Abstract—There is a need for an imaging technique that can reliably identify and characterize the vulnerability of atherosclerotic plaques. Catheter-based intravascular ultrasound (IVUS) is one of the imaging tools of the clinical evaluation of atherosclerosis. However, histopathological information obtained with IVUS imaging is limited. We present and discuss the applicability of a combined intravascular photoacoustic (IVPA) and intravascular ultrasound (IVUS) imaging approach to assess both vessel structure and tissue composition thus identifying rupture-prone atherosclerotic plaques. Photoacoustic (or optoacoustic and, generally, thermoacoustic) imaging relies on the absorption of electromagnetic energy, such as light, and the subsequent emission of an acoustic wave. Therefore, the amplitude and temporal characteristics of the photoacoustic signal is primarily determined by optical absorption properties of different types of tissues and can be used to differentiate the lipid, fibrous and fibro-cellular components of an inflammatory lesion. Simultaneous IVUS and IVPA imaging studies were conducted using 40 MHz clinical IVUS imaging catheter interfaced with a pulsed laser system. The performance of the IVPA/IVUS imaging was assessed using phantoms with point targets and vessel-mimicking phantoms. To detect the lipids in the plaque, ex-vivo IVPA imaging studies of a normal and an atherosclerotic rabbit aorta were performed at a 532 nm wavelength. To assess plaque composition, multi-wavelength (680-950 nm) spectroscopic IVPA imaging studies were carried out. Finally, molecular and cellular IVPA imaging was demonstrated using plasmonic nanoparticles. Overall, our studies suggest that plaque detection and characterization can be improved using the combined IVPA/IVUS imaging. I. INTRODUCTION ORONARY atherosclerotic disease is the major cause of cardiovascular related deaths in the United States and other countries. There is an urgent clinical need to identify the composition of vulnerable plaques. Clinical decision making in the appropriate use of therapeutic and interventional strategies is strongly dependent on the type of vulnerable plaques. In this paper, we demonstrate an in- vivo imaging technology – intravascular ultrasound and Manuscript received April 27, 2008. This work was supported in part by the American Heart Association under grant 0655033Y and National Institutes of Health under grants EB004963, EB008101 and HL084076. S.Y. Emelianov, * B. Wang, J. Su, A. Karpiouk, E. Yantsen, and S. Sethuraman are with the Department of Biomedical Engineering, University of Texas at Austin, Austin, TX 78712 USA ( * corresponding author: 512- 471-1733; fax: 512-471-0616; e-mail: emelian@ mail.utexas.edu). K. Sokolov is with the Department of Imaging Physics, University of Texas M.D. Anderson Cancer Center, Houston, TX 77030 USA. J. Amirian and R. Smalling are with the Division of Cardiology, University of Texas Health Science Center, Houston, TX 77030 USA. photoacoustic imaging techniques, capable of direct assessment of both functional and morphological properties of coronary atherosclerotic plaques [1]-[4]. II. INTRAVASCULAR ULTRASOUND AND PHOTOACOUSTIC IMAGING Catheter-based intravascular ultrasound (IVUS) is a relatively new approach to the arterial vascular wall imaging that is used in many interventional laboratories to guide procedures. IVUS is an invasive modality that permits direct and real-time imaging of atheroma and provides high-quality cross-sectional or even volumetric views of the vessel and atherosclerotic disease with spatial resolution from 60 to 150 μm. Although image quality and resolution of IVUS has improved steadily, IVUS imaging alone cannot reliable detect and, more importantly, differentiate vulnerable plaques. To overcome the limitations of IVUS imaging, we introduced intravascular photoacoustic (IVPA) imaging to facilitate the discrimination of atheroma. Photoacoustic imaging technology, in principle, merges two imaging fields – optics and ultrasound. In this technique, ultrasonic waves are produced by a pulsed laser excitation under the conditions of thermal and stress confinement. IVPA imaging can offer several advantages in imaging atherosclerotic plaques including the potential to detect most of the factors associated with vulnerable plaques including active inflammation, thin fibrous cap with a large lipid core, endothelial denudation, fissured plaque, severe stenosis, and calcified nodules. Overall, intravascular ultrasound and intravascular photoacoustic imaging can visualize both morphological and functional changes in the vessel wall to allow diagnosis, disease characterization and more precise evaluation of the effects of treatment. The experimental system for intravascular photoacoustic and intravascular ultrasonic imaging is presented in Fig. 1. The optical excitation for photoacoustic imaging was provided by a Q-switched Nd:YAG laser capable of producing 5-ns long pulses of green (532-nm) light with a maximum pulse repetition frequency of 20 Hz. The optical beam was diffused to provide homogeneous optical excitation of the sample from the outside and to insure that the laser beam intensity per pulse is limited to 1 mJ/cm 2 . This energy is well below the maximum permissible exposure of 20 mJ/cm 2 (ANSI-Z136.1). The sample was immersed in a water tank for ultrasonic coupling between the sample and a single element, 2.5F, 0.83-mm diameter, 40-MHz IVUS imaging catheter Intravascular Ultrasound and Photoacoustic Imaging Stanislav Emelianov, Member, IEEE, Bo Wang, Member, IEEE, Jimmy Su, Andrei Karpiouk, Evgeniya Yantsen, Konstantin Sokolov, James Amirian, Richard Smalling, and Shriram Sethuraman C 30th Annual International IEEE EMBS Conference Vancouver, British Columbia, Canada, August 20-24, 2008 978-1-4244-1815-2/08/$25.00 ©2008 IEEE. 2