A new device that combines two microimaging technologies can reveal both the detailed anatomy of arterial linings and biological activities that, in coronary arteries, could indicate the risk of heart attacks or the formation of clots in arterial stents.
In their report receiving early online release in Nature Medicine, Massachusetts General Hospital (MGH) investigators describe using an intra-arterial catheter combining both optical frequency-domain imaging (OFDI) and near-infrared fluorescence (NIRF) imaging to obtain simultaneous structural and molecular images of internal arterial surfaces in rabbits.
"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," says Gary Tearney, MD, PhD, of the Wellman Center for Photomedicine and the MGH Pathology Department, co-senior author of the article.
Developed at the Wellman Center, OFDI utilizes a fiberoptic 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, 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 – a clot that blocks bloodflow through the stent – 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 like clotting and inflammation. Recognizing the potential advantage 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 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 was able to detect fibrin on implanted stents – including areas 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 biological differences 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," says Jaffer, co-senior 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 anti-clotting medications, which can cause excess bleeding." Clinical adoption of the integrated technology will require FDA approval of the molecular contrast agents used in NIRF.
Tearney is a professor of Pathology and Jaffer an assistant professor of Medicine at Harvard Medical School. Hongki Yoo, PhD, of the MGH Wellman Center and Jin Won Kim, MD, PhD, MGH Cardiovascular Research Center, are co-lead authors of the Nature Medicine report. Additional co-authors are Milen Shishkov, PhD, Eman Namati, PhD, and Brett Bouma, PhD, Wellman Center; Jason McCarthy, PhD, MGH Center for Systems Biology; Theodore Morse, PhD, and Roman Shubochkin, PhD, Boston University Photonics Center; and Vasilis Ntziachristos, PhD, Technical University of Munich.
The study was supported by grants from the National Institutes of Health, the Center for Integration of Medicine and Innovative Technology, the American Heart Association, Howard Hughes Medical Institute and the CardioVascular Research Foundation. Massachusetts General Hospital has filed patent applications on the combined OFDI and NIRF technology.
Celebrating the 200th anniversary of its founding in 1811, Massachusetts General Hospital (http://www.massgeneral.org) is the original and largest teaching hospital of Harvard Medical School. MGH conducts the largest hospital-based research program in the United States, with an annual research budget of nearly $700 million and major research centers in AIDS, cardiovascular research, cancer, computational and integrative biology, cutaneous biology, human genetics, medical imaging, neurodegenerative disorders, regenerative medicine, reproductive biology, systems biology, transplantation biology and photomedicine.
Sue McGreevey | EurekAlert!
Medical gamma-ray camera is now palm-sized
23.05.2017 | Waseda University
Computer accurately identifies and delineates breast cancers on digital tissue slides
11.05.2017 | Case Western Reserve University
Staphylococcus aureus is a feared pathogen (MRSA, multi-resistant S. aureus) due to frequent resistances against many antibiotics, especially in hospital infections. Researchers at the Paul-Ehrlich-Institut have identified immunological processes that prevent a successful immune response directed against the pathogenic agent. The delivery of bacterial proteins with RNA adjuvant or messenger RNA (mRNA) into immune cells allows the re-direction of the immune response towards an active defense against S. aureus. This could be of significant importance for the development of an effective vaccine. PLOS Pathogens has published these research results online on 25 May 2017.
Staphylococcus aureus (S. aureus) is a bacterium that colonizes by far more than half of the skin and the mucosa of adults, usually without causing infections....
Physicists from the University of Würzburg are capable of generating identical looking single light particles at the push of a button. Two new studies now demonstrate the potential this method holds.
The quantum computer has fuelled the imagination of scientists for decades: It is based on fundamentally different phenomena than a conventional computer....
An international team of physicists has monitored the scattering behaviour of electrons in a non-conducting material in real-time. Their insights could be beneficial for radiotherapy.
We can refer to electrons in non-conducting materials as ‘sluggish’. Typically, they remain fixed in a location, deep inside an atomic composite. It is hence...
Two-dimensional magnetic structures are regarded as a promising material for new types of data storage, since the magnetic properties of individual molecular building blocks can be investigated and modified. For the first time, researchers have now produced a wafer-thin ferrimagnet, in which molecules with different magnetic centers arrange themselves on a gold surface to form a checkerboard pattern. Scientists at the Swiss Nanoscience Institute at the University of Basel and the Paul Scherrer Institute published their findings in the journal Nature Communications.
Ferrimagnets are composed of two centers which are magnetized at different strengths and point in opposing directions. Two-dimensional, quasi-flat ferrimagnets...
An Australian-Chinese research team has created the world's thinnest hologram, paving the way towards the integration of 3D holography into everyday...
24.05.2017 | Event News
23.05.2017 | Event News
22.05.2017 | Event News
26.05.2017 | Life Sciences
26.05.2017 | Life Sciences
26.05.2017 | Physics and Astronomy