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 associatedwith 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.