Dui Qin

Acoustic signal characteristics of laser induced cavitation in DDFP droplet: Spectrum and time-frequency analysis

Cavitation has great application potential in microvessel damage and targeted drug delivery. Concerning cavitation, droplet vaporization has been widely investigated in vitro and in vivo with plasmonic nanoparticles. Droplets with a liquid dodecafluoropentane (DDFP) core enclosed in an albumin shell have a stable and simple structure with good characteristics of laser absorbing; thus, DDFP droplets could be an effective aim for laser-induced cavitation. The DDPF droplet was prepared and perfused in a mimic microvessel in the optical microscopic system with a passive acoustic detection module. Three patterns of laser-induced cavitation in the droplets were observed. The emitted acoustic signals showed specific spectrum components at specific time points. It was suggested that a nanosecond laser pulse could induce cavitation in DDPF droplets, and specific acoustic signals would be emitted. Analyzing its characteristics could aid in monitoring the laser-induced cavitation process in droplets, which is meaningful to theranostic application.

Modeling photoacoustic cavitation nucleation and bubble dynamics with modified classical nucleation theory

Photoacoustic cavitation (PAC) is the formation of bubbles in liquids using a focused laser and a pre-established ultrasound synchronously. The decreased threshold of each modality and the precise location of cavitation determined by the focused laser are both significant in the targeted theranostics. In this study, PAC nucleation was described using the modified classical nucleation theory by Kashchievs scaling function. A two-stage model of the PAC bubble dynamics was presented based on the two different bubble behaviors. It was clarified that both negative acoustic pressure and laser-induced temperature rise, resulting in the decrease in critical radius and the increase in nucleation rate, and thereby contribute to the increase in nucleation probability in the confocal region. Ultrasound determined the whole PAC bubble dynamics with temperature-dependent parameters, while the laser mainly contributed to its initial conditions. Moreover, the effects of certain parameters on PAC were further discussed, including the relative acoustic phase when a laser is introduced (φ), laser pulse duration (τ(L)), laser focus radius (R(f)), and ultrasound amplitude (P(A)). The model would be helpful in understanding the PAC process and further in introducing PAC to potential targeted theranostics.

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.

Optic and acoustic detection of laser-induced optical breakdown in DDFP

Laser induced optical breakdown (LIOB) or laser induced cavitation (LIC) in water has been investigated widely. Several patterns of LIC bubble are involved. However, LIOB in water needs relatively high laser intensity and extremely short pulse length in femtosecond. In the study, low intensity laser in nanoseconds was utilized in the LIOB in dodecafluoropentane (DDFP), and then the optical and acoustic detection were performed to reveal the characteristics of bubble dynamics and acoustic signal emitted from the cavitation site. LIOB was realized in the confocal system of laser, acoustic detection and microscopic imaging. A single pulse laser of 521 nm wavelength, with a 3-5 ns pulse width and average power of 50 μJ, was employed in the experiment after being focused on 200μm cellulose tube by 40× and 0.8 numerical aperture objective lens. High speed camera was used to acquire the images during LIOB, bubble formation and collapse. Passive acoustic detection (PCD) was performed by 10 MHz focused transducer connected via an amplifier to a high speed digitizer. The spectrum analysis and joint time-frequency analysis (JTFA) were performed to show the characteristics of LIOB in DDFP. Comparing to LIOB in water, focused laser at lower intensity could induce optical breakdown in DDFP liquid with longer bubble life time. Three patterns were observed and the difference is closely related with the circumstance temperature. The life time of bubbles correspond to their maximum radius. The original temperature is closely related with the cavitation forming time. In acoustic detection, significant RF signal were recorded by PCD when LIOB occurred. Its spectrum analysis and joint time-frequency analysis revealed LIOB happened in the duration of 3 μs, and the spectrum of LIOB signal was mainly distributed between 0-12MHz, with characteristics of specific frequencies of n×f. These characteristics of LIOB bubble in DDFP gives information for analyzing LIOB, suggesting acoustically monitored LIOB has potential as an important tool in diagnosis and in vivo.

Occlusion and rupture of ex vivo capillary bifurcation due to acoustic droplet vaporization

Gas embolotherapy (GE) consists in the occlusion of tumor blood vessels using gas emboli induced by acoustic droplet vaporization (ADV), to create tumor starvation and localized drug delivery. Therefore, the occlusion and rupture of capillary bifurcation due to ADV was investigated in an ex vivo rat mesentery model using a confocal acousto-optical high-speed microscope system. Following ADV bubble formation, coalescence, and translational movement, the growing bubbles lodged in and then occluded two different capillary bifurcations. Capillary rupture was induced at the bubble lodging area, immediately followed by gas extravasation and bubble dislodging. Before and after bubble lodgment/occlusion, a local microvessel invagination was observed due to the interactions between ADV bubbles and the microvessel itself, indicating a contribution to the capillary rupture. Understanding the transient dynamics of ADV bubble, the bubble–microvessel interaction and the consequent mechanical bio-effects in GE is of the...

Optical and acoustic study on phase transition of nanodroplets: Acoustic droplet vaporization versus photoacoustic cavitation

The phase transition of nanodroplet has great potential in localized therapy, e.g. gas embolotherapy, drug delivery and the extravascular tumor-targeted theranostics. To improve the temporal and spatial resolution and reduce the energy threshold of nanodroplet phase transition, photoacoustic cavitation (PAC) using synergistic laser and ultrasound was introduced and compared with acoustic droplet vaporization (ADV) in the study.

PHOTOACOUSTIC CAVITATION OF NANODROPLETS: HIGH SPEED OBSERVATION AND ACOUSTIC SIGNAL ANALYSIS

Perfluorocarbon (PFC) nanodroplet has a longer lifespan and small volume to circulate freely in blood microcirculation. Its phase transition has great potential in localized therapy. Photoacoustic cavitation, a new approach involving synergetic laser and ultrasound to achieve the phase transition of PFC nanodroplets, could improve the spatial and temporal resolution and reduce the energy threshold compared to individual use of either modalities. In this study, we present a confocal microscopic system to induce photoacoustic cavitation of nanodroplets and study its characteristics by high speed observation and acoustic detection. Upon excitation by laser and ultrasound pulses, the liquid–gas phase transition of PFC nanodroplets and subsequent bubble dynamics were demonstrated. Two distinct bubble formation patterns were observed. It is associated with the size distribution of the droplets within the confocal volume of laser and ultrasound. Moreover, the detected acoustic signals suggested the presence of s...

Optical and acoustic observation of photodisruption in two liquid perfluorocarbons induced by nanosecond laser

Photodisruption can be used to generate microbubble or microbubbles in vivo, thus has potential as an important tool in theranostics. However, high laser intensity and extremely short pulse length in femtosecond, and thus the high cost limit its wide applications. In the study, photodisruption induced by nanosecond laser pulse in two liquid perfluorocarbons (PFCs), perfluoropentane (PFP) and perfluorohexane (PFH), were realized and detected in optical and acoustic way to reveal the effective parameters for photodisruption. A confocal microscopic system was performed to record the bubble dynamics by high speed photography, and simultaneously the acoustic signal emitted during photodisruption. A 532 nm laser, with pulse duration of 3 ns and average power of 50 μJ, was focused to the cellulose tube where the laser, acoustic detection and microscopic imaging were aligned and PFCs were injected. Passive acoustic detection (PCD) was realized by a 1 mm needle hydrophone connected via a receiver amplifier to a high speed digitizer. The spectrum analysis and time-frequency analysis were used to show the acoustic characteristics of photodisruption in liquid PFCs. Then, the laser energy thresholds of photodisruption and the influences of ambient temperature on photodisruption were revealed. The bubble behavior mainly followed three patterns in PFP but two patterns in PFH. The difference among patterns was closely related with the ambient temperature. In acoustic detection, significant signals were recorded by PCD once photodisruption occurred in either PFP or PFH. The PCD signals of PFP and PFH showed difference in time-domain. However, their frequency spectrums were mainly distributed between 0-2 MHz and seemed without significant difference. The time-frequency analysis verified their difference in time-domain. The physical process of photodisruption was closely associated with both laser parameters and liquid properties. It was indicated that the thresholds for PFP and PFH were 43.33 μJ and 45 μJ, respectively. But the increasing ambient temperature was helpful to photodisruption in both PFP and PFH.

Laser-Induced Cavitation and Photoacoustic Cavitation

As a physical phenomenon, cavitation can be induced by several factors, including heating, acoustic pressure, and high-energy light, for which a focused laser has been widely used.