Endoscopic Coregistered Ultrasound Imaging and Precision Histotripsy: Initial In Vivo Evaluation

Abstract

Objective. Initial performance evaluation of a system for simultaneous high-resolution ultrasound imaging and focused mechanical submillimeter histotripsy ablation in rat brains. Impact Statement. This study used a novel combination of high-resolution imaging and histotripsy in an endoscopic form. This would provide neurosurgeons with unprecedented accuracy in targeting and executing nonthermal ablations in minimally invasive surgeries. Introduction. Histotripsy is a safe and effective nonthermal focused ablation technique. However, neurosurgical applications, such as brain tumor ablation, are difficult due to the presence of the skull. Current devices are too large to use in the minimally invasive approaches surgeons prefer. We have developed a combined imaging and histotripsy endoscope to provide neurosurgeons with a new tool for this application. Methods. The histotripsy component had a 10 mm diameter, operating at 6.3 MHz. Affixed within a cutout hole in its center was a 30 MHz ultrasound imaging array. This coregistered pair was used to ablate brain tissue of anesthetized rats while imaging. Histological sections were examined, and qualitative descriptions of ablations and basic shape descriptive statistics were generated. Results. Complete ablations with submillimeter area were produced in seconds, including with a moving device. Ablation progress could be monitored in real time using power Doppler imaging, and B-mode was effective for monitoring post-ablation bleeding. Collateral damage was minimal, with a 100 μm maximum distance of cellular damage from the ablation margin. Conclusion. The results demonstrate a promising hardware suite to enable precision ablations in endoscopic procedures or fundamental preclinical research in histotripsy, neuroscience, and cancer.

Freeform Etching of Microchannels in Hydrogels by Ultrasonic Cavitation

“…The transducer was controlled by way of a function generator and a custom control board, with the input voltage provided by a high voltage power supply. A unique feature of the pHIFU system employed here was the ability to image the cavitation process by way of a second imaging transducer element [ 32 ] (Figure 1A,B; Figure S2, Supporting Information). For co‐registered imaging, the imaging transducer can be inserted into the center of the histotripsy transducer to visualize the plane containing the focal ablation zone.…”

“…For co‐registered imaging, the imaging transducer can be inserted into the center of the histotripsy transducer to visualize the plane containing the focal ablation zone. [ 32 ]…”

“…At higher voltages, this relationship becomes nonlinear as previously reported. [ 32 ] There was no evidence of pre‐focal cavitation in the prefocal region.…”

“…pHIFU Etching: The pHIFU pulses consisted of 8 cycle bursts at 5.7 MHz and were generated using a 10 mm aperture transducer with a 7 mm nominal focal distance and elliptically shaped aluminum lens. [32,46] High frequencies were chosen relative to other frequencies typically used for cavitation (≤1 MHz) to achieve small and uniform diameter channels. Due to the maximum pressure/voltage of the transducer at 5.7 MHz, this was an appropriate frequency to reach the cavitation threshold.…”

“…The low-voltage output and device geometry values were used as parameters in the HITU Simulator v2.0 modeling software to estimate the nonlinear Pa V À1 at high voltages. [32,50] Imaging of Microchannels: Bright-field images of microchannels were obtained using a Nikon Eclipse Ti microscope (Nikon Instruments) and then analyzed with ImageJ to measure the length and width of the microchannels. Ablation volume was calculated from bright-field images at two different views (top and side) using ImageJ.…”