Shukuan Lu

High-contrast active cavitation imaging technique based on multiple bubble wavelet transform

In this study, a unique method that combines the ultrafast active cavitation imaging technique with multiple bubble wavelet transform (MBWT) for improving cavitation detection contrast was presented. The bubble wavelet was constructed by the modified Keller-Miksis equation that considered the mutual effect among bubbles. A three-dimensional spatial model was applied to simulate the spatial distribution of multiple bubbles. The effects of four parameters on the signal-to-noise ratio (SNR) of cavitation images were evaluated, including the following: initial radii of bubbles, scale factor in the wavelet transform, number of bubbles, and the minimum inter-bubble distance. And the other two spatial models and cavitation bubble size distributions were introduced in the MBWT method. The results suggested that in the free-field experiments, the averaged SNR of images acquired by the MBWT method was improved by 7.16 ± 0.09 dB and 3.14 ± 0.14 dB compared with the values of images acquired by the B-mode and single bubble wavelet transform (SBWT) methods. In addition, in the tissue experiments, the averaged cavitation-to-tissue ratio of cavitation images acquired by the MBWT method was improved by 4.69 ± 0.25 dB and 1.74± 0.29 dB compared with that of images acquired by B-mode and SBWT methods.

Efficient and controllable thermal ablation induced by short-pulsed HIFU sequence assisted with perfluorohexane nanodroplets

A HIFU sequence with extremely short pulse duration and high pulse repetition frequency can achieve thermal ablation at a low acoustic power using inertial cavitation. Because of its cavitation-dependent property, the therapeutic outcome is unreliable when the treatment zone lacks cavitation nuclei. To overcome this intrinsic limitation, we introduced perfluorocarbon nanodroplets as extra cavitation nuclei into short-pulsed HIFU-mediated thermal ablation. Two types of nanodroplets were used with perfluorohexane (PFH) as the core material coated with bovine serum albumin (BSA) or an anionic fluorosurfactant (FS) to demonstrate the feasibility of this study. The thermal ablation process was recorded by high-speed photography. The inertial cavitation activity during the ablation was revealed by sonoluminescence (SL). The high-speed photography results show that the thermal ablation volume increased by ∼643% and 596% with BSA-PFH and FS-PFH, respectively, than the short-pulsed HIFU alone at an acoustic power of 19.5 W. Using nanodroplets, much larger ablation volumes were created even at a much lower acoustic power. Meanwhile, the treatment time for ablating a desired volume significantly reduced in the presence of nanodroplets. Moreover, by adjusting the treatment time, lesion migration towards the HIFU transducer could also be avoided. The SL results show that the thermal lesion shape was significantly dependent on the inertial cavitation in this short-pulsed HIFU-mediated thermal ablation. The inertial cavitation activity became more predictable by using nanodroplets. Therefore, the introduction of PFH nanodroplets as extra cavitation nuclei made the short-pulsed HIFU thermal ablation more efficient by increasing the ablation volume and speed, and more controllable by reducing the acoustic power and preventing lesion migration.

Passive acoustic mapping of cavitation using eigenspace-based robust Capon beamformer in ultrasound therapy

Pulse-echo imaging technique can only play a role when high intensity focused ultrasound (HIFU) is turned off due to the interference between the primary HIFU signal and the transmission pulse. Passive acoustic mapping (PAM) has been proposed as a tool for true real-time monitoring of HIFU therapy. However, the most-used PAM algorithm based on time exposure acoustic (TEA) limits the quality of cavitation image. Recently, robust Capon beamformer (RCB) has been used in PAM to provide improved resolution and reduced artifacts over TEA-based PAM, but the presented results have not been satisfactory. In the present study, we applied an eigenspace-based RCB (EISRCB) method to further improve the PAM image quality. The optimal weighting vector of the proposed method was found by projecting the RCB weighting vector onto the desired vector subspace constructed from the eigenstructure of the covariance matrix. The performance of the proposed PAM was validated by both simulations and in vitro histotripsy experiments. The results suggested that the proposed PAM significantly outperformed the conventionally used TEA and RCB-based PAM. The comparison results between pulse-echo images of the residual bubbles and cavitation images showed the potential of our proposed PAM in accurate localization of cavitation activity during HIFU therapy.

Nakagami-m parametric imaging for characterization of thermal coagulation and cavitation erosion induced by HIFU

Nowadays, both thermal and mechanical ablation techniques of HIFU associated with cavitation have been developed for noninvasive treatment. A specific challenge for the successful clinical implementation of HIFU is to achieve real-time imaging for the evaluation and determination of therapy outcomes such as necrosis or homogenization. Ultrasound Nakagami-m parametric imaging highlights the degrading shadowing effects of bubbles and can be used for tissue characterization. The aim of this study is to investigate the performance of Nakagami-m parametric imaging for evaluating and differentiating thermal coagulation and cavitation erosion induced by HIFU. Lesions were induced in basic bovine serum albumin (BSA) phantoms and ex vivo porcine livers using a 1.6 MHz single-element transducer. Thermal and mechanical lesions induced by two types of HIFU sequences respectively were evaluated using Nakagami-m parametric imaging and ultrasound B-mode imaging. The lesion sizes estimated using Nakagami-m parametric imaging technique were all closer to the actual sizes than those of B-mode imaging. The p-value obtained from the t-test between the mean m values of thermal coagulation and cavitation erosion was smaller than 0.05, demonstrating that the m values of thermal lesions were significantly different from that of mechanical lesions, which was confirmed by ex vivo experiments and histologic examination showed that different changes result from HIFU exposure, one of tissue dehydration resulting from the thermal effect, and the other of tissue homogenate resulting from mechanical effect. This study demonstrated that Nakagami-m parametric imaging is a potential real-time imaging technique for evaluating and differentiating thermal coagulation and cavitation erosion.

Bubble‐echo based deconvolution of contrast‐enhanced ultrasound imaging: Simulation and experimental validations

PURPOSE Improvement of both the imaging resolution and the contrast-to-tissue ratio (CTR) is a current emphasis of contrast-enhanced ultrasound (CEUS) for microvascular perfusion imaging. Based on the strong nonlinear characteristics of contrast agents, the CTRs have been significantly enhanced using various advanced CEUS methods. However, the imaging resolution of these methods is limited by the finite bandwidth of the imaging process. This study aimed to propose a bubble-echo based deconvolution (BED) method for CEUS with both improved resolution and CTR. METHOD The method is built on a modified convolution model and uses novel bubble-echo based point-spread-functions to reconstruct the images by regularized inverse Wiener filtering. Performances of the proposed BED for three CEUS modes are investigated through simulations and in vivo perfusion experiments. RESULTS BED of fundamental imaging was found to have the highest improvement in imaging resolution with the resolution gain up to 2.0 ± 0.2 times, which was comparable to the approved cepstrum-based deconvolution (CED). BED of second-harmonic imaging had the best performance in CTR with an enhancement of 9.8 ± 2.3 dB, which was much higher than CED. Pulse inversion BED had both a better resolution and a higher CTR. CONCLUSION All results indicate that BED could obtain CEUS image with both an improved resolution and a high CTR, which has important significance to microvascular perfusion evaluation in deep tissue.

Passive acoustic mapping of cavitation based on frequency sum and robust capon beamformer

Real-time dynamic monitoring of cavitation is essential for the safety and efficiency of high intensity focused ultrasound (HIFU) therapy. Unlike pulse-echo imaging, which can only be of use while HIFU is turned off, passive acoustic mapping (PAM) can enable monitoring of cavitation during HIFU exposure. But the conventional used PAM has low resolution and interference artifacts. For this, a unique PAM algorithm that combines frequency-sum beamforming with robust Capon beamformer (FS-RCB-PAM) was proposed in this study.

Precisely controlled cavitation during the perfluorocarbon (PFC) nanodroplets assisted HIFU surgery

Previous study has demonstrated that pulsed HIFU with tens of microseconds pulse duration (PD) and 10kHz PRF is effective for cavitation generation. Meanwhile, with the assistance of PFC nanodroplets, cavitation can be further enhanced. Despite of higher efficiency, we also need cavitation to be precisely controlled and confined for sake of therapeutic safety, especially during the implementation of HIFU surgery in fine organs like brain, neuro, or blood vessel. Smaller focus is obtained by designing very large or spherical shaped transducers, which also cause some inconveniences for treatment. In our study, we propose a combinated ultrasound wave sequence to realize precisely controlled cavitation during PFC nanodroplets assisted HIFU to simultaneously achieve efficient and accurate therapy.

Manipulation of microbubbles in rabbit blood vessel by using ultrasonic standing wave — An in vitro study

Microbubble and its cavitation combined with ultrasound have been explored to improve the theranostics of vascular diseases. Inspiring achievements have been obtained in molecular imaging, drug delivery, and thrombolysis by using microbubbles. However, microbubbles flow along the vessel axis in the blood laminar flow, preventing the microbubbles from contacting with the targeting endothelium. Hence, transporting microbubbles to the desired site has the potential to improve the corresponding medical applications.

Real-time monitoring of controllable cavitation erosion in a vessel phantom with passive acoustic mapping

Cavitation erosion in blood vessel plays an important role in ultrasound thrombolysis, drug delivery, and other clinical applications. The controllable superficial vessel erosion based on ultrasonic standing wave (USW) has been used to effectively prevent vessel ruptures and haemorrhages, and optical method is used to observe the experiments. But optical method can only work in transparent media. Compared with standard B-mode imaging, passive acoustic mapping (PAM) can monitor erosion in real time and has better sensitivity of cavitation detection. However, the conventionally used PAM has limitations in imaging resolution and artifacts. In this study, a unique PAM method that combined the robust Capon beamformer (RCB) with the sign coherence factor (SCF) was proposed to monitor the superficial vessel erosion in real time. The performance of the proposed method was validated by simulations. In vitro experiments showed that the lateral (axial) resolution of the proposed PAM was 2.31±0.51 (3.19±0.38) times higher than time exposure acoustics (TEA)-based PAM and 1.73±0.38 (1.76±0.48) times higher than RCB-based PAM, and the cavitation-to-artifact ratio (CAR) of the proposed PAM could be improved by 22.5±3.2dB and 7.1±1.2dB compared with TEA and RCB-based PAM. These results showed that the proposed PAM can precisely monitor the superficial vessel erosion and the erosion shift after USW modulation. This work may have the potential of developing a useful tool for precise spatial control and real-time monitoring of the superficial vessel erosion.

Reduced clot debris size using standing waves formed via high intensity focused ultrasound

The feasibility of utilizing high intensity focused ultrasound (HIFU) to induce thrombolysis has been demonstrated previously. However, clinical concerns still remain related to the clot debris produced via fragmentation of the original clot potentially being too large and hence occluding downstream vessels, causing hazardous emboli. This study investigates the use of standing wave fields formed via HIFU to disintegrate the thrombus while achieving a reduced clot debris size in vitro. The results showed that the average diameter of the clot debris calculated by volume percentage was smaller in the standing wave mode than in the travelling wave mode at identical ultrasound thrombolysis settings. Furthermore, the inertial cavitation dose was shown to be lower in the standing wave mode, while the estimated cavitation bubble size distribution was similar in both modes. These results show that a reduction of the clot debris size with standing waves may be attributed to the particle trapping of the acoustic pot...