A new device that combines optical frequency domain imaging (OFDI) and near-infrared fluorescence (NIRF) imaging can reveal the detailed anatomy of arterial linings and the biological activities that might indicate risk of a heart attack or the formation of clots in arterial stents. In a report published online Nov. 6, 2011, in Nature Medicine (doi:10.1038/nm.2555), Massachusetts General Hospital (MGH) researchers describe using an intra-arterial catheter that combines the techniques to simultaneously obtain structural and molecular images of internal arterial surfaces in live 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 artery with an implanted arterial stent (blue) and fibrin deposits (red-yellow). Courtesy of Hongki Yoo and Jin Won Kim, and the laboratories of Gary Tearney and Farouc Jaffer, Massachusetts General Hospital. “There is an important need to better understand the in vivo molecular and structural features of coronary atherothrombotic vascular disease,” said Dr. Farouc Jaffer of MGH’s Cardiology Div. “We believed that combining a molecular and a structural imaging approach would provide a powerful, clinically translatable approach to simultaneously understand these features.” The new diagnostic tool could provide relevant information to diagnose coronary artery disease and vulnerable plaque, and to evaluate stent healing, said Gary Tearney of the Wellman Center for Photomedicine and the MGH pathology department. 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. Although OFDI can guide procedures like coronary artery angioplasty and can 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, the same tissue that normally coats the arterial surface, but they also can become coated with clot-inducing fibrin, which may put patients at risk for stent thrombosis – and OFDI cannot distinguish between the two. Intravascular NIRF technology was developed in the MGH Cardiovascular Research Center (CVRC) in collaboration with colleagues at the Technical University of Munich in Germany. The process uses special imaging agents to detect cells and molecules involved in vascular processes such as inflammation and clotting. Recognizing the potential advantage of combining both technologies, the Wellman researchers worked with the MGH-CVRC team, led by Jaffer, to develop the concept. The integrated OFDI-NIRF imaging system they created incorporates the same intravascular probe that is used for OFDI alone. The team confirmed that the system can provide detailed structural images of a stent implanted in a cadaveric human coronary artery and can accurately identify the presence of fibrin on the stent. In a series of experiments in living rabbits, the OFDI-NIRF system detected fibrin on implanted stents – including areas where it was not detected by OFDI alone – and identified 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. “Because of the complementary nature of microstructural and molecular imaging, this combined technology is a powerful investigational and diagnostic tool,” Tearney explained. “It will allow us, for the first time, to investigate the interplay between molecular activity and structure in living arteries. From a clinical standpoint, it will allow us to better characterize the artery wall of patients to identify vulnerable plaque prior to events and determine stents that may be at risk for thrombosis.” Clinical adoption of the integrated technology will require FDA approval of the molecular contrast agents used in NIRF. The research team intends to conduct a clinical study in the upcoming year, and hopes to investigate the relationships between structural, molecular and functional characteristics of atherosclerotic plaques that place patients at risk for coronary events. MGH has filed patent applications on the combined technology.