Use of in vivo near-infrared laser confocal endomicroscopy with indocyanine green to detect the boundary of infiltrative tumor

2011 ◽  
Vol 115 (6) ◽  
pp. 1131-1138 ◽  
Author(s):  
Nikolay L. Martirosyan ◽  
Daniel D. Cavalcanti ◽  
Jennifer M. Eschbacher ◽  
Peter M. Delaney ◽  
Adrienne C. Scheck ◽  
...  
Keyword(s):  
Indocyanine Green ◽  
Tumor Cells ◽  
Near Infrared ◽  
Tumor Resection ◽  
Tumor Detection ◽  
Normal Brain ◽  
Tumor Margins ◽  
Confocal Endomicroscopy ◽  
Infiltrative Tumor

Object Infiltrative tumor resection is based on regional (macroscopic) imaging identification of tumorous tissue and the attempt to delineate invasive tumor margins in macroscopically normal-appearing tissue, while preserving normal brain tissue. The authors tested miniaturized confocal fiberoptic endomicroscopy by using a near-infrared (NIR) imaging system with indocyanine green (ICG) as an in vivo tool to identify infiltrating glioblastoma cells and tumor margins. Methods Thirty mice underwent craniectomy and imaging in vivo 14 days after implantation with GL261-luc cells. A 0.4 mg/kg injection of ICG was administered intravenously. The NIR images of normal brain, obvious tumor, and peritumoral zones were collected using the handheld confocal endomicroscope probe. Histological samples were acquired from matching imaged areas for correlation of tissue images. Results In vivo NIR wavelength confocal endomicroscopy with ICG detects fluorescence of tumor cells. The NIR and ICG macroscopic imaging performed using a surgical microscope correlated generally to tumor and peritumor regions, but NIR confocal endomicroscopy performed using ICG revealed individual tumor cells and satellites within peritumoral tissue; a definitive tumor border; and striking fluorescent microvascular, cellular, and subcellular structures (for example, mitoses, nuclei) in various tumor regions correlating with standard clinical histological features and known tissue architecture. Conclusions Macroscopic fluorescence was effective for gross tumor detection, but NIR confocal endomicroscopy performed using ICG enhanced sensitivity of tumor detection, providing real-time true microscopic histological information precisely related to the site of imaging. This first-time use of such NIR technology to detect cancer suggests that combined macroscopic and microscopic in vivo ICG imaging could allow interactive identification of microscopic tumor cell infiltration into the brain, substantially improving intraoperative decisions.

Use of Indocyanine Green Near-Infrared Laser Confocal Endomicroscopy In Vivo: Potential to Intraoperatively Detect the Boundary of Infiltrative Tumor

Neurosurgery ◽  
2010 ◽  
Vol 67 (2) ◽  
pp. 562-562 ◽  
Author(s):  
Nikolay L. Martirosyan ◽  
Daniel Dutra Cavalcanti ◽  
Jennifer M. Eschbacher ◽  
Peter Delaney ◽  
Mohammed G. Abdelwahab ◽  
...  
Keyword(s):  
Indocyanine Green ◽  
Near Infrared ◽  
Infrared Laser ◽  
Confocal Endomicroscopy ◽  
Infiltrative Tumor

scholarly journals A novel indocyanine green-based fluorescent marker for guiding surgical tumor resection

2021 ◽  
pp. 2150013
Author(s):  
Jiawei Ge ◽  
Justin D. Opfermann ◽  
Hamed Saeidi ◽  
Katherine A. Huenerberg ◽  
Christopher D. Badger ◽  
...  
Keyword(s):  
Indocyanine Green ◽  
Feasibility Study ◽  
Near Infrared ◽  
Ex Vivo ◽  
Tumor Resection ◽  
Fluorescent Marker ◽  
India Ink ◽  
Long Term Treatment ◽  
Mouse Study

Surgical tumor resection is a common approach to cancer treatment. India Ink tattoos are widely used to aid tumor resection by localizing and mapping the tumor edge at the surface. However, India Ink tattoos are easily obscured during electrosurgical resection, and fade in intensity over time. In this work, a novel near-infrared (NIR) fluorescent marker is introduced as an alternative. The NIR marker was made by mixing indocyanine green (ICG), biocompatible cyanoacrylate, and acetone. The marking strategy was evaluated in a chronic ex vivo feasibility study using porcine tissues, followed by a chronic in vivo mouse study while compared with India Ink. In both studies, signal-to-noise (SNR) ratios and dimensions of the NIR markers and/or India Ink over the study period were calculated and reported. Electrocautery was performed on the last day of the mouse study after mice were euthanized, and SNR ratios and dimensions were quantified and compared. Biopsy was performed at all injection sites and slides were examined by a pathologist. The proposed NIR marker achieved (i) consistent visibility in the 26-day feasibility study and (ii) improved durability, visibility, and biocompatibility when compared to traditional India Ink over the six-week period in an in vivo mouse model. These effects persist after electrocautery whereas the India Ink markers were obscured. The use of a NIR fluorescent presurgical marking strategy has the potential for intraoperative tracking during long-term treatment protocols.

scholarly journals EXTH-70. ENHANCEMENT OF ANTITUMOR ACTIVITY BY USING 5-ALA–MEDIATED SONODYNAMIC THERAPY TO INDUCE APOPTOSIS AND NECROSIS IN A MOUSE GLIOMA MODEL

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi97-vi97
Author(s):  
Satoshi Suehiro ◽  
Takanori Ohnishi ◽  
Akihiro Inoue ◽  
Daisuke Yamashita ◽  
Masahiro Nishikawa ◽  
...  
Keyword(s):  
Tumor Cells ◽  
Malignant Gliomas ◽  
Glioma Cells ◽  
High Intensity Focused Ultrasound ◽  
Control Group ◽  
Normal Brain ◽  
Sonodynamic Therapy ◽  
Cytotoxic Effects

Abstract OBJECTIVE High invasiveness of malignant gliomas frequently causes local tumor recurrence. To control such recurrence, novel therapies targeted toward infiltrating glioma cells are required. Here, we examined cytotoxic effects of sonodynamic therapy (SDT) combined with a sonosensitizer, 5-aminolevulinic acid (5-ALA), on malignant gliomas both in vitro and in vivo. METHODS In vitro cytotoxicity of 5-ALA-SDT was evaluated in U87 and U251 glioma cells and in U251Oct-3/4 glioma stemlike cells. Treatment-related apoptosis was analyzed using flow cytometry. Intracellular reactive oxygen species (ROS) were measured and the role of ROS in treatment-related cytotoxicity was examined. Effects of 5-ALA-SDT with high-intensity focused ultrasound (HIFU) on tumor growth, survival of glioma-transplanted mice, and histological features of the mouse brains were investigated. RESULTS The 5-ALA-SDT inhibited cell growth and changed cell morphology. Flow cytometric analysis indicated that 5-ALA-SDT induced apoptotic cell death. The 5-ALA-SDT generated higher ROS than in the control group, and inhibition of ROS generation completely eliminated the cytotoxic effects of 5-ALA-SDT. In the in vivo study, 5-ALA-SDT with HIFU greatly prolonged survival of the tumor-bearing mice compared with that of the control group (p < 0.05). Histologically, 5-ALA-SDT produced mainly necrosis of the tumor tissue in the focus area and induced apoptosis of the tumor cells in the perifocus area around the target of the HIFU-irradiated field. Normal brain tissues around the ultrasonic irradiation field of HIFU remained intact. CONCLUSIONS The 5-ALA-SDT was cytotoxic toward malignant gliomas. Generation of ROS by the SDT was thought to promote apoptosis of glioma cells. The 5-ALA-SDT with HIFU induced tumor necrosis in the focus area and apoptosis in the perifocus area of the HIFU-irradiated field. These results suggest that 5-ALA-SDT with HIFU may present a less invasive and tumor-specific therapy, not only for a tumor mass but also for infiltrating tumor cells in malignant gliomas.

scholarly journals The Use of Fluorescent Anti-CEA Antibodies to Label, Resect and Treat Cancers: A Review

Biomolecules ◽  
2021 ◽  
Vol 11 (12) ◽  
pp. 1819
Author(s):  
Michael A. Turner ◽  
Thinzar M. Lwin ◽  
Siamak Amirfakhri ◽  
Hiroto Nishino ◽  
Robert M. Hoffman ◽  
...  
Keyword(s):  
Near Infrared ◽  
Fluorescent Dyes ◽  
Review Article ◽  
In Vivo Studies ◽  
Murine Models ◽  
Exclusion Criteria ◽  
Major Barrier ◽  
Tumor Margins ◽  
Cancer Types

A major barrier to the diagnosis and effective treatment of solid-tumor cancers is the difficulty in detection and visualization of tumor margins in primary and metastatic disease. The use of fluorescence can augment the surgeon’s ability to detect cancer and aid in its resection. Several cancer types express carcinoembryonic antigen (CEA) including colorectal, pancreatic and gastric cancer. Antibodies to CEA have been developed and tagged with near-infrared fluorescent dyes. This review article surveyed the use of CEA antibodies conjugated to fluorescent probes for in vivo studies since 1990. PubMed and Google Scholar databases were queried, and 900 titles and abstracts were screened. Fifty-nine entries were identified as possibly meeting inclusion/exclusion criteria and were reviewed in full. Forty articles were included in the review and their citations were screened for additional entries. A total of 44 articles were included in the final review. The use of fluorescent anti-CEA antibodies has been shown to improve detection and resection of tumors in both murine models and clinically. The cumulative results indicate that fluorescent-conjugated anti-CEA antibodies have important potential to improve cancer diagnosis and surgery. In an emerging technology, anti-CEA fluorescent antibodies have also been successfully used for photoimmunotherapy treatment for cancer.

scholarly journals Indocyanine Green-Nexturastat A-PLGA Nanoparticles Combine Photothermal and Epigenetic Therapy for Melanoma

Nanomaterials ◽  
2020 ◽  
Vol 10 (1) ◽  
pp. 161 ◽  
Author(s):  
Debbie K. Ledezma ◽  
Preethi B. Balakrishnan ◽  
Juliana Cano-Mejia ◽  
Elizabeth E. Sweeney ◽  
Melissa Hadley ◽  
...  
Keyword(s):  
Indocyanine Green ◽  
Near Infrared ◽  
Specific Activity ◽  
Melanoma Cells ◽  
Plga Nanoparticles ◽  
Epigenetic Therapy ◽  
Photothermal Heating ◽  
Epigenetic Drug

In this study, we describe poly (lactic-co-glycolic) acid (PLGA)-based nanoparticles that combine photothermal therapy (PTT) with epigenetic therapy for melanoma. Specifically, we co-encapsulated indocyanine green (ICG), a PTT agent, and Nexturastat A (NextA), an epigenetic drug within PLGA nanoparticles (ICG-NextA-PLGA; INAPs). We hypothesized that combining PTT with epigenetic therapy elicits favorable cytotoxic and immunomodulatory responses that result in improved survival in melanoma-bearing mice. We utilized a nanoemulsion synthesis scheme to co-encapsulate ICG and NextA within stable and monodispersed INAPs. The INAPs exhibited concentration-dependent and near-infrared (NIR) laser power-dependent photothermal heating characteristics, and functioned as effective single-use agents for PTT of melanoma cells in vitro. The INAPs functioned as effective epigenetic therapy agents by inhibiting the expression of pan-histone deacetylase (HDAC) and HDAC6-specific activity in melanoma cells in vitro. When used for both PTT and epigenetic therapy in vitro, the INAPs increased the expression of co-stimulatory molecules and major histocompatibility complex (MHC) Class I in melanoma cells relative to controls. These advantages persisted in vivo in a syngeneic murine model of melanoma, where the combination therapy slowed tumor progression and improved median survival. These findings demonstrate the potential of INAPs as agents of PTT and epigenetic therapy for melanoma.

scholarly journals Protein enhanced NIR-IIb emission of indocyanine green for functional bioimaging

2020 ◽  
Author(s):  
Mubin He ◽  
Di Wu ◽  
Yuhuang Zhang ◽  
Xiaoxiao Fan ◽  
Hui Lin ◽  
...  
Keyword(s):  
Indocyanine Green ◽  
Fluorescence Imaging ◽  
Clinical Application ◽  
Spatial Resolution ◽  
Near Infrared ◽  
Protein Solutions ◽  
Lymph System ◽  
Fetal Bovine ◽  
Auto Fluorescence

AbstractFluorescence imaging performed in the 1500-1700 nm spectral range (labeled as near-infrared IIb, NIR-IIb) promises high imaging contrast and spatial resolution for its little photon scattering effect and minimum auto-fluorescence. Though inorganic and organic probes have been developed for NIR-IIb bioimaging, most are in preclinical stage, hampering further clinical application. Herein, we showed that indocyanine green (ICG), an US Food and Drug Administration (FDA)-approved agent, exhibited remarkable amount of NIR-IIb emission when dissolved into different protein solutions, including human serum albumin, rat bile, and fetal bovine serum. We performed fluorescence imaging in NIR-IIb window to visualize structures of lymph system, extrahepatic biliary tract and cerebrovascular. Results demonstrated that proteins promoted NIR-IIb emission of ICG in vivo and that NIR-IIb imaging with ICG preserved higher signal-to-background ratio (SBR) and spatial resolution compared with the conventional near-infrared II (NIR-II) fluorescence imaging. Our findings confirm that NIR-IIb fluorescence imaging can be successfully performed using the clinically approved agent ICG. Further clinical application in NIR-IIb region would hopefully be carried out with appropriate ICG-protein solutions.

Human serum albumin (HSA) coated liposomal indocyanine green for in vivo tumor imaging

RSC Advances ◽  
2016 ◽  
Vol 6 (18) ◽  
pp. 15220-15225 ◽  
Author(s):  
Siqin Chen ◽  
Gongjie Yu ◽  
Bo Zhang ◽  
Yinsong Wang ◽  
Ning Zhang ◽  
...  
Keyword(s):  
Human Serum Albumin ◽  
Serum Albumin ◽  
Indocyanine Green ◽  
Human Serum ◽  
Near Infrared ◽  
Tumor Imaging ◽  
Fluorescent Nanoprobe

In this study, a near-infrared (NIR) fluorescent nanoprobe based on indocyanine green (ICG) was synthesized.

scholarly journals Laser scanning confocal endomicroscopy in the neurosurgical operating room: a review and discussion of future applications

2014 ◽  
Vol 36 (2) ◽  
pp. E9 ◽  
Author(s):  
Michael A. Mooney ◽  
Aqib H. Zehri ◽  
Joseph F. Georges ◽  
Peter Nakaji
Keyword(s):  
Confocal Microscopy ◽  
Brain Neoplasms ◽  
Laser Scanning ◽  
Tumor Resection ◽  
Emerging Technology ◽  
Future Directions ◽  
Technical Aspects ◽  
Confocal Endomicroscopy ◽  
Made In

Laser scanning confocal endomicroscopy (LSCE) is an emerging technology for examining brain neoplasms in vivo. While great advances have been made in macroscopic fluorescence in recent years, the ability to perform confocal microscopy in vivo expands the potential of fluorescent tumor labeling, can improve intraoperative tissue diagnosis, and provides real-time guidance for tumor resection intraoperatively. In this review, the authors highlight the technical aspects of confocal endomicroscopy and fluorophores relevant to the neurosurgeon, provide a comprehensive summary of LSCE in animal and human neurosurgical studies to date, and discuss the future directions and potential for LSCE in neurosurgery.

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