Assessment of Collaborative Robot (Cobot)-Assisted Histotripsy for Venous Clot Ablation.

OBJECTIVE: The application of bubble-based ablation with the focus ultrasound therapy histotripsy is gaining traction for the treatment of venous thrombosis, among other pathologies. For extensive clot burden, the histotripsy source must be translated to ensure uniform bubble activity throughout the vascular obstruction. The purpose of this study was to evaluate the targeting accuracy of a histotripsy system comprised of a focused source, ultrasound image guidance, and a collaborative robot (cobot) positioner. The system was designed with a primary emphasis for treating deep vein thrombosis. METHODS: Studies to test treatment planning and targeting bubble activity with the histotripsy-cobot system were conducted in an in vitro clot model. A tissue-mimicking phantom was also targeted with the system, and the predicted and actual areas of liquefaction were compared to gauge the spatial accuracy of ablation. RESULTS: The system provided submillimeter accuracy for both tracking along an intended path (within 0.6 mm of a model vessel) and targeting bubble activity within the venous clot model (0.7 mm from the center of the clot). Good correlation was observed between the planned and actual liquefaction locations in the tissue phantom, with an average Dice similarity coefficient of 77.8%, and average Hausdorff distance of 1.6 mm. CONCLUSION: Cobots provide an effective means to apply histotripsy pulses over a treatment volume, with the ablation precision contingent on the quality of image guidance. SIGNIFICANCE: Overall, these results demonstrate cobots can be used to guide histotripsy ablation for targets that extend beyond the natural focus of the transducer.

Phase and amplitude evolution of backscattering by a sphere scanned through an acoustic vortex beam: Measured helicity projections.

While acoustic vortex beams have many potential applications, the full implication of the phase information available in scattering experiments has not been developed. The present paper concerns observables in measured near-backward scattering from a sphere in water raster scanned through a first-order acoustic vortex beam. Symmetrically placed transducer elements were operated in a transmit-receive mode. Helicity-dependent projections of the spatial evolution of the scattering were used to display magnitude and phase information. The resulting phase swirl patterns were projection dependent and especially sensitive to the transverse position of the sphere. The magnitude also depended on the sphere's position relative to the beam's axial null.

In Vitro Thrombolytic Efficacy of Single- and Five-Cycle Histotripsy Pulses and rt-PA.

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 0-30 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.

In vitro assessment of stiffness-dependent histotripsy bubble cloud activity in gel phantoms and blood clots.

As a bubble-based ablative therapy, the efficacy of histotripsy has been demonstrated in healthy or acutely diseased models. Chronic conditions associated with stiff tissues may require additional bubble activity prior to histotripsy liquefaction. In this study, histotripsy pulses were generated in agarose phantoms of Young's moduli ranging from 12.3 to 142 kPa, and in vitro clot models with mild and strong platelet-activated retraction. Bubble cloud emissions were tracked with passive cavitation imaging, and the threshold acoustic power associated with phantom liquefaction was extracted with receiver operator characteristic analysis. The power of histotripsy-generated emissions and the degree of liquefaction were tabulated for both clot models. For the agarose phantoms, the acoustic power associated with liquefaction increased with Young's modulus. When grouped based on agarose concentration, only two arms displayed a significant difference in the liquefaction threshold acoustic power (22.1 kPa versus 142 kPa Young's modulus). The bubble cloud dynamics tracked with passive cavitation imaging indicated no strong changes in the bubble dynamics based on the phantom stiffness. For identical histotripsy exposure, the power of acoustic emissions and degree of clot lysis did not vary based on the clot model. Overall, these results indicate that a fixed threshold acoustic power mapped with passive cavitation imaging can be utilized for predicting histotripsy liquefaction over a wide range of tissue stiffness.

Observation and modulation of the dissolution of histotripsy-induced bubble clouds with high-frame rate plane wave imaging.

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.

Assessment of histotripsy-induced liquefaction with diagnostic ultrasound and magnetic resonance imaging in vitro and ex vivo.

Histotripsy is a therapeutic ultrasound modality under development to liquefy tissue mechanically via bubble clouds. Image guidance of histotripsy requires both quantification of the bubble cloud activity and accurate delineation of the treatment zone. In this study, magnetic resonance (MR) and diagnostic ultrasound imaging were combined to assess histotripsy treatment in vitro and ex vivo. Mechanically ablative histotripsy pulses were applied to agarose phantoms or porcine livers. Bubble cloud emissions were monitored with passive cavitation imaging (PCI), and hyperechogenicity via plane wave imaging. Changes in the medium structure due to bubble activity were assessed with diagnostic ultrasound using conventional B-mode imaging and T 1-, T 2-, and diffusion-weighted MR images acquired at 3 Tesla. Liquefaction zones were correlated with diagnostic ultrasound and MR imaging via receiver operating characteristic (ROC) analysis and Dice similarity coefficient (DSC) analysis. Diagnostic ultrasound indicated strong bubble activity for all samples. Histotripsy-induced changes in sample structure were evident on conventional B-mode and T 2-weighted images for all samples, and were dependent on the sample type for T 1- and diffusion-weighted imaging. The greatest changes observed on conventional B-mode or MR imaging relative to baseline in the samples did not necessarily indicate the regions of strongest bubble activity. Areas under the ROC curve for predicting phantom or liver liquefaction were significantly greater than 0.5 for PCI power, plane wave and conventional B-mode grayscale, T 1, T 2, and ADC. The acoustic power mapped via PCI provided a better prediction of liquefaction than assessment of the liquefaction zone via conventional B-mode or MR imaging for all samples. The DSC values for T 2-weighted images were greater than those derived from conventional B-mode images. These results indicate diagnostic ultrasound and MR imaging provide complimentary sets of information, demonstrating that multimodal imaging is useful for assessment of histotripsy liquefaction.

The influence of gas diffusion on bubble persistence in shock-scattering histotripsy.

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.