The importance of coronary atherosclerosis and its clinical manifestations cannot be overstated;in this country, half a million people die from acute myocardial infarction every year and an equal number of patients survive with substantial morbidity. Coronary atherosclerosis is an inflammatory process governed by dysregulated endothelium, leukocytes, macrophages, and smooth muscle cells. These cells conspire to form lesions within the artery wall, effectuate plaque progression or regression, and play a critical role in precipitating thrombosis, which can block blood flow to the heart. Progress towards improving the understanding, diagnosis, and treatment of coronary artery disease has been slowed by our inability to observe these cells in the coronary arteries of living human patients. Our laboratory has been on the forefront of pushing the resolution limits of coronary imaging in vivo. In the parent R01, we developed an intracoronary imaging technology, optical frequency domain imaging (OFDI), that makes it practical to obtain 10-?m resolution, three-dimensional images of the coronary wall in the clinical setting. Now that OFDI has been transferred to the commercial sector, we will focus our efforts on developing the next generation coronary imaging technology, one that will provide images at a resolution of 1-?m. This advance will enable the investigation of macromolecules and cells involved in the pathophysiology of CAD and will allow clinicians to diagnose and treat this disease based on cellular information obtained from their patients'coronary arteries. The research strategy of this project parallels that of our previous development and translation of intracoronary OFDI. First, new ?OCT technology will be designed and fabricated, focusing on solving catheter and system- level challenges. Alongside this development process, we will validate the accuracy of ?OCT ex vivo for identifying relevant cellular and subcellular features of the coronary wall, using histopathology as a gold standard. The safety, feasibility, and efficacy of ?OCT will then be evaluated in 25 patients undergoing coronary intervention. !

Public Health Relevance

Coronary artery disease, the number one cause of death in the US, is caused by cells in the walls of the arteries that supply blood to the heart. These cells are too small to be visualized using modern medical imaging technologies. By providing a new imaging method that will allow scientists and physicians to see these cells in patients, this research will change how we study, diagnose, and treat this disease.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL076398-08
Application #
8387004
Study Section
Biomedical Imaging Technology Study Section (BMIT)
Program Officer
Fleg, Jerome
Project Start
2004-04-01
Project End
2015-11-30
Budget Start
2012-12-01
Budget End
2013-11-30
Support Year
8
Fiscal Year
2013
Total Cost
$750,739
Indirect Cost
$294,093
Name
Massachusetts General Hospital
Department
Type
DUNS #
073130411
City
Boston
State
MA
Country
United States
Zip Code
02199
Kashiwagi, Manabu; Liu, Linbo; Chu, Kengyeh K et al. (2014) Feasibility of the assessment of cholesterol crystals in human macrophages using micro optical coherence tomography. PLoS One 9:e102669
Liu, Linbo; Chu, Kengyeh K; Houser, Grace H et al. (2013) Method for quantitative study of airway functional microanatomy using micro-optical coherence tomography. PLoS One 8:e54473
Gonzalo, Nieves; Tearney, Guillermo J; van Soest, Gijs et al. (2011) Witnessed coronary plaque rupture during cardiac catheterization. JACC Cardiovasc Imaging 4:437-8
Liu, Linbo; Gardecki, Joseph A; Nadkarni, Seemantini K et al. (2011) Imaging the subcellular structure of human coronary atherosclerosis using micro-optical coherence tomography. Nat Med 17:1010-4
Yoo, Hongki; Kim, Jin Won; Shishkov, Milen et al. (2011) Intra-arterial catheter for simultaneous microstructural and molecular imaging in vivo. Nat Med 17:1680-4
Suter, Melissa J; Nadkarni, Seemantini K; Weisz, Giora et al. (2011) Intravascular optical imaging technology for investigating the coronary artery. JACC Cardiovasc Imaging 4:1022-39
Choma, Michael A; Suter, Melissa J; Vakoc, Benjamin J et al. (2011) Physiological homology between Drosophila melanogaster and vertebrate cardiovascular systems. Dis Model Mech 4:411-20
Waxman, Sergio; Freilich, Mark I; Suter, Melissa J et al. (2010) A case of lipid core plaque progression and rupture at the edge of a coronary stent: elucidating the mechanisms of drug-eluting stent failure. Circ Cardiovasc Interv 3:193-6
Ha, J Y; Shishkov, M; Colice, M et al. (2010) Compensation of motion artifacts in catheter-based optical frequency domain imaging. Opt Express 18:11418-27
Choma, Michael A; Suter, Melissa J; Vakoc, Benjamin J et al. (2010) Heart wall velocimetry and exogenous contrast-based cardiac flow imaging in Drosophila melanogaster using Doppler optical coherence tomography. J Biomed Opt 15:056020

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