Ultrasound imaging of extravascular molecular targets with light and optically triggered nanoscale contrast agents

To obtain high sensitivity, specificity, and signal/contrast-to-noise ratio imaging of disease, detection of biomarkers or biochemical and cellular processes is often needed. Typically, such information is gathered using imaging contrast agents. Unfortunately, microbubbles—most common ultrasound contrast agent, are too large to escape vascular compartments. Thus, contrast-enhanced molecular ultrasound imaging is often limited to molecular markers on the vascular endothelium and other intravascular targets. Recently, we introduced several high-resolution, high-sensitivity, depth-resolved ultrasound-based molecular imaging techniques augmented with nanometer scale imaging contrast agents capable of visualizing molecular signatures of cells in context of structural and functional properties of tissue. In this presentation, several examples of molecular ultrasound imaging based on synergistic combination of light and sound will be given. Specifically, clinical problems including detection and phenotyping of primary tumor, assessment of micrometastatic lesions in sentinel lymph node, and image-guided cancer cell therapy will be described. Design and synthesis of clinically relevant contrast nanoagents with properties desired for cellular/molecular ultrasound imaging will be discussed. Finally, the presentation will conclude with the analysis of how molecular ultrasound can change both fundamental medical science and the utility of clinical ultrasound imaging in diagnostic and therapeutic applications.