Targeted Near-Infrared Fluorescence Imaging of Atherosclerosis: Clinical and Intracoronary Evaluation of Indocyanine Green

Johan Verjans, Eric A. Osborn, Giovanni J. Ughi, Marcella A. Calfon Press, Ehsan Hamidi, Antonios P. Antoniadis, Michail I. Papafaklis, Mark F. Conrad, Peter Libby, Peter H. Stone, Richard P. Cambria, Guillermo J. Tearney, Farouc A. Jaffer

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

Objectives This study sought to determine whether indocyanine green (ICG)–enhanced near-infrared fluorescence (NIRF) imaging can illuminate high-risk histologic plaque features of human carotid atherosclerosis, and in coronary atheroma of living swine, using intravascular NIRF-optical coherence tomography (OCT) imaging. Background New translatable imaging approaches are needed to identify high-risk biological signatures of atheroma. ICG is a U.S. Food and Drug Administration–approved NIRF imaging agent that experimentally targets plaque macrophages and lipid in areas of enhanced endothelial permeability. However, it is unknown whether ICG can target atheroma in patients. Methods Eight patients were enrolled in the BRIGHT-CEA (Indocyanine Green Fluorescence Uptake in Human Carotid Artery Plaque) trial. Five patients were injected intravenously with ICG 99 ± 25 min before clinically indicated carotid endarterectomy. Three saline-injected endarterectomy patients served as control subjects. Excised plaques underwent analysis by intravascular NIRF-OCT, reflectance imaging, microscopy, and histopathology. Next, following ICG intravenous injection, in vivo intracoronary NIRF-OCT and intravascular ultrasound imaged 3 atheroma-bearing coronary arteries of a diabetic, cholesterol-fed swine. Results ICG was well tolerated; no adverse clinical events occurred up to 30 days post-injection. Multimodal NIRF imaging including intravascular NIRF-OCT revealed that ICG accumulated in all endarterectomy specimens. Plaques from saline-injected control patients exhibited minimal NIRF signal. In the swine experiment, intracoronary NIRF-OCT identified ICG uptake in all intravascular ultrasound–identified plaques in vivo. On detailed microscopic evaluation, ICG localized to plaque areas exhibiting impaired endothelial integrity, including disrupted fibrous caps, and within areas of neovascularization. Within human plaque areas of endothelial abnormality, ICG was spatially related to localized zones of plaque macrophages and lipid, and, notably, intraplaque hemorrhage. Conclusions This study demonstrates that ICG targets human plaques exhibiting endothelial abnormalities and provides new insights into its targeting mechanisms in clinical and experimental atheroma. Intracoronary NIRF-OCT of ICG may offer a novel, clinically translatable approach to image pathobiological aspects of coronary atherosclerosis. (Indocyanine Green Fluorescence Uptake in Human Carotid Artery Plaque [BRIGHT-CEA]; NCT01873716)

LanguageEnglish
Pages1087-1095
Number of pages9
JournalJACC: Cardiovascular Imaging
Volume9
Issue number9
DOIs
Publication statusPublished - 1 Sep 2016
Externally publishedYes

Keywords

  • atherosclerosis
  • endothelium
  • indocyanine green
  • inflammation
  • intraplaque hemorrhage
  • intravascular imaging
  • lipid
  • molecular imaging
  • near-infrared fluorescence

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging
  • Cardiology and Cardiovascular Medicine

Cite this

Verjans, Johan ; Osborn, Eric A. ; Ughi, Giovanni J. ; Calfon Press, Marcella A. ; Hamidi, Ehsan ; Antoniadis, Antonios P. ; Papafaklis, Michail I. ; Conrad, Mark F. ; Libby, Peter ; Stone, Peter H. ; Cambria, Richard P. ; Tearney, Guillermo J. ; Jaffer, Farouc A. / Targeted Near-Infrared Fluorescence Imaging of Atherosclerosis : Clinical and Intracoronary Evaluation of Indocyanine Green. In: JACC: Cardiovascular Imaging. 2016 ; Vol. 9, No. 9. pp. 1087-1095.
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abstract = "Objectives This study sought to determine whether indocyanine green (ICG)–enhanced near-infrared fluorescence (NIRF) imaging can illuminate high-risk histologic plaque features of human carotid atherosclerosis, and in coronary atheroma of living swine, using intravascular NIRF-optical coherence tomography (OCT) imaging. Background New translatable imaging approaches are needed to identify high-risk biological signatures of atheroma. ICG is a U.S. Food and Drug Administration–approved NIRF imaging agent that experimentally targets plaque macrophages and lipid in areas of enhanced endothelial permeability. However, it is unknown whether ICG can target atheroma in patients. Methods Eight patients were enrolled in the BRIGHT-CEA (Indocyanine Green Fluorescence Uptake in Human Carotid Artery Plaque) trial. Five patients were injected intravenously with ICG 99 ± 25 min before clinically indicated carotid endarterectomy. Three saline-injected endarterectomy patients served as control subjects. Excised plaques underwent analysis by intravascular NIRF-OCT, reflectance imaging, microscopy, and histopathology. Next, following ICG intravenous injection, in vivo intracoronary NIRF-OCT and intravascular ultrasound imaged 3 atheroma-bearing coronary arteries of a diabetic, cholesterol-fed swine. Results ICG was well tolerated; no adverse clinical events occurred up to 30 days post-injection. Multimodal NIRF imaging including intravascular NIRF-OCT revealed that ICG accumulated in all endarterectomy specimens. Plaques from saline-injected control patients exhibited minimal NIRF signal. In the swine experiment, intracoronary NIRF-OCT identified ICG uptake in all intravascular ultrasound–identified plaques in vivo. On detailed microscopic evaluation, ICG localized to plaque areas exhibiting impaired endothelial integrity, including disrupted fibrous caps, and within areas of neovascularization. Within human plaque areas of endothelial abnormality, ICG was spatially related to localized zones of plaque macrophages and lipid, and, notably, intraplaque hemorrhage. Conclusions This study demonstrates that ICG targets human plaques exhibiting endothelial abnormalities and provides new insights into its targeting mechanisms in clinical and experimental atheroma. Intracoronary NIRF-OCT of ICG may offer a novel, clinically translatable approach to image pathobiological aspects of coronary atherosclerosis. (Indocyanine Green Fluorescence Uptake in Human Carotid Artery Plaque [BRIGHT-CEA]; NCT01873716)",
keywords = "atherosclerosis, endothelium, indocyanine green, inflammation, intraplaque hemorrhage, intravascular imaging, lipid, molecular imaging, near-infrared fluorescence",
author = "Johan Verjans and Osborn, {Eric A.} and Ughi, {Giovanni J.} and {Calfon Press}, {Marcella A.} and Ehsan Hamidi and Antoniadis, {Antonios P.} and Papafaklis, {Michail I.} and Conrad, {Mark F.} and Peter Libby and Stone, {Peter H.} and Cambria, {Richard P.} and Tearney, {Guillermo J.} and Jaffer, {Farouc A.}",
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Verjans, J, Osborn, EA, Ughi, GJ, Calfon Press, MA, Hamidi, E, Antoniadis, AP, Papafaklis, MI, Conrad, MF, Libby, P, Stone, PH, Cambria, RP, Tearney, GJ & Jaffer, FA 2016, 'Targeted Near-Infrared Fluorescence Imaging of Atherosclerosis: Clinical and Intracoronary Evaluation of Indocyanine Green', JACC: Cardiovascular Imaging, vol. 9, no. 9, pp. 1087-1095. https://doi.org/10.1016/j.jcmg.2016.01.034

Targeted Near-Infrared Fluorescence Imaging of Atherosclerosis : Clinical and Intracoronary Evaluation of Indocyanine Green. / Verjans, Johan; Osborn, Eric A.; Ughi, Giovanni J.; Calfon Press, Marcella A.; Hamidi, Ehsan; Antoniadis, Antonios P.; Papafaklis, Michail I.; Conrad, Mark F.; Libby, Peter; Stone, Peter H.; Cambria, Richard P.; Tearney, Guillermo J.; Jaffer, Farouc A.

In: JACC: Cardiovascular Imaging, Vol. 9, No. 9, 01.09.2016, p. 1087-1095.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Targeted Near-Infrared Fluorescence Imaging of Atherosclerosis

T2 - JACC: Cardiovascular Imaging

AU - Verjans, Johan

AU - Osborn, Eric A.

AU - Ughi, Giovanni J.

AU - Calfon Press, Marcella A.

AU - Hamidi, Ehsan

AU - Antoniadis, Antonios P.

AU - Papafaklis, Michail I.

AU - Conrad, Mark F.

AU - Libby, Peter

AU - Stone, Peter H.

AU - Cambria, Richard P.

AU - Tearney, Guillermo J.

AU - Jaffer, Farouc A.

PY - 2016/9/1

Y1 - 2016/9/1

N2 - Objectives This study sought to determine whether indocyanine green (ICG)–enhanced near-infrared fluorescence (NIRF) imaging can illuminate high-risk histologic plaque features of human carotid atherosclerosis, and in coronary atheroma of living swine, using intravascular NIRF-optical coherence tomography (OCT) imaging. Background New translatable imaging approaches are needed to identify high-risk biological signatures of atheroma. ICG is a U.S. Food and Drug Administration–approved NIRF imaging agent that experimentally targets plaque macrophages and lipid in areas of enhanced endothelial permeability. However, it is unknown whether ICG can target atheroma in patients. Methods Eight patients were enrolled in the BRIGHT-CEA (Indocyanine Green Fluorescence Uptake in Human Carotid Artery Plaque) trial. Five patients were injected intravenously with ICG 99 ± 25 min before clinically indicated carotid endarterectomy. Three saline-injected endarterectomy patients served as control subjects. Excised plaques underwent analysis by intravascular NIRF-OCT, reflectance imaging, microscopy, and histopathology. Next, following ICG intravenous injection, in vivo intracoronary NIRF-OCT and intravascular ultrasound imaged 3 atheroma-bearing coronary arteries of a diabetic, cholesterol-fed swine. Results ICG was well tolerated; no adverse clinical events occurred up to 30 days post-injection. Multimodal NIRF imaging including intravascular NIRF-OCT revealed that ICG accumulated in all endarterectomy specimens. Plaques from saline-injected control patients exhibited minimal NIRF signal. In the swine experiment, intracoronary NIRF-OCT identified ICG uptake in all intravascular ultrasound–identified plaques in vivo. On detailed microscopic evaluation, ICG localized to plaque areas exhibiting impaired endothelial integrity, including disrupted fibrous caps, and within areas of neovascularization. Within human plaque areas of endothelial abnormality, ICG was spatially related to localized zones of plaque macrophages and lipid, and, notably, intraplaque hemorrhage. Conclusions This study demonstrates that ICG targets human plaques exhibiting endothelial abnormalities and provides new insights into its targeting mechanisms in clinical and experimental atheroma. Intracoronary NIRF-OCT of ICG may offer a novel, clinically translatable approach to image pathobiological aspects of coronary atherosclerosis. (Indocyanine Green Fluorescence Uptake in Human Carotid Artery Plaque [BRIGHT-CEA]; NCT01873716)

AB - Objectives This study sought to determine whether indocyanine green (ICG)–enhanced near-infrared fluorescence (NIRF) imaging can illuminate high-risk histologic plaque features of human carotid atherosclerosis, and in coronary atheroma of living swine, using intravascular NIRF-optical coherence tomography (OCT) imaging. Background New translatable imaging approaches are needed to identify high-risk biological signatures of atheroma. ICG is a U.S. Food and Drug Administration–approved NIRF imaging agent that experimentally targets plaque macrophages and lipid in areas of enhanced endothelial permeability. However, it is unknown whether ICG can target atheroma in patients. Methods Eight patients were enrolled in the BRIGHT-CEA (Indocyanine Green Fluorescence Uptake in Human Carotid Artery Plaque) trial. Five patients were injected intravenously with ICG 99 ± 25 min before clinically indicated carotid endarterectomy. Three saline-injected endarterectomy patients served as control subjects. Excised plaques underwent analysis by intravascular NIRF-OCT, reflectance imaging, microscopy, and histopathology. Next, following ICG intravenous injection, in vivo intracoronary NIRF-OCT and intravascular ultrasound imaged 3 atheroma-bearing coronary arteries of a diabetic, cholesterol-fed swine. Results ICG was well tolerated; no adverse clinical events occurred up to 30 days post-injection. Multimodal NIRF imaging including intravascular NIRF-OCT revealed that ICG accumulated in all endarterectomy specimens. Plaques from saline-injected control patients exhibited minimal NIRF signal. In the swine experiment, intracoronary NIRF-OCT identified ICG uptake in all intravascular ultrasound–identified plaques in vivo. On detailed microscopic evaluation, ICG localized to plaque areas exhibiting impaired endothelial integrity, including disrupted fibrous caps, and within areas of neovascularization. Within human plaque areas of endothelial abnormality, ICG was spatially related to localized zones of plaque macrophages and lipid, and, notably, intraplaque hemorrhage. Conclusions This study demonstrates that ICG targets human plaques exhibiting endothelial abnormalities and provides new insights into its targeting mechanisms in clinical and experimental atheroma. Intracoronary NIRF-OCT of ICG may offer a novel, clinically translatable approach to image pathobiological aspects of coronary atherosclerosis. (Indocyanine Green Fluorescence Uptake in Human Carotid Artery Plaque [BRIGHT-CEA]; NCT01873716)

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KW - endothelium

KW - indocyanine green

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KW - intraplaque hemorrhage

KW - intravascular imaging

KW - lipid

KW - molecular imaging

KW - near-infrared fluorescence

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