scholarly journals Real-Time Fluorescence Imaging Using Indocyanine Green to Assess Therapeutic Effects of Near-Infrared Photoimmunotherapy in Tumor Model Mice

2020 ◽  
Vol 19 ◽  
pp. 153601212093496
Author(s):  
Adrian Rosenberg ◽  
Daiki Fujimura ◽  
Ryuhei Okada ◽  
Aki Furusawa ◽  
Fuyuki Inagaki ◽  
...  
Keyword(s):  
Indocyanine Green ◽  
Real Time ◽  
Fluorescence Imaging ◽  
Near Infrared ◽  
Imaging System ◽  
Tumor Model ◽  
Therapeutic Effects ◽  
Tumor Perfusion ◽  
Background Ratio

Background: Near-infrared photoimmunotherapy (NIR-PIT) is a cancer therapy that causes an increase in tumor perfusion, a phenomenon termed the super-enhanced permeability and retention effect. Currently, in vivo treatment efficacy of NIR-PIT is observable days after treatment, but monitoring would be improved by more acute detection of intratumor change. Fluorescence imaging may detect increased tumor perfusion immediately after treatment. Methods: In the first experiment, athymic nude mouse models bearing unilateral subcutaneous flank tumors were treated with either NIR-PIT or laser therapy only. In the second experiment, mice bearing bilateral flank tumors were treated with NIR-PIT only on the left-sided tumor. In both groups, immediately after treatment, indocyanine green was injected at different doses intravenously, and mice were monitored with the Shimadzu LIGHTVISION fluorescence imaging system for 1 hour. Results: Tumor-to-background ratio of fluorescence intensity increased over the 60 minutes of monitoring in treated mice but did not vary significantly in control mice. Tumor-to-background ratio was highest in the 1 mg kg−1 and 0.3 mg kg−1 doses. In mice with bilateral tumors, tumor-to-untreated tumor ratio increased similarly. Conclusions: Acute changes in tumor perfusion after NIR-PIT can be detected by real-time fluorescence imaging.

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

2018 ◽  
Vol 115 (17) ◽  
pp. 4465-4470 ◽  
Author(s):  
Jessica A. Carr ◽  
Daniel Franke ◽  
Justin R. Caram ◽  
Collin F. Perkinson ◽  
Mari Saif ◽  
...  
Keyword(s):  
Indocyanine Green ◽  
Real Time ◽  
Fluorescence Imaging ◽  
Near Infrared ◽  
Emission Spectra ◽  
Nir Fluorescence ◽  
Near Infrared Dye ◽  
Silicon Based ◽  
Shortwave Infrared

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

scholarly journals Shortwave Infrared Fluorescence Imaging with the Clinically Approved Near-Infrared Dye Indocyanine Green

2017 ◽  
Author(s):  
Jessica A. Carr ◽  
Daniel Franke ◽  
Justin R. Caram ◽  
Collin F. Perkinson ◽  
Vasileios Askoxylakis ◽  
...  
Keyword(s):  
Indocyanine Green ◽  
Real Time ◽  
Fluorescence Imaging ◽  
Near Infrared ◽  
Infrared Region ◽  
Fluorescence Angiography ◽  
Nir Fluorescence ◽  
Near Infrared Dye ◽  
Shortwave Infrared

AbstractFluorescence imaging is a method of real-time molecular tracking in vivo that has enabled many clinical technologies. Imaging in the shortwave infrared region (SWIR, 1-2 μm) promises higher contrast, sensitivity, and penetration depths compared to conventional visible and near-infrared (NIR) fluorescence imaging. However, adoption of SWIR imaging in clinical settings has been limited, due in part to the absence of FDA-approved fluorophores with peak emission in the SWIR. Here, we show that commercially available NIR dyes, including the FDA-approved contrast agent indocyanine green (ICG), exhibit optical properties suitable for in vivo SWIR fluorescence imaging. Despite the fact that their emission reaches a maximum in the NIR, these dyes can be imaged non-invasively in vivo in the SWIR spectral region, even beyond 1500 nm. We demonstrate real-time fluorescence angiography at wavelengths beyond 1300 nm using ICG at clinically relevant doses. Furthermore, we show tumortargeted SWIR imaging with trastuzumab labeled with IRDye 800CW, a NIR dye currently being tested in multiple phase II clinical trials. Our findings suggest that high-contrast SWIR fluorescence imaging can be implemented alongside existing imaging modalities by switching the detection of conventional NIR fluorescence systems from silicon-based NIR cameras to emerging indium gallium arsenide (InGaAs) SWIR cameras. Using ICG in particular opens the possibility of translating SWIR fluorescence imaging to human clinical applications.

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.

scholarly journals Real-time navigation during hepatectomy using fusion indocyanine green-fluorescence imaging: protocol for a prospective cohort study

BMJ Open ◽  
2019 ◽  
Vol 9 (8) ◽  
pp. e030233 ◽  
Author(s):  
Hidetoshi Gon ◽  
Shohei Komatsu ◽  
Sae Murakami ◽  
Masahiro Kido ◽  
Motofumi Tanaka ◽  
...  
Keyword(s):  
Body Weight ◽  
Indocyanine Green ◽  
Fluorescence Imaging ◽  
Imaging System ◽  
Imaging Techniques ◽  
Liver Tumours ◽  
Imaging Protocol ◽  
Indocyanine Green Fluorescence ◽  
Fluorescence Imaging System

IntroductionIn-vivo fluorescence imaging techniques using indocyanine green (ICG) to identify liver tumours and hepatic segment boundaries have been recently developed. The purpose of this study is to evaluate the efficacy of fusion ICG-fluorescence imaging for navigation during hepatectomy.Methods and analysisThis will be an exploratory single-arm clinical trial; patients with liver tumours will undergo hepatectomy using the ICG-fluorescence imaging system. In total, 110 patients with liver tumours scheduled for elective hepatectomy will be included in this study. Preoperatively, ICG will be intravenously injected at a dose of 0.5 mg/kg body weight within 2 days. To detect liver tumours intraoperatively, the hepatic surface will be initially observed using the ICG-fluorescence imaging system. After identifying and clamping the portal pedicle corresponding to the hepatic segments, including the liver tumours to be resected, additional ICG will be injected intravenously at a dose of 0.5 mg/kg body weight to identify the boundaries of the hepatic segments. The primary outcome measure will be the success or failure of the ICG-fluorescence imaging system in identifying hepatic segments. The secondary outcomes will be the success or failure in identifying liver tumours, liver function indicators, operative time, blood loss, rate of postoperative complications and recurrence-free survival. The findings obtained through this study are expected to help to establish the utility of ICG-fluorescence imaging systems, and therefore contribute to prognostic outcome improvements in patients undergoing hepatectomy for various causes.Ethics and disseminationThe protocol has been approved by the Kobe University Clinical Research Ethical Committee. The findings of this study will be disseminated widely through peer-reviewed publications and conference presentations.Trial registration numberUMIN000031054 and jRCT1051180070

scholarly journals Non-invasive synchronous monitoring of neutrophil migration using whole body near-infrared fluorescence-based imaging

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Jack Leslie ◽  
Stuart M. Robinson ◽  
Fiona Oakley ◽  
Saimir Luli
Keyword(s):  
Real Time ◽  
Fluorescence Imaging ◽  
Near Infrared ◽  
Spectral Unmixing ◽  
Whole Body ◽  
Spectral Signature ◽  
Cell Labelling ◽  
Cellular Interactions ◽  
Non Invasive

AbstractAdvances in fluorescence imaging coupled with the generation of near infrared probes have significantly improved the capabilities of non-invasive, real-time imaging in whole animals. In this study we were able to overcome a limitation of in vivo fluorescence imaging and have established a dual cell tracking method where two different cell types can be monitored according to the spectral signature of the cell labelling fluorophore. Using a mouse model of acute liver injury, we have characterised the in vivo migration patterns of wild type and transgenic neutrophils with impaired chemotaxis. Here, we were able to demonstrate that IVIS provides a sensitive multiplexing technology to differentiate two different cell populations based on the spectral signature of the cell labelling fluorophores. This spectral unmixing methodology has the potential to uncover multidimensional cellular interactions involved in many diseases such as fibrosis and cancer. In vivo spectral un-mixing provides a useful tool for monitoring multiple biological process in real-time in the same animal.

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

2012 ◽  
Vol 6 (1) ◽  
pp. 80-84 ◽  
Author(s):  
Toru Funayama ◽  
Masataka Sakane ◽  
Tetsuya Abe ◽  
Isao Hara ◽  
Eiichi Ozeki ◽  
...  
Keyword(s):  
Indocyanine Green ◽  
Fluorescence Imaging ◽  
Rat Model ◽  
Near Infrared ◽  
Imaging Modality ◽  
Intraoperative Imaging ◽  
Spinal Metastasis ◽  
Vena Cava ◽  
Nir Fluorescence

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.

scholarly journals Real-Time In Vivo Detection and Monitoring of Bacterial Infection Based on NIR-II Imaging

2021 ◽  
Vol 9 ◽  
Author(s):  
Sijia Feng ◽  
Huizhu Li ◽  
Chang Liu ◽  
Mo Chen ◽  
Huaixuan Sheng ◽  
...  
Keyword(s):  
Bacterial Infection ◽  
Real Time ◽  
Bacterial Infections ◽  
Near Infrared ◽  
Imaging System ◽  
Bacterial Load ◽  
Dynamic Imaging ◽  
In Vivo Detection

Treatment according to the dynamic changes of bacterial load in vivo is critical for preventing progression of bacterial infections. Here, we present a lead sulfide quantum dots (PbS QDs) based second near-infrared (NIR-II) fluorescence imaging strategy for bacteria detection and real-time in vivo monitoring. Four strains of bacteria were labeled with synthesized PbS QDs which showed high bacteria labeling efficiency in vitro. Then bacteria at different concentrations were injected subcutaneously on the back of male nude mice for in vivo imaging. A series of NIR-II images taken at a predetermined time manner demonstrated changing patterns of photoluminescence (PL) intensity of infected sites, dynamically imaging a changing bacterial load in real-time. A detection limit around 102–104 CFU/ml was also achieved in vivo. Furthermore, analysis of pathology of infected sites were performed, which showed high biocompatibility of PbS QDs. Therefore, under the guidance of our developed NIR-II imaging system, real-time detection and spatiotemporal monitoring of bacterial infection in vivo can be achieved, thus facilitating anti-infection treatment under the guidance of the dynamic imaging of bacterial load in future.

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