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

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.

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

Journal of Neurosurgery ◽

10.3171/2011.8.jns11559 ◽

2011 ◽

Vol 115 (6) ◽

pp. 1131-1138 ◽

Cited By ~ 67

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.

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Fluorescence-guided surgery using indocyanine green in dogs with superficial solid tumours

Veterinary Record ◽

10.1136/vr.105554 ◽

2020 ◽

Vol 187 (7) ◽

pp. 273-273

Author(s):

Sophie Favril ◽

Eline Abma ◽

Emmelie Stock ◽

Nausikaa Devriendt ◽

Bart Van Goethem ◽

...

Keyword(s):

Indocyanine Green ◽

Near Infrared ◽

Ex Vivo ◽

False Positive Rate ◽

Tumour Tissue ◽

Surrounding Tissue ◽

Tumour Resection ◽

Nirf Imaging ◽

Tumour Delineation

BackgroundNear-infrared fluorescence (NIRF) imaging is a relatively novel technique that can aid surgeons during intraoperative tumour identification.MethodsNine canine oncology patients (five mammary gland tumours, three mast cell tumours and one melanoma) received intravenous indocyanine green (ICG). After 24 hours, tumours were resected and fluorescence intensities of tumours and surroundings were evaluated. Additional wound bed tissue was resected if residual fluorescence was present after tumour resection. Ex vivo, fluorescence-guided dissection was performed to separate tumour from surrounding tissue.ResultsIntraoperative NIRF-guided tumour delineation was feasible in four out of nine dogs. Wound bed imaging after tumour removal identified nine additional fluorescent lesions, of which four contained tumour tissue. One of these four true positive in vivo lesions was missed by standard-of-care inspection. Ex vivo fluorescence-guided tumour dissection showed a sensitivity of 72 per cent and a specificity of 80 per cent in discriminating between tumour and surrounding tissue.ConclusionThe value of ICG for intraoperative tumour delineation seems more limited than originally thought. Although NIRF imaging using ICG did identify remaining tumour tissue in the wound bed, a high false positive rate was also observed.

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P11: NEAR INFRARED FLUORESCENT CHOLANGIOGRAPHY IN LAPAROSCOPIC CHOLECYSTECTOMY: A SINGLE CENTRE FEASIBILITY STUDY. THE OPTIMUM DOSING REGIME, LIMITATIONS AND WHERE NEXT?

British Journal of Surgery ◽

10.1093/bjs/znab117.096 ◽

2021 ◽

Vol 108 (Supplement_1) ◽

Author(s):

G Armstrong ◽

G Toogood ◽

DG Jayne ◽

AM Smith

Keyword(s):

Laparoscopic Cholecystectomy ◽

Bile Duct ◽

Indocyanine Green ◽

Feasibility Study ◽

Near Infrared ◽

Intravenous Dose ◽

Structure Identification ◽

Dosing Regimen ◽

Single Centre ◽

Fluorescent Cholangiography

Abstract Introduction This study explored near-infrared fluorescent cholangiography (NIRFC) with Indocyanine Green (ICG) during laparoscopic cholecystectomy (LC) surgery in a tertiary referral hepatobiliary unit. ICG binds to albumin and is excreted in bile. NIRFC utilises the fluorescent and excretory properties of ICG to provide dynamic extrahepatic bile duct mapping during LC. Method Non-randomised single centre feasibility study. Twenty-two participants were sequentially allocated to four dosing subgroups prior to NIRFC assisted LC. Each received a single intravenous dose of ICG prior to LC with the Stryker Novadaq NIR laparoscope. The biliary anatomy was assessed with NIRFC at three time-points, detection was compared to radiological cholangiogram where available and surgeon satisfaction was assessed. Result Eight participants received 2.5mg ICG 20-40min before surgery, four 0.25mg/kg 20-40min, five 90min – 180min and five 12 – 36 hour pre-operatively. Average age 50 years (S.D±15), BMI 27.5m2 (S.D±3.6), 6/22 were acute LC procedures. The prolonged dosing interval produced increased extrahepatic biliary structure identification (p = 0.016), reduced noise to signal ratio and was consistently preferred by the operating surgeon. NIRFC was inferior to radiological cholangiogram (n = 10) (p = 0.014) for bile duct mapping. We observed iatrogenic bile spillage saturating the field and obscuring structure differentiation and peri-hilar inflammation impeding fluorescent detection in acute LC. Conclusion The dosing regimen 0.25mg/kg ICG 12 to 36 hours prior to surgery provides optimum NIRFC structure visualisation. Fluorescent tissue penetrance is limited in acute peri-hilar inflammation. More research in to the efficiency of NIRFC in emergency LC is required. Take-home message An intravenous dose of 0.25mg/kg of Indocyanine Green 12 to 36 hours before surgery is the optimum dosing regimen for increased extra-hepatic bile duct structures with near infrared fluorescent cholangiography. The role of NIRFC in acute laparoscopic cholecystectomy surgery remains ill-defined.

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Applications of Vibrational Spectroscopy for Analysis of Connective Tissues

Molecules ◽

10.3390/molecules26040922 ◽

2021 ◽

Vol 26 (4) ◽

pp. 922

Author(s):

William Querido ◽

Shital Kandel ◽

Nancy Pleshko

Keyword(s):

Raman Spectroscopy ◽

Vibrational Spectroscopy ◽

Near Infrared ◽

Ex Vivo ◽

Biological Tissues ◽

Label Free ◽

Connective Tissues ◽

Bone Properties ◽

Composition And Structure

Advances in vibrational spectroscopy have propelled new insights into the molecular composition and structure of biological tissues. In this review, we discuss common modalities and techniques of vibrational spectroscopy, and present key examples to illustrate how they have been applied to enrich the assessment of connective tissues. In particular, we focus on applications of Fourier transform infrared (FTIR), near infrared (NIR) and Raman spectroscopy to assess cartilage and bone properties. We present strengths and limitations of each approach and discuss how the combination of spectrometers with microscopes (hyperspectral imaging) and fiber optic probes have greatly advanced their biomedical applications. We show how these modalities may be used to evaluate virtually any type of sample (ex vivo, in situ or in vivo) and how “spectral fingerprints” can be interpreted to quantify outcomes related to tissue composition and quality. We highlight the unparalleled advantage of vibrational spectroscopy as a label-free and often nondestructive approach to assess properties of the extracellular matrix (ECM) associated with normal, developing, aging, pathological and treated tissues. We believe this review will assist readers not only in better understanding applications of FTIR, NIR and Raman spectroscopy, but also in implementing these approaches for their own research projects.

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Indocyanine-green-loaded microbubbles for localization of sentinel lymph node using near-infrared fluorescence/ultrasound imaging: a feasibility study

RSC Advances ◽

10.1039/c5ra26814a ◽

2016 ◽

Vol 6 (56) ◽

pp. 50513-50520 ◽

Cited By ~ 10

Author(s):

Long Wang ◽

Yihe Hu ◽

Qinghai Peng ◽

Jiawei Zhou ◽

Qichang Zhou ◽

...

Keyword(s):

Lymph Node ◽

Sentinel Lymph Node ◽

Indocyanine Green ◽

Radiation Exposure ◽

Ultrasound Imaging ◽

Feasibility Study ◽

Cancer Metastasis ◽

Near Infrared ◽

False Negative ◽

Near Infrared Fluorescence

Current strategies for sentinel lymph node (SLN) biopsy to detect cancer metastasis have some limitations such as the associated radiation exposure and high false-negative rates due to dye particles through the true SLNs to contiguous LNs.

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Efficient Photoacoustic Imaging With Biomimetic Mesoporous Silica-Based Nanoparticles

Frontiers in Bioengineering and Biotechnology ◽

10.3389/fbioe.2021.762956 ◽

2021 ◽

Vol 9 ◽

Author(s):

Chuangjia Huang ◽

Xiaoling Guan ◽

Hui Lin ◽

Lu Liang ◽

Yingling Miao ◽

...

Keyword(s):

Mesoporous Silica ◽

Near Infrared ◽

Ex Vivo ◽

Photoacoustic Imaging ◽

Mesoporous Silica Nanoparticles ◽

Good Biocompatibility ◽

Targeting Ability ◽

Body Clearance

Indocyanine green (ICG), a near-infrared (NIR) fluorescent dye approved by the Food and Drug Administration (FDA), has been extensively used as a photoacoustic (PA) probe for PA imaging. However, its practical application is limited by poor photostability in water, rapid body clearance, and non-specificity. Herein, we fabricated a novel biomimetic nanoprobe by coating ICG-loaded mesoporous silica nanoparticles with the cancer cell membrane (namely, CMI) for PA imaging. This probe exhibited good dispersion, large loading efficiency, good biocompatibility, and homologous targeting ability to Hela cells in vitro. Furthermore, the in vivo and ex vivo PA imaging on Hela tumor-bearing nude mice demonstrated that CMI could accumulate in tumor tissue and display a superior PA imaging efficacy compared with free ICG. All these results demonstrated that CMI might be a promising contrast agent for PA imaging of cervical carcinoma.

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Real-Time Optical Monitoring of Endotracheal Tube Displacement

Biosensors ◽

10.3390/bios10110174 ◽

2020 ◽

Vol 10 (11) ◽

pp. 174

Author(s):

Ramzan Ullah ◽

Karl Doerfer ◽

Pawjai Khampang ◽

Faraneh Fathi ◽

Wenzhou Hong ◽

...

Keyword(s):

Endotracheal Tube ◽

Real Time ◽

Near Infrared ◽

Ex Vivo ◽

Light Emitting Diode ◽

Clinical Care ◽

Cost Effective ◽

Infrared Light ◽

In Vivo Experiments

Proper ventilation of a patient with an endotracheal tube (ETT) requires proper placement of the ETT. We present a sensitive, noninvasive, operator-free, and cost-effective optical sensor, called Opt-ETT, for the real-time assessment of ETT placement and alerting of the clinical care team should the ETT become displaced. The Opt-ETT uses a side-firing optical fiber, a near-infrared light-emitting diode, two photodetectors with an integrated amplifier, an Arduino board, and a computer loaded with a custom LabVIEW program to monitor the position of the endotracheal tube inside the windpipe. The Opt-ETT generates a visual and audible warning if the tube moves over a distance set by the operator. Displacement prediction is made using a second-order polynomial fit to the voltages measured from each detector. The system is tested on ex vivo porcine tissues, and the accuracy is determined to be better than 1.0 mm. In vivo experiments with a pig are conducted to test the performance and usability of the system.

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Evaluation to Differentiate between Tumor Lesions and the Parenchyma in Partial Nephrectomies for Renal Tumors Based on Quantitative Fluorescence Imaging Using Indocyanine Green Dye

Current Urology ◽

10.1159/000499289 ◽

2019 ◽

Vol 13 (2) ◽

pp. 74-81

Author(s):

Norihito Soga ◽

Akihito Inoko ◽

Jun Furusawa ◽

Yuji Ogura

Keyword(s):

Indocyanine Green ◽

Success Rate ◽

Fluorescence Imaging ◽

Partial Nephrectomy ◽

Near Infrared ◽

Clear Cell ◽

Ex Vivo ◽

Renal Tumors ◽

Contrast Imaging ◽

Malignant Lesions

Introduction: Near-infrared fluorescence imaging with indocyanine green is a useful tool during partial nephrectomy. Because an accurate method for judging hasn't been established yet, the success rate may be slightly different and inconsistent. Materials and Methods: A total of 21 cases with suspected renal cancers who had undergone a partial nephrectomy were enrolled. We examined differences in the success rate between malignant lesions and the parenchyma by quantifying fluorescence in the pre-resection and ex vivo phases. Results: Pre-resection imaging showed a significant degradation of fluorescence in the focused lesion in 76.2% (16/21) of cases. A significant degradation was observed in 73.7% (14/19) of the total malignant lesions, 70.5% (12/17) of cases with a clear cell lesion, 100% (2/2) of cases with non-clear cell lesions, and 100% (2/2) of benign angiomyolipomas. In contrast, imaging of the ex vivo resected specimens showed a significant degradation in fluorescence of the focused lesions in 85.7% (18/21) of cases. A significantly degradation was observed in 84.2% (16/19) of the total malignant lesions, 82.3% (14/17) of cases with a clear cell lesion, 100% (2/2) of cases with non-clear cell lesions, and 100% (2/2) of benign angiomyolipomas. Conclusion: We firstly evaluated the efficacy of quantitative indocyanine green-based fluorescence as an objective method.

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In-vivo near-infrared optical imaging of growing osteosarcoma cell lesions xenografted in mice: dual-channel quantitative evaluation of volume and mineralization

Acta Radiologica ◽

10.1258/ar.2011.110131 ◽

2011 ◽

Vol 52 (9) ◽

pp. 978-988 ◽

Cited By ~ 8

Author(s):

Hitoshi Nakayama ◽

Tomoyuki Kawase ◽

Kazuhiro Okuda ◽

Larry F Wolff ◽

Hiromasa Yoshie

Keyword(s):

Optical Imaging ◽

Near Infrared ◽

Imaging Technique ◽

Ex Vivo ◽

Acquisition Time ◽

Osteosarcoma Cell ◽

Dual Channel ◽

Nir Imaging ◽

Ex Vivo Imaging

Background In a previous study using a rodent osteosarcoma-grafted rat model, in which cell-dependent mineralization was previously demonstrated to proportionally increase with growth, we performed a quantitative analysis of mineral deposit formation using 99mTc-HMDP and found some weaknesses, such as longer acquisition time and narrower dynamic ranges (i.e. images easily saturated). The recently developed near-infrared (NIR) optical imaging technique is expected to non-invasively evaluate changes in living small animals in a quantitative manner. Purpose To test the feasibility of NIR imaging with a dual-channel system as a better alternative for bone scintigraphy by quantitatively evaluating mineralization along with the growth of osteosarcoma lesions in a mouse-xenograft model. Material and Methods The gross volume and mineralization of osteosarcoma lesions were evaluated in living mice simultaneously with dual-channels by NIR dye-labeled probes, 2-deoxyglucose (DG) and pamidronate (OS), respectively. To verify these quantitative data, retrieved osteosarcoma lesions were then subjected to ex-vivo imaging, weighing under wet conditions, microfocus-computed tomography (μCT) analysis, and histopathological examination. Results Because of less scattering and no anatomical overlapping, as generally shown, specific fluorescence signals targeted to the osteosarcoma lesions could be determined clearly by ex-vivo imaging. These data were well positively correlated with the in-vivo imaging data ( r > 0.8, P < 0.02). Other good to excellent correlations ( r > 0.8, P < 0.02) were observed between DG accumulation and tumor gross volume and between OS accumulation and mineralization volume. Conclusion This in-vivo NIR imaging technique using DG and OS is sensitive to the level to simultaneously detect and quantitatively evaluate the growth and mineralization occuring in this type of osteosarcoma lesions of living mice without either invasion or sacrifice. By possible mutual complementation, this dual imaging system might be useful for accurate diagnosis even in the presence of overlapping tissues.

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

Nanomaterials ◽

10.3390/nano10010161 ◽

2020 ◽

Vol 10 (1) ◽

pp. 161 ◽

Cited By ~ 4

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.

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