Energy Research Company (ERCo), in a collaboration with The City College of New York (CCNY) and Columbia University Medical Center (CUMC), proposes developing the Vulnerable Plaque Amplified Optical Analyzer (VPAOA): a fiber optic catheter instrument based on patented amplified spectroscopy technology for detecting and analyzing vulnerable plaque (VP) in coronary arteries. VP is a type of arterial plaque that is susceptible to sudden rupture, often resulting in a heart attack or stroe and death. An estimated 70% of sudden heart attack fatalities are due to the formation of a thrombosis following the rupture of a VP. When the fibrous cap that covers a VP is less than 65mm thick, it is too thin to contain the plaque in the face of common stresses and is susceptible to sudden rupture. With over 700,000 heart attacks in the U.S. each year, technology to diagnose VP and measure VP caps can be transformative for public health, potentially saving thousands of lives and hundreds of millions of dollars in medical costs per year in the U.S. alone. The sensor proposed in this project will detect VP and measure the thickness of the fibrous caps, giving cardiologists the predictive knowledge of unstable plaques needed to prevent heart attacks most effectively. Conclusively detecting VP is not possible with traditional clinical tools such as intravascular ultrasound (IVUS), optical coherence tomography (OCT), and high-resolution magnetic resonance imaging (MRI). These are imaging, not diagnostic, methods and are therefore limited by their poor sensitivity and ability to predict rupture of VP. Even the new near infrared (NIR) techniques can only provide limited information about a plaque, and are plagued by the strong absorption of NIR radiation by water. The proposed device overcomes these limitations and provides in-vivo diagnostic information and imaging of VP. Objectives: Phase I of the project will result in a proof-of-concept prototype device tested on human artery specimens exhibiting different types of plaques. Phase II will result in an advanced prototype suitable for testing in a medical center laboratory on suitable animals with VP as preparation for human testing. Phase I Specific Aims and Methods to be Employed: CCNY will build an amplified spectroscopy system on a laboratory bench and demonstrate signal amplification on human arterial specimens exhibiting plaques. ERCo will build a prototype fiber optic catheter probe system capable of generating and analyzing the amplified spectra. Finally, the catheter probe system will be tested for the ability to i) discriminate between VP and non-VP specimens, and ii) measure cap thicknesses of VP plaques with high accuracy. This will be done with blind tests on specimens analyzed by gold standard pathology methods at CUMC.