Abstract

The goal of this proposal is to develop and validate a device for measuring the chemical and molecular composition of coronary atherosclerotic plaques in living human patients. The ability to measure chemicals and molecules in human coronary arteries could improve our understanding of plaque formation, plaque progression, the events leading to coronary thrombosis, and the response to pharmacologic therapy. Intracoronary Raman spectroscopy is a promising technology for obtaining this information. With Raman spectroscopy, a laser illuminates a tissue sample and a small portion of the light imparts some of its energy to the tissue's chemical bonds. Since the amount of energy lost is specific to each individual chemical bond, the spectrum of the Raman scattered light can be used to determine the tissue's chemical and molecular composition. We have recently developed a prototype catheter and have demonstrated that Raman spectra can be obtained from a single spot within the coronary arteries of living swine. In this proposal, we will develop a next-generation Raman system and catheter that fulfills the requirements for human use and that is capable of obtaining high-quality Raman spectral maps along the circumference of a coronary artery, and possibly even over entire coronary segments. While Raman spectroscopy has already been shown to be capable of measuring many plaque chemicals and molecules, we will additionally investigate its potential to measure other molecules that are currently thought to precipitate acute coronary syndromes, including those associated with necrotic core lesions, the extracellular matrix, and oxidative stress. Finally, we will conduct a clinical study in 60 patients to demonstrate the safety and feasibility of intracoronary Raman spectroscopy. This study will provide insight on the clinical utility of this new method by comparing chemical and molecular information obtained from patients with different presentations of coronary artery disease. ? ? ?

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
1R01HL093717-01
Application #
7514130
Study Section
Biomedical Imaging Technology Study Section (BMIT)
Program Officer
Buxton, Denis B
Project Start
2008-09-20
Project End
2012-07-31
Budget Start
2008-09-20
Budget End
2009-07-31
Support Year
1
Fiscal Year
2008
Total Cost
$790,817
Indirect Cost

  Institution

Name
Massachusetts General Hospital
Department
Type
DUNS #
073130411
City
Boston
State
MA
Country
United States
Zip Code
02199

  Publications

Ughi, Giovanni J; Wang, Hao; Gerbaud, Edouard et al. (2016) Clinical Characterization of Coronary Atherosclerosis With Dual-Modality OCT and Near-Infrared Autofluorescence Imaging. JACC Cardiovasc Imaging 9:1304-1314
Verjans, Johan W; Osborn, Eric A; Ughi, Giovanni J et al. (2016) Targeted Near-Infrared Fluorescence Imaging of Atherosclerosis: Clinical and Intracoronary Evaluation of Indocyanine Green. JACC Cardiovasc Imaging 9:1087-1095
Suter, Melissa J; Kashiwagi, Manabu; Gallagher, Kevin A et al. (2015) Optimizing flushing parameters in intracoronary optical coherence tomography: an in vivo swine study. Int J Cardiovasc Imaging 31:1097-106
Ughi, Giovanni J; Verjans, Johan; Fard, Ali M et al. (2015) Dual modality intravascular optical coherence tomography (OCT) and near-infrared fluorescence (NIRF) imaging: a fully automated algorithm for the distance-calibration of NIRF signal intensity for quantitative molecular imaging. Int J Cardiovasc Imaging 31:259-68
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
Fleming, Christine P; Eckert, Jocelyn; Halpern, Elkan F et al. (2013) Depth resolved detection of lipid using spectroscopic optical coherence tomography. Biomed Opt Express 4:1269-84
Fard, Ali M; Vacas-Jacques, Paulino; Hamidi, Ehsan et al. (2013) Optical coherence tomography--near infrared spectroscopy system and catheter for intravascular imaging. Opt Express 21:30849-58
Hara, Tetsuya; Bhayana, Brijesh; Thompson, Brian et al. (2012) Molecular imaging of fibrin deposition in deep vein thrombosis using fibrin-targeted near-infrared fluorescence. JACC Cardiovasc Imaging 5:607-15
Coron, E; Auksorius, E; Pieretti, A et al. (2012) Full-field optical coherence microscopy is a novel technique for imaging enteric ganglia in the gastrointestinal tract. Neurogastroenterol Motil 24:e611-21
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

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