A new device that combines optical frequency domain imaging (OFDI) and near-infrared fluorescence (NIRF) imaging can reveal both the detailed anatomy of arterial linings and the biological activities that might indicate the risk of heart attacks or the formation of clots in arterial stents. In a report published in Nature Medicine, Massachusetts General Hospital (MGH) investigators describe using an intra-arterial catheter that combines imaging techniques to obtain simultaneously both structural and molecular images of internal arterial surfaces in rabbits. A combination of optical frequency domain imaging (OFDI) and near-infrared fluorescence (NIRF) imaging helps examine arterial health. Shown here is a 3-D cutaway view of an OFDI-NIRF data set obtained from a rabbit iliac artery with an implanted NIR fluorescent-fibrin labeled stent in vivo. Structural components were segmented and color-coded in OFDI images for clear visualization. Gray: artery wall; blue: stent; red-yellow: NIR fluorescent fibrin. (Images: Massachusetts General Hospital) “The ability to measure both microstructural and molecular information from the same location in the artery wall could provide a much better diagnostic tool for assessing vascular pathology — information that is highly relevant for diagnosing coronary artery disease, vulnerable plaque and evaluating stent healing,” said Gary Tearney of the Wellman Center for Photomedicine and the MGH Pathology Department, co-senior author of the article. Developed at the Wellman Center, OFDI uses a fiber optic probe with a constantly rotating laser tip to create detailed molecular images of interior surfaces, such as arterial walls. While OFDI can be used to guide procedures like coronary artery angioplasty and to confirm the correct positioning of metal stents inserted to keep cleared arteries open, its ability to determine important details of stent healing is limited: Properly healed stents become covered with endothelium, but they also can become coated with clot-inducing fibrin, which may put patients at risk for stent thrombosis — and OFDI cannot distinguish between endothelium and fibrin on a stent. Shown is a 3-D fly-through view of an OFDI-NIRF data set obtained from an aorta of an atherosclerotic rabbit injected with a protease-activatable fluorescent agent in vivo. Gray: artery wall; red-yellow: NIR fluorescent protease activity. Intravascular NIRF technology was developed in the MGH Cardiovascular Research Center (CVRC) in collaboration with colleagues at the Technical University of Munich. The process uses special imaging agents to detect cells and molecules involved in vascular processes such as clotting and inflammation. Recognizing the potential advantage of combining both technologies, the Wellman researchers worked with the MGH-CVRC team, led by Farouc Jaffer of the MGH Heart Center, to develop an integrated OFDI-NIRF imaging system incorporated in the same intravascular probe used for OFDI alone. The team first confirmed that the system could provide detailed structural images of a stent implanted in a cadaveric human coronary artery and could accurately identify the presence of fibrin on the stent. In a series of experiments in living rabbits, the OFDI-NIRF system could detect fibrin on implanted stents — including areas where it was not detected by OFDI alone — and could identify the presence of both atherosclerotic plaques and enzymatic activity associated with inflammation and plaque rupture. The enzyme signal detected by NIRF was not uniform throughout the imaged plaques, indicating biological differences that could be relevant to prognosis and treatment planning. Dual-modality cross-sectional OFDI-NIRF images of an iliac artery of an atherosclerotic rabbit injected with protease-activatable fluorescent agent in vivo. Left: OFDI; right: NIRF; bottom: OFDI-NIRF fusion. “At present we are not able to predict which patients may develop stent thrombosis, but integrated OFDI-NIRF can assess many key factors linked to the risk of clot formation,” Jaffer said. “If OFDI-NIRF is validated in clinical studies, patients at risk for stent thrombosis could undergo a ‘stent checkup’ to determine how well the stent is healing. Patients with unhealed stents could be advised to take or continue taking specific anticlotting medications. Patients with well-healed stents, on the other hand, could potentially discontinue anticlotting medications, which can cause excess bleeding.” Clinical adoption of the integrated technology will require FDA approval of the molecular contrast agents used in NIRF. For more information, visit: www.massgeneral.org/wellman
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