Stanford Advisors


All Publications


  • Respiratory Motion Effects and Mitigation Strategies on Boiling Histotripsy in Porcine Liver and Kidney IEEE TRANSACTIONS ON ULTRASONICS FERROELECTRICS AND FREQUENCY CONTROL Ponomarchuk, E. M., Thomas, G. L., Song, M., Wang, Y., Totten, S., Schade, G. R., Khokhlova, V. A., Khokhlova, T. D. 2025; 72 (6): 837-846

    Abstract

    Boiling histotripsy (BH) is a pulsed high-intensity focused ultrasound (HIFU)-based method of extracorporeal nonthermal tissue disintegration under real-time ultrasound (US) guidance. Respiratory motion in abdominal targets can affect BH precision and completeness. This study compares two motion mitigation strategies based on pulse/echo US motion tracking: robotic arm-based unidirectional motion compensation by HIFU transducer manipulation and BH pulse gating during expiratory pause. BH ablations were generated in the liver and kidney of anesthetized pigs with 2-10-ms pulses using a 256-element 1.5-MHz HIFU array. A coaxial US imaging probe was used for targeting, tracking skin surface, and monitoring real-time bubble activity. The axial [anterior-posterior (AP)] displacement of the skin surface was found to be synchronous with liver and kidney motion in both cranio-caudal (CC) and AP directions. BH lesions were produced either with no motion mitigation, or with pulse gating, or with 1-D motion compensation. Dimensions of completely fractionated and affected tissue areas were measured histologically. In liver, gating and motion compensation improved fractionation completeness within targeted volumes and reduced off-target tissue damage in AP direction versus no motion mitigation; only gating reduced off-target damage in CC direction. In kidney, gating improved BH completeness in both directions versus no mitigation, but did not affect off-target damage due to lower displacement amplitudes in the kidney comparable with gating tolerance limits. In both liver and kidney, gating increased treatment time by 24%. These results suggest that BH pulse gating using US-based AP skin surface tracking is an adequate approach for treating organs with pronounced 3-D respiratory motion.

    View details for DOI 10.1109/TUFFC.2025.3559458

    View details for Web of Science ID 001499682800012

    View details for PubMedID 40202884

  • Dynamic mode decomposition based Doppler monitoring of de novo cavitation induced by pulsed HIFU: an in vivo feasibility study. Scientific reports Song, M., Sapozhnikov, O. A., Khokhlova, V. A., Son, H., Totten, S., Wang, Y., Khokhlova, T. D. 2024; 14 (1): 22295

    Abstract

    Pulsed high-intensity focused ultrasound (pHIFU) has the capability to induce de novo cavitation bubbles, offering potential applications for enhancing drug delivery and modulating tissue microenvironments. However, imaging and monitoring these cavitation bubbles during the treatment presents a challenge due to their transient nature immediately following pHIFU pulses. A planewave bubble Doppler technique demonstrated its potential, yet this Doppler technique used conventional clutter filter that was originally designed for blood flow imaging. Our recent study introduced a new approach employing dynamic mode decomposition (DMD) to address this in an ex vivo setting. This study demonstrates the feasibility of the application of DMD for in vivo Doppler monitoring of the cavitation bubbles in porcine liver and identifies the candidate monitoring metrics for pHIFU treatment. We propose a fully automated bubble mode identification method using k-means clustering and an image contrast-based algorithm, leading to the generation of DMD-filtered bubble images and corresponding Doppler power maps after each HIFU pulse. These power Doppler maps are then correlated with the extent of tissue damage determined by histological analysis. The results indicate that DMD-enhanced power Doppler map can effectively visualize the bubble distribution with high contrast, and the Doppler power level correlates with the severity of tissue damage by cavitation. Further, the temporal characteristics of the bubble modes, specifically the decay rates derived from DMD, provide information of the bubble dissolution rate, which are correlated with tissue damage level-slower rates imply more severe tissue damage.

    View details for DOI 10.1038/s41598-024-73787-w

    View details for PubMedID 39333771

  • Histology-based quantification of boiling histotripsy outcomes via ResNet-18 network: Towards mechanical dose metrics ULTRASONICS Ponomarchuk, E., Thomas, G., Song, M., Krokhmal, A., Kvashennikova, A., Wang, Y., Khokhlova, V., Khokhlova, T. 2024; 138: 107225

    Abstract

    This work was focused on the newly developed ultrasonic approach for non-invasive surgery - boiling histotripsy (BH) - recently proposed for mechanical ablation of tissues using pulsed high intensity focused ultrasound (HIFU). The BH lesion is known to depend in size and shape on exposure parameters and mechanical properties, structure and composition of tissue being treated. The aim of this work was to advance the concept of BH dose by investigating quantitative relationships between the parameters of the lesion, pulsing protocols, and targeted tissue properties. A HIFU focus of a 1.5 MHz 256-element array driven by power-enhanced Verasonics system was electronically steered along the grid within 12 × 4 × 12 mm volume to produce volumetric lesions in porcine liver (soft, with abundant collagenous structures) and bovine myocardium (stiff, homogenous cellular) ex vivo tissues with various pulsing protocols (1-10 ms pulses, 1-15 pulses per point). Quantification of the lesion size and completeness was performed through serial histological sectioning, and a computer vision approach using a combination of manual and automated detection of fully fractionated and residual tissue based on neural network ResNet-18 was developed. Histological sample fixation led to underestimation of BH ablation rate compared to the ultrasound-based estimations, and provided similar qualitative feedback as did gross inspection. This suggests that gross observation may be sufficient for qualitatively evaluating the BH treatment completeness. BH efficiency in liver tissue was shown to be insensitive to the changes in pulsing protocol within the tested parameter range, whereas in bovine myocardium the efficiency increased with either increasing pulse length or number of pulses per point or both. The results imply that one universal mechanical dose metric applicable to an arbitrary tissue type is unlikely to be established. The dose metric as a product of the BH pulse duration and the number of pulses per sonication point (BHD1) was shown to be more relevant for initial planning of fractionation of collagenous tissues. The dose metric as a number of pulses per point (BHD2) is more suitable for the treatment planning of softer targets primarily containing cellular tissue, allowing for significant acceleration of treatment using shorter pulses.

    View details for DOI 10.1016/j.ultras.2023.107225

    View details for Web of Science ID 001144927000001

    View details for PubMedID 38141356