[Ultrasound contrast agents--physical basics]

The concept of ultrasound contrast agents (UCA) is based on the inherent physical and acoustical properties of gas-filled microbubbles within an ultrasonic (US) field. Depending on the magnitude of the incident US wave different scattering behavior occurs. While it is linear for low acoustic pressures, increasing it leads to the occurrence of nonlinear effects, such as emission of harmonics. High pressure results in destruction of the bubbles producing a highly nonlinear echo signal. Using these specific acoustic signatures opens new perspectives for the development of bubble-specific imaging techniques such as harmonic or intermittent imaging. This review deals with the physical properties of the gas-filled microbubbles, their behavior within an ultrasonic field, and the use of the bubbles' acoustic signatures for contrast-specific imaging. Novel applications such as tissue-specific microbubbles, targeted imaging, and therapeutic applications using the bubbles as vehicles for drug or gene delivery are discussed as well as acoustically induced bioeffects and considerations for the safe use of UCA from an acoustic standpoint.