Abstract 12988: First-in-Human Evaluation of Indocyanine Green for Targeted Optical Imaging of Atherosclerosis: Implications for Inflamed, High-Risk Plaques
BACKGROUND: High-resolution strategies to image inflammation could improve the assessment of high-risk atherosclerotic plaques. We investigated whether indocyanine green (ICG), an FDA approved near-infrared fluorescence (NIRF) agent, can target atheroma in patients undergoing carotid endarterectomy (CEA). Additionally, we performed a first in vivo ICG-enhanced intracoronary NIRF and optical frequency domain imaging (OFDI) in porcine atherosclerotic coronary arteries.
METHODS: Five patients received ICG intravenously prior to elective CEA (0.25 mg/kg, up to 25mg). Three patients injected with saline served as controls. CEAs were resected 99±25 minutes after injection. Ex vivo photoacoustic tomography (PAT)-ultrasound (US), intravascular NIRF-OFDI, fluorescence reflectance imaging (FRI), fluorescence microscopy, and histopathology was performed.
Intravascular NIRF-OFDI imaging was performed in atherosclerotic coronary arteries of a diabetic, cholesterol-fed swine. After injecting ICG intravenously, we performed three-vessel x-ray angiography, intravascular ultrasound (IVUS) and NIRF-OFDI to evaluate ICG coronary plaque uptake.
RESULTS: No adverse events occurred up to 30 days after ICG injection. Multi-wavelength PAT readily detected ICG deposition within resected atheroma; little PAT endogenous signal related to residual blood was noted in control plaques. Intravascular NIRF similarly revealed positive signal adjacent to stenotic areas in all injected patients; minimal ICG signal was evident in controls. Microscopic analysis revealed ICG co-localization with plaque macrophage accumulation. One patient with recent plaque rupture showed the highest ICG uptake at the macrophage-rich rupture site.
All three swine coronary arteries examined revealed that all ICG-positive areas on intracoronary NIRF-OFDI corresponded to plaque by IVUS. Plaque-free zones were uniformly ICG negative.
CONCLUSIONS: This study demonstrates that ICG enables optical molecular imaging of plaque macrophages in patients with severe atherosclerosis. PAT-US and intravascular NIRF-OFDI offer novel clinically translatable approaches to image inflamed carotid and coronary plaques via ICG absorption and ICG fluorescence, respectively.
Author Disclosures: J. Verjans: None. E.O. Osborn: None. G. Ughi: None. C.W. Kessinger: None. S. Mallidi: None. T. Hasan: None. M.A. Calfon: None. P.H. Stone: None. R.P. Cambria: None. G.J. Tearney: Research Grant; Modest; Canon, Merck. Ownership Interest; Modest; Massachusetts General Hospital has a patent licensing arrangement with Terumo Corporation. Dr. Tearney has the right to receive licensing income from this licensing agreement.. Consultant/Advisory Board; Modest; Samsung. F.A. Jaffer: Research Grant; Modest; Merck, Kowa, Siemens.
- © 2014 by American Heart Association, Inc.