Dual-Frequency Chirp Excitation for Passive Cavitation Imaging in the Brain

One of the main challenges that impede cavitation-mediated imaging in the brain is restricted opening of the blood-brain barrier (BBB) making it difficult to locate cavitating microbubbles (MBs). Passive cavitation imaging (PCI) has received attention due to the possibility of performing real-time monitoring by listening to acoustic cavitation. However, the long excitation pulses associated with PCI degrade its axial resolution. The present study combined a coded excitation technique with a dual-frequency chirp (DFC) excitation method to prevent interference from the nonlinear components of MBs' cavitation. The use of DFC excitation generates a low-frequency (0.4, 0.5, or 0.6 MHz) chirp component as the envelope of the signal-driving MBs' cavitation with a dual-frequency pulse ( ω1 = 1.35 MHz and ω2 = 1.65 MHz, ω1 = 1.3 MHz and ω2 = 1.7 MHz, and ω1 = 1.25 MHz and ω2 = 1.75 MHz). The cavitation of MBs was passively imaged utilizing a chirp component with pulse compression to maintain abundant insonation energy without any reduction in the axial imaging resolution. In vitro experiments showed that the DFC method improved the signal-to-noise ratio by 42.2% and the axial resolution by 4.1-fold compared with using a conventional long-pulse waveform. Furthermore, the cavitating MBs driven by different ultrasound (US) energy (0, 0.3, 0.6, and 0.9 MPa, N = 3 for each group) in the rat brain with an intact skull still could be mapped by DFC. Our successful demonstration of using the DFC method to image cavitation-induced BBB opening affords an alternative tool for assessing cavitation-dependent drug delivery to the brain, with the benefit of real-time and high convenient integration with current US imaging devices.