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J Thorac Cardiovasc Surg 2009;138:133-140
© 2009 The American Association for Thoracic Surgery

Evolving Technology/Basic Science

Real-time assessment of cardiac perfusion, coronary angiography, and acute intravascular thrombi using dual-channel near-infrared fluorescence imaging

Eiichi Tanaka, MD, PhDa,b, Frederick Y. Chen, MD, PhDc, Robert Flaumenhaft, MD, PhDd, Gwenda J. Graham, PhDd, Rita G. Laurence, BSa, John V. Frangioni, MD, PhDa,e,*

a Division of Hematology/Oncology, Beth Israel Deaconess Medical Center, Boston, Mass
d Division of Hemostasis and Thrombosis, Beth Israel Deaconess Medical Center, Boston, Mass
e Department of Radiology, Beth Israel Deaconess Medical Center, Boston, Mass
b Department of Surgical Oncology, Hokkaido University Graduate School of Medicine, Sapporo, Japan
c Division of Cardiac Surgery, Brigham and Women's Hospital, Boston, Mass

Received for publication April 11, 2008; revisions received July 29, 2008; accepted for publication September 6, 2008.

* Address for reprint: John V. Frangioni, MD, PhD, Beth Israel Deaconess Medical Center, Room SL-B05, 330 Brookline Ave, Boston, MA 02215. (Email: jfrangio{at}bidmc.harvard.edu).

Objectives: We have developed an image-guided surgical system based on invisible near-infrared fluorescent light. Presently, the only clinically available near-infrared fluorophore is indocyanine green, which fluoresces at approximately 800 nm and is used for coronary angiography. Our objective was to determine whether methylene blue, already US Food and Drug Administration approved for other indications, has useful near-infrared fluorescence properties for image-guided cardiac surgery.

Methods: The optical properties of methylene blue were measured after dissolution in 100% serum. Biodistribution and clearance were quantified in organs and tissue after intravenous bolus injection of 2 mg/kg methylene blue in 3 rats. Coronary arteriography and cardiac perfusion were imaged in real time after intravenous bolus injection of 1 mg/kg methylene blue in 5 pigs with coronary obstructions. Coronary angiography and acute thrombi were assessed by using 800-nm fluorophores, indocyanine green, and IR-786–labeled platelets, respectively.

Results: The peak absorbance and emission of methylene blue as a near-infrared fluorophore occur at 667 nm and 686 nm, respectively. After intravenous injection, methylene blue provides highly sensitive coronary angiography. A lipophilic cation, methylene blue is extracted rapidly into tissue, with myocardium displaying unusually high uptake. Methylene blue permits real-time visualization and quantitative assessment of myocardial perfusion. Because of absent spectral overlap, use of 2 independent fluorophores in our imaging system permits simultaneous quantification of perfusion, venous drainage, and/or intravascular thrombi.

Conclusions: Methylene blue is an effective near-infrared fluorophore that provides direct visualization of coronary arteriography and cardiac perfusion. In conjunction with approximately 800-nm near-infrared fluorophores, important functional assessments during cardiac surgery are also possible.

Abbreviations and Acronyms CABG = coronary artery bypass grafting; FBS = fetal bovine serum; FDA = US Food and Drug Administration; HEPES = N-2-hydroxyethylpiperazine-N-2-ethanesulfonic acid; ICG = indocyanine green; LAD = left anterior descending coronary artery; MB = methylene blue; NIR = near-infrared; QY = quantum yield






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