WE-C-218-01: Ultrasound Contrast Agents

Medical ultrasound has long been used in clinical applications both as a primary modality and as a supplement to other diagnostic procedures. The basis for ultrasound imaging is the transmission of high frequency (megaHertz) sound waves that propagate through tissue. These sound waves backscatter from the interfaces between tissue components with different acoustic properties and are detected by the imaging system, allowing the creation of images based on tissue characteristics and spatial location. Thus, traditional ultrasound has focused primarily on the imaging of anatomical structures and analysis of blood flow in large vessels. Unfortunately, blood is a weak scatterer, which can make vascular diagnostic applications (example: echocardiography) challenging especially with larger patients. Contrast agents help to improve on this shortcoming by enhancing the visualization of blood flow, thus improving the quality of diagnostics. The use of contrast agents for ultrasound was first reported in 1968 when Gramiak and Shah discovered that there was an increased backscatter of ultrasound caused by injected microbubbles. This is because the mismatch in acoustic impedance (a function of an object's density and compressibility) between the microbubble gas core and blood (or tissue) is several orders of magnitude, which results in substantially higher scattering from a bubble than an equivalent volume of tissue or blood. Additionally, microbubbles oscillate in response to an ultrasound field, and respond non-linearly to acoustic pulses even at low energies, unlike tissue. The non-linear property of microbubbles in an ultrasound field allows for the use of various pulsing and signal processing strategies to detect the backscattered signal from contrast agents and segment it from tissue, thus providing a high contrast-to- noise ratio. Due to these unique acoustic properties, a clinical ultrasound system can detect even single microbubble contrast agents, providing exquisite sensitivity and the ability to perform advanced diagnostic procedures. Over the last several decades, ultrasound contrast agents have been improved for enhanced stability and increased persistence times. Although preclinical studies as well as clinical use in Europe and Asia strongly suggest that the use of contrast ultrasound can substantially improve diagnostic capabilities in both cardiology and radiology applications, contrast use in the US is still very limited. Obstacles to the widespread use of microbubbles include safety concerns, the need for optimization of approaches for contrast use, and general understanding of their potential by physicians. This course covers the basic principles of contrast agents used in ultrasound imaging including their stability, shell properties and their behavior within an acoustic field. In addition, we will cover many new techniques that are being evaluated in preclinical studies including: p er fus ion-based techniques, molecular imaging, gene therapy, drug delivery, and acoustic angiography. Finally, basic safety concerns and biological effects will be reviewed.

1. Understand the basic principles of ultrasound contrast agents a. What are microbubble contrast agents? b. Properties of microbubbles c. Safety concerns and biological effects 2. Understand basic contrast imaging techniques a. Harmonic and suharmonic imaging techniques b. Pulse inversion techniques 3. Understand the use of contrast agents in various vascular applications a. Traditional methods (Cardiovascular, Abdominal) b. Advanced perfusion imaging techniques 4. Understand the role of contrast agents in preclinical applications a. Ultrasound molecular imaging b. Gene therapy c. Drug delivery d. Acoustic angiography.