doi:10.1016/j.ultrasmedbio.2007.07.004 ● Original Contribution MAPPING SPATIAL AND TEMPORAL CHANGES IN CAROTID ATHEROSCLEROSIS FROM THREE-DIMENSIONAL ULTRASOUND IMAGES MICAELA EGGER,* BERNARD CHIU,* ‡ J. DAVID SPENCE,* § AARON FENSTER,* †‡ and GRACE PARRAGA* †‡ *Imaging Research Laboratories, Robarts Research Institute, London, Ontario, Canada; † Department of Medical Biophysics, The University of Western Ontario, London, Ontario, Canada; ‡ Graduate Program in Biomedical Engineering, The University of Western Ontario, London, Ontario, Canada; and § Stroke Prevention and Atherosclerosis Clinic, Robarts Research Institute, London, Ontario, Canada (Received 17 May 2007; revised 20 June 2007; in final form 12 July 2007) Abstract—This study was designed to evaluate changes in carotid atherosclerosis using plaque and wall thickness maps derived from three-dimensional ultrasound (3DUS) images. Five subjects with carotid stenosis were scanned at baseline and 3 mo as part of a placebo-controlled intensive statin treatment study and three subjects with moderate atherosclerosis were scanned at baseline and again within 14  2 d. 3DUS-derived vessel wall volume (VWV) was measured using manual segmentation to provide segmentation contours that were used to generate scan and rescan carotid atherosclerosis thickness maps and thickness difference maps. There was no significant difference in VWV between scan and rescan for the three subjects scanned twice in 2 wk or the single subject treated with placebo. There was a significant difference between scan and rescan VWV for carotid stenosis subjects treated with atorvastatin (p < 0.001). Carotid atherosclerosis thickness difference maps showed visual qualitative evidence of thickness changes in vessel wall and plaque thickness in the common carotid artery for all statin-treated subjects and no change in a placebo-treated subject and subjects scanned twice in 2 wk. Carotid atherosclerosis thickness difference maps generated from 3DUS images provide evidence of vessel wall and plaque thickness changes for all subjects assessed. (E-mail: gep@imaging.robarts.ca) © 2007 World Federation for Ultrasound in Medicine & Biology. Key Words: Atherosclerosis, 3D Ultrasound, Thickness maps, Vessel wall volume, Carotid plaque, Stenosis. INTRODUCTION Despite our improved understanding of the mechanisms of atherosclerosis, it is still difficult to evaluate and confirm the positive clinical effects and outcomes asso- ciated with lipid lowering therapies by visually inspect- ing the coronary and carotid vessels (Brown et al. 1990, 2001). The discordance between clinical and angio- graphic findings (Tardif 2000) has been attributed to a number of factors, including the fact that in some cases, arterial wall and plaque changes cannot be detected using angiography due to the limitations imposed by the rep- resentation of three-dimensional (3D) vessels with single or even multiple two-dimensional (2D) images. In addi- tion, it has been postulated that specific changes resulting from lipid lowering and other therapies do not result in wall or bulk plaque changes that are readily measured using standard clinical imaging equipment. In other words, such potential plaque or wall-specific changes resulting from lipid lowering therapy comprise athero- sclerotic phenotypes that may not have been, as of yet, visualized, identified or quantified. While early evidence for atherosclerosis regression came from animal (Armstrong et al. 1970; Fritz et al. 1976; Vesselinovitch et al. 1974; Wagner and Clarkson 1977) and postmortem studies (Crawford et al. 1977), regression has been difficult to prove in vivo in clinical studies (Newby 2006). Recent results from carotid ultra- sound (Ashrafian et al. 2007; Mercuri et al. 1996; Nolt- ing et al. 2003; Smilde et al. 2001; Taylor et al. 2002), intravascular ultrasound (Jensen et al. 2004; Nissen et al. 2003, 2004, 2006; Takagi et al. 1997) and magnetic Address correspondence to: Grace Parraga, PhD, Imaging Re- search Laboratories, Robarts Research Institute, The University of Western Ontario, PO Box 5015, 100 Perth Drive, London, Ontario, Canada N6A 5K8. E-mail: gep@imaging.robarts.ca Ultrasound in Med. & Biol., Vol. 34, No. 1, pp. 64 –72, 2008 Copyright © 2007 World Federation for Ultrasound in Medicine & Biology Printed in the USA. All rights reserved 0301-5629/08/$–see front matter 64