Minho Song

All Publications

• Doppler-based assessment of boiling histotripsy-induced volumetric tissue liquefaction in vivo. Ultrasonics Song, M., Thomas, G. P., Khokhlova, V. A., Wang, Y., Totten, S. I., Sapozhnikov, O. A., Schade, G. R., Khokhlova, T. 2025; 156: 107775

  Abstract

  Boiling histotripsy (BH) is a promising method for mechanical tissue fractionation and liquefaction, utilizing millisecond-long high-intensity focused ultrasound (HIFU) pulses with shock fronts. Recent study has reported that cavitation bubbles induced during the BH pulse can move within the liquefied treated volume for a few milliseconds to seconds after each BH pulse ends. These bubble motions can be observed by ultrasound Doppler measurements, with maximum Doppler velocity showing significant potential as a metric to determine the treatment completion, as previously demonstrated in ex vivo setting. Here, this velocity metric was tested based on the results of in vivo pig experiments, along with tissue liquefaction levels evaluated from histology. A 256-element 1.5MHz spiral HIFU array with a center opening for the imaging probe installation was used for BH pulse control. A sequence of 10ms BH pulses with a 1Hz pulse repetition frequency (PRF) was delivered to the predesigned two-dimensional target grid to generate large liquefied volumes. A small aperture (around 2cm) imaging probe was mounted at the center opening of HIFU transducer and used for planewave Doppler and B-mode imaging. To increase the maximum measurable Doppler velocity, a high PRF regime was applied instead of the conventional pulse-echo regime. The results showed that the maximum velocity increased over the treatment from 40 to 100cm/s as the tissue progressively changed from intact to completely liquefied. The distribution of elevational averaged maximum velocity along the lateral target volumes aligned well with the lesion shown in the corresponding histological image and statistically significantly correlated with the liquefaction grade. A maximum velocity above 84cm/s ensured the complete liquefaction level, reinforcing its potential as a metric to determine successful treatment.

  View details for DOI 10.1016/j.ultras.2025.107775

  View details for PubMedID 40752065

• 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. P. 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

• Dynamic Mode Decomposition for Transient Cavitation Bubbles Imaging in Pulsed High-Intensity Focused Ultrasound Therapy. IEEE transactions on ultrasonics, ferroelectrics, and frequency control Song, M., Sapozhnikov, O. A., Khokhlova, V. A., Khokhlova, T. D. 2024; 71 (5): 596-606

  Abstract

  Pulsed high-intensity focused ultrasound (pHIFU) can induce sparse de novo inertial cavitation without the introduction of exogenous contrast agents, promoting mild mechanical disruption in targeted tissue. Because the bubbles are small and rapidly dissolve after each HIFU pulse, mapping transient bubbles and obtaining real-time quantitative metrics correlated with tissue damage are challenging. Prior work introduced Bubble Doppler, an ultrafast power Doppler imaging method as a sensitive means to map cavitation bubbles. The main limitation of that method was its reliance on conventional wall filters used in Doppler imaging and its optimization for imaging blood flow rather than transient scatterers. This study explores Bubble Doppler enhancement using dynamic mode decomposition (DMD) of a matrix created from a Doppler ensemble for mapping and extracting the characteristics of transient cavitation bubbles. DMD was first tested in silico with a numerical dataset mimicking the spatiotemporal characteristics of backscattered signal from tissue and bubbles. The performance of DMD filter was compared to other widely used Doppler wall filter-singular value decomposition (SVD) and infinite impulse response (IIR) high-pass filter. DMD was then applied to an ex vivo tissue dataset where each HIFU pulse was immediately followed by a plane wave Doppler ensemble. In silico DMD outperformed SVD and IIR high-pass filter and ex vivo provided physically interpretable images of the modes associated with bubbles and their corresponding temporal decay rates. These DMD modes can be trackable over the duration of pHIFU treatment using k-means clustering method, resulting in quantitative indicators of treatment progression.

  View details for DOI 10.1109/TUFFC.2024.3387351

  View details for PubMedID 38598407

  View details for PubMedCentralID PMC11141145

• 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

• Quantitative Assessment of Boiling Histotripsy Progression Based on Color Doppler Measurements. IEEE transactions on ultrasonics, ferroelectrics, and frequency control Song, M., Thomas, G. P., Khokhlova, V. A., Sapozhnikov, O. A., Bailey, M. R., Maxwell, A. D., Yuldashev, P. V., Khokhlova, T. D. 2022; 69 (12): 3255-3269

  Abstract

  Boiling histotripsy (BH) is a mechanical tissue liquefaction method that uses sequences of millisecond-long high intensity focused ultrasound (HIFU) pulses with shock fronts. The BH treatment generates bubbles that move within the sonicated volume due to acoustic radiation force. Since the velocity of the bubbles and tissue debris is expected to depend on the lesion size and liquefaction completeness, it could provide a quantitative metric of the treatment progression. In this study, the motion of bubble remnants and tissue debris immediately following BH pulses was investigated using high-pulse repetition frequency (PRF) plane-wave color Doppler ultrasound in ex vivo myocardium tissue. A 256-element 1.5 MHz spiral HIFU array with a coaxially integrated ultrasound imaging probe (ATL P4-2) produced 10 ms BH pulses to form volumetric lesions with electronic beam steering. Prior to performing volumetric BH treatments, the motion of intact myocardium tissue and anticoagulated bovine blood following isolated BH pulses was assessed as two limiting cases. In the liquid blood the velocity of BH-induced streaming at the focus reached over 200 cm/s, whereas the intact tissue was observed to move toward the HIFU array consistent with elastic rebound of tissue. Over the course of volumetric BH treatments tissue motion at the focus locations was dependent on the axial size of the forming lesion relative to the corresponding size of the HIFU focal area. For axially small lesions, the maximum velocity after the BH pulse was directed toward the HIFU transducer and monotonically increased over time from about 20-100 cm/s as liquefaction progressed, then saturated when tissue was fully liquefied. For larger lesions obtained by merging multiple smaller lesions in the axial direction, the high-speed streaming away from the HIFU transducer was observed at the point of full liquefaction. Based on these observations, the maximum directional velocity and its location along the HIFU propagation axis were proposed and evaluated as candidate metrics of BH treatment completeness.

  View details for DOI 10.1109/TUFFC.2022.3212266

  View details for PubMedID 36197870

  View details for PubMedCentralID PMC9741864