Although primarily known as an ablative modality, histotripsy can increase the efficacy of lytic therapy in a retracted venous clot model. Bubble cloud oscillations are the primary mechanism of action for histotripsy, and the type of bubble activity is dependent on the pulse duration. A retracted human venous clot model was perfused with and without the thrombolytic recombinant tissue plasminogen activator (rt-PA). The clot was exposed to histotripsy pulses of single-or five-cycle duration and peak negative pressures of 0À30 MPa. Bubble activity within the clot was monitored via passive cavitation imaging. The combination of histotripsy and rt-PA was more efficacious than rt-PA alone for single-and five-cycle pulses with peak negative pressures of 25 and 20 MPa, respectively. For both excitation schemes, the detected acoustic emissions correlated with the degree of thrombolytic efficacy. These results indicate that rt-PA and single-or multicycle histotripsy pulses enhance thrombolytic therapy.

We present direct measurement of Kirkwood-Rihaczek (KR)distribution for spatial properties of coherent light beam in terms of position and momentum (angle) coordinates. We employ a two-local oscillator (LO) balanced heterodyne detection (BHD) to simultaneously extract distribution of transverse position and momentum of a light beam. The two-LO BHD could measure KR distribution for any complex wave field (including quantum mechanical wave function) without applying tomography methods (inverse Radon transformation). Transformation of KR distribution to Wigner, Glauber Sudarshan P-and Husimi or Q-distributions in spatial coordinates are illustrated through experimental data. The direct measurement of KR distribution could provide local information of wave field, which is suitable for studying particle properties of a quantum system. While Wigner function is suitable for studying wave properties such as interference, and hence provides nonlocal information of the wave field. The method developed here can be used for exploring spatial quantum state for quantum mapping and computing, optical phase space imaging for biomedical applications.

Bubble cloud persistence reduces the efficacy of mechanical liquefaction with shock-scattering histotripsy. In this study, the contribution of gas transfer to bubble longevity was investigated in silico by solving the equations for bubble oscillations and diffusion in parallel. The bubble gas content increased more than 5 orders of magnitude during the expansion phase, arresting the inertial collapse. The residual gas bubble required more than 15 ms for passive dissolution post excitation, consistent with experimental observation. These results demonstrate gas diffusion is an important factor in the persistence of histotripsy-induced cavitation.

Focused ultrasound therapies are a noninvasive means to ablate tissue. Histotripsy utilizes short ultrasound pulses with sufficient tension to nucleate bubble clouds that impart lethal strain to the surrounding tissues. Tracking bubble cloud dissolution between the application of histotripsy pulses is critical to ensure treatment efficacy. In this study, plane wave B-mode imaging was employed to monitor bubble cloud motion and grayscale at frame rates up to 11.25 kHz. Minimal changes in the area or position of the bubble clouds were observed 50 ms post excitation. The bubble cloud grayscale was observed to decrease with the square root of time, indicating a diffusion-driven process. These results were qualitatively consistent with an analytic model of gas diffusion during the histotripsy process. Finally, the rate of bubble cloud dissolution was found to be dependent on the output of the imaging pulse, indicating an interaction between the bubble cloud and imaging parameters. Overall, these results highlight the utility of plane wave B-mode imaging for monitoring histotripsy bubble clouds.

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