Nan Chang

Sonoluminescence characterization of inertial cavitation inside a BSA phantom treated by pulsed HIFU

The aim of this study was to investigate the inertial cavitation inside a phantom treated by pulsed HIFU (pHIFU). Basic bovine serum albumin (BSA) phantoms without any inherent ultrasound contrast agents (UCAs) or phase-shift nano-emulsions (PSNEs) were used. During the treatment, sonoluminescence (SL) recordings were performed to characterize the spatial distribution of inertial cavitation adjacent to the focal region. High-speed photographs and thermal coagulations, comparing with the SL results, were also recorded and presented. A series of pulse parameters (pulse duration (PD) was between 1 and 23 cycles and pulse repetition frequency (PRF) was between 0.5kHz and 100kHz) were performed to make a systematic investigation under certain acoustic power (APW). Continuous HIFU (cHIFU) investigation was also performed to serve as control group. It was found that, when APW was 19.5W, pHIFU with short PD was much easier to form SL adjacent to the focal region inside the phantom, while it was difficult for cHIFU to generate cavitation bubbles. With appropriate PD and PRF, the residual bubbles of the previous pulses could be stimulated by the incident pulses to oscillate in a higher level and even violently collapse, resulting to enhanced physical thermogenesis. The experimental results showed that the most violent inertial cavitation occurs when PD was set to 6 cycles (5μs) and PRF to 10kHz, while the highest level of thermal coagulation was observed when PD was set to 10 cycles. The cavitational and thermal characteristics were in good correspondence, exhibiting significant potentiality regarding to inject-free cavitation bubble enhanced thermal ablation under lower APW, compared to the conventional thermotherapy.

In situ observation of single cell response to acoustic droplet vaporization: Membrane deformation, permeabilization, and blebbing

In this study, the bioeffects of acoustic droplet vaporization (ADV) on adjacent cells were investigated by evaluating the real-time cell response at the single-cell level in situ, using a combined ultrasound-exposure and optical imaging system. Two imaging modalities, high-speed and fluorescence imaging, were used to observe ADV bubble dynamics and to evaluate the impact on cell membrane permeabilization (i.e., sonoporation) using propidium iodide (PI) uptake as an indicator. The results indicated that ADV mainly led to irreversible rather than reversible sonoporation. Further, the rate of irreversible sonoporation significantly increased with increasing nanodroplet concentration, ultrasound amplitude, and pulse duration. The results suggested that sonoporation is correlated to the rapid formation, expansion, and contraction of ADV bubbles near cells, and strongly depends on ADV bubble size and bubble-to-cell distance when subjected to short ultrasound pulses (1 μs). Moreover, the displacement of ADV bubbles was larger when using a long ultrasound pulse (20 μs), resulting in considerable cell membrane deformation and a more irreversible sonoporation rate. During sonoporation, cell membrane blebbing as a recovery manoeuvre was also investigated, indicating the essential role of Ca2+ influx in the membrane blebbing response. This study has helped us gain further insights into the dynamic behavior of ADV bubbles near cells, ADV bubble-cell interactions, and real-time cell response, which are invaluable in the development of optimal approaches for ADV-associated theranostic applications.

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.

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.

Acoustic droplet vaporization and inertial cavitation thresholds and efficiencies of nanodroplets emulsions inside the focused region using a dual-frequency ring focused ultrasound

In this work, in order to develop a low-acoustic-intensity, high-efficiency and precise-treatment strategy, the vaporization of droplets and the inertial cavitation of vaporized microbubbles, using a dual-frequency focused ultrasound transducer, were investigated. The effect of a low frequency (LF), 1.1-MHz, sonication on droplet vaporization and the following inertial cavitation by the introduction of a high frequency (HF), 5-MHz, sonication was studied. It is shown that acoustic droplet vaporization (ADV) threshold is the lowest at dual-frequency sonication (LF of 18.9 W/cm2 and HF of 4.1 W/cm2); moreover, the ADV efficiency is the highest at intensity threshold. The ADV area can be minimized to 2 mm2 using a dual-frequency sonication (LF of 38.1 W/cm2 and HF of 8.5 W/cm2). The IC area and efficiency can also be modulated using a dual-frequency sonication. Consequently, it can be concluded that in contrast to the single-frequency sonication, using the dual-frequency ultrasound, the vaporization of nanodroplets and the following inertial cavitation of the vaporized microbubbles can be modulated. Besides, a dual-frequency can result in the minimum ADV/IC area, lowest ADV/IC threshold, and highest ADV/IC efficiency.

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.

Phase-shift nano-emulsions induced cavitation and ablation during high intensity focused ultrasound exposure

Phase-shift Nano-emulsions (PSNEs) with a small initial diameter in nanoscale have the potential to leak out of the blood vessels and to accumulate at target point of tissue. At desired location, PSNEs can undergo acoustic droplet vaporization (ADV) process, change into gas bubbles and enhance focused ultrasound efficiency. The aim of this work was to provide spatial and temporal information on PSNE induced cavitation and ablation effects during pulsed high intensity focused ultrasound (HIFU) exposure. The PSNEs were composed of perfluorohaxane (PFH) and bovine serum albumin (BSA), and then uniformly distributed in a transparent polyacrylamide phantom. The Sonoluminescence (SL) method was employed to visualize the cavitation distribution and formation process of PSNEs induced cavitation. For the phantom which was used for ablation observation, heat sensitive BSA was added. When the temperature generated by ultrasound exposure was high enough to denature BSA, the transparent phantom would turn out white le...

Cavitation Control and Applications

Cavitation is an important phenomenon that can occur both during diagnostic and therapeutic applications. It is not only an indicator of the transient high pressure and temperature induced by intense bubble collapse, but it also mediates mechanical and thermal effects. As far as mechanical effects, collapsing bubbles can emit shock waves and liquid jets, which are considered the main mechanisms that cause mechanical damage (Kodama and Tomita in Appl Phys B 70:139–149, 2000).