“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,” stated Gary Tearney, MD, PhD, of the Wellman Center for Photomedicine and the pathology department of Massachusetts General Hospital (MGH; Boston, MA, USA), cosenior author of the article, published online November 2011 in the journal Nature Medicine.

Developed at the Wellman Center, OFDI utilizes a fiber-optic probe with a constantly rotating laser tip to create detailed molecular images of interior surfaces such as arterial walls. Whereas 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, the same tissue that normally coats the arterial surface; but stents can become coated with the clot-inducing protein fibrin, which may put patients at risk for stent thrombosis, and OFDI cannot determine the molecular composition of tissue covering a stent.

Intravascular NIRF technology was developed in the MGH Cardiovascular Research Center (CVRC), in collaboration with colleagues at the Technical University of Munich, and uses special imaging agents to detect cells and molecules involved in vascular processes such as clotting and inflammation. Recognizing the potential benefits of combining both technologies, the Wellman researchers worked with the MGH-CVRC team, led by Farouc Jaffer, MD, PhD, of the MGH Heart Center to develop an integrated OFDI-NIRF imaging system integrated in the same intravascular probe used for OFDI alone.

The investigators first validated that the system could provide precise structural images of a stent implanted in a cadaveric human coronary artery and could effectively identify the presence of fibrin on the stent. In a series of experiments in living rabbits, the OFDI-NIRF system was able to identify fibrin on implanted stents--including regions where it was not detected by OFDI alone--and to 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 biologic disparities that could be relevant to prognosis and treatment planning.

“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,” said Dr. Jaffer, cosenior author of the Nature Medicine report. “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 anti-clotting 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 US Food and Drug Administration (FDA) approval of the molecular contrast agents used in NIRF.

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