The main constituent of an ultrasound contrast agent (UCA) is gas-filled microbubbles. An average UCA contains billions per ml. These microbubbles are excellent ultrasound scatterers due to their high compressibility. In an ultrasound field they act as resonant systems, resulting in harmonic energy in the backscattered ultrasound signal, such as energy at the subharmonic, ultraharmonic and higher harmonic frequencies. This harmonic energy is exploited for contrast enhanced imaging to discriminate the contrast agent from surrounding tissue. The amount of harmonic energy that the contrast agent bubbles generate depends on the bubble characteristics in combination with the ultrasound field applied. This paper summarizes different strategies to characterize the UCAs. These strategies can be divided into acoustic and optical methods, which focus on the linear or nonlinear responses of the contrast agent bubbles. In addition, the characteristics of individual bubbles can be determined or the bubbles can be examined when they are part of a population. Recently, especially optical methods have proven their value to study individual bubbles. This paper concludes by showing some examples of optically observed typical behavior of contrast bubbles in ultrasound fields.

Compressive 3D ultrasound imaging is possible with only one sensor and a simple aperture coding mask.

Ultrasound insonification of microbubbles can locally increase vascular permeability to enhance drug delivery. To control and optimize the therapeutic potential, we need to better understand the underlying biological mechanisms of the drug delivery pathways. The aim of this in vitro study was to elucidate the microbubble-endothelial cell interaction using the Brandaris 128 ultra-high-speed camera (up to 25 Mfps) coupled to a custom-built Nikon confocal microscope, to visualize both microbubble oscillation and the cellular response. Sonoporation and opening of cell-cell contacts by single α_Vβ₃-targeted microbubbles (n = 152) was monitored up to 4 min after ultrasound insonification (2 MHz, 100-400 kPa, 10 cycles). Sonoporation occurred when microbubble excursion amplitudes exceeded 0.7 μm. Quantification of the influx of the fluorescent model drug propidium iodide upon sonoporation showed that the size of the created pore increased for larger microbubble excursion amplitudes. Microbubble-mediated opening of cell-cell contacts occurred as a cellular response upon sonoporation and did not correlate with the microbubble excursion amplitude itself. The initial integrity of the cell-cell contacts affected the susceptibly to drug delivery, since cell-cell contacts opened more often when cells were only partially attached to their neighbors (48%) than when fully attached (14%). The drug delivery outcomes were independent of nonlinear microbubble behavior, microbubble location, and cell size. In conclusion, by studying the microbubble-cell interaction at nanosecond and nanometer resolution the relationship between drug delivery pathways and their underlying mechanisms was further unraveled. These novel insights will aid the development of safe and efficient microbubble-mediated drug delivery.

This paper presents a front-end application-specified integrated circuit (ASIC) integrated with a 2-D PZT matrix transducer that enables in-probe digitization with acceptable power dissipation for the next-generation endoscopic and catheter-based 3-D ultrasound imaging systems. To achieve power-efficient massively parallel analog-to-digital conversion (ADC) in a 2-D array, a 10-bit 30 MS/s beamforming ADC that merges the subarray beamforming and digitization functions in the charge domain is proposed. It eliminates the need for costly intermediate buffers, thus significantly reducing both power consumption and silicon area. Self-calibrated charge references are implemented in each subarray to further optimize the system-level power efficiency. High-speed datalinks are employed in combination with the subarray beamforming scheme to realize a 36-fold channel-count reduction and an aggregate output data rate of 6 Gb/s for a prototype receive array of $24 \times 6$ elements. The ASIC achieves a record power efficiency of 0.91 mW/element during receive. Its functionality has been demonstrated in both electrical and acoustic imaging experiments.