Feasibility of Clinical Application of Ultrasound Molecular Imaging

Abstract

Ultrasound imaging has been utilized for the non-invasive and real-time observation of pathophysiological conditions in clinical settings. To enhance blood flow signals, microbubbles that are quite different in acoustic impedance from blood have been utilized as the contrast agent for ultrasound imaging. Unfortunately, the initial performance of intravenous contrast-enhanced ultrasound imaging was hampered by the pulmonary circulation due to the size of the microbubbles. Additionally, the detection of microbubbles was not easy because of the weak signals derived from the bubbles. However, recent improvements in the bubble physics and ultrasound imaging technologies have enabled non-invasive assessment of organ perfusion by intravenous administration of microbubbles (Chahal & Senior, 2010; Porter & Xie, 2010; Wilson & Burns, 2010). Of note, the fate of intravenously administrated microbubbles is similar to that of red blood cells (Keller et al., 1989; Jayaweera et al., 1994). Many contrast agents for contrast-enhanced ultrasound imaging are now clinically available all over the world (Table 1). On the other hand, ultrasound molecular imaging, which visualizes molecular dynamics in situ by detecting the signals derived from retained microbubbles in the target regions, has been recently developed. As microbubbles are the intravascular blood flow tracer, ultrasound molecular imaging predominantly targets activated leukocytes and molecules expressed on endothelial cells. Many papers have been published regarding the diagnostic utility of ultrasound molecular imaging for the detection of inflammation, atherosclerosis and tumor angiogenesis (Villanueva & Wagner, 2008; Leong-Poi, 2009; Lindner, 2009; Chadderdon & Kaul, 2010; Deshpande et al., 2010). The utility of molecular imaging has been demonstrated using several modalities, including positron emission tomography (PET), magnetic resonance imaging (MRI) and near-infrared fluorescence (NIRF) (Jaffer & Weissleder, 2005). Although PET and MRI provide accurate diagnostic information, the versatility of these two modalities is limited. On the other hand, ultrasound examination is cost effective and is able to be performed at the bedside. Therefore, the adaptation of ultrasound molecular imaging for clinical settings is desired. For the clinical translation of ultrasound molecular imaging, however, some bottlenecks need to be overcome at the same time, including the development of clinically translatable targeted bubbles and the improvement of ultrasound imaging techniques. This chapter summarizes the recent advances in the preparation of targeted bubbles and ultrasound