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Title: Shortwave infrared fluorescence imaging with the clinically approved near-infrared dye indocyanine green

Abstract

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

Authors:
ORCiD logo; ; ORCiD logo; ; ; ; ; ; ; ;
Publication Date:
Research Org.:
Massachusetts Inst. of Technology (MIT), Cambridge, MA (United States)
Sponsoring Org.:
USDOE Office of Science (SC)
OSTI Identifier:
1432122
Alternate Identifier(s):
OSTI ID: 1540274
Grant/Contract Number:  
FG02-07ER46454
Resource Type:
Published Article
Journal Name:
Proceedings of the National Academy of Sciences of the United States of America
Additional Journal Information:
Journal Name: Proceedings of the National Academy of Sciences of the United States of America Journal Volume: 115 Journal Issue: 17; Journal ID: ISSN 0027-8424
Publisher:
Proceedings of the National Academy of Sciences
Country of Publication:
United States
Language:
English
Subject:
37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CHEMISTRY; Science & Technology; Other Topics; shortwave infrared; biomedical imaging; fluorescence imaging; near infrared; indocyanine green

Citation Formats

Carr, Jessica A., Franke, Daniel, Caram, Justin R., Perkinson, Collin F., Saif, Mari, Askoxylakis, Vasileios, Datta, Meenal, Fukumura, Dai, Jain, Rakesh K., Bawendi, Moungi G., and Bruns, Oliver T. Shortwave infrared fluorescence imaging with the clinically approved near-infrared dye indocyanine green. United States: N. p., 2018. Web. doi:10.1073/pnas.1718917115.
Carr, Jessica A., Franke, Daniel, Caram, Justin R., Perkinson, Collin F., Saif, Mari, Askoxylakis, Vasileios, Datta, Meenal, Fukumura, Dai, Jain, Rakesh K., Bawendi, Moungi G., & Bruns, Oliver T. Shortwave infrared fluorescence imaging with the clinically approved near-infrared dye indocyanine green. United States. doi:10.1073/pnas.1718917115.
Carr, Jessica A., Franke, Daniel, Caram, Justin R., Perkinson, Collin F., Saif, Mari, Askoxylakis, Vasileios, Datta, Meenal, Fukumura, Dai, Jain, Rakesh K., Bawendi, Moungi G., and Bruns, Oliver T. Fri . "Shortwave infrared fluorescence imaging with the clinically approved near-infrared dye indocyanine green". United States. doi:10.1073/pnas.1718917115.
@article{osti_1432122,
title = {Shortwave infrared fluorescence imaging with the clinically approved near-infrared dye indocyanine green},
author = {Carr, Jessica A. and Franke, Daniel and Caram, Justin R. and Perkinson, Collin F. and Saif, Mari and Askoxylakis, Vasileios and Datta, Meenal and Fukumura, Dai and Jain, Rakesh K. and Bawendi, Moungi G. and Bruns, Oliver T.},
abstractNote = {Fluorescence imaging is a method of real-time molecular tracking in vivo that has enabled many clinical technologies. Imaging in the shortwave IR (SWIR; 1,000–2,000 nm) promises higher contrast, sensitivity, and penetration depths compared with conventional visible and near-IR (NIR) fluorescence imaging. However, adoption of SWIR imaging in clinical settings has been limited, partially due to the absence of US Food and Drug Administration (FDA)-approved fluorophores with peak emission in the SWIR. Here, we show that commercially available NIR dyes, including the FDA-approved contrast agent indocyanine green (ICG), exhibit optical properties suitable for in vivo SWIR fluorescence imaging. Even though their emission spectra peak in the NIR, these dyes outperform commercial SWIR fluorophores and can be imaged in the SWIR, even beyond 1,500 nm. We show real-time fluorescence imaging using ICG at clinically relevant doses, including intravital microscopy, noninvasive imaging in blood and lymph vessels, and imaging of hepatobiliary clearance, and show increased contrast compared with NIR fluorescence imaging. Furthermore, we show tumor-targeted SWIR imaging with IRDye 800CW-labeled trastuzumab, an NIR dye being tested in multiple clinical trials. Our findings suggest that high-contrast SWIR fluorescence imaging can be implemented alongside existing imaging modalities by switching the detection of conventional NIR fluorescence systems from silicon-based NIR cameras to emerging indium gallium arsenide-based SWIR cameras. Using ICG in particular opens the possibility of translating SWIR fluorescence imaging to human clinical applications. Furthermore, our findings suggest that emerging SWIR-fluorescent in vivo contrast agents should be benchmarked against the SWIR emission of ICG in blood.},
doi = {10.1073/pnas.1718917115},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
number = 17,
volume = 115,
place = {United States},
year = {2018},
month = {4}
}

Journal Article:
Free Publicly Available Full Text
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DOI: 10.1073/pnas.1718917115

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Cited by: 29 works
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Works referenced in this record:

The use of fluorescent dyes and probes in surgical oncology
journal, January 2010

  • te Velde, E. A.; Veerman, Th.; Subramaniam, V.
  • European Journal of Surgical Oncology (EJSO), Vol. 36, Issue 1
  • DOI: 10.1016/j.ejso.2009.10.014

Fluorescence Imaging In Vivo at Wavelengths beyond 1500 nm
journal, October 2015

  • Diao, Shuo; Blackburn, Jeffrey L.; Hong, Guosong
  • Angewandte Chemie International Edition, Vol. 54, Issue 49
  • DOI: 10.1002/anie.201507473

Image-guided cancer surgery using near-infrared fluorescence
journal, July 2013

  • Vahrmeijer, Alexander L.; Hutteman, Merlijn; van der Vorst, Joost R.
  • Nature Reviews Clinical Oncology, Vol. 10, Issue 9
  • DOI: 10.1038/nrclinonc.2013.123

Rare-earth doped particles with tunable infrared emissions for biomedical imaging
journal, January 2013

  • van Saders, Bryan; Al-Baroudi, Lara; Tan, Mei Chee
  • Optical Materials Express, Vol. 3, Issue 5
  • DOI: 10.1364/OME.3.000566

Deep optical imaging of tissue using the second and third near-infrared spectral windows
journal, May 2014

  • Sordillo, Laura A.; Pu, Yang; Pratavieira, Sebastião
  • Journal of Biomedical Optics, Vol. 19, Issue 5
  • DOI: 10.1117/1.JBO.19.5.056004

Penetration depth of photons in biological tissues from hyperspectral imaging in shortwave infrared in transmission and reflection geometries
journal, December 2016


All-optical anatomical co-registration for molecular imaging of small animals using dynamic contrast
journal, August 2007


Preclinical Efficacy of Ado-trastuzumab Emtansine in the Brain Microenvironment
journal, November 2015

  • Askoxylakis, Vasileios; Ferraro, Gino B.; Kodack, David P.
  • JNCI: Journal of the National Cancer Institute, Vol. 108, Issue 2
  • DOI: 10.1093/jnci/djv313

Near-Infrared Fluorescence Imaging in Humans with Indocyanine Green: A Review and Update~!2009-12-07~!2009-12-23~!2010-05-26~!
journal, June 2010

  • Marshall, Milton V.; Rasmussen, John C.; Tan, I-Chih
  • The Open Surgical Oncology Journal, Vol. 2, Issue 2
  • DOI: 10.2174/1876504101002020012

Rare-earth-doped biological composites as in vivo shortwave infrared reporters
journal, July 2013

  • Naczynski, D. J.; Tan, M. C.; Zevon, M.
  • Nature Communications, Vol. 4, Issue 1
  • DOI: 10.1038/ncomms3199

Relative and absolute determination of fluorescence quantum yields of transparent samples
journal, July 2013

  • Würth, Christian; Grabolle, Markus; Pauli, Jutta
  • Nature Protocols, Vol. 8, Issue 8
  • DOI: 10.1038/nprot.2013.087

Through-skull fluorescence imaging of the brain in a new near-infrared window
journal, August 2014


In vivo near-infrared fluorescence imaging
journal, October 2003


Optical Properties of Skin, Subcutaneous, and Muscle Tissues: a Review
journal, January 2011

  • Bashkatov, Alexey N.; Genina, Elina A.; Tuchin, Valery V.
  • Journal of Innovative Optical Health Sciences, Vol. 04, Issue 01
  • DOI: 10.1142/S1793545811001319

Electrophile-Integrating Smiles Rearrangement Provides Previously Inaccessible C4′- O -Alkyl Heptamethine Cyanine Fluorophores
journal, December 2014

  • Nani, Roger R.; Shaum, James B.; Gorka, Alexander P.
  • Organic Letters, Vol. 17, Issue 2
  • DOI: 10.1021/ol503398f

Biological Imaging Using Nanoparticles of Small Organic Molecules with Fluorescence Emission at Wavelengths Longer than 1000 nm
journal, October 2013

  • Tao, Zhimin; Hong, Guosong; Shinji, Chihiro
  • Angewandte Chemie International Edition, Vol. 52, Issue 49
  • DOI: 10.1002/anie.201307346

Kinetics of Indocyanine Green Removal from the Blood
journal, July 1970


A review of performance of near-infrared fluorescence imaging devices used in clinical studies
journal, January 2015

  • Zhu, B.; Sevick-Muraca, E. M.
  • The British Journal of Radiology, Vol. 88, Issue 1045
  • DOI: 10.1259/bjr.20140547

Ultrafast fluorescence imaging in vivo with conjugated polymer fluorophores in the second near-infrared window
journal, June 2014

  • Hong, Guosong; Zou, Yingping; Antaris, Alexander L.
  • Nature Communications, Vol. 5, Issue 1
  • DOI: 10.1038/ncomms5206

Translation of Near-Infrared Fluorescence Imaging Technologies: Emerging Clinical Applications
journal, February 2012


Multifunctional in vivo vascular imaging using near-infrared II fluorescence
journal, November 2012

  • Hong, Guosong; Lee, Jerry C.; Robinson, Joshua T.
  • Nature Medicine, Vol. 18, Issue 12
  • DOI: 10.1038/nm.2995

Use of Indocyanine Green During Robot-assisted Ureteral Reconstructions
journal, February 2015


1.3 μm emitting SrF2:Nd3+ nanoparticles for high contrast in vivo imaging in the second biological window
journal, October 2014


Continuous injection synthesis of indium arsenide quantum dots emissive in the short-wavelength infrared
journal, November 2016

  • Franke, Daniel; Harris, Daniel K.; Chen, Ou
  • Nature Communications, Vol. 7, Issue 1
  • DOI: 10.1038/ncomms12749

Lymphatic imaging in humans with near-infrared fluorescence
journal, February 2009


Optical properties of human skin, subcutaneous and mucous tissues in the wavelength range from 400 to 2000 nm
journal, July 2005

  • Bashkatov, A. N.; Genina, E. A.; Kochubey, V. I.
  • Journal of Physics D: Applied Physics, Vol. 38, Issue 15
  • DOI: 10.1088/0022-3727/38/15/004

Pharmacokinetics of biliary excretion in man. VI. Indocyanine green
journal, January 1988

  • Meijer, D. K. F.; Weert, B.; Vermeer, G. A.
  • European Journal of Clinical Pharmacology, Vol. 35, Issue 3
  • DOI: 10.1007/BF00558268

Indocyanine green fluorescence in second near-infrared (NIR-II) window
journal, November 2017


Selection of Quantum Dot Wavelengths for Biomedical Assays and Imaging
journal, January 2003


Cyanine polyene reactivity: scope and biomedical applications
journal, January 2015

  • Gorka, Alexander P.; Nani, Roger R.; Schnermann, Martin J.
  • Organic & Biomolecular Chemistry, Vol. 13, Issue 28
  • DOI: 10.1039/C5OB00788G

Absorption and fluorescence spectroscopic investigation of indocyanine green
journal, May 1996

  • Philip, R.; Penzkofer, A.; Bäumler, W.
  • Journal of Photochemistry and Photobiology A: Chemistry, Vol. 96, Issue 1-3
  • DOI: 10.1016/1010-6030(95)04292-X

Flavylium Polymethine Fluorophores for Near- and Shortwave Infrared Imaging
journal, September 2017

  • Cosco, Emily D.; Caram, Justin R.; Bruns, Oliver T.
  • Angewandte Chemie International Edition, Vol. 56, Issue 42
  • DOI: 10.1002/anie.201706974

Quantum dots versus organic dyes as fluorescent labels
journal, August 2008

  • Resch-Genger, Ute; Grabolle, Markus; Cavaliere-Jaricot, Sara
  • Nature Methods, Vol. 5, Issue 9
  • DOI: 10.1038/nmeth.1248

Prospective Comparison of Intraoperative Vascular Monitoring Technologies During Cerebral Aneurysm Surgery
journal, March 2011


Shortwave Infrared in Vivo Imaging with Gold Nanoclusters
journal, September 2017


Indocyanine Green (ICG) Fluorescent Cholangiography During Robotic Cholecystectomy: Results of 184 Consecutive Cases in a Single Institution
journal, March 2014

  • Daskalaki, Despoina; Fernandes, Eduardo; Wang, Xiaoying
  • Surgical Innovation, Vol. 21, Issue 6
  • DOI: 10.1177/1553350614524839

Brightness-equalized quantum dots
journal, October 2015

  • Lim, Sung Jun; Zahid, Mohammad U.; Le, Phuong
  • Nature Communications, Vol. 6, Issue 1
  • DOI: 10.1038/ncomms9210

A small-molecule dye for NIR-II imaging
journal, November 2015

  • Antaris, Alexander L.; Chen, Hao; Cheng, Kai
  • Nature Materials, Vol. 15, Issue 2
  • DOI: 10.1038/nmat4476

Successful Translation of Fluorescence Navigation During Oncologic Surgery: A Consensus Report
journal, October 2015


Advancing Surgical Vision with Fluorescence Imaging
journal, January 2016


Comparing indocyanine green videoangiography to the gold standard of intraoperative digital subtraction angiography used in aneurysm surgery
journal, February 2013

  • Washington, Chad W.; Zipfel, Gregory J.; Chicoine, Michael R.
  • Journal of Neurosurgery, Vol. 118, Issue 2
  • DOI: 10.3171/2012.10.JNS11818

Near-infrared fluorescent probes in cancer imaging and therapy: an emerging field
journal, March 2014

  • Yi, Xiaomin; Wang, Fuli; Qin, Weijun
  • International Journal of Nanomedicine
  • DOI: 10.2147/IJN.S60206

Light-absorbing properties, stability, and spectral stabilization of indocyanine green
journal, April 1976


A Review of Indocyanine Green Fluorescent Imaging in Surgery
journal, January 2012

  • Alander, Jarmo T.; Kaartinen, Ilkka; Laakso, Aki
  • International Journal of Biomedical Imaging, Vol. 2012
  • DOI: 10.1155/2012/940585

Next-generation in vivo optical imaging with short-wave infrared quantum dots
journal, April 2017

  • Bruns, Oliver T.; Bischof, Thomas S.; Harris, Daniel K.
  • Nature Biomedical Engineering, Vol. 1, Issue 4
  • DOI: 10.1038/s41551-017-0056

Infrared-Emitting Colloidal Nanocrystals: Synthesis, Assembly, Spectroscopy, and Applications
journal, April 2007

  • Rogach, Andrey L.; Eychmüller, Alexander; Hickey, Stephen G.
  • Small, Vol. 3, Issue 4
  • DOI: 10.1002/smll.200600625

Near-Infrared Emitting PbS Quantum Dots for in Vivo Fluorescence Imaging of the Thrombotic State in Septic Mouse Brain
journal, August 2016


Biological imaging without autofluorescence in the second near-infrared region
journal, August 2015


Using the shortwave infrared to image middle ear pathologies
journal, August 2016

  • Carr, Jessica A.; Valdez, Tulio A.; Bruns, Oliver T.
  • Proceedings of the National Academy of Sciences, Vol. 113, Issue 36
  • DOI: 10.1073/pnas.1610529113

Sentinel lymph node biopsy using indocyanine green fluorescence in early-stage breast cancer: a meta-analysis
journal, November 2016

  • Sugie, Tomoharu; Ikeda, Takafumi; Kawaguchi, Atsushi
  • International Journal of Clinical Oncology, Vol. 22, Issue 1
  • DOI: 10.1007/s10147-016-1064-z

Current trends and emerging future of indocyanine green usage in surgery and oncology: A literature review
journal, April 2011

  • Polom, Karol; Murawa, Dawid; Rho, Young-soo
  • Cancer, Vol. 117, Issue 21
  • DOI: 10.1002/cncr.26087

In Vivo Fluorescence Imaging with Ag 2 S Quantum Dots in the Second Near-Infrared Region
journal, September 2012

  • Hong, Guosong; Robinson, Joshua T.; Zhang, Yejun
  • Angewandte Chemie International Edition, Vol. 51, Issue 39
  • DOI: 10.1002/anie.201206059

Review of short-wave infrared spectroscopy and imaging methods for biological tissue characterization
journal, March 2015

  • Wilson, Robert H.; Nadeau, Kyle P.; Jaworski, Frank B.
  • Journal of Biomedical Optics, Vol. 20, Issue 3
  • DOI: 10.1117/1.JBO.20.3.030901

A Theory of Intensity Distribution in Band Systems
journal, December 1926