Targeted Contrast-Enhanced Ultrasound: An Emerging Technology in Abdominal and Pelvic Imaging

Abstract

In vivo molecular imaging provides the ability to measure expression levels of molecules by quantifying imaging signals generated with the help of contrast agents accumulating at sites of molecular target expression. These contrast agents can be directed to bind various molecular targets in vivo (eg, proteins, DNA, etc), thereby quantifying disease processes at the molecular level in various disease processes. Thus, molecular imaging has the potential to obtain tissue expression profiles in a volumetric manner without invasive tissue sampling procedures and without the limitation of potential sampling errors from biopsies. Emerging research in ultrasound technology and contrast agent design for ultrasound imaging has paved the way for targeted contrast-enhanced ultrasound imaging to be translated to clinical applications in the near future.1–6 Ultrasound imaging is a widely available, inexpensive, and real-time imaging modality that does not expose patients to irradiation. It is already the first-line imaging modality for assessment of many diseases in the abdomen and pelvis. Through the introduction of ultrasound contrast agents (eg, lipid-shelled, gas-filled, 1- to 4-micron-sized microbubbles), the sensitivity and specificity of ultrasound for detection and characterization of for example focal liver lesions7,8 has been substantially improved. Recently, targeted contrast-enhanced ultrasound (molecular ultrasound) imaging has gained great momentum in preclinical research by the introduction of ultrasound contrast microbubbles that are targeted at molecular markers overexpressed on the vasculature of certain diseases (Figure 1A and Supplementary Figure 1). By combining the advantages of ultrasound with the ability to image molecular signatures of diseases, molecular ultrasound has great potential as a highly sensitive and quantitative method that could be used for various clinical applications, including screening for early stage diseases (such as cancer); further characterization of focal lesions and quantitative monitoring of disease processes at the molecular level; assisting in image-guided procedures (eg, biopsy, surgery, or ablation); enhancing drug delivery; and confirming target expression for treatment planning and monitoring (including novel drug candidates in preclinical studies).1,4,6,9,10 Figure 1 Principles of nontargeted and molecularly targeted contrast-enhanced ultrasound imaging with contrast microbubbles. (A) The gas core of lipid- or protein-shelled microbubbles (left) makes them highly echogenic compared to surrounding tissue and blood. ... We describe herein concepts and applications in contrast-enhanced and molecular ultrasound imaging with particular focus on imaging cancer and inflammatory diseases in the abdomen and pelvis.