|
1
|
Szpunar M, Aebisher D, Wal A. Changes in absorption spectra of indocyanine green after visible light exposure and cold dark storage. SPECTROCHIMICA ACTA. PART A, MOLECULAR AND BIOMOLECULAR SPECTROSCOPY 2025; 336:126048. [PMID: 40112752 DOI: 10.1016/j.saa.2025.126048] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/23/2024] [Revised: 03/07/2025] [Accepted: 03/11/2025] [Indexed: 03/22/2025]
Abstract
Indocyanine green (ICG) is commonly used as a fluorescent cardiovascular imaging agent, but its stability under different conditions remains insufficiently studied. This research examines the photochemical stability and aggregation behaviour of ICG in aqueous solutions subjected to visible light irradiation and during cold, dark storage. ICG solutions at different concentrations were exposed to visible light, and changes in absorption spectra were monitored over time. Exponential decreases in the absorption maxima were observed for both monomeric and dimeric ICG during irradiation. These changes were modelled, allowing for the description of decay processes caused by irradiation for monomers and dimmers, respectively. Furthermore, after a month of dark storage at 4 °C, a decrease in absorption was observed, accompanied by the formation of J-aggregates. These results indicate that ICG undergoes significant structural changes that may affect its fluorescence properties, with potential applications for use in photodynamic therapy. More research is needed to explore the impact of these changes on the performance of ICG in vivo.
Collapse
Affiliation(s)
| | - David Aebisher
- Department of Photomedicine and Physical Chemistry, Medical College of the University of Rzeszów, Rzeszów, Poland
| | - Andrzej Wal
- Institute of Physics, College of Natural Sciences, University of Rzeszów, Rzeszów, Poland
| |
Collapse
|
|
2
|
Yu X, Jin J, Si Y, Zhang H, Song Z. A peptide-based fluorescent bioprobe for EphA2-overexpressing tumor targeting and image-guided surgical resection. Bioorg Med Chem 2025; 120:118090. [PMID: 39904197 DOI: 10.1016/j.bmc.2025.118090] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/12/2024] [Revised: 01/22/2025] [Accepted: 01/25/2025] [Indexed: 02/06/2025]
Abstract
Fluorescence-guided surgery (FGS) is an emerging and highly promising surgical technique in clinic. Owing to its real-time and visual characteristics, it assists in achieving clear pictures on lesion site, tumor boundary and degree of metastasis, which will definitely improve surgery accuracy and minimize cancer recurrence as much as possible. Herein, we report a near-infrared fluorescent bioprobe, YK80, which utilizes a modified heptamethine cyanine dye as the fluorophore and a self-assembling peptide targeting Ephrin receptor A2 (EphA2) proteins as the ligand. The design strategy and the synthetic route to YK80 are described, and then optical properties, pharmacokinetics, binding affinity between YK80 and the protein are further investigated. YK80 shows high affinity (KD ≈ 100 nM) with EphA2-expressing cancer cells and excellent targeting ability in mouse models bearing colorectal tumors. Meanwhile, indocyanine green (ICG), the commonly used non-targeted fluorescent contrast agent is employed as the comparison for in vivo experiments. However, ICG owns no such capability towards cancer cells or solid tumors. Thus, YK80 could potentially serve as a targeted contrast agent for image-guided surgery and this successful example will boost the development of medical imaging, surgical methods as well as translational medicine.
Collapse
Affiliation(s)
- Xudong Yu
- Department of Gastroenterology, Yiwu Central Hospital, the Affiliated Yiwu Hospital of Wenzhou Medical University, Yiwu, Zhejiang Province, China.
| | - Jianfei Jin
- Zhejiang Yike Biotech. Co., Ltd, Yiwu, Zhejiang Province, China
| | - Yun Si
- Zhejiang Yike Biotech. Co., Ltd, Yiwu, Zhejiang Province, China
| | - Huanmin Zhang
- Zhejiang Yike Biotech. Co., Ltd, Yiwu, Zhejiang Province, China
| | - Zhegang Song
- Zhejiang Yike Biotech. Co., Ltd, Yiwu, Zhejiang Province, China.
| |
Collapse
|
|
3
|
Liao WT, Chang DM, Lin MX, Chou TS, Tung YC, Hsiao JK. Multifaceted Functional Liposomes: Theranostic Potential of Liposomal Indocyanine Green and Doxorubicin for Enhanced Anticancer Efficacy and Imaging. Pharmaceutics 2025; 17:344. [PMID: 40143009 PMCID: PMC11944616 DOI: 10.3390/pharmaceutics17030344] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/23/2025] [Revised: 03/03/2025] [Accepted: 03/05/2025] [Indexed: 03/28/2025] Open
Abstract
Background/Objectives: Liposomal drug formulations improve anticancer treatment efficacy and reduce toxicity by altering pharmacokinetics and biodistribution. Indocyanine Green (ICG), an FDA-approved near-infrared imaging agent, exhibits photosensitivity, photothermal effects, and potential ferroptosis induction, enhancing anticancer activity. Doxorubicin (DOX), widely used for treating breast, ovarian, and liver cancers, is limited by cardiotoxicity, requiring dosage control. Incorporating ICG and DOX into liposomes enables medical imaging, controlled drug release, reduced administration frequency, and fewer side effects. This study aims to develop liposomes encapsulating both ICG and DOX and evaluate their theranostic potential in in vitro and in vivo lung adenocarcinoma models. Methods: Liposomes containing ICG and DOX (Lipo-ICG/DOX) were synthesized using an active loading method and characterized for size (~140 nm), lipid, and drug concentrations. In vitro studies using A549 lung cancer cells assessed liposome uptake via fluorescence microscopy, while in vivo xenograft models evaluated therapeutic efficacy. Results: Lipo-ICG/DOX showed uptake in A549 cells, with ICG localizing in lysosomes and DOX in nuclei. Treatment reduced cell viability significantly by day three. In vivo imaging demonstrated the retention of liposomes in tumor sites, with ICG signals observed in the liver and intestines, indicating metabolic routes. When combined with 780 nm light exposure, liposomes slowed tumor growth over 12 days. Mechanistic studies revealed combined ferroptosis and apoptosis induction. Conclusions: Lipo-ICG/DOX demonstrates strong theranostic potential, integrating imaging and therapy for lung adenocarcinoma. This multifunctional formulation offers a promising strategy for improving cancer treatment efficacy while minimizing side effects.
Collapse
Affiliation(s)
- Wei-Ting Liao
- Department of Medical Imaging, Taipei Tzu Chi General Hospital, Buddhist Tzu-Chi Medical Foundation, New Taipei City 23142, Taiwan; (W.-T.L.); (M.-X.L.); (T.-S.C.)
- School of Medicine, Tzu Chi University, Hualien 97004, Taiwan
| | - Dao-Ming Chang
- Research Center for Applied Sciences, Academia Sinica, Taipei 11529, Taiwan;
| | - Meng-Xian Lin
- Department of Medical Imaging, Taipei Tzu Chi General Hospital, Buddhist Tzu-Chi Medical Foundation, New Taipei City 23142, Taiwan; (W.-T.L.); (M.-X.L.); (T.-S.C.)
| | - Te-Sen Chou
- Department of Medical Imaging, Taipei Tzu Chi General Hospital, Buddhist Tzu-Chi Medical Foundation, New Taipei City 23142, Taiwan; (W.-T.L.); (M.-X.L.); (T.-S.C.)
| | - Yi-Chung Tung
- Research Center for Applied Sciences, Academia Sinica, Taipei 11529, Taiwan;
| | - Jong-Kai Hsiao
- Department of Medical Imaging, Taipei Tzu Chi General Hospital, Buddhist Tzu-Chi Medical Foundation, New Taipei City 23142, Taiwan; (W.-T.L.); (M.-X.L.); (T.-S.C.)
- School of Medicine, Tzu Chi University, Hualien 97004, Taiwan
| |
Collapse
|
|
4
|
Zajac J, Liu A, Hassan S, Gibson A. Mechanisms of delayed indocyanine green fluorescence and applications to clinical disease processes. Surgery 2024; 176:386-395. [PMID: 38749795 PMCID: PMC11246809 DOI: 10.1016/j.surg.2024.03.053] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2023] [Revised: 03/15/2024] [Accepted: 03/28/2024] [Indexed: 07/16/2024]
Abstract
BACKGROUND Delayed indocyanine green fluorescence imaging is under investigation in various clinical disease processes. Understanding the mechanisms of indocyanine green accumulation and retention is essential to correctly interpreting and analyzing imaging data. The purpose of this scoping review was to synthesize what is known about the mechanism of indocyanine green retention at the cellular level to better understand the clinical nuances of delayed indocyanine green imaging and identify critical gaps in our knowledge to guide future studies. METHODS We performed a scoping review of 7,087 citations after performing database searches of PubMed, Scopus, the Cochrane Library, and the Web of Science Core Collection electronic databases. Studies were eligible for inclusion if they were peer-reviewed original research discussing the mechanism of indocyanine green retention in the results section in disease processes involving inflammation and/or necrosis, including cancer, and were available in English. Data were extracted using Covidence software. RESULTS Eighty-nine studies were included in the final analysis. Several features of indocyanine green retention were identified. CONCLUSION We identified several mechanistic features involved in indocyanine green accumulation in diseased tissue that overall had distinct mechanisms of indocyanine green retention in tumors, nontumor inflammation, and necrosis. Our study also reveals new insights on how inflammatory infiltrate influences indocyanine green fluorescence imaging. These findings are noteworthy because they add to our understanding of how fluorescence-guided surgery may be optimized based on the pathology of interest via specific indocyanine green dosing and timing of image acquisition.
Collapse
Affiliation(s)
- Jocelyn Zajac
- Department of Surgery, University of Wisconsin School of Medicine and Public Health, Madison, WI
| | - Aiping Liu
- Department of Surgery, University of Wisconsin School of Medicine and Public Health, Madison, WI
| | - Sameeha Hassan
- Department of Surgery, University of Wisconsin School of Medicine and Public Health, Madison, WI
| | - Angela Gibson
- Department of Surgery, University of Wisconsin School of Medicine and Public Health, Madison, WI.
| |
Collapse
|
|
5
|
Symeonidis S, Mantzoros I, Anestiadou E, Ioannidis O, Christidis P, Bitsianis S, Bisbinas V, Zapsalis K, Karastergiou T, Athanasiou D, Apostolidis S, Angelopoulos S. Near-infrared cholangiography with intragallbladder indocyanine green injection in minimally invasive cholecystectomy. World J Gastrointest Surg 2024; 16:1017-1029. [PMID: 38690057 PMCID: PMC11056669 DOI: 10.4240/wjgs.v16.i4.1017] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/15/2023] [Revised: 02/02/2024] [Accepted: 03/18/2024] [Indexed: 04/22/2024] Open
Abstract
Laparoscopic cholecystectomy (LC) remains one of the most commonly performed procedures in adult and paediatric populations. Despite the advances made in intraoperative biliary anatomy recognition, iatrogenic bile duct injuries during LC represent a fatal complication and consist an economic burden for healthcare systems. A series of methods have been proposed to prevent bile duct injury, among them the use of indocyanine green (ICG) fluorescence. The most commonly reported method of ICG injection is the intravenous administration, while literature is lacking studies investigating the direct intragallbladder ICG injection. This narrative mini-review aims to assess the potential applications, usefulness, and limitations of intragallbladder ICG fluorescence in LC. Authors screened the available international literature to identify the reports of intragallbladder ICG fluorescence imaging in minimally invasive cholecystectomy, as well as special issues regarding its use. Literature search retrieved four prospective cohort studies, three case-control studies, and one case report. In the three case-control studies selected, intragallbladder near-infrared cholangiography (NIRC) was compared with standard LC under white light, with intravenous administration of ICG for NIRC and with standard intraoperative cholangiography (IOC). In total, 133 patients reported in the literature have been administered intragallbladder ICG administration for biliary mapping during LC. Literature includes several reports of intragallbladder ICG administration, but a standardized technique has not been established yet. Published data suggest that NIRC with intragallbladder ICG injection is a promising method to achieve biliary mapping, overwhelming limitations of IOC including intervention and radiation exposure, as well as the high hepatic parenchyma signal and time interval needed in intravenous ICG fluorescence. Evidence-based guidelines on the role of intragallbladder ICG fluorescence in LC require the assessment of further studies and multicenter data collection into large registries.
Collapse
Affiliation(s)
- Savvas Symeonidis
- Fourth Department of Surgery, Medical School, Aristotle University of Thessaloniki, Thessaloniki 57010, Greece
| | - Ioannis Mantzoros
- Fourth Department of Surgery, Medical School, Aristotle University of Thessaloniki, Thessaloniki 57010, Greece
| | - Elissavet Anestiadou
- Fourth Department of Surgery, Medical School, Aristotle University of Thessaloniki, Thessaloniki 57010, Greece
| | - Orestis Ioannidis
- Fourth Department of Surgery, Medical School, Aristotle University of Thessaloniki, Thessaloniki 57010, Greece
| | - Panagiotis Christidis
- Fourth Department of Surgery, Medical School, Aristotle University of Thessaloniki, Thessaloniki 57010, Greece
| | - Stefanos Bitsianis
- Fourth Department of Surgery, Medical School, Aristotle University of Thessaloniki, Thessaloniki 57010, Greece
| | - Vasiliki Bisbinas
- ENT Department, Royal Cornwall Hospitals NHS Trust, Cornwall TR1 3LJ, United Kingdom
| | - Konstantinos Zapsalis
- Fourth Department of Surgery, Medical School, Aristotle University of Thessaloniki, Thessaloniki 57010, Greece
| | - Trigona Karastergiou
- Fourth Department of Surgery, Medical School, Aristotle University of Thessaloniki, Thessaloniki 57010, Greece
| | - Dimitra Athanasiou
- Fourth Department of Surgery, Medical School, Aristotle University of Thessaloniki, Thessaloniki 57010, Greece
| | - Stylianos Apostolidis
- 1st Propedeutic Surgical Department, University Hospital of Thessaloniki, Aristotle University of Thessaloniki, Thessaloniki 54636, Greece
| | - Stamatios Angelopoulos
- Fourth Department of Surgery, Medical School, Aristotle University of Thessaloniki, Thessaloniki 57010, Greece
| |
Collapse
|
|
6
|
Shen S, Qiu J, Huo D, Xia Y. Nanomaterial-Enabled Photothermal Heating and Its Use for Cancer Therapy via Localized Hyperthermia. SMALL (WEINHEIM AN DER BERGSTRASSE, GERMANY) 2024; 20:e2305426. [PMID: 37803412 PMCID: PMC10922052 DOI: 10.1002/smll.202305426] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/29/2023] [Revised: 09/12/2023] [Indexed: 10/08/2023]
Abstract
Photothermal therapy (PTT), which employs nanoscale transducers delivered into a tumor to locally generate heat upon irradiation with near-infrared light, shows great potential in killing cancer cells through hyperthermia. The efficacy of such a treatment is determined by a number of factors, including the amount, distribution, and dissipation of the generated heat, as well as the type of cancer cell involved. The amount of heat generated is largely controlled by the number of transducers accumulated inside the tumor, the absorption coefficient and photothermal conversion efficiency of the transducer, and the irradiance of the light. The efficacy of treatment depends on the distribution of the transducers in the tumor and the penetration depth of the light. The vascularity and tissue thermal conduction both affect the dissipation of heat and thereby the distribution of temperature. The successful implementation of PTT in the clinic setting critically depends on techniques for real-time monitoring and management of temperature.
Collapse
Affiliation(s)
- Song Shen
- The Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA, 30332, USA
- College of Pharmaceutical Sciences, Jiangsu University, Zhenjiang, Jiangsu, 212013, China
| | - Jichuan Qiu
- The Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA, 30332, USA
| | - Da Huo
- The Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA, 30332, USA
| | - Younan Xia
- The Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA, 30332, USA
- School of Chemistry and Biochemistry, Georgia Institute of Technology, Atlanta, GA, 30332, USA
| |
Collapse
|
|
7
|
Park HS, Shim MJ, Kim Y, Ko TY, Choi JH, Ahn YC. Multimodal real-time imaging with laser speckle contrast and fluorescent contrast. Photodiagnosis Photodyn Ther 2024; 45:103912. [PMID: 38043762 DOI: 10.1016/j.pdpdt.2023.103912] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2023] [Revised: 11/16/2023] [Accepted: 11/28/2023] [Indexed: 12/05/2023]
Abstract
INTRODUCTION Laser speckle contrast imaging (LSCI) can achieve real-time 2D perfusion maps non-invasively. However, LSCI is still difficult to use in general clinical applications because of movement sensitivity and limitations in blood flow analysis. To overcome this, fluorescence imaging (FI) is combined with LSCI using a light source with a wavelength of 785 nm in near-infrared (NIR) region and validates to visualize real-time blood perfusion. MATERIALS AND METHODS The system was performed using Intralipid and indocyanine green (ICG) in a flow phantom that has three tubes and controlled the flow rate in 0-150 μl/min range. First, real-time LSCI was monitored and measured the change in speckle contrast by reperfusion. Then, we visualized blood perfusion of a rabbit ear under the non-invasive condition by intravenous injection using a total of five different ICG concentration solutions from 128 μM to 3.22 mM. RESULTS The combined system achieved the performance of processing laser speckle images at about 37-38 fps, and we simultaneously confirmed the fluorescence of ICG and changes in speckle contrast due to intralipid as a light scatterer. In addition, we obtained real-time contrast variation and fluorescent images occurring in rabbit's blood perfusion. CONCLUSIONS The aim of this study is to provide a real-time diagnostic imaging system that can be used in general clinical applications. LSCI and FI are combined complementary for observing tissue perfusion using a single NIR light source. The combined system could achieve real-time visualization of blood perfusion non-invasively.
Collapse
Affiliation(s)
- Hyun-Seo Park
- Industry 4.0 Convergence Bionics Engineering, Pukyong National University, Busan 48513, South Korea
| | - Min-Jae Shim
- Department of Biomedical Engineering, Pukyong National University, Busan 48513, South Korea
| | - Yikeun Kim
- Department of Biomedical Engineering, Ulsan National Institute of Science and Technology, Ulsan 44919, South Korea
| | - Taek-Yong Ko
- Kosin University Gospel Hospital, Busan 49267, South Korea
| | - Jin-Hyuk Choi
- Kosin University Gospel Hospital, Busan 49267, South Korea
| | - Yeh-Chan Ahn
- Industry 4.0 Convergence Bionics Engineering, Pukyong National University, Busan 48513, South Korea; Department of Biomedical Engineering, Pukyong National University, Busan 48513, South Korea.
| |
Collapse
|
|
8
|
Giammanco G, Veneziano R, Dunn B, Such N, Cressman JR, Chitnis PV. DNA-Based Near-Infrared Voltage Sensors. ACS Sens 2023; 8:3680-3686. [PMID: 37725687 PMCID: PMC10616843 DOI: 10.1021/acssensors.3c01429] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/13/2023] [Accepted: 09/14/2023] [Indexed: 09/21/2023]
Abstract
Indocyanine green (ICG) is an FDA approved dye widely used for fluorescence imaging in research, surgical navigation, and medical diagnostics. However, ICG has a few drawbacks, such as concentration-dependent aggregation and absorbance, nonspecific cellular targeting, and rapid photobleaching. Here, we report a novel DNA-based nanosensor platform that utilizes monomers of ICG and cholesterol. Using DNA origami, we can attach ICG to a DNA structure, maintaining its concentration, preserving its near-infrared (NIR) absorbance, and allowing attachment of targeting moieties. We characterized the nanosensors' absorbance, stability in blood, and voltage sensing in vitro. This study presents a novel DNA-based ICG nanosensor platform for cellular voltage sensing for future in vivo applications.
Collapse
Affiliation(s)
- Giovanni Giammanco
- Department
of Bioengineering, George Mason University, Fairfax, Virginia 22030, United States
| | - Remi Veneziano
- Department
of Bioengineering, George Mason University, Fairfax, Virginia 22030, United States
- Institute
for Advanced Biomedical Research, George
Mason University, Manassas, Virginia 20110, United States
| | - Bryce Dunn
- Department
of Bioengineering, George Mason University, Fairfax, Virginia 22030, United States
| | - Nicholas Such
- Department
of Bioengineering, George Mason University, Fairfax, Virginia 22030, United States
| | - John R. Cressman
- Department
of Physics, George Mason University, Fairfax, Virginia 22030, United States
| | - Parag V. Chitnis
- Department
of Bioengineering, George Mason University, Fairfax, Virginia 22030, United States
- Center
for Adaptive Systems for Brain-body Interactions, George Mason University, Fairfax, Virginia 22030, United States
| |
Collapse
|
|
9
|
Marcos-Vidal A, Heidari P, Xu S, Wood BJ, Mahmood U. Advantages of a Photodiode Detector Endoscopy System in Fluorescence-Guided Percutaneous Liver Biopsies. OPTICS 2023; 4:340-350. [PMID: 38075027 PMCID: PMC10701657 DOI: 10.3390/opt4020025] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Indexed: 05/13/2024]
Abstract
Image-guided liver biopsies can improve their success rate when combined with the optical detection of Indocyanine Green (ICG) fluorescence accumulated in tumors. Previous works used a camera coupled to a thin borescope to capture and quantify images from fluorescence emission during procedures; however, light-scattering prevented the formation of sharp images, and the time response for weakly fluorescent tumors was very low. Instead, replacing the camera with a photodiode detector shows an improved temporal resolution in a more compact and lighter device. This work presents the new design in a comparative study between both detection technologies, including an assessment of the temporal response and sensitivity to the presence of background fluorescence.
Collapse
Affiliation(s)
- Asier Marcos-Vidal
- Department of Radiology, Harvard Medical School, Massachusetts General Hospital, Charlestown, MA 02129, USA
| | - Pedram Heidari
- Department of Radiology, Harvard Medical School, Massachusetts General Hospital, Charlestown, MA 02129, USA
| | - Sheng Xu
- Center for Interventional Oncology, Radiology and Imaging Sciences, Clinical Center, National Institutes of Health, Bethesda, MD 20892, USA
| | - Bradford J. Wood
- Center for Interventional Oncology, Radiology and Imaging Sciences, Clinical Center, National Institutes of Health, Bethesda, MD 20892, USA
| | - Umar Mahmood
- Department of Radiology, Harvard Medical School, Massachusetts General Hospital, Charlestown, MA 02129, USA
| |
Collapse
|
|
10
|
Sikkenk DJ, Sterkenburg AJ, Schmidt I, Gorpas D, Nagengast WB, Consten ECJ. Detection of Tumour-Targeted IRDye800CW Tracer with Commercially Available Laparoscopic Surgical Systems. Diagnostics (Basel) 2023; 13:diagnostics13091591. [PMID: 37174982 PMCID: PMC10178288 DOI: 10.3390/diagnostics13091591] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2023] [Revised: 04/22/2023] [Accepted: 04/27/2023] [Indexed: 05/15/2023] Open
Abstract
(1) Introduction: Near-infrared fluorescence (NIRF) combined with tumour-targeted tracers, such as bevacizumab-800CW, could aid surgical decision-making. This study explored the use of IRDye800CW, conjugated to bevacizumab, with four commercially available NIRF laparoscopes optimised for indocyanine green (ICG). (2) Methods: A (lymph node) phantom was made from a calibration device for NIRF and tissue-mimicking material. Serial dilutions of bevacizumab-800CW were made and ICG functioned as a reference. System settings, working distance, and thickness of tissue-mimicking material were varied to assess visibility of the fluorescence signal and tissue penetration. Tests were performed with four laparoscopes: VISERA ELITE II, Olympus; IMAGE1 S™ 4U Rubina, KARL STORZ; ENDOCAM Logic 4K platform, Richard Wolf; da Vinci Xi, Intuitive Surgical. (3) Results: The lowest visible bevacizumab-800CW concentration ranged between 13-850 nM (8-512 times diluted stock solution) for all laparoscopes, but the tracer was not visible through 0.8 cm of tissue in all systems. In contrast, ICG was still visible at a concentration of 0.4 nM (16,384 times diluted) and through 1.6-2.4 cm of tissue. Visibility and tissue penetration generally improved with a reduced working distance and manually adjusted system settings. (4) Conclusion: Depending on the application, bevacizumab-800CW might be sufficiently visible with current laparoscopes, but optimisation would widen applicability of tumour-targeted IRDye800CW tracers.
Collapse
Affiliation(s)
- Daan J Sikkenk
- Department of Surgery, University Medical Centre Groningen, University of Groningen, Hanzeplein 1, 9713 GZ Groningen, The Netherlands
- Department of Surgery, Meander Medical Centre, Maatweg 3, 3813 TZ Amersfoort, The Netherlands
| | - Andrea J Sterkenburg
- Department of Gastroenterology, University Medical Centre Groningen, University of Groningen, Hanzeplein 1, 9713 GZ Groningen, The Netherlands
| | - Iris Schmidt
- Department of Gastroenterology, University Medical Centre Groningen, University of Groningen, Hanzeplein 1, 9713 GZ Groningen, The Netherlands
| | - Dimitris Gorpas
- Institute of Biological and Medical Imaging, Helmholtz Zentrum München (GmbH), Ingolstädter Landstraße 1, D-85764 Neuherberg, Germany
- Chair of Biological Imaging, Center for Translational Cancer Research (TranslaTUM), Technical University of Munich, Ismaninger Straße 22, D-81675 Munich, Germany
| | - Wouter B Nagengast
- Department of Gastroenterology, University Medical Centre Groningen, University of Groningen, Hanzeplein 1, 9713 GZ Groningen, The Netherlands
| | - Esther C J Consten
- Department of Surgery, University Medical Centre Groningen, University of Groningen, Hanzeplein 1, 9713 GZ Groningen, The Netherlands
- Department of Surgery, Meander Medical Centre, Maatweg 3, 3813 TZ Amersfoort, The Netherlands
| |
Collapse
|
|
11
|
Imaging of Indocyanine Green-Human Serum Albumin (ICG-HSA) Complex in Secreted Protein Acidic and Rich in Cysteine (SPARC)-Expressing Glioblastoma. Int J Mol Sci 2023; 24:ijms24010850. [PMID: 36614294 PMCID: PMC9821702 DOI: 10.3390/ijms24010850] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2022] [Revised: 12/19/2022] [Accepted: 12/27/2022] [Indexed: 01/05/2023] Open
Abstract
Glioblastoma is the most common and fatal primary glioma and has a severe prognosis. It is a challenge for neurosurgeons to remove brain tumor tissues completely by resection. Meanwhile, fluorescence-guided surgery (FGS) is a technique used in glioma surgery to enhance the visualization of tumor edges to clarify the extent of tumor resection. Indocyanine green (ICG) is the only FDA-approved NIR fluorescent agent. It non-covalently binds to human serum albumin (HSA). Secreted protein acidic and rich in cysteine (SPARC) is an extracellular glycoprotein expressed in gliomas and binds to albumin, suggesting that it plays an important role in tumor uptake of the ICG-HSA complex. Here we demonstrate the binding properties of HSA or SPARC to ICG using surface plasmon resonance and saturation binding assay. According to in vitro and in vivo studies, the results showed that the uptake of ICG-HSA complex was higher in SPARC-expressing glioblastoma cell line and tumor region compared with the uptake of free ICG. Here, we visualized the SPARC-dependent uptake of ICG and ICG-HSA complex in U87MG. Our results demonstrated that the ICG-HSA complex is likely to be used as an efficient imaging agent targeting SPARC-expressing tumors, especially glioblastoma.
Collapse
|
|
12
|
Demarchi MS, Karenovics W, Bédat B, Triponez F. Near-infrared fluorescent imaging techniques for the detection and preservation of parathyroid glands during endocrine surgery. Innov Surg Sci 2022; 7:87-98. [PMID: 36561508 PMCID: PMC9742281 DOI: 10.1515/iss-2021-0001] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/01/2021] [Accepted: 04/14/2021] [Indexed: 12/25/2022] Open
Abstract
Objectives In over 30% of all thyroid surgeries, complications arise from transient and definitive hypoparathyroidism, underscoring the need for real-time identification and preservation of parathyroid glands (PGs). Here, we evaluate the promising intraoperative optical technologies available for the identification, preservation, and functional assessment of PGs to enhance endocrine surgery. Methods We performed a review of the literature to identify published studies on fluorescence imaging in thyroid and parathyroid surgery. Results Fluorescence imaging is a well-demonstrated approach for both in vivo and in vitro localization of specific cells or tissues, and is gaining popularity as a technique to detect PGs during endocrine surgery. Autofluorescence (AF) imaging and indocyanine green (ICG) angiography are two emerging optical techniques to improve outcomes in thyroid and parathyroid surgeries. Near-infrared-guided technology has significantly contributed to the localization of PGs, through the detection of glandular AF. Perfusion through the PGs can be visualized with ICG, which can also reveal the blood supply after dissection. Conclusions Near infrared AF and ICG angiography, providing a valuable spatial and anatomical information, can decrease the incidence of complications in thyroid surgery.
Collapse
Affiliation(s)
- Marco Stefano Demarchi
- Department of Thoracic and Endocrine Surgery, Faculty of Medicine, University Hospitals of Geneva, Geneva, Switzerland
| | - Wolfram Karenovics
- Department of Thoracic and Endocrine Surgery, Faculty of Medicine, University Hospitals of Geneva, Geneva, Switzerland
| | - Benoît Bédat
- Department of Thoracic and Endocrine Surgery, Faculty of Medicine, University Hospitals of Geneva, Geneva, Switzerland
| | - Frédéric Triponez
- Department of Thoracic and Endocrine Surgery, Faculty of Medicine, University Hospitals of Geneva, Geneva, Switzerland
| |
Collapse
|
|
13
|
Merkle CW, Augustin M, Harper DJ, Glösmann M, Baumann B. Degeneration of Melanin-Containing Structures Observed Longitudinally in the Eyes of SOD1-/- Mice Using Intensity, Polarization, and Spectroscopic OCT. Transl Vis Sci Technol 2022; 11:28. [PMID: 36259678 PMCID: PMC9587514 DOI: 10.1167/tvst.11.10.28] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/02/2022] Open
Abstract
Purpose Melanin plays an important function in maintaining eye health, however there are few metrics that can be used to study retinal melanin content in vivo. Methods The slope of the spectral coefficient of variation (SSCoV) is a novel biomarker that measures chromophore concentration by analyzing the local divergence of spectral intensities using optical coherence tomography (OCT). This metric was validated in a phantom and applied in a longitudinal study of superoxide dismutase 1 knockout (SOD1−/−) mice, a model for wet and dry age-related macular degeneration. We also examined a new feature of interest in standard OCT image data, the ratio of maximum intensity in the retinal pigment epithelium to that of the choroid (RC ratio). These new biomarkers were supported by polarization-sensitive OCT and histological analysis. Results SSCoV correlated well with depolarization metrics both in phantom and in vivo with both metrics decreasing more rapidly in SOD1−/− mice with age (P < 0.05). This finding is correlated with reduced melanin pigmentation in the choroid over time. The RC ratio clearly differentiated the SOD1−/− and control groups (P < 0.0005) irrespective of time and may indicate lower retinal pigment epithelium melanin in the SOD1−/− mice. Histological analysis showed decreased melanin content and potential differences in melanin granule shape in SOD1−/− mice. Conclusions SSCoV and RC ratio biomarkers provided insights into the changes of retinal melanin in the SOD1−/− model longitudinally and noninvasively. Translational Relevance These biomarkers were designed with the potential for rapid adoption by existing clinical OCT systems without requiring new hardware.
Collapse
Affiliation(s)
- Conrad W Merkle
- Center for Medical Physics and Biomedical Engineering, Medical University of Vienna, Austria
| | - Marco Augustin
- Center for Medical Physics and Biomedical Engineering, Medical University of Vienna, Austria
| | - Danielle J Harper
- Center for Medical Physics and Biomedical Engineering, Medical University of Vienna, Austria
| | - Martin Glösmann
- Core Facility for Research and Technology, University of Veterinary Medicine Vienna, Austria
| | - Bernhard Baumann
- Center for Medical Physics and Biomedical Engineering, Medical University of Vienna, Austria
| |
Collapse
|
|
14
|
Iritani K, Teshima M, Shimoda H, Shinomiya H, Otsuki N, Nibu K. Intraoperative quantitative assessment of parathyroid blood flow during total thyroidectomy using indocyanine green fluorescence imaging - surgical strategies for preserving the function of parathyroid glands. Laryngoscope Investig Otolaryngol 2022; 7:1251-1258. [PMID: 36000062 PMCID: PMC9392388 DOI: 10.1002/lio2.868] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2022] [Revised: 06/24/2022] [Accepted: 07/03/2022] [Indexed: 11/24/2022] Open
Abstract
Objective We investigated the factors affecting postoperative parathyroid gland (PTG) function and devised an objective index to predict the postoperative PTG function during total thyroidectomy. Method This was a retrospective clinical review of 21 consecutive patients who were diagnosed with papillary thyroid carcinoma and underwent total thyroidectomy. The maximum intensity ratio (MIR) was determined as the maximum fluorescence intensity after ICG injection divided by the intensity before ICG injection. Results Postoperative hypoparathyroidism is significantly associated with simultaneous central neck dissection (CND) and lateral neck dissection (LND) (p = .032). The Spearman correlation test showed a moderate correlation between the MIR and iPTH levels (p = .0047). The optimal MIR cutoff value for predicting postoperative hypoparathyroidism was 2.14 with area under the curve = 0.904 (sensitivity: 0.769 and specificity: 1.00). Conclusion CND + LND was significantly associated with postoperative hypoparathyroidism. MIR was found useful in predicting the postoperative PTG function. Level of Evidence 3b
Collapse
Affiliation(s)
- Keisuke Iritani
- Department of Otolaryngology‐Head and Neck SurgeryKobe University Graduate School of MedicineKobeJapan
| | - Masanori Teshima
- Department of Otolaryngology‐Head and Neck SurgeryKobe University Graduate School of MedicineKobeJapan
| | - Hikari Shimoda
- Department of Otolaryngology‐Head and Neck SurgeryKobe University Graduate School of MedicineKobeJapan
| | - Hirotaka Shinomiya
- Department of Otolaryngology‐Head and Neck SurgeryKobe University Graduate School of MedicineKobeJapan
| | - Naoki Otsuki
- Department of Otolaryngology‐Head and Neck SurgeryKobe University Graduate School of MedicineKobeJapan
| | - Ken‐ichi Nibu
- Department of Otolaryngology‐Head and Neck SurgeryKobe University Graduate School of MedicineKobeJapan
| |
Collapse
|
|
15
|
Zhang X, Yan Z, Meng Z, Li N, Jia Q, Shen Y, Ji Y. Radionuclide 131I-labeled albumin-indocyanine green nanoparticles for synergistic combined radio-photothermal therapy of anaplastic thyroid cancer. Front Oncol 2022; 12:889284. [PMID: 35957867 PMCID: PMC9358776 DOI: 10.3389/fonc.2022.889284] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2022] [Accepted: 06/27/2022] [Indexed: 11/17/2022] Open
Abstract
Objectives Anaplastic thyroid cancer (ATC) cells cannot retain the radionuclide iodine 131 (131I) for treatment due to the inability to uptake iodine. This study investigated the feasibility of combining radionuclides with photothermal agents in the diagnosis and treatment of ATC. Methods 131I was labeled on human serum albumin (HSA) by the standard chloramine T method. 131I-HSA and indocyanine green (ICG) were non-covalently bound by a simple stirring to obtain 131I-HSA-ICG nanoparticles. Characterizations were performed in vitro. The cytotoxicity and imaging ability were investigated by cell/in vivo experiments. The radio-photothermal therapy efficacy of the nanoparticles was evaluated at the cellular and in vivo levels. Results The synthesized nanoparticles had a suitable size (25–45 nm) and objective biosafety. Under the irradiation of near-IR light, the photothermal conversion efficiency of the nanoparticles could reach 24.25%. In vivo fluorescence imaging and single-photon emission CT (SPECT)/CT imaging in small animals confirmed that I-HSA-ICG/131I-HSA-ICG nanoparticles could stay in tumor tissues for 4–6 days. Compared with other control groups, 131I-HSA-ICG nanoparticles had the most significant ablation effect on tumor cells under the irradiation of an 808-nm laser. Conclusions In summary, 131I-HSA-ICG nanoparticles could successfully perform dual-modality imaging and treatment of ATC, which provides a new direction for the future treatment of iodine-refractory thyroid cancer.
Collapse
|
|
16
|
Soundararajan R, Hsu TW, Qin Y, Huang SL. Depth-dependent in vivo human skin backscattering spectra extraction from full-field optical coherence tomography. JOURNAL OF BIOPHOTONICS 2022; 15:e202100249. [PMID: 34662510 DOI: 10.1002/jbio.202100249] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/10/2021] [Revised: 09/25/2021] [Accepted: 10/09/2021] [Indexed: 06/13/2023]
Abstract
With homemade active crystalline fibers, we generated bright and broadband light sources for full-field optical coherence tomography, offering deep penetration into skin tissues with cellular resolution at a high frame rate. Extraction of backscattered spectra from the tissue has potential applications in biomedicine. The hysteresis nonlinearity of the piezoelectric transducer actuating the Mirau interferometer has been greatly reduced by a feedforward compensation approach. The linearized hysteresis response enables us to extract depth-dependent spectra accurately. To validate, the complex dispersion of a fused silica plate was characterized with 2% error. Further validation on an in vitro setting, the backscattered spectra from indocyanine green pigment and nonpigmented microspheres were obtained and verified. For in vivo skin measurement, the backscattered spectra show depth-dependent spectral shift and bandwidth variation due to the complex skin anatomy and pigment absorption. Such a high-speed spectra acquisition of in vivo deep tissue backscattering could lead to disease diagnosis in clinical settings.
Collapse
Affiliation(s)
- Rajendran Soundararajan
- Graduate Institute of Photonics and Optoelectronics, National Taiwan University, Taipei, Taiwan
| | - Ting-Wei Hsu
- Graduate Institute of Photonics and Optoelectronics, National Taiwan University, Taipei, Taiwan
| | - Yanding Qin
- Institute of Robotics and Automatic Information System, College of Artificial Intelligence, Nankai University, Tianjin, China
- Tianjin Key Laboratory of Intelligent Robotics, Nankai University, Tianjin, China
| | - Sheng-Lung Huang
- Graduate Institute of Photonics and Optoelectronics, National Taiwan University, Taipei, Taiwan
- Department of Electrical Engineering, National Taiwan University, Taipei, Taiwan
| |
Collapse
|
|
17
|
Kim J, Kim JM, Ha M, Oh JW, Nam JM. Polysorbate- and DNA-Mediated Synthesis and Strong, Stable, and Tunable Near-Infrared Photoluminescence of Plasmonic Long-Body Nanosnowmen. ACS NANO 2021; 15:19853-19863. [PMID: 34807582 DOI: 10.1021/acsnano.1c07319] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/13/2023]
Abstract
Direct photoluminescence (PL) from metal nanoparticles (NPs) without chemical dyes is promising for sensing and imaging applications since this offers a highly tunable platform for controlling and enhancing the signals in various conditions and does not suffer from photobleaching or photoblinking. It is, however, difficult to synthesize metal NPs with a high quantum yield (QY), particularly in the near-infrared (NIR) region where deep penetration and reduced light scattering are advantageous for bioimaging. Herein, we designed and synthesized Au-Ag long-body nanosnowman structures (LNSs), facilitated by polysorbate 20 (Tween 20). The DNA-engineered conductive junction between the head and body parts results in a charge transfer plasmon (CTP) mode in the NIR region. The junction morphology can be controlled by the DNA sequence on the Au core, and polythymine and polyadenine induced thick and thin junctions, respectively. We found that the LNSs with a thicker conductive junction generates the stronger CTP peak and PL signal than the LNSs with a thinner junction. The Au-Ag LNSs showed much higher intensities in both PL and QY than widely studied Au nanorods with similar localized surface plasmon resonance wavelengths, and notably, the LNSs displayed high photostability and robust, sustainable PL signals under continuous laser exposure for >15 h. Moreover, the PL emission from Au-Ag LNSs could be imaged in a deeper scattering medium than fluorescent silica NPs. Finally, highly robust PL-based cell images can be obtained using Au-Ag LNSs without significant signal change while repetitively imaging cells. The results offer the insights in plasmonic NIR probe design, and show that chemical dye-free LNSs can be a very promising candidate with a high QY and a robust, reliable NIR PL signal for NIR sensing and imaging applications.
Collapse
Affiliation(s)
- Jiyeon Kim
- Department of Chemistry, Seoul National University, Seoul 08826, South Korea
| | - Jae-Myoung Kim
- Department of Chemistry, Seoul National University, Seoul 08826, South Korea
| | - Minji Ha
- Department of Chemistry, Seoul National University, Seoul 08826, South Korea
| | - Jeong-Wook Oh
- Department of Chemistry, Seoul National University, Seoul 08826, South Korea
| | - Jwa-Min Nam
- Department of Chemistry, Seoul National University, Seoul 08826, South Korea
| |
Collapse
|
|
18
|
Wermelink B, Ma KF, Haalboom M, El Moumni M, de Vries JPPM, Geelkerken RH. A Systematic Review and Critical Appraisal of Peri-Procedural Tissue Perfusion Techniques and their Clinical Value in Patients with Peripheral Arterial Disease. Eur J Vasc Endovasc Surg 2021; 62:896-908. [PMID: 34674935 DOI: 10.1016/j.ejvs.2021.08.017] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2021] [Revised: 07/19/2021] [Accepted: 08/13/2021] [Indexed: 02/07/2023]
Abstract
OBJECTIVE Many techniques have been introduced to enable quantification of tissue perfusion in patients with peripheral arterial disease (PAD). Currently, none of these techniques is widely used to analyse real time tissue perfusion changes during endovascular or surgical revascularisation procedures. The aim of this systematic review was to provide an up to date overview of the peri-procedural applicability of currently available techniques, diagnostic accuracy of assessing tissue perfusion and the relationship with clinical outcomes. DATA SOURCES MEDLINE, Embase, CINAHL, and the Cochrane Central Register of Controlled Trials. REVIEW METHODS This systematic review was conducted in accordance with the Preferred Reporting Items for Systematic review and Meta-Analysis (PRISMA) guidelines. Four electronic databases were searched up to 31 12 2020 for eligible articles: MEDLINE, Embase, CINAHL and the Cochrane Central Register of Controlled Trials. Eligible articles describing a perfusion measurement technique, used in a peri-procedural setting before and within 24 hours after the revascularisation procedure, with the aim of determining the effect of intervention in patients with PAD, were assessed for inclusion. The QUADAS-2 tool was used to assess the risk of bias and applicability of the studies. RESULTS An overview of 10 techniques found in 26 eligible articles focused on study protocols, research goals, and clinical outcomes is provided. Non-invasive techniques included laser speckle contrast imaging, micro-lightguide spectrophotometry, magnetic resonance imaging perfusion, near infrared spectroscopy, skin perfusion pressure, and plantar thermography. Invasive techniques included two dimensional perfusion angiography, contrast enhanced ultrasound, computed tomography perfusion imaging, and indocyanine green angiography. The results of the 26 eligible studies, which were mostly of poor quality according to QUADAS-2, were without exception, not sufficient to substantiate implementation in daily clinical practice. CONCLUSION This systematic review provides an overview of 10 tissue perfusion assessment techniques for patients with PAD. It seems too early to appoint one of them as a reference standard. The scope of future research in this domain should therefore focus on clinical accuracy, reliability, and validation of the techniques.
Collapse
Affiliation(s)
- Bryan Wermelink
- University of Twente, Multi-Modality Medical Imaging Group, TechMed Centre, Enschede, The Netherlands; Department of Vascular Surgery, Medisch Spectrum Twente, Enschede, The Netherlands.
| | - Kirsten F Ma
- Department of Surgery, Division of Vascular Surgery, University Medical Centre Groningen, University of Groningen, Groningen, The Netherlands
| | - Marieke Haalboom
- Medical School Twente, Medisch Spectrum Twente, Enschede, The Netherlands
| | - Mostafa El Moumni
- Department of Surgery, Division of Trauma Surgery, University Medical Centre Groningen, University of Groningen, Groningen, The Netherlands
| | - Jean-Paul P M de Vries
- Department of Surgery, Division of Vascular Surgery, University Medical Centre Groningen, University of Groningen, Groningen, The Netherlands
| | - Robert H Geelkerken
- University of Twente, Multi-Modality Medical Imaging Group, TechMed Centre, Enschede, The Netherlands; Department of Vascular Surgery, Medisch Spectrum Twente, Enschede, The Netherlands
| |
Collapse
|
|
19
|
Kedrzycki MS, Leiloglou M, Chalau V, Chiarini N, Thiruchelvam PTR, Hadjiminas DJ, Hogben KR, Rashid F, Ramakrishnan R, Darzi AW, Elson DS, Leff DR. The Impact of Temporal Variation in Indocyanine Green Administration on Tumor Identification During Fluorescence Guided Breast Surgery. Ann Surg Oncol 2021; 28:5617-5625. [PMID: 34347221 PMCID: PMC8418597 DOI: 10.1245/s10434-021-10503-2] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/21/2021] [Accepted: 07/07/2021] [Indexed: 01/05/2023]
Abstract
BACKGROUND On average, 21% of women in the USA treated with Breast Conserving Surgery (BCS) undergo a second operation because of close positive margins. Tumor identification with fluorescence imaging could improve positive margin rates through demarcating location, size, and invasiveness of tumors. We investigated the technique's diagnostic accuracy in detecting tumors during BCS using intravenous indocyanine green (ICG) and a custom-built fluorescence camera system. METHODS In this single-center prospective clinical study, 40 recruited BCS patients were sub-categorized into two cohorts. In the first 'enhanced permeability and retention' (EPR) cohort, 0.25 mg/kg ICG was injected ~ 25 min prior to tumor excision, and in the second 'angiography' cohort, ~ 5 min prior to tumor excision. Subsequently, an in-house imaging system was used to image the tumor in situ prior to resection, ex vivo following resection, the resection bed, and during grossing in the histopathology laboratory to compare the technique's diagnostic accuracy between the cohorts. RESULTS The two cohorts were matched in patient and tumor characteristics. The majority of patients had invasive ductal carcinoma with concomitant ductal carcinoma in situ. Tumor-to-background ratio (TBR) in the angiography cohort was superior to the EPR cohort (TBR = 3.18 ± 1.74 vs 2.10 ± 0.92 respectively, p = 0.023). Tumor detection reached sensitivity and specificity scores of 0.82 and 0.93 for the angiography cohort and 0.66 and 0.90 for the EPR cohort, respectively (p = 0.1051 and p = 0.9099). DISCUSSION ICG administration timing during the angiography phase compared with the EPR phase improved TBR and diagnostic accuracy. Future work will focus on image pattern analysis and adaptation of the camera system to targeting fluorophores specific to breast cancer.
Collapse
Affiliation(s)
- Martha S Kedrzycki
- Hamlyn Centre, Institute of Global Health Innovation, Imperial College London, London, UK.,Department of Surgery and Cancer, Imperial College London, London, UK.,Department of Breast Surgery, Charing Cross Hospital, Imperial College Healthcare NHS Trust, London, UK
| | - Maria Leiloglou
- Hamlyn Centre, Institute of Global Health Innovation, Imperial College London, London, UK. .,Department of Surgery and Cancer, Imperial College London, London, UK.
| | - Vadzim Chalau
- Hamlyn Centre, Institute of Global Health Innovation, Imperial College London, London, UK.,Department of Surgery and Cancer, Imperial College London, London, UK
| | - Nicolas Chiarini
- Department of Surgery and Cancer, Imperial College London, London, UK
| | - Paul T R Thiruchelvam
- Department of Surgery and Cancer, Imperial College London, London, UK.,Department of Breast Surgery, Charing Cross Hospital, Imperial College Healthcare NHS Trust, London, UK
| | - Dimitri J Hadjiminas
- Department of Breast Surgery, Charing Cross Hospital, Imperial College Healthcare NHS Trust, London, UK
| | - Katy R Hogben
- Department of Breast Surgery, Charing Cross Hospital, Imperial College Healthcare NHS Trust, London, UK
| | - Faiza Rashid
- Department of Histopathology, Charing Cross Hospital, Imperial College Healthcare NHS Trust, London, UK
| | - Rathi Ramakrishnan
- Department of Histopathology, Charing Cross Hospital, Imperial College Healthcare NHS Trust, London, UK
| | - Ara W Darzi
- Hamlyn Centre, Institute of Global Health Innovation, Imperial College London, London, UK.,Department of Surgery and Cancer, Imperial College London, London, UK
| | - Daniel S Elson
- Hamlyn Centre, Institute of Global Health Innovation, Imperial College London, London, UK.,Department of Surgery and Cancer, Imperial College London, London, UK
| | - Daniel R Leff
- Hamlyn Centre, Institute of Global Health Innovation, Imperial College London, London, UK.,Department of Surgery and Cancer, Imperial College London, London, UK.,Department of Breast Surgery, Charing Cross Hospital, Imperial College Healthcare NHS Trust, London, UK
| |
Collapse
|
|
20
|
Ioussoufovitch S, Cohen DJF, Milej D, Diop M. Compressed sensing time-resolved spectrometer for quantification of light absorbers in turbid media. BIOMEDICAL OPTICS EXPRESS 2021; 12:6442-6460. [PMID: 34745748 PMCID: PMC8547999 DOI: 10.1364/boe.433427] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/08/2021] [Revised: 08/20/2021] [Accepted: 09/10/2021] [Indexed: 06/13/2023]
Abstract
Time-resolved (TR) spectroscopy is well-suited to address the challenges of quantifying light absorbers in highly scattering media such as living tissue; however, current TR spectrometers are either based on expensive array detectors or rely on wavelength scanning. Here, we introduce a TR spectrometer architecture based on compressed sensing (CS) and time-correlated single-photon counting. Using both CS and basis scanning, we demonstrate that-in homogeneous and two-layer tissue-mimicking phantoms made of Intralipid and Indocyanine Green-the CS method agrees with or outperforms uncompressed approaches. Further, we illustrate the superior depth sensitivity of TR spectroscopy and highlight the potential of the device to quantify absorption changes in deeper (>1 cm) tissue layers.
Collapse
Affiliation(s)
- Seva Ioussoufovitch
- Western University, Faculty of Engineering, School of Biomedical Engineering, Collaborative Training Program in Musculoskeletal Health Research, Bone & Joint Institute, 1151 Richmond St., London, N6A 5C1, Canada
| | - David Jonathan Fulop Cohen
- Western University, Schulich School of Medicine & Dentistry, Department of Medical Biophysics, 1151 Richmond St., London, N6A 5C1, Canada
| | - Daniel Milej
- Western University, Schulich School of Medicine & Dentistry, Department of Medical Biophysics, 1151 Richmond St., London, N6A 5C1, Canada
- Lawson Health Research Institute, Imaging Program, 268 Grosvenor St., London, N6A 4V2, Canada
| | - Mamadou Diop
- Western University, Faculty of Engineering, School of Biomedical Engineering, Collaborative Training Program in Musculoskeletal Health Research, Bone & Joint Institute, 1151 Richmond St., London, N6A 5C1, Canada
- Western University, Schulich School of Medicine & Dentistry, Department of Medical Biophysics, 1151 Richmond St., London, N6A 5C1, Canada
- Lawson Health Research Institute, Imaging Program, 268 Grosvenor St., London, N6A 4V2, Canada
| |
Collapse
|
|
21
|
Stewart HL, Birch DJS. Fluorescence Guided Surgery. Methods Appl Fluoresc 2021; 9. [PMID: 34399409 DOI: 10.1088/2050-6120/ac1dbb] [Citation(s) in RCA: 30] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/25/2021] [Accepted: 08/16/2021] [Indexed: 01/22/2023]
Abstract
Fluorescence guided surgery (FGS) is an imaging technique that allows the surgeon to visualise different structures and types of tissue during a surgical procedure that may not be as visible under white light conditions. Due to the many potential advantages of fluorescence guided surgery compared to more traditional clinical imaging techniques such as its higher contrast and sensitivity, less subjective use, and ease of instrument operation, the research interest in fluorescence guided surgery continues to grow over various key aspects such as fluorescent probe development and surgical system development as well as its potential clinical applications. This review looks to summarise some of the emerging opportunities and developments that have already been made in fluorescence guided surgery in recent years while highlighting its advantages as well as limitations that need to be overcome in order to utilise the full potential of fluorescence within the surgical environment.
Collapse
Affiliation(s)
- Hazel L Stewart
- Translational Healthcare Technologies Group, Centre for Inflammation Research, Queen's Medical Research Institute, University of Edinburgh, Edinburgh BioQuarter, 47 Little France Crescent, Edinburgh, EH16 4TJ, United Kingdom
| | - David J S Birch
- Department of Physics, The Photophysics Research Group, University of Strathclyde, SUPA, John Anderson Building, 107 Rottenrow East, Glasgow G4 0NG, United Kingdom
| |
Collapse
|
|
22
|
Ma L, Fei B. Comprehensive review of surgical microscopes: technology development and medical applications. JOURNAL OF BIOMEDICAL OPTICS 2021; 26:JBO-200292VRR. [PMID: 33398948 PMCID: PMC7780882 DOI: 10.1117/1.jbo.26.1.010901] [Citation(s) in RCA: 55] [Impact Index Per Article: 13.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/10/2020] [Accepted: 12/04/2020] [Indexed: 05/06/2023]
Abstract
SIGNIFICANCE Surgical microscopes provide adjustable magnification, bright illumination, and clear visualization of the surgical field and have been increasingly used in operating rooms. State-of-the-art surgical microscopes are integrated with various imaging modalities, such as optical coherence tomography (OCT), fluorescence imaging, and augmented reality (AR) for image-guided surgery. AIM This comprehensive review is based on the literature of over 500 papers that cover the technology development and applications of surgical microscopy over the past century. The aim of this review is threefold: (i) providing a comprehensive technical overview of surgical microscopes, (ii) providing critical references for microscope selection and system development, and (iii) providing an overview of various medical applications. APPROACH More than 500 references were collected and reviewed. A timeline of important milestones during the evolution of surgical microscope is provided in this study. An in-depth technical overview of the optical system, mechanical system, illumination, visualization, and integration with advanced imaging modalities is provided. Various medical applications of surgical microscopes in neurosurgery and spine surgery, ophthalmic surgery, ear-nose-throat (ENT) surgery, endodontics, and plastic and reconstructive surgery are described. RESULTS Surgical microscopy has been significantly advanced in the technical aspects of high-end optics, bright and shadow-free illumination, stable and flexible mechanical design, and versatile visualization. New imaging modalities, such as hyperspectral imaging, OCT, fluorescence imaging, photoacoustic microscopy, and laser speckle contrast imaging, are being integrated with surgical microscopes. Advanced visualization and AR are being added to surgical microscopes as new features that are changing clinical practices in the operating room. CONCLUSIONS The combination of new imaging technologies and surgical microscopy will enable surgeons to perform challenging procedures and improve surgical outcomes. With advanced visualization and improved ergonomics, the surgical microscope has become a powerful tool in neurosurgery, spinal, ENT, ophthalmic, plastic and reconstructive surgeries.
Collapse
Affiliation(s)
- Ling Ma
- University of Texas at Dallas, Department of Bioengineering, Richardson, Texas, United States
| | - Baowei Fei
- University of Texas at Dallas, Department of Bioengineering, Richardson, Texas, United States
- University of Texas Southwestern Medical Center, Department of Radiology, Dallas, Texas, United States
| |
Collapse
|
|
23
|
Staubach P, Scharl A, Ignatov A, Ortmann O, Inwald EC, Hildebrandt T, Gerken M, Klinkhammer-Schalke M, Scharl S, Papathemelis T. Sentinel lymph node detection by means of indocyanine green using the Karl Storz VITOM ® fluorescence camera: a comparison between primary sentinel lymph node biopsy versus sentinel lymph node biopsy after neoadjuvant chemotherapy. J Cancer Res Clin Oncol 2020; 147:1813-1823. [PMID: 33230583 DOI: 10.1007/s00432-020-03461-x] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2020] [Accepted: 11/06/2020] [Indexed: 11/28/2022]
Abstract
PURPOSE The usage of radioactive Technetium99m (Tc99m) colloid for the purpose of sentinel lymph node biopsy (SLNB) in early breast cancer is considered the gold standard in Germany. However, new tracers, such as near-infrared (NIR) imaging agents like indocyanine green (ICG) could offer an alternative in future, as they overcome drawbacks associated with radioactive Technetium99m (Tc99m) like limited availability, high costs and radioactivity exposure for both patients and surgeons. METHODS In this double-arm retrospective study, we sought to establish the usefulness of indocyanine green as an alternative or an addition to the conventional Technetium99m (Tc99m) in the identification of the SLN in early breast cancer. RESULTS Among the 161 patients who underwent primary SLNB, 34 patients had at least 1 SLN with metastasis. Among these patients with SLN metastasis, 33 had the SLN detected by ICG; while 31 had the SLN detected by Tc99m. The conventional Technetium99m radiotracer failed to detect 2 patients with metastasis in this Arm of the study. Among the 87 patients who underwent SLNB after NACT, 13 patients had at least 1 SLN with metastasis. Among these 13 patients with SLN metastasis, ICG and Tc99m had detected the SLN among 12 patients, while 1 patient had been detected by ICG alone. CONCLUSIONS Our results show that ICG is as effective as the radioisotope for SLNB even among patients who have undergone NACT. This trial is registered with the German Clinical Trial Register, ID: DRKS00013606.
Collapse
Affiliation(s)
- Petronilla Staubach
- Department of Obstetrics and Gynecology, St. Marien Hospital, Amberg, Germany.
| | - Anton Scharl
- Department of Obstetrics and Gynecology, St. Marien Hospital, Amberg, Germany
| | - Atanas Ignatov
- Department of Obstetrics and Gynecology, University Hospital Regensburg, Landshuter Str. 65, 93053, Regensburg, Germany
| | - Olaf Ortmann
- Department of Obstetrics and Gynecology, University Hospital Regensburg, Landshuter Str. 65, 93053, Regensburg, Germany
| | - Elisabeth C Inwald
- Department of Obstetrics and Gynecology, University Hospital Regensburg, Landshuter Str. 65, 93053, Regensburg, Germany
| | - Thomas Hildebrandt
- Department of Obstetrics and Gynecology, University Hospital Erlangen-Nuremberg, Maximilianspl. 2, 91054, Erlangen, Germany
| | - Michael Gerken
- Tumor Center of the University of Regensburg, Institute for Quality Assurance and Health Services Research, Regensburg, Germany
| | - Monika Klinkhammer-Schalke
- Tumor Center of the University of Regensburg, Institute for Quality Assurance and Health Services Research, Regensburg, Germany
| | - Sophia Scharl
- Department of Radiooncology and Radiotherapy, Technical University Hospital Munich, Ismaninger Str. 22, 81675, Munich, Germany
| | - Thomas Papathemelis
- Department of Obstetrics and Gynecology, St. Marien Hospital, Amberg, Germany
| |
Collapse
|
|
24
|
Hyperthermal paclitaxel-bound albumin nanoparticles co-loaded with indocyanine green and hyaluronidase for treating pancreatic cancers. Arch Pharm Res 2020; 44:182-193. [PMID: 32803685 DOI: 10.1007/s12272-020-01264-9] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2020] [Accepted: 08/11/2020] [Indexed: 02/08/2023]
Abstract
Albumin nanoparticles have become an attractive cancer nanomedicine platform due to their pharmaceutical advantages. Recently, photothermal therapy has been extensively applied to cancer treatment due to heat-induced tumor ablation. Herein, we fabricated albumin nanoparticles (HSA-NPs) loaded with paclitaxel (PTX), indocyanine green (ICG; a hyperthermal agent) and hyaluronidase (HAase) that breaks down hyaluronan, a major component of the extracellular matrix (ECM) in tumors. Synthesis was based on a slightly modified nanoparticle albumin-bound (Nab™) technique. The prepared nanoparticles (PTX/ICG/HAase-HSA-NPs) had a spherical shape with an average size of ~ 110 nm and a zeta potential of ~ -30.4 mV. They displayed good colloidal stability and typical patterns of ICG, HSA and HAase in UV-VIS-NIR and circular dichroism spectroscopic analysis. PTX/ICG/HAase-HSA-NPs were found to have excellent hyperthermal effects in response to near-infrared laser irradiation (808 nm) (up to > 50 °C over 4 min). The hyperthermia conducted by PTX/ICG/HAase-HSA-NPs resulted in significant cytotoxicity to pancreatic AsPC-1 cells at both severe (> 50 °C) and mild (41-42 °C) hyperthermal states in conjunction with the inherent cytotoxic activity of paclitaxel. Furthermore, the confocal images of AsPC-1 cell spheroids proved PTX/ICG/HAase-HSA-NPs were able to permeate deeply into the three-dimensional tumor tissue mimicry structure. Most of all, PTX/ICG/HAase-HSA-NPs maintained all these physicochemical and anti-cancer properties irrespective of the amount of embedded HAase (1-5 mg). Our results demonstrated that PTX/ICG/HAase-HSA-NPs are a promising hyperthermal/chemotherapeutic anticancer agent.
Collapse
|
|
25
|
Sevieri M, Silva F, Bonizzi A, Sitia L, Truffi M, Mazzucchelli S, Corsi F. Indocyanine Green Nanoparticles: Are They Compelling for Cancer Treatment? Front Chem 2020; 8:535. [PMID: 32766203 PMCID: PMC7378786 DOI: 10.3389/fchem.2020.00535] [Citation(s) in RCA: 28] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2020] [Accepted: 05/25/2020] [Indexed: 12/14/2022] Open
Abstract
Indocyanine green (ICG) is a Food and Drug Administration–approved near-infrared fluorescent dye, employed as an imaging agent for different clinical applications due to its attractive physicochemical properties, high sensitivity, and safety. However, free ICG suffers from some drawbacks, such as relatively short circulation half-life, concentration-dependent aggregation, and rapid clearance from the body, which would confine its feasible application in oncology. Here, we aim to discuss encapsulation of ICG within a nanoparticle formulation as a strategy to overcome some of its current limitations and to enlarge its possible applications in cancer diagnosis and treatment. Our purpose is to provide a short but exhaustive overview of clinical outcomes that these nanocomposites would provide, discussing opportunities, limitations, and possible impacts with regard to the main clinical needs in oncology.
Collapse
Affiliation(s)
- Marta Sevieri
- Laboratorio di Nanomedicina, Dipartimento di Scienze Biomediche e Cliniche "L. Sacco", Università di Milano, Milan, Italy
| | - Filippo Silva
- Laboratorio di Nanomedicina, Dipartimento di Scienze Biomediche e Cliniche "L. Sacco", Università di Milano, Milan, Italy
| | - Arianna Bonizzi
- Laboratorio di Nanomedicina, Dipartimento di Scienze Biomediche e Cliniche "L. Sacco", Università di Milano, Milan, Italy
| | - Leopoldo Sitia
- Laboratorio di Nanomedicina, Dipartimento di Scienze Biomediche e Cliniche "L. Sacco", Università di Milano, Milan, Italy
| | - Marta Truffi
- Laboratorio di Nanomedicina e Imaging Molecolare, Istituti Clinici Scientifici Spa-Società Benefit IRCCS, Pavia, Italy
| | - Serena Mazzucchelli
- Laboratorio di Nanomedicina, Dipartimento di Scienze Biomediche e Cliniche "L. Sacco", Università di Milano, Milan, Italy
| | - Fabio Corsi
- Laboratorio di Nanomedicina, Dipartimento di Scienze Biomediche e Cliniche "L. Sacco", Università di Milano, Milan, Italy.,Laboratorio di Nanomedicina e Imaging Molecolare, Istituti Clinici Scientifici Spa-Società Benefit IRCCS, Pavia, Italy
| |
Collapse
|
|
26
|
Nikinmaa S, Alapulli H, Auvinen P, Vaara M, Rantala J, Kankuri E, Sorsa T, Meurman J, Pätilä T. Dual-light photodynamic therapy administered daily provides a sustained antibacterial effect on biofilm and prevents Streptococcus mutans adaptation. PLoS One 2020; 15:e0232775. [PMID: 32374766 PMCID: PMC7202659 DOI: 10.1371/journal.pone.0232775] [Citation(s) in RCA: 23] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2020] [Accepted: 04/21/2020] [Indexed: 12/19/2022] Open
Abstract
Antibacterial photodynamic therapy (aPDT) and antibacterial blue light (aBL) are emerging treatment methods auxiliary to mechanical debridement for periodontitis. APDT provided with near-infrared (NIR) light in conjunction with an indocyanine green (ICG) photosensitizer has shown efficacy in several dental in-office-treatment protocols. In this study, we tested Streptococcus mutans biofilm sensitivity to either aPDT, aBL or their combination dual-light aPDT (simultaneous aPDT and aBL) exposure. Biofilm was cultured by pipetting diluted Streptococcus mutans suspension with growth medium on the bottom of well plates. Either aPDT (810 nm) or aBL (405 nm) or a dual-light aPDT (simultaneous 810 nm aPDT and 405 nm aBL) was applied with an ICG photosensitizer in cases of aPDT or dual-light, while keeping the total given radiant exposure constant at 100 J/cm2. Single-dose light exposures were given after one-day or four-day biofilm incubations. Also, a model of daily treatment was provided by repeating the same light dose daily on four-day and fourteen-day biofilm incubations. Finally, the antibacterial action of the dual-light aPDT with different energy ratios of 810 nm and 405 nm of light were examined on the single-day and four-day biofilm protocols. At the end of each experiment the bacterial viability was assessed by colony-forming unit method. Separate samples were prepared for confocal 3D biofilm imaging. On a one-day biofilm, the dual-light aPDT was significantly more efficient than aBL or aPDT, although all modalities were bactericidal. On a four-day biofilm, a single exposure of aPDT or dual-light aPDT was more efficient than aBL, resulting in a four logarithmic scale reduction in bacterial counts. Surprisingly, when the same amount of aPDT was repeated daily on a four-day or a fourteen-day biofilm, bacterial viability improved significantly. A similar improvement in bacterial viability was observed after repetitive aBL application. This viability improvement was eliminated when dual-light aPDT was applied. By changing the 405 nm to 810 nm radiant exposure ratio in dual-light aPDT, the increase in aBL improved the antibacterial action when the biofilm was older. In conclusion, when aPDT is administered repeatedly to S. mutans biofilm, a single wavelength-based aBL or aPDT leads to a significant biofilm adaptation and increased S. mutans viability. The combined use of aBL light in synchrony with aPDT arrests the adaptation and provides significantly improved and sustained antibacterial efficacy.
Collapse
Affiliation(s)
- Sakari Nikinmaa
- Department of Neuroscience and Biomedical Engineering, Aalto University, Espoo, Finland
- Koite Health Oy, Espoo, Finland
| | - Heikki Alapulli
- Department of Oral and Maxillofacial Diseases, University of Helsinki, Helsinki, Finland
| | - Petri Auvinen
- Institute of Biotechnology, University of Helsinki, Helsinki, Finland
| | - Martti Vaara
- Northern Antibiotics, Espoo, Finland
- Department of Bacteriology and Immunology, University of Helsinki, Medical School, Helsinki, Finland
| | | | - Esko Kankuri
- Department of Pharmacology, University of Helsinki, Helsinki, Finland
| | - Timo Sorsa
- Department of Oral and Maxillofacial Diseases, University of Helsinki, Helsinki, Finland
- Department of Oral Diseases, Karolinska Institute, Huddinge, Sweden
| | - Jukka Meurman
- Department of Neuroscience and Biomedical Engineering, Aalto University, Espoo, Finland
- Department of Oral and Maxillofacial Diseases, University of Helsinki, Helsinki, Finland
| | - Tommi Pätilä
- Department of Neuroscience and Biomedical Engineering, Aalto University, Espoo, Finland
- Koite Health Oy, Espoo, Finland
- Department of Congenital Heart Surgery and Organ Transplantation, New Children’s Hospital, University of Helsinki, Helsinki, Finland
- * E-mail:
| |
Collapse
|
|
27
|
Jao ML, Wang YY, Wong HP, Bachhav S, Liu KC. Intracholecystic administration of indocyanine green for fluorescent cholangiography during laparoscopic cholecystectomy-A two-case report. Int J Surg Case Rep 2020; 68:193-197. [PMID: 32172195 PMCID: PMC7075798 DOI: 10.1016/j.ijscr.2020.02.054] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2019] [Revised: 02/18/2020] [Accepted: 02/20/2020] [Indexed: 12/17/2022] Open
Abstract
It is difficult to visualize extra-hepatic biliary anatomy clearly because of long-presence of ICG in liver when administered intravenously. Intracholecystic ICG injection illuminates extra-hepatic biliary tree preferentially thus reducing background hepatic noise. Surgeons can experience more satisfaction with the use of fluorescent cholangiography during laparoscopic cholecystectomy when the intracystic route of ICG administration is utilized. Introduction The utility of intracystic administration of indocyanine green for near-infrared fluorescent cholangiography in acute calculous cholecystitis initially treated with percutaneous transhepatic gallbladder drainage (PTGBD) was described in this report. Presentation of case Two cases who underwent near-infrared fluorescent cholangiography guided interval laparoscopic cholecystectomy two weeks post-PTGBD were studied retrospectively. Both patients were diagnosed with moderate acute calculous cholecystitis based on diagnostic criteria of the Tokyo guidelines. Two routes of indocyanine green administration were utilized during surgery, first through direct intracystic administration through PTGBD tube (5 ml of 12.5 mg ICG) to achieve critical view of safety and then intravenous administration (1 ml of 2.5 mg ICG) to visualize cystic artery. Discussion Both patients had critical view of safety visualized clearly with ICG with the operation time of 84 and 125 min in cases 1 and 2, respectively without any intra or postoperative complications. Conclusion In comparison with intravenous ICG administration, trans-PTGBD ICG route can provide better signal-to-noise ratio by avoiding hepatic fluorescence and thus increasing the bile duct to liver contrast. However, ICG may enter the lymphatic system through necrotic and inflammatory gallbladder mucosa, of which lymph spillage during gallbladder dissection can obscure the fluorescent view.
Collapse
Affiliation(s)
- Man-Ling Jao
- Department of Surgery, Show Chwan Memorial Hospital, Changhua, Taiwan
| | - Yen-Yu Wang
- IRCAD/AITS-Asian Institute of TeleSurgery, Chang Bing Show Chwan Hospital, Changhua, Taiwan
| | - Hon Phin Wong
- Department of Surgery, Show Chwan Memorial Hospital, Changhua, Taiwan.
| | - Sayali Bachhav
- IRCAD/AITS-Asian Institute of TeleSurgery, Chang Bing Show Chwan Hospital, Changhua, Taiwan
| | - Kai-Che Liu
- IRCAD/AITS-Asian Institute of TeleSurgery, Chang Bing Show Chwan Hospital, Changhua, Taiwan
| |
Collapse
|
|
28
|
Petrovic LZ, Xavierselvan M, Kuriakose M, Kennedy MD, Nguyen CD, Batt JJ, Detels KB, Mallidi S. Mutual impact of clinically translatable near-infrared dyes on photoacoustic image contrast and in vitro photodynamic therapy efficacy. JOURNAL OF BIOMEDICAL OPTICS 2020; 25:1-12. [PMID: 32112541 PMCID: PMC7048201 DOI: 10.1117/1.jbo.25.6.063808] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/18/2019] [Accepted: 02/05/2020] [Indexed: 05/29/2023]
Abstract
Photodynamic therapy (PDT), a spatially localized phototoxic therapy that involves irradiation of a photosensitizer (PS) with specific wavelengths of light, has shown exceptional promise in impacting cancer treatment outcomes, particularly oral cancer. To reduce PDT outcome variability, attempts toward image-guided personalized PDT are being pursued by monitoring PS uptake either via fluorescence or photoacoustic imaging (PAI), a nonionizing modality dependent on optical absorption properties of the tissue. PAI-guided PDT requires a near-infrared contrast agent for deep tissue imaging with minimal photobleaching effect. We evaluate the impact of PDT agent, benzoporphyrin derivative (BPD), on PAI agent indocyanine green (ICG) and vice versa, given that they have different optical absorption properties and singlet oxygen quantum yields for PDT. Specifically, we demonstrate in two oral squamous cell carcinoma lines (FaDu and SCC4) that ICG has minimal effect on BPD PDT efficacy when irradiated with either a continuous or pulsed laser. Furthermore, the impact of BPD on ICG photodegradation was monitored with PAI in tissue-mimicking phantoms. These studies inform us that the combination of BPD and ICG can be utilized for PAI-guided PDT. However, researchers need to consider the photodegradation effects of ICG in the presence of BPD when designing their drug delivery strategies for PAI-guided PDT.
Collapse
Affiliation(s)
- Ljubica Z. Petrovic
- Tufts University, Department of Biomedical Engineering, Medford, Massachusetts, United States
| | - Marvin Xavierselvan
- Tufts University, Department of Biomedical Engineering, Medford, Massachusetts, United States
| | - Maju Kuriakose
- Tufts University, Department of Biomedical Engineering, Medford, Massachusetts, United States
| | - Michael D. Kennedy
- Tufts University, Department of Biomedical Engineering, Medford, Massachusetts, United States
| | - Christopher D. Nguyen
- Tufts University, Department of Biomedical Engineering, Medford, Massachusetts, United States
| | - Julian J. Batt
- Tufts University, Department of Biomedical Engineering, Medford, Massachusetts, United States
| | - Kelsey B. Detels
- Tufts University, Department of Biomedical Engineering, Medford, Massachusetts, United States
| | - Srivalleesha Mallidi
- Tufts University, Department of Biomedical Engineering, Medford, Massachusetts, United States
| |
Collapse
|
|
29
|
Di Marco AN, Palazzo FF. Near-infrared autofluorescence in thyroid and parathyroid surgery. Gland Surg 2020; 9:S136-S146. [PMID: 32175254 DOI: 10.21037/gs.2020.01.04] [Citation(s) in RCA: 35] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Contrast-free autofluorescence (AF) of the parathyroid glands (PTGs) and thyroid tissue occurs in the near-infrared (NIR) spectrum on excitation by light in the upper range of the visible spectrum or lower NIR spectrum. In vivo, PTGs autofluoresce more brightly than thyroid (by a factor of 2-20 times) and appear as a bright spot against surrounding thyroid, muscle or fat on a processed image which is generated in real-time. NIR-AF of PTGs was first described in 2009 although NIR-AF had previously been used in several other clinical applications. Since then there has been a great amount of interest in the use of NIR-AF in thyroid and parathyroid surgery with over 25 published reports of the utilisation of both self-built and proprietary NIR-AF devices in neck endocrine surgery. All of these reports have confirmed the feasibility of NIR-AF intraoperatively and its ability to detect PTGs, although the reported accuracy varies from 90-100%. Reports of the effect of NIR-AF on relevant clinical endpoints i.e., post-operative hypoparathyroidism in thyroidectomy and persistent disease in parathyroidectomy are however scant. There has been one multicentre clinical trial of NIR-AF in thyroidectomy but this did not report clinical outcomes and two single-centre, non-randomised studies which did report post-operative hypoparathyroidism but with differing results: one showing no benefit in 106 NIR-AF vs. 163 controls and one, a reduction of early hypocalcaemia from 20% to 5% in 93 NIR-AF patients vs. 420 controls. There were only 2 cases of permanent hypoparathyroidism across both studies and therefore no significant observable difference in this key outcome variable. In parathyroidectomy, possible variability of the AF signal due to composition of a PTG adenoma, secondary/tertiary disease and MEN1 as well as depth-penetration preventing detection of sub-surface PTGs would imply that NIR-AF in its current form is not well-placed to improve cure-rates in hyperparathyroidism, which may already be as high as 98%. Thus far, no study has addressed this. Despite the promising results of NIR-AF, the absence of data demonstrating an improvement in outcomes and the cost of its use currently limit its use in routine clinical practice, especially in a publicly funded healthcare system with budgetary constraints. However, it can be utilised in research settings and this should be undertaken within the context of well-designed and conducted randomised, multi-centre, appropriately powered studies, which will assist in establishing its role in neck endocrine surgery.
Collapse
Affiliation(s)
- Aimee N Di Marco
- Department of Endocrine Surgery, Hammersmith Hospital, Imperial College Healthcare NHS Trust, London, UK.,Department of Surgery & Cancer, Imperial College, London, UK
| | - Fausto F Palazzo
- Department of Endocrine Surgery, Hammersmith Hospital, Imperial College Healthcare NHS Trust, London, UK.,Department of Surgery & Cancer, Imperial College, London, UK
| |
Collapse
|
|
30
|
Daly MJ, Chan H, Muhanna N, Akens MK, Wilson BC, Irish JC, Jaffray DA. Intraoperative cone-beam CT spatial priors for diffuse optical fluorescence tomography. ACTA ACUST UNITED AC 2019; 64:215007. [DOI: 10.1088/1361-6560/ab4917] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
|
|
31
|
Zhang DY, Singhal S, Lee JYK. Optical Principles of Fluorescence-Guided Brain Tumor Surgery: A Practical Primer for the Neurosurgeon. Neurosurgery 2019; 85:312-324. [PMID: 30085129 DOI: 10.1093/neuros/nyy315] [Citation(s) in RCA: 45] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2017] [Accepted: 06/18/2018] [Indexed: 01/21/2023] Open
Abstract
Fluorescence-guided surgery is a rapidly growing field that has produced some of the most important innovations in surgical oncology in the past decade. These intraoperative imaging technologies provide information distinguishing tumor tissue from normal tissue in real time as the surgery proceeds and without disruption of the workflow. Many of these fluorescent tracers target unique molecular or cellular features of tumors, which offers the opportunity for identifying pathology with high precision to help surgeons achieve their primary objective of a maximal safe resection. As novel fluorophores and fluorescent probes emerge from preclinical development, a practical understanding of the principles of fluorescence remains critical for evaluating the clinical utility of these agents and identifying opportunities for further innovation. In this review, we provide an "in-text glossary" of the fundamental principles of fluorescence with examples of direct applications to fluorescence-guided brain surgery. We offer a detailed discussion of the various advantages and limitations of the most commonly used intraoperative imaging agents, including 5-aminolevulinic acid, indocyanine green, and fluorescein, with a particular focus on the photophysical properties of these specific agents as they provide a framework through which to understand the new agents that are entering clinical trials. To this end, we conclude with a survey of the fluorescent properties of novel agents that are currently undergoing or will soon enter clinical trials for the intraoperative imaging of brain tumors.
Collapse
Affiliation(s)
- Daniel Y Zhang
- Department of Neurosurgery, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania
| | - Sunil Singhal
- Department of Surgery, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania
| | - John Y K Lee
- Department of Neurosurgery, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania
| |
Collapse
|
|
32
|
Daly MJ, Wilson BC, Irish JC, Jaffray DA. Navigated non-contact fluorescence tomography. ACTA ACUST UNITED AC 2019; 64:135021. [DOI: 10.1088/1361-6560/ab1f33] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/02/2023]
|
|
33
|
Roberts S, Strome A, Choi C, Andreou C, Kossatz S, Brand C, Williams T, Bradbury M, Kircher MF, Reshetnyak YK, Grimm J, Lewis JS, Reiner T. Acid specific dark quencher QC1 pHLIP for multi-spectral optoacoustic diagnoses of breast cancer. Sci Rep 2019; 9:8550. [PMID: 31189972 PMCID: PMC6561946 DOI: 10.1038/s41598-019-44873-1] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2019] [Accepted: 05/20/2019] [Indexed: 12/29/2022] Open
Abstract
Breast cancer is the most common type of malignant growth in women. Early detection of breast cancer, as well as the identification of possible metastatic spread poses a significant challenge because of the structural and genetic heterogeneity that occurs during the progression of the disease. Currently, mammographies, biopsies and MRI scans are the standard of care techniques used for breast cancer diagnosis, all of which have their individual shortfalls, especially when it comes to discriminating tumors and benign growths. With this in mind, we have developed a non-invasive optoacoustic imaging strategy that targets the acidic environment of breast cancer. A pH low insertion peptide (pHLIP) was conjugated to the dark quencher QC1, yielding a non-fluorescent sonophore with high extinction coefficient in the near infrared that increases signal as a function of increasing amounts of membrane insertion. In an orthotopic murine breast cancer model, pHLIP-targeted optoacoustic imaging allowed us to differentiate between healthy and breast cancer tissues with high signal/noise ratios. In vivo, the sonophore QC1-pHLIP could detect malignancies at higher contrast than its fluorescent analog ICG-pHLIP, which was developed for fluorescence-guided surgical applications. PHLIP-type optoacoustic imaging agents in clinical settings are attractive due to their ability to target breast cancer and a wide variety of other malignant growths for diagnostic purposes. Intuitively, these agents could also be used for visualization during surgery.
Collapse
Affiliation(s)
- Sheryl Roberts
- Department of Radiology, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, New York, 10065, USA
| | - Arianna Strome
- Department of Radiology, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, New York, 10065, USA
| | - Crystal Choi
- Department of Radiology, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, New York, 10065, USA
| | - Chrysafis Andreou
- Department of Radiology, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, New York, 10065, USA
| | - Susanne Kossatz
- Department of Radiology, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, New York, 10065, USA
| | - Christian Brand
- Department of Radiology, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, New York, 10065, USA
| | - Travis Williams
- Department of Radiology, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, New York, 10065, USA
| | - Michelle Bradbury
- Department of Radiology, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, New York, 10065, USA.,Molecular Pharmacology Program, Sloan Kettering Institute for Cancer Research, New York, New York, 10065, USA
| | - Moritz F Kircher
- Department of Radiology, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, New York, 10065, USA.,Molecular Pharmacology Program, Sloan Kettering Institute for Cancer Research, New York, New York, 10065, USA.,Center for Molecular Imaging and Nanotechnology (CMINT), Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA.,Department of Radiology, Weill Cornell Medical College, 1300 York Avenue, New York, New York, 10065, USA.,Department of Imaging, Dana-Farber Cancer Institute/Harvard Medical School, Boston, MA 02215, USA
| | - Yana K Reshetnyak
- Department of Physics, University of Rhode Island, 2 Lippitt Rd, Kingston, RI, 02881, USA
| | - Jan Grimm
- Department of Radiology, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, New York, 10065, USA.,Department of Radiology, Weill Cornell Medical College, 1300 York Avenue, New York, New York, 10065, USA.,Department of Molecular Pharmacology, Memorial Sloan Kettering Cancer Center, New York, New York, USA.,Department of Pharmacology, Weill Cornell Medical College, New York, NY, USA
| | - Jason S Lewis
- Department of Radiology, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, New York, 10065, USA.,Department of Radiology, Weill Cornell Medical College, 1300 York Avenue, New York, New York, 10065, USA.,Department of Pharmacology, Weill Cornell Medical College, New York, NY, USA.,Molecular Pharmacology Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA.,Radiochemistry and Molecular Imaging Probes Core, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Thomas Reiner
- Department of Radiology, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, New York, 10065, USA. .,Department of Radiology, Weill Cornell Medical College, 1300 York Avenue, New York, New York, 10065, USA. .,Chemical Biology Program, Memorial Sloan Kettering Cancer Center, New York City, NY, 10065, United States.
| |
Collapse
|
|
34
|
Filippi M, Garello F, Pasquino C, Arena F, Giustetto P, Antico F, Terreno E. Indocyanine green labeling for optical and photoacoustic imaging of mesenchymal stem cells after in vivo transplantation. JOURNAL OF BIOPHOTONICS 2019; 12:e201800035. [PMID: 30471202 DOI: 10.1002/jbio.201800035] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/30/2018] [Revised: 11/19/2018] [Accepted: 11/20/2018] [Indexed: 06/09/2023]
Abstract
The transplantation of mesenchymal stem cells (MSCs) holds great promise for the treatment of a plethora of human diseases, but new noninvasive procedures are needed to monitor the cell fate in vivo. Already largely used in medical diagnostics, the fluorescent dye indocyanine green (ICG) is an established dye to track limited numbers of cells by optical imaging (OI), but it can also be visualized by photoacoustic imaging (PAI), which provides a higher spatial resolution than pure near infrared fluorescence imaging (NIRF). Because of its successful use in clinical and preclinical examinations, we chose ICG as PAI cell labeling agent. Optimal incubation conditions were defined for an efficient and clinically translatable MSC labeling protocol, such that no cytotoxicity or alterations of the phenotypic profile were observed, and a consistent intracellular uptake of the molecule was achieved. Suspensions of ICG-labeled cells were both optically and optoacoustically detected in vitro, revealing a certain variability in the photoacoustic spectra acquired by varying the excitation wavelength from 680 to 970 nm. Intramuscular engraftments of ICG-labeled MSCs were clearly visualized by both PAI and NIRF over few days after transplantation in the hindlimb of healthy mice, suggesting that the proposed technique retains a considerable potential in the field of transplantation-focused research and therapy. Stem cells were labeled with the Food and Drug Administration (FDA)-approved fluorescent dye ICG, and detected by both PAI and OI, enabling to monitor the cell fate safely, in dual modality, and with good sensitivity and improved spatial resolution.
Collapse
Affiliation(s)
- Miriam Filippi
- Molecular and Preclinical Imaging Centers, Department of Molecular Biotechnology and Health Sciences, University of Turin, Torino, Italy
| | - Francesca Garello
- Molecular and Preclinical Imaging Centers, Department of Molecular Biotechnology and Health Sciences, University of Turin, Torino, Italy
| | - Chiara Pasquino
- Department of Molecular Biotechnology and Health Sciences, University of Turin, Torino, Italy
| | - Francesca Arena
- Molecular and Preclinical Imaging Centers, Department of Molecular Biotechnology and Health Sciences, University of Turin, Torino, Italy
| | - Pierangela Giustetto
- Molecular and Preclinical Imaging Centers, Department of Molecular Biotechnology and Health Sciences, University of Turin, Torino, Italy
| | - Federica Antico
- Department of Molecular Biotechnology and Health Sciences, University of Turin, Torino, Italy
| | | |
Collapse
|
|
35
|
Huang SW, Ou JJ, Wong HP. The use of indocyanine green imaging technique in patient with hepatocellular carcinoma. Transl Gastroenterol Hepatol 2018; 3:95. [PMID: 30603731 DOI: 10.21037/tgh.2018.10.15] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/29/2018] [Accepted: 10/29/2018] [Indexed: 01/22/2023] Open
Abstract
Near-infrared indocyanine green (ICG) fluorescence application in liver cancer surgery have been reported in the literature since 2008. To date, most reports emphasized not only to the safety, feasibility and reproducibility, but also the potential benefits of its clinical applications in term of demarcating segmentation for an anatomical resection, tumor identification to achieve tumor free resection margin, detection of small unidentifiable subcapsular nodules as well as extrahepatic metastatic lesions, and fluorescence cholangiography. The purpose of this review is to present the fundamental concept of the interpretation of fluorescence enhancement by different timing through intravascular ICG distribution to liver and biliary washout; to describe step-by-step technical aspects of its use in different purposes, and to expose the diagnostic and therapeutic perspectives of this innovative imaging technique in liver cancer surgery.
Collapse
Affiliation(s)
- Shih-Wei Huang
- Division of General Surgery, Department of Surgery, Show Chwan Memorial Hospital, Changhua, Taiwan.,IRCAD/AITS-Asian Institute of TeleSurgery, Show Chwan Health Care System, Changhua, Taiwan
| | - Jing-Jim Ou
- Department of Surgery, Chang Bing Show Chwan Memorial Hospital, Lukang Town, Changhua, Taiwan
| | - Hon Phin Wong
- Division of General Surgery, Department of Surgery, Show Chwan Memorial Hospital, Changhua, Taiwan.,IRCAD/AITS-Asian Institute of TeleSurgery, Show Chwan Health Care System, Changhua, Taiwan
| |
Collapse
|
|
36
|
Okumura M, Ichihara H, Matsumoto Y. Hybrid liposomes showing enhanced accumulation in tumors as theranostic agents in the orthotopic graft model mouse of colorectal cancer. Drug Deliv 2018; 25:1192-1199. [PMID: 29790374 PMCID: PMC6058724 DOI: 10.1080/10717544.2018.1475517] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/06/2023] Open
Abstract
Hybrid liposomes (HLs) can be prepared by simply sonicating a mixture of vesicular and micellar molecules in a buffer solution. This study aimed to elucidate the therapeutic effects and ability of HLs to detect (diagnosis) cancer in an orthotopic graft mouse model of colorectal cancer with HCT116 cells for the use of HLs as theranostic agents. In the absence of a chemotherapeutic drug, HLs exhibited therapeutic effects by inhibiting the growth of HCT116 colorectal cancer cells in vitro, possibly through an increase in apoptosis. Intravenously administered HLs also caused a remarkable reduction in the relative cecum weight in an orthotopic graft mouse model of colorectal cancer. A decrease in tumor size in the cecal sections was confirmed by histological analysis using HE staining. TUNEL staining indicated an induction of apoptosis in HCT116 cells in the orthotopic graft mouse model of colorectal cancer. For the detection (diagnosis) of colorectal cancer by HLs, the accumulation of HLs encapsulating a fluorescent probe (ICG) was observed in HCT116 cells in the in vivo colorectal cancer model following intravenous administration. These data indicate that HLs can accumulate in tumor cells in the cecum of the orthotopic graft mouse model of colorectal cancer for a prolonged period of time, and inhibit the growth of HCT116 cells.
Collapse
Affiliation(s)
- Masaki Okumura
- a Division of Applied Life Science, Graduate School of Engineering , Sojo University , Nishi-ku, Kumamoto , Japan
| | - Hideaki Ichihara
- a Division of Applied Life Science, Graduate School of Engineering , Sojo University , Nishi-ku, Kumamoto , Japan
| | - Yoko Matsumoto
- a Division of Applied Life Science, Graduate School of Engineering , Sojo University , Nishi-ku, Kumamoto , Japan
| |
Collapse
|
|
37
|
Near-Infrared Fluorescence Lymph Node Navigation Using Indocyanine Green for Gastric Cancer Surgery. ACTA ACUST UNITED AC 2018. [DOI: 10.7602/jmis.2018.21.3.95] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
|
|
38
|
Joshi BP, Wang TD. Targeted Optical Imaging Agents in Cancer: Focus on Clinical Applications. CONTRAST MEDIA & MOLECULAR IMAGING 2018; 2018:2015237. [PMID: 30224903 PMCID: PMC6129851 DOI: 10.1155/2018/2015237] [Citation(s) in RCA: 59] [Impact Index Per Article: 8.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/26/2018] [Revised: 05/27/2018] [Accepted: 07/04/2018] [Indexed: 12/13/2022]
Abstract
Molecular imaging is an emerging strategy for in vivo visualization of cancer over time based on biological mechanisms of disease activity. Optical imaging methods offer a number of advantages for real-time cancer detection, particularly in the epithelium of hollow organs and ducts, by using a broad spectral range of light that spans from visible to near-infrared. Targeted ligands are being developed for improved molecular specificity. These platforms include small molecule, peptide, affibody, activatable probes, lectin, and antibody. Fluorescence labeling is used to provide high image contrast. This emerging methodology is clinically useful for early cancer detection by identifying and localizing suspicious lesions that may not otherwise be seen and serves as a guide for tissue biopsy and surgical resection. Visualizing molecular expression patterns may also be useful to determine the best choice of therapy and to monitor efficacy. A number of these imaging agents are overcoming key challenges for clinical translation and are being validated in vivo for a wide range of human cancers.
Collapse
Affiliation(s)
- Bishnu P. Joshi
- Division of Gastroenterology, Department of Internal Medicine, School of Medicine, University of Michigan, 109 Zina Pitcher Place, BSRB 1722, Ann Arbor, MI 48109, USA
| | - Thomas D. Wang
- Division of Gastroenterology, Department of Internal Medicine, School of Medicine, University of Michigan, 109 Zina Pitcher Place, BSRB 1722, Ann Arbor, MI 48109, USA
- Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI 48109, USA
- Department of Mechanical Engineering, University of Michigan, Ann Arbor, MI 48109, USA
| |
Collapse
|
|
39
|
Jeong SH, Jang JH, Cho HY, Lee YB. Soft- and hard-lipid nanoparticles: a novel approach to lymphatic drug delivery. Arch Pharm Res 2018; 41:797-814. [PMID: 30074202 DOI: 10.1007/s12272-018-1060-0] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/09/2018] [Accepted: 07/25/2018] [Indexed: 12/31/2022]
Abstract
With the current advance in nanotechnology, the development has accelerated of a number of nanoparticle-type drugs such as nano-emulsions, lipid emulsions, liposomes, and cell therapeutics. With these developments, attempts are being made to apply these new drugs to healing many intractable diseases related to antibody production, autoimmune disorders, cancer, and organ transplantation in both clinical and nonclinical trials. Drug delivery to the lymphatic system is indispensable for treating these diseases, but the core technologies related to the in vivo distribution characteristics and lymphatic delivery evaluation of these particle-type drugs have not yet been established. Additionally, the core technologies for setting up the pharmacotherapeutic aspects such as their usage and dosages in the development of new drugs do not meet the needs of the market. Therefore, it is necessary to consider dividing these particle-type drugs into soft-lipid nanoparticles that can change size in the process of body distribution and hard-lipid nanoparticles whose surfaces are hardened and whose sizes do not easily change in vivo; these soft- and hard-lipid nanoparticles likely possess different biodistribution characteristics including delivery to the lymphatic system. In this review, we summarize the different types, advantages, limitations, possible remedies, and body distribution characteristics of soft- and hard-lipid nanoparticles based on their administration routes. We also emphasize that it will be necessary to fully understand the differences in distribution between these soft- and hard-lipid nanoparticle-type drugs and to establish pharmacokinetic models for their more ideal lymphatic delivery.
Collapse
Affiliation(s)
- Seung-Hyun Jeong
- College of Pharmacy, Chonnam National University, 77 Yongbong-ro, Buk-gu, Gwangju, 61186, Republic of Korea
| | - Ji-Hun Jang
- College of Pharmacy, Chonnam National University, 77 Yongbong-ro, Buk-gu, Gwangju, 61186, Republic of Korea
| | - Hea-Young Cho
- College of Pharmacy, CHA University, 335 Pangyo-ro, Bundang-gu, Seongnam-si, Gyeonggi-Do, 13488, Republic of Korea
| | - Yong-Bok Lee
- College of Pharmacy, Chonnam National University, 77 Yongbong-ro, Buk-gu, Gwangju, 61186, Republic of Korea.
| |
Collapse
|
|
40
|
Lapierre-Landry M, Connor TB, Carroll J, Tao YK, Skala MC. Photothermal optical coherence tomography of indocyanine green in ex vivo eyes. OPTICS LETTERS 2018; 43:2470-2473. [PMID: 29856406 PMCID: PMC8148624 DOI: 10.1364/ol.43.002470] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/09/2018] [Accepted: 04/25/2018] [Indexed: 05/03/2023]
Abstract
Indocyanine green (ICG) is routinely used during surgery to stain the inner limiting membrane (ILM) and provide contrast on white light surgical microscopy. While translation of optical coherence tomography (OCT) for intraoperative imaging during ophthalmic surgery has enhanced visualization, the ILM remains difficult to distinguish from underlying retinal structures and ICG does not provide additional OCT contrast. We present photothermal OCT (PT-OCT) for high-specificity detection of ICG on retinal OCT images. We demonstrate our technique by performing an ILM peel in ex vivo eyes using low ICG concentrations and laser powers. These results establish the feasibility of PT-OCT for intraoperative guidance during retinal surgery.
Collapse
Affiliation(s)
- Maryse Lapierre-Landry
- Department of Biomedical Engineering, Vanderbilt University, 2201 West End Ave., Nashville, Tennessee 37235, USA
- Morgridge Institute for Research, 330 N Orchard St., Madison, Wisconsin 53715, USA
| | - Thomas B. Connor
- Department of Ophthalmology & Visual Sciences, The Medical College of Wisconsin, 8701 W Watertown Plank Rd., Milwaukee, Wisconsin 53226, USA
| | - Joseph Carroll
- Department of Ophthalmology & Visual Sciences, The Medical College of Wisconsin, 8701 W Watertown Plank Rd., Milwaukee, Wisconsin 53226, USA
| | - Yuankai K. Tao
- Department of Biomedical Engineering, Vanderbilt University, 2201 West End Ave., Nashville, Tennessee 37235, USA
| | - Melissa C. Skala
- Morgridge Institute for Research, 330 N Orchard St., Madison, Wisconsin 53715, USA
- Department of Biomedical Engineering, University of Wisconsin, 1550 Engineering Drive, Madison, Wisconsin 53706, USA
| |
Collapse
|
|
41
|
Swider E, Daoudi K, Staal AHJ, Koshkina O, van Riessen NK, van Dinther E, de Vries IJM, de Korte CL, Srinivas M. Clinically-Applicable Perfluorocarbon-Loaded Nanoparticles For In vivo Photoacoustic, 19F Magnetic Resonance And Fluorescent Imaging. Nanotheranostics 2018; 2:258-268. [PMID: 29868350 PMCID: PMC5984288 DOI: 10.7150/ntno.26208] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/26/2018] [Accepted: 05/14/2018] [Indexed: 12/14/2022] Open
Abstract
Photoacoustic imaging (PAI) is an emerging biomedical imaging technique that is now coming to the clinic. It has a penetration depth of a few centimeters and generates useful endogenous contrast, particularly from melanin and oxy-/deoxyhemoglobin. Indocyanine green (ICG) is a Food and Drug Administration-approved contrast agents for human applications, which can be also used in PAI. It is a small molecule dye with limited applications due to its fast clearance, rapid protein binding, and bleaching effect. Methods: Here, we entrap ICG in a poly(lactic-co-glycolic acid) nanoparticles together with a perfluorocarbon (PFC) using single emulsion method. These nanoparticles and nanoparticle-loaded dendritic cells were imaged with PA, 19F MR, and fluorescence imaging in vitro and in vivo. Results: We formulated particles with an average diameter of 200 nm. The encapsulation of ICG within nanoparticles decreased its photobleaching and increased the retention of the signal within cells, making it available for applications such as cell imaging. As little as 0.1x106 cells could be detected in vivo with PAI using automated spectral unmixing. Furthermore, we observed the accumulation of ICG signal in the lymph node after subcutaneous injection of nanoparticles. Conclusion: We show that we can label primary human dendritic cells with the nanoparticles and image them in vitro and in vivo, in a multimodal manner. This work demonstrates the potential of combining PAI and 19F MRI for cell imaging and lymph node detection using nanoparticles that are currently produced at GMP-grade for clinical use.
Collapse
Affiliation(s)
- Edyta Swider
- Department of Tumor Immunology, Radboud University Medical Center, Nijmegen, The Netherlands
| | - Khalid Daoudi
- Medical UltraSound Imaging Center (MUSIC), Department of Radiology and Nuclear Medicine, Radboud University Medical Center, Nijmegen, The Netherlands
| | - Alexander H. J. Staal
- Department of Tumor Immunology, Radboud University Medical Center, Nijmegen, The Netherlands
| | - Olga Koshkina
- Department of Tumor Immunology, Radboud University Medical Center, Nijmegen, The Netherlands
| | - N. Koen van Riessen
- Department of Tumor Immunology, Radboud University Medical Center, Nijmegen, The Netherlands
| | - Eric van Dinther
- Department of Tumor Immunology, Radboud University Medical Center, Nijmegen, The Netherlands
| | - I. Jolanda M. de Vries
- Department of Tumor Immunology, Radboud University Medical Center, Nijmegen, The Netherlands
- Department of Medical Oncology, Radboud University Medical Center, Nijmegen, The Netherlands
| | - Chris L. de Korte
- Medical UltraSound Imaging Center (MUSIC), Department of Radiology and Nuclear Medicine, Radboud University Medical Center, Nijmegen, The Netherlands
| | - Mangala Srinivas
- Department of Tumor Immunology, Radboud University Medical Center, Nijmegen, The Netherlands
| |
Collapse
|
|
42
|
Chen Z, Deán-Ben XL, Gottschalk S, Razansky D. Performance of optoacoustic and fluorescence imaging in detecting deep-seated fluorescent agents. BIOMEDICAL OPTICS EXPRESS 2018; 9:2229-2239. [PMID: 29760983 PMCID: PMC5946784 DOI: 10.1364/boe.9.002229] [Citation(s) in RCA: 32] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/19/2017] [Revised: 03/08/2018] [Accepted: 03/09/2018] [Indexed: 05/03/2023]
Abstract
Fluorescent contrast agents are widely employed in biomedical research. While many studies have reported deep tissue imaging of fluorescent moieties using either fluorescence-based or absorption-based (optoacoustic) imaging systems, no systematic comparison has been performed regarding the actual performance of these imaging modalities in detecting deep-seated fluorescent agents. Herein, an integrated imager combining epi-fluorescence and volumetric optoacoustic imaging capabilities has been employed in order to evaluate image degradation with depth for several commonly-used near-infrared dyes in both modes. We performed controlled experiments in tissue-mimicking phantoms containing deeply embedded targets filled with different concentrations of Alexa Fluor 700, Alexa Fluor 750, indocyanine green (ICG) and IRDye 800CW. The results are further corroborated by multi-modal imaging of ICG through mouse tissues in vivo. It is shown that optoacoustics consistently provides better sensitivity in differentiating fluorescent targets located at depths beyond 2 mm in turbid tissues, as quantified by evaluating image contrast, signal to noise ratio and spatial resolution performance.
Collapse
Affiliation(s)
- Zhenyue Chen
- Institute for Biological and Medical Imaging (IBMI), Helmholtz Center Munich, Ingolstädter Landstr. 1, 85764 Neuherberg, Germany
| | - Xosé Luís Deán-Ben
- Institute for Biological and Medical Imaging (IBMI), Helmholtz Center Munich, Ingolstädter Landstr. 1, 85764 Neuherberg, Germany
| | - Sven Gottschalk
- Institute for Biological and Medical Imaging (IBMI), Helmholtz Center Munich, Ingolstädter Landstr. 1, 85764 Neuherberg, Germany
| | - Daniel Razansky
- Institute for Biological and Medical Imaging (IBMI), Helmholtz Center Munich, Ingolstädter Landstr. 1, 85764 Neuherberg, Germany
- Faculty of Medicine, Technical University of Munich, Ismaninger Str. 22, 81675 Munich, Germany
| |
Collapse
|
|
43
|
Lin JS, Wang CJ, Li WT. Photodynamic therapy of balloon-injured rat carotid arteries using indocyanine green. Lasers Med Sci 2018; 33:1123-1130. [PMID: 29594740 DOI: 10.1007/s10103-018-2488-7] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/24/2017] [Accepted: 03/19/2018] [Indexed: 12/11/2022]
Abstract
Photodynamic therapy (PDT) has been used to inhibit intimal hyperplasia in injured arteries. Because of the limited tissue penetration of visible light, an endovascular light source with a guided wire is often required for effective treatment. Indocyanine green (ICG), a near-infrared (NIR) photosensitizer, has been used in PDT for cancers. An extracorporeal light source may be used for shallow tissue because of the better tissue penetration of NIR light. The aim of this study was to evaluate the effect of ICG-PDT using extracorporeal NIR light on the inhibition of intimal hyperplasia in balloon-injured carotid arteries. A balloon injury (BI) model was used to induce intimal hyperplasia of carotid artery. Sprague-Dawley rats were divided into control, BI, BI + 1 × PDT, and BI + 2 × PDT groups. The control group underwent a sham procedure. PDT was performed 7 days after BI. In the BI + 1 × PDT group, ICG was administered 1 h before light irradiation. External illumination with 780-nm light-emitting diode light at a fluence of 4 J/cm2 was applied. For the BI + 2 × PDT group, PDT was performed again at day 7, following the first PDT. Hematoxylin and eosin (H & E) staining was performed to assess vessel morphology. Arterial wall thickness was significantly larger in the BI group compared with the control group. ICG-PDT significantly reduced arterial wall thickness compared with the BI group. Repeated PDT further decreased arterial wall thickness to the level of the control group. These findings indicate a promising approach for the treatment of restenosis of carotid arteries.
Collapse
Affiliation(s)
- Jih-Shyong Lin
- Division of Cardiology, Department of Internal Medicine, Taoyuan General Hospital, Ministry of Health and Welfare, Taoyuan, 330, Taiwan, Republic of China
- Department of Biomedical Engineering, Chung Yuan Christian University, 200 Chung Pei Road, Taoyuan, 320, Taiwan, Republic of China
| | - Chia-Jung Wang
- Department of Biomedical Engineering, Chung Yuan Christian University, 200 Chung Pei Road, Taoyuan, 320, Taiwan, Republic of China
| | - Wen-Tyng Li
- Department of Biomedical Engineering, Chung Yuan Christian University, 200 Chung Pei Road, Taoyuan, 320, Taiwan, Republic of China.
- Center for Biomedical Technology and Center for Nanotechnology, Chung Yuan Christian University, Taoyuan, 320, Taiwan, Republic of China.
| |
Collapse
|
|
44
|
Nguyen JQM, McWade M, Thomas G, Beddard BT, Herington JL, Paria BC, Schwartz HS, Halpern JL, Holt GE, Mahadevan-Jansen A. Development of a modular fluorescence overlay tissue imaging system for wide-field intraoperative surgical guidance. J Med Imaging (Bellingham) 2018. [PMID: 29531968 DOI: 10.1117/1.jmi.5.2.021220] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/09/2023] Open
Abstract
Fluorescence imaging is a well-established optical modality that has been used to localize and track fluorophores in vivo and has demonstrated great potential for surgical guidance. Despite the variety of fluorophores currently being researched, many existing intraoperative fluorescence imaging systems are specifically designed for a limited number of applications. We present a modular wide-field fluorescence overlay tissue imaging system for intraoperative surgical guidance that is comprised of commercially available standardized components. Its modular layout allows for the accommodation of a broad range of fluorophores, fields of view (FOV), and spatial resolutions while maintaining an integrated portable design for intraoperative use. Measurements are automatic and feature a real-time projection overlay technique that intuitively displays fluorescence maps directly onto a [Formula: see text] FOV from a working distance of 35 cm. At a 20-ms exposure time, [Formula: see text] samples of indocyanine green could be measured with high signal-to-noise ratio and was later tested in an in vivo mouse model before finally being demonstrated for intraoperative autofluorescence imaging of human soft tissue sarcoma margins. The system's modular design and ability to enable naked-eye visualization of wide-field fluorescence allow for the flexibility to adapt to numerous clinical applications and can potentially extend the adoption of fluorescence imaging for intraoperative use.
Collapse
Affiliation(s)
| | - Melanie McWade
- Vanderbilt University, Biophotonics Center, Nashville, Tennessee, United States
| | - Giju Thomas
- Vanderbilt University, Biophotonics Center, Nashville, Tennessee, United States
| | - Bryce T Beddard
- Vanderbilt University, Biophotonics Center, Nashville, Tennessee, United States
| | - Jennifer L Herington
- Vanderbilt University, Department of Pediatrics, Nashville, Tennessee, United States
| | - Bibhash C Paria
- Vanderbilt University, Department of Pediatrics, Nashville, Tennessee, United States
| | - Herbert S Schwartz
- Vanderbilt University Medical Center, Department of Orthopaedic Surgery and Rehabilitation, Nashville, Tennessee, United States
| | - Jennifer L Halpern
- Vanderbilt University Medical Center, Department of Orthopaedic Surgery and Rehabilitation, Nashville, Tennessee, United States
| | - Ginger E Holt
- Vanderbilt University Medical Center, Department of Orthopaedic Surgery and Rehabilitation, Nashville, Tennessee, United States
| | | |
Collapse
|
|
45
|
Ye J, Liu G, Liu P, Zhang S, Shao P, Smith ZJ, Liu C, Xu RX. Benchtop and animal validation of a portable fluorescence microscopic imaging system for potential use in cholecystectomy. JOURNAL OF BIOMEDICAL OPTICS 2018; 23:1-4. [PMID: 29473349 DOI: 10.1117/1.jbo.23.2.020504] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/10/2017] [Accepted: 01/19/2018] [Indexed: 06/08/2023]
Abstract
We propose a portable fluorescence microscopic imaging system (PFMS) for intraoperative display of biliary structure and prevention of iatrogenic injuries during cholecystectomy. The system consists of a light source module, a camera module, and a Raspberry Pi computer with an LCD. Indocyanine green (ICG) is used as a fluorescent contrast agent for experimental validation of the system. Fluorescence intensities of the ICG aqueous solution at different concentration levels are acquired by our PFMS and compared with those of a commercial Xenogen IVIS system. We study the fluorescence detection depth by superposing different thicknesses of chicken breast on an ICG-loaded agar phantom. We verify the technical feasibility for identifying potential iatrogenic injury in cholecystectomy using a rat model in vivo. The proposed PFMS system is portable, inexpensive, and suitable for deployment in resource-limited settings.
Collapse
Affiliation(s)
- Jian Ye
- University of Science and Technology of China, Department of Precision Machinery and Precision Instr, China
| | - Guanghui Liu
- University of Science and Technology of China, Department of Precision Machinery and Precision Instr, China
| | - Peng Liu
- University of Science and Technology of China, Department of Precision Machinery and Precision Instr, China
| | - Shiwu Zhang
- University of Science and Technology of China, Department of Precision Machinery and Precision Instr, China
| | - Pengfei Shao
- University of Science and Technology of China, Department of Precision Machinery and Precision Instr, China
| | - Zachary J Smith
- University of Science and Technology of China, Department of Precision Machinery and Precision Instr, China
| | - Chenhai Liu
- Anhui Provincial Hospital, Department of General Surgery, Hefei, Anhui, China
| | - Ronald X Xu
- University of Science and Technology of China, Department of Precision Machinery and Precision Instr, China
- Ohio State University, Department of Biomedical Engineering, Columbus, Ohio, United States
| |
Collapse
|
|
46
|
Karlsson JKG, Woodford OJ, Mustroph H, Harriman A. Cyanine dyes as ratiometric fluorescence standards for the far-red spectral region. Photochem Photobiol Sci 2018; 17:99-106. [DOI: 10.1039/c7pp00333a] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/30/2023]
Abstract
Absolute fluorescence quantum yields are reported for a group of commercially available dyes suitable for use as secondary standards across the far-red spectral window.
Collapse
Affiliation(s)
- Joshua K. G. Karlsson
- Molecular Photonics Laboratory
- School of Chemistry
- Bedson Building
- Newcastle University
- Newcastle upon Tyne
| | - Owen J. Woodford
- Molecular Photonics Laboratory
- School of Chemistry
- Bedson Building
- Newcastle University
- Newcastle upon Tyne
| | - Heinz Mustroph
- FEW Chemicals GmbH
- Ortsteil Wolfen
- 06766 Bitterfeld-Wolfen
- Germany
| | - Anthony Harriman
- Molecular Photonics Laboratory
- School of Chemistry
- Bedson Building
- Newcastle University
- Newcastle upon Tyne
| |
Collapse
|
|
47
|
Effect of photodynamic therapy based on indocyanine green on expression of apoptosis-related genes in human gingival fibroblast cells. Photodiagnosis Photodyn Ther 2017; 19:33-36. [DOI: 10.1016/j.pdpdt.2017.04.007] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2017] [Revised: 04/04/2017] [Accepted: 04/09/2017] [Indexed: 11/21/2022]
|
|
48
|
Mačianskienė R, Almanaitytė M, Treinys R, Navalinskas A, Benetis R, Jurevičius J. Spectral characteristics of voltage-sensitive indocyanine green fluorescence in the heart. Sci Rep 2017; 7:7983. [PMID: 28801595 PMCID: PMC5554165 DOI: 10.1038/s41598-017-08168-7] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/04/2017] [Accepted: 07/07/2017] [Indexed: 11/09/2022] Open
Abstract
Indocyanine green (ICG) fluorescent dye has been approved by the FDA for use in medical diagnostics. Recently, we demonstrated that ICG dye has voltage-sensitive properties with a dual-component (fast and slow) response in the Langendorff-perfused rabbit heart. Here, we extended our studies by showing the different spectral properties of both components for analysis of the fractional change in ICG fluorescence in response to voltage changes. We used light from four LEDs to obtain excitation; emission was measured using an EMCCD camera with band-pass filters and a spectrometer. We applied a graphical model with Gaussian functions to construct and evaluate the individual emission curves and calculated the voltage-sensitive portion of each component of the ICG fluorescence in the rabbit heart. The results revealed that each isolated component (fast and slow) emanates from a unique ICG pool in a different environment within the cell membrane and that each component is also composed of two constituents (ICG-monomeric and ICG-aggregated). We propose the existence of different voltage-sensitive mechanisms for the components: (I) electrochromism and field-induced reorientation for the fast component; and (II) field-induced dye squeezing that amplifies intermolecular interactions, resulting in self-quenching of the dye fluorescence, for the slow component.
Collapse
Affiliation(s)
- Regina Mačianskienė
- Institute of Cardiology, Lithuanian University of Health Sciences, Kaunas, Lithuania
| | - Mantė Almanaitytė
- Institute of Cardiology, Lithuanian University of Health Sciences, Kaunas, Lithuania
| | - Rimantas Treinys
- Institute of Cardiology, Lithuanian University of Health Sciences, Kaunas, Lithuania
| | - Antanas Navalinskas
- Institute of Cardiology, Lithuanian University of Health Sciences, Kaunas, Lithuania
| | - Rimantas Benetis
- Institute of Cardiology, Lithuanian University of Health Sciences, Kaunas, Lithuania
| | - Jonas Jurevičius
- Institute of Cardiology, Lithuanian University of Health Sciences, Kaunas, Lithuania.
| |
Collapse
|
|
49
|
Herynek V, Gálisová A, Srinivas M, van Dinther EAW, Kosinová L, Ruzicka J, Jirátová M, Kriz J, Jirák D. Pre-Microporation Improves Outcome of Pancreatic Islet Labelling for Optical and 19F MR Imaging. Biol Proced Online 2017; 19:6. [PMID: 28674481 PMCID: PMC5488379 DOI: 10.1186/s12575-017-0055-4] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2017] [Accepted: 06/01/2017] [Indexed: 01/02/2023] Open
Abstract
Background In vitro labelling of cells and small cell structures is a necessary step before in vivo monitoring of grafts. We modified and optimised a procedure for pancreatic islet labelling using bimodal positively charged poly(lactic-co-glycolic acid) nanoparticles with encapsulated perfluoro crown ethers and indocyanine green dye via microporation and compared the method with passive endocytosis. Results Pancreatic islets were microporated using two pulses at various voltages. We tested a standard procedure (poration in the presence of nanoparticles) and a modified protocol (pre-microporation in a buffer only, and subsequent islet incubation with nanoparticles on ice for 10 min). We compared islet labelling by microporation with labelling by endocytosis, i.e. pancreatic islets were incubated for 24 h in a medium with suspended nanoparticles. In order to verify the efficiency of the labelling procedures, we used 19F magnetic resonance imaging, optical fluorescence imaging and confocal microscopy. The experiment confirmed that microporation, albeit fast and effective, is invasive and may cause substantial harm to islets. To achieve sufficient poration and to minimise the reduction of viability, the electric field should be set at 20 kV/m (two pulses, 20 ms each). Poration in the presence of nanoparticles was found to be unsuitable for the nanoparticles used. The water suspension of nanoparticles (which served as a surfactant) was slightly foamy and microbubbles in the suspension were responsible for sparks causing the destruction of islets during poration. However, pre-microporation (poration of islets in a buffer only) followed by 10-min incubation with nanoparticles was safer. Conclusions For labelling of pancreatic islets using poly(lactic-co-glycolic acid) nanoparticles, the modified microporation procedure with low voltage was found to be safer than the standard microporation procedure. The modified procedure was fast, however, efficiency was lower compared to endocytosis.
Collapse
Affiliation(s)
- Vít Herynek
- MR Unit, Radiodiagnostic and Interventional Radiology Department, Institute for Clinical and Experimental Medicine, Vídeňská 1958/9, Prague, Czech Republic
| | - Andrea Gálisová
- MR Unit, Radiodiagnostic and Interventional Radiology Department, Institute for Clinical and Experimental Medicine, Vídeňská 1958/9, Prague, Czech Republic
| | - Mangala Srinivas
- Department of Tumor Immunology, Radboud University Medical Centre, Route 278, Geert Grooteplein 28, Nijmegen, Netherlands
| | - Eric A W van Dinther
- Department of Tumor Immunology, Radboud University Medical Centre, Route 278, Geert Grooteplein 28, Nijmegen, Netherlands
| | - Lucie Kosinová
- Centre of Experimental Medicine, Institute for Clinical and Experimental Medicine, Vídeňská 1958/9, Prague, Czech Republic
| | - Jiri Ruzicka
- MR Unit, Radiodiagnostic and Interventional Radiology Department, Institute for Clinical and Experimental Medicine, Vídeňská 1958/9, Prague, Czech Republic.,Department of Tissue Culture and Stem Cells, Institute of Experimental Medicine AS CR, Vídeňská 1083, 142 20, Prague, Czech Republic
| | - Markéta Jirátová
- MR Unit, Radiodiagnostic and Interventional Radiology Department, Institute for Clinical and Experimental Medicine, Vídeňská 1958/9, Prague, Czech Republic
| | - Jan Kriz
- Diabetes Centre, Institute for Clinical and Experimental Medicine, Vídeňská 1958/9, Prague, Czech Republic
| | - Daniel Jirák
- MR Unit, Radiodiagnostic and Interventional Radiology Department, Institute for Clinical and Experimental Medicine, Vídeňská 1958/9, Prague, Czech Republic
| |
Collapse
|
|
50
|
Surgery beyond the visible light spectrum: theoretical and applied methods for localization of the male urethra during transanal total mesorectal excision. Tech Coloproctol 2017; 21:413-424. [PMID: 28589242 DOI: 10.1007/s10151-017-1641-9] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/02/2017] [Accepted: 05/13/2017] [Indexed: 02/08/2023]
Abstract
The risk of urethral injury during transanal total mesorectal excision (taTME) is delineated, and potential risk factors for iatrogenic transection are reviewed. A variety of applied and theoretical techniques can be used by surgeons to diminish the risk of injury in males undergoing this operation. Many of the approaches utilize non-optic media and wavelengths beyond the visible light spectrum which can enhance the surgeon's frame of reference. The aim of the present study was to assess the techniques and theoretical approaches to urethral localization during taTME. Future directions in surgical imaging are also discussed, including the use of organic dyes, quantum dots, and carbon nanotubes; collectively, technology that could someday provide surgeons with an ability to identify anatomic structures prone to injury.
Collapse
|