Real-time assessment of cardiac perfusion, coronary angiography, and acute intravascular thrombi using dual-channel near-infrared fluorescence imaging.
OBJECTIVE
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.
Tanaka
Eiichi
E
Division of Hematology/Oncology, Beth Israel Deaconess Medical Center, Boston, Mass 02215, USA.
Chen
Frederick Y
FY
Flaumenhaft
Robert
R
Graham
Gwenda J
GJ
Laurence
Rita G
RG
Frangioni
John V
JV
D000818:Animals; D006348:Cardiac Surgical Procedures; D017023:Coronary Angiography; D003326:Coronary Circulation; D003328:Coronary Thrombosis / Q000175:diagnosis*; D005456:Fluorescent Dyes / Q000493:pharmacokinetics; D007275:Injections, Intravenous; D007430:Intraoperative Care; D008751:Methylene Blue / Q000493:pharmacokinetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D013050:Spectrometry, Fluorescence / Q000295:instrumentation* / Q000379:methods; D019265:Spectroscopy, Near-Infrared / Q000295:instrumentation* / Q000379:methods; D034421:Sus scrofa
D005456:Fluorescent Dyes; D008751:Methylene Blue