Recent developments in ultrasound imaging and ultrasound contrast agents (UCAs) improved diagnostic confidence in echography and set into motion their combined use as a tool for drug delivery and therapeutic monitoring. Non-invasive, precise and targeted delivery of drug molecules to pathological tissues by employing different mechanisms of drug release is becoming feasible. Areas covered: We sought to describe: the nature and features of UCAs; outline current contrast-specific imaging modes; before describing a variety of strategies for using ultrasound and microbubbles as a drug delivery system. Our expert opinion focusses on results and prospects of using ultrasound and microbubbles as a dual modality for drug delivery and therapeutic monitoring. Expert opinion: Today, ultrasound and microbubbles present a realistic prospect as drug delivery tools that have been demonstrated in a variety of animal models and clinical indications. Besides delivering drugs, ultrasound and microbubbles have demonstrated added value through therapeutic monitoring and assessment. Successful evaluation of the sonoporation mechanism(s), ultrasound parameters, drug type and dose will need to be addressed before translating this technology for clinic use. Ultimately, the development of a strategy for monitoring targeted delivery and its implementation in clinical practice would advance therapeutic treatment to a new qualitative level.
Capacitive micromachined ultrasonic transducers (cMUTs) provide promising ultrasonic technology that could become an alternative to piezoelectric probes for medical applications. cMUTs could be very valuable for contrast-enhanced ultrasound imaging based on higher harmonics detection. However, their use is restricted by the intrinsic nonlinearity of the cMUT transmitters themselves, because it is difficult to distinguish between the nonlinearity of the microbubbles and the nonlinearity arising from the emitting transducer. A number of approaches have been proposed in recent years to cancel the nonlinearity of cMUTs. However, these techniques have limitations in terms of implementation with current ultrasound scanner electronics. The solution to be comparable with classical methods should not need precharacterization of the probe or changing the bias voltage (amplitude or polarity) but does need good sensitivity and a high frame rate to avoid motion artifacts. We propose here proof of a concept of an adapted amplitude modulation sequence with cMUT where transmit elements operate alternately. We show that this method, which is currently used with piezoelectric probes, is fully applicable to cMUT probes and the intrinsic nonlinearity of the transmitter is no longer an issue.
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