Histotripsy Bubble Cloud Contrast With Chirp-Coded Excitation in Preclinical 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 an 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 (CTR) 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 <inline-formula> <tex-math notation="LaTeX">mu text{s} </tex-math></inline-formula> pulse duration). The CTR was improved for subharmonic contrast relative to fundamental contrast (both chirped and standard imaging pulses) by 4.25 dB ± 1.36 dB in phantoms and 3.84 dB ± 6.42 dB <italic>in vivo</italic>. 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.