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.
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.
Authors: Edward G Soltesz; Sungjee Kim; Rita G Laurence; Alec M DeGrand; Cherie P Parungo; Delphine M Dor; Lawrence H Cohn; Moungi G Bawendi; John V Frangioni; Tomislav Mihaljevic Journal: Ann Thorac Surg Date: 2005-01 Impact factor: 4.330
Authors: Robert Flaumenhaft; Eiichi Tanaka; Gwenda J Graham; Alec M De Grand; Rita G Laurence; Kozo Hoshino; Roger J Hajjar; John V Frangioni Journal: Circulation Date: 2006-12-18 Impact factor: 29.690
Authors: V Falk; T Walther; H Kitzinger; T Rauch; A Diegeler; R Autschbach; F W Mohr Journal: Thorac Cardiovasc Surg Date: 1998-02 Impact factor: 1.827
Authors: Nimesh D Desai; Senri Miwa; David Kodama; Taadaki Koyama; Gideon Cohen; Marc P Pelletier; Eric A Cohen; George T Christakis; Bernard S Goldman; Stephen E Fremes Journal: J Thorac Cardiovasc Surg Date: 2006-07-28 Impact factor: 5.209
Authors: J H Chesebro; I P Clements; V Fuster; L R Elveback; H C Smith; W T Bardsley; R L Frye; D R Holmes; R E Vlietstra; J R Pluth; R B Wallace; F J Puga; T A Orszulak; J M Piehler; H V Schaff; G K Danielson Journal: N Engl J Med Date: 1982-07-08 Impact factor: 91.245
Authors: Shunsuke Ohnishi; Stephen J Lomnes; Rita G Laurence; Andrew Gogbashian; Giuliano Mariani; John V Frangioni Journal: Mol Imaging Date: 2005 Jul-Sep Impact factor: 4.488
Authors: Antonio Piñero; Julián Illana; Carlos García-Palenciano; Francisco Cañizarese; Manuel Canteras; Victoria Cañadillas; Eugenia Durán; Pascual Parilla Journal: Arch Surg Date: 2004-11
Authors: John T Nguyen; Yoshitomo Ashitate; Ian A Buchanan; Ahmed M S Ibrahim; Sylvain Gioux; Priti P Patel; John V Frangioni; Bernard T Lee Journal: J Surg Res Date: 2012-05-24 Impact factor: 2.192
Authors: Yoshitomo Ashitate; Andrew Levitz; Min Ho Park; Hoon Hyun; Vivek Venugopal; GwangLi Park; Georges El Fakhri; Maged Henary; Sylvain Gioux; John V Frangioni; Hak Soo Choi Journal: Chem Commun (Camb) Date: 2016-08-11 Impact factor: 6.222
Authors: Q R J G Tummers; F P R Verbeek; B E Schaafsma; M C Boonstra; J R van der Vorst; G-J Liefers; C J H van de Velde; J V Frangioni; A L Vahrmeijer Journal: Eur J Surg Oncol Date: 2014-02-22 Impact factor: 4.424
Authors: Sharad Gupta; Muhammad R Chatni; Ayala L N Rao; Valentine I Vullev; Lihong V Wang; Bahman Anvari Journal: Nanoscale Date: 2013-01-21 Impact factor: 7.790
Authors: David K Bwambok; Bilal El-Zahab; Santhosh K Challa; Min Li; Lin Chandler; Gary A Baker; Isiah M Warner Journal: ACS Nano Date: 2009-12-22 Impact factor: 15.881