RESUMEN
Focused ultrasound (FUS) combined with microbubbles (MBs) has emerged as a promising strategy for transiently opening the blood-brain barrier (BBB) to enhance drug permeability in the brain. Current FUS systems for BBB opening use piezoelectric transducers as transmitters and receivers. While capacitive micromachined ultrasonic transducers (CMUTs) have been suggested as a FUS receiver alternative due to their broad bandwidth, their capabilities as transmitters have not been investigated. This is mainly due to the intrinsic nonlinear behavior of CMUTs which complicates the detection of MB generated harmonic signals and their low pressure output at FUS frequencies. Various methods have been proposed to mitigate CMUT nonlinearity; however, these approaches have primarily targeted contrast enhanced ultrasound imaging. In this study, we propose the use of polyphase modulation (PM) technique to isolate MB emissions when CMUTs are employed as transmitters for BBB opening. Our calculations for a human scale FUS system with multiple CMUT transmitters show that 10 kPa peak negative pressure at 150 mm focal distance will be sufficient for MB excitation for BBB opening. Experimental findings indicate that this pressure level can be easily generated at 400-800 kHz using a readily available CMUT. Furthermore, more than 50 dB suppression of the fundamental harmonic signal is obtained in free field and transcranial hydrophone measurements by processing receive signals in response to phase modulated transmit waveforms. In-vitro validation of PM is also conducted using Definity MB flowing through a tube phantom. MB-filled tube phantoms show adequate nonlinear signal isolation and SNR for MB harmonic detection. Together our findings indicate that PM can effectively mitigate CMUT harmonic generation, thereby creating new opportunities for wideband transmission and receive operation for BBB opening in clinical and preclinical applications.
RESUMEN
Intravascular ultrasound (IVUS) is a well-established diagnostic method that provides images of the vessel wall and atherosclerotic plaques. We investigate the potential for phased-array IVUS utilizing coded excitation (CE) for improving the penetration depth and image signal-to-noise ratio (SNR). It is realized on a new experimental broadband capacitive micromachined ultrasound transducer (CMUT) array, operated in collapse mode, with 96 elements placed at the circumference of a catheter tip with a 1.2- mm diameter. We characterized the array performance for CE imaging and showed that the -6-dB device bandwidth at a 30-V dc biasing is 25 MHz with a 20-MHz center frequency, with a transmit sensitivity of 37 kPa/V at that frequency. We designed a linear frequency modulation code to improve penetration depth by compensating for high-frequency attenuation while preserving resolution by a mismatched filter reconstruction. We imaged a wire phantom and a human coronary artery plaque. By assessing the image quality of the reconstructed wire phantom image, we achieved 60- and 70- µm axial resolutions using the short pulse and coded signal, respectively, and gained 8 dB in SNR for CE. Our developed system shows 20-frames/s, pixel-based beam-formed, real-time IVUS images.
