different assumptions about the cognitive architecture of the agents. For example, a principle-based norm assumes that agents can reflect upon the consequences of their actions; a rule-based formulation only assumes that agents can avoid violations. In this paper we present several cognitive agent architectures for self-monitoring and compliance. We show how different assumptions about the cognitive architecture lead to different information needs when assessing compliance. The approach is validated with a case study of horizontal monitoring, an approach to corporate tax auditing recently introduced by the Dutch Customs and Tax Authority.

  17. Green chemistry: development trajectory

    NASA Astrophysics Data System (ADS)

    Moiseev, I. I.

    2013-07-01

    Examples of applications of green chemistry methods in heavy organic synthesis are analyzed. Compounds, which can be produced by the processing of the biomass, and the criteria for the selection of the most promising products are summarized. The current status of the ethanol production and processing is considered. The possibilities of the use of high fatty acid triglycerides, glycerol, succinic acid, and isoprene are briefly discussed. The bibliography includes 67 references.

  18. AFFECTIVE GUIDANCE OF INTELLIGENT AGENTS: How Emotion Controls Cognition1

    PubMed Central

    Clore, Gerald L.; Palmer, Janet E.

    2008-01-01

    Emotions and moods color cognition. In this article, we outline how emotions affect judgments and cognitive performance of human agents. We argue that affective influences are due, not to the affective reactions themselves, but to the information they carry about value, a potentially useful finding for creators of artificial agents. The kind of influence that occurs depends on the focus of the agent at the time. When making evaluative judgments, for example, agents may experience positive affect as a positive attitude toward a person or object. But when an agent focuses on a cognitive task, positive affect may act like performance feedback, with positive affect giving a green light to cognitive, relational processes. By contrast, negative affect tends to inhibit relational processing, resulting in a more perceptual, stimulus-specific processing. One result is that many textbook phenomena from cognitive psychology occur readily in happy moods, but are inhibited in sad moods. PMID:19255620

  19. Underwater green laser vibrometry

    NASA Astrophysics Data System (ADS)

    Antończak, Arkadiusz J.; Kozioł, Paweł; Wąż, Adam T.; Sotor, Jarosław Z.; Dudzik, Grzegorz; Kaczmarek, Paweł R.; Abramski, Krzysztof M.

    2012-06-01

    We have developed a laser vibrometer based on an monolithic single-frequency green laser operating at 532 nm. This wavelength can be particularly useful in the case of underwater vibrometry, especially with regard to the minimum of water absorption for this wavelength range (blue-green window). Using polarizing optics, we proposed a configuration that allows the elimination of parasitic reflections at the air-glass-water boundary. A measurement of heterodyne signals as a mixing result of scattered and reference beams has been performed. The study was conducted in aqueous medium for the scattering waterproof paper and retro-reflective surface. In both configurations we have obtained signals with a relatively high S/N ratio > 20 dB (for scattering surface) and > 31 dB (for retro-reflective tape) with the Resolution Bandwidth RBW 10 kHz for a vibrometer output power of 5 mW and the distance to the moving object 1.2 m (including 0.3 m in air). In our opinion, laser Doppler vibrometry LDV based on high-performance single frequency solid-state lasers with a wavelength range corresponding to the blue-green window allows effective measurement of vibration in the underwater environment.

  20. INL Green Building Strategy

    SciTech Connect

    Jennifer Dalton

    2005-05-01

    Green buildings, also known as sustainable buildings, resource efficient buildings, and high performance buildings, are structures that minimize the impact on the environment by using less energy and water, reducing solid waste and pollutants, and limiting the depletion of natural resources. As Idaho National Laboratory (INL) becomes the nation’s premier nuclear energy research laboratory, the physical infrastructure will be established to help accomplish the mission. This infrastructure, particularly the buildings, should incorporate green design features in order to be environmentally responsible and reflect an image of progressiveness and innovation to the public and prospective employees. With this in mind, the recommendations described in this strategy are intended to form the INL foundation for green building standards. The recommendations in this strategy are broken down into three levels: Baseline Minimum, Leadership in Energy and Environmental Design (LEED)Certification, and Innovative. Baseline Minimum features should be included in all new occupied buildings no matter what the purpose or size. These features do not require significant research, design, or capital costs and yet they can reduce Operation and Maintenance (O&M) costs and produce more environmentally friendly buildings. LEED Certification features are more aggressive than the Baseline Minimums in that they require documentation, studies, and/or additional funding. Combined with the Baseline Minimums, many of the features in this level will need to be implemented to achieve the goal of LEED certification. LEED Silver certification should be the minimum goal for all new buildings (including office buildings, laboratories, cafeterias, and visitor centers) greater than 25,000 square feet or a total cost of $10 million. Innovative features can also contribute to LEED certification, but are less mainstream than those listed in the previous two levels. These features are identified as areas where