A feasibility study was undertaken in order to investigate alternative noninvasive treatment options for atherosclerosis. In particular, the aim of this study was to investigate the potential use of Dual-Mode Ultrasound Arrays (DMUAs) for image guided treatment of atheromatous plaques. DMUAs offer a unique treatment paradigm for image-guided surgery allowing for robust image-based identification of tissue targets for localized application of HIFU. In this study we present imaging and therapeutic results form a 3.5 MHz, 64-element fenestrated prototype DMUA for targeting lesions in the femoral artery of familial hypercholesterolemic (FH) swine. Before treatment, diagnostic ultrasound was used to verify the presence of plaque in the femoral artery of the swine. Images obtained with the DMUA and a diagnostic (HST 15-8) transducer housed in the fenestration were analyzed and used for guidance in targeting of the plaque. Discrete therapeutic shots with an estimated focal intensity of 4000-5600 W/cm2 and 500-2000 msec duration were performed at several planes in the plaque. During therapy, pulsed HIFU was interleaved with single transmit focus imaging from the DMUA and M2D imaging from the diagnostic transducer for further analysis of lesion formation. After therapy, the swine's were recovered and later sacrificed after 4 and 7 days for histological analysis of lesion formation. At sacrifice, the lower half of the swine was perfused and the femoral artery with adjoining muscle was fixed and stained with H&E to characterize HIFU-induced lesions. Histology has confirmed that localized thermal lesion formation within the plaque was achieved according to the planned lesion maps. Furthermore, the damage was confined to the plaque tissue without damage to the intima. These results offer the promise of a new treatment potentially suited for vulnerable plaques. The results also provide the first real-time demonstration of DMUA technology in targeting fine tissue structures for precise lesion formation in the presence or arterial pulsation and tissue motion. In this paper, we show results from targeting both proximal and distal sides of the vessel wall with a series of 5 - 7 discrete shots in each plane (typically three planes per plaque). Experiments to demonstrate a full treatment forming contiguous lesion within the target plaque are currently underway.