Histotripsy bubble cloud contrast with chirp-coded excitation in pre-clinical models.

Histotripsy is a focused ultrasound therapy for tissue ablation via the generation of bubble clouds. These effects can be achieved noninvasively, making sensitive and specific bubble imaging essential for histotripsy guidance. Plane wave ultrasound imaging can track bubble clouds with excellent temporal resolution, but there is a significant reduction in echoes when deep seated organs are targeted. Chirp-coded excitation uses wideband, long duration imaging pulses to increase signals at depth and promote nonlinear bubble oscillations. In this study, we evaluated histotripsy bubble contrast with chirp-coded excitation in scattering gel phantoms and a subcutaneous mouse tumor model. A range of imaging pulse durations were tested, and compared to a standard plane wave pulse sequence. Received chirped signals were processed with matched filters to highlight components associated with either fundamental or subharmonic (bubble-specific) frequency bands. The contrast-to-tissue ratio was improved in scattering media for subharmonic contrast relative to fundamental contrast (both chirped and standard imaging pulses) with the longest-duration chirped pulse tested (7.4 μs pulse duration). The contrast-to-tissue ratio was improved for subharmonic contrast relative to fundamental contrast (both chirped and standard imaging pulses) by up to 4.25 ± 1.36 dB in phantoms and up to 3.84 ± 6.42 dB in vivo. No systematic changes were observed in the bubble cloud size or dissolution rate between sequences, indicating image resolution was maintained with the long-duration imaging pulses. Overall, this study demonstrates the feasibility of specific histotripsy bubble cloud visualization with chirp-coded excitation.