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Background: Thrombosis triggered by platelet activation plays a vital role in the pathogenesis of cardiovascular and cerebrovascular diseases. Objective: This study aims to find platelet combined biomarkers for cardiovascular diseases and investigate the possibility of Concanavalin A (ConA) acting on platelets as a new pharmacological target. Methods: High-throughput Technology and bioinformatics analysis were combined and groups of microarray chip gene expression profiles for acute myocardial infarction (AMI) and sickle cell disease (SCD) were obtained using GEO database screening. R language limma package was used to obtain differentially expressed genes (DEGs). GO, KEGG, and other databases were utilized to perform the enrichment analysis of DEGs’ functions, pathways, etc. PPI network was constructed using STRING database and Cytoscape software, and MCC algorithm was used to obtain the 200 core genes of the two groups of DEGs. Core targets were confirmed by constructing an intersection area screening. A type of molecular probe, ConA, was molecularly docked with the above core targets on the Zdock, HEX, and 3D-DOCK servers. Result: We found six core markers, CD34, SOCS2, ABL1, MTOR, VEGFA, and SMURF1, which were simultaneously related to both diseases, and the docking effect showed that VEGFA is the best-performing. Conclusion: VEGFA is most likely to reduce its expression by binding to ConA, which could affect the downstream regulation of the PI3K/Akt signaling pathway during platelet activation. Some other core targets also have the opportunity to interact with ConA to affect platelet-activated thrombosis and trigger changes in cardiovascular events.

Yeast is an integral part of our environment. The detection of yeast is of great significance in many fields. The impedance-based sensor with interdigital microelectrodes is a promising method to establish a simple and portable detection system. However, the positions of yeast cells greatly influence the impedance variation and eventually the sensitivity of detection. In this study, an impedimetric biosensor with ultrasonic-assisted cell alignment for yeast detection was proposed. In order to verify the feasibility of this biosensor, finite element modeling was conducted using the software COMSOL. The acoustic pressure field and the acoustic radiation force exerted on yeast cells were investigated. Cell positions in the microfluidic channel were determined using the fluid particle tracking module. After that, the impedance between the microelectrodes was calculated. Yeast suspensions with different cell concentrations were used as the tested samples for the simulation. The proposed sensor showed a higher sensitivity than the conventional impedimetric biosensor on which the cells were randomly located. It can be used for the detection of microorganisms. This finite element modeling provided an effective approach for the design of biosensors.

Objective. Acoustic cavitation and its mechanical effects (e.g. stress and strain) play a primary role in ultrasound applications. Introducing encapsulated microbubbles as cavitation nuclei and utilizing dual-frequency ultrasound excitation are highly effective approaches to reduce cavitation thresholds and enhance cavitation effects. However, the cavitation dynamics of encapsulated microbubbles and the resultant stress/strain in viscoelastic tissues under dual-frequency excitation are poorly understood, especially for the enhancement effects caused by a dual-frequency approach. The goal of this study was to numerically investigate the dynamics of a lipid-coated microbubble and the spatiotemporal distributions of the stress and strain under dual-frequency excitation. Approach. The Gilmore–Zener bubble model was coupled with a shell model for the nonlinear changes of both shell elasticity and viscosity to accurately simulate the cavitation dynamics of lipid-coated microbubbles in viscoelastic tissues. Then, the spatiotemporal evolutions of the cavitation-induced stress and strain in the surrounding tissues were characterized quantitatively. Finally, the influences of some paramount parameters were examined to optimize the outcomes. Main results. We demonstrated that the cavitation dynamics and associated stress/strain were prominently enhanced by a dual-frequency excitation, highlighting positive correlations between the maximum bubble expansion and the maximum stress/strain. Moreover, the results showed that the dual-frequency ultrasound with smaller differences in its frequencies and pressure amplitudes could enhance the bubble oscillations and stress/strain more efficiently, whereas the phase difference manifested small influences under these conditions. Additionally, the dual-frequency approach seemed to show a stronger enhancement effect with the shell/tissue viscoelasticity increasing to a certain extent. Significance. This study might contribute to optimizing the dual-frequency operation in terms of cavitation dynamics and its mechanical effects for high-efficient ultrasound applications.

The cavitation dynamics and mechanical stress in viscoelastic tissues, as the primary mechanisms of some ultrasound therapies, are extremely complex due to the interactions of cavitation bubble with adjacent bubbles and surrounding tissues. Therefore, the cavitation dynamics and resultant mechanical stress of two-interacting bubbles in the viscoelastic tissues are numerically investigated, especially focusing on the effects of the adjacent bubble. The results demonstrate that the mechanical stress is highly dependent on the bubble dynamics. The compressive stress and tensile stress are generated at the stage of bubble expansion and collapse stage, respectively. Furthermore, within the initial parameters examined in this paper, the effects of the adjacent bubble will distinctly suppress the radial expansion of the small bubble and consequently lead its associated stresses to decrease. Owing to the superimposition of two stress fields, the mechanical stresses surrounding the small bubble in the direction of the neighboring bubble are smaller than those in other directions. For two interacting cavitation bubbles, the suppression effects of the nearby bubble on both the cavitation dynamics and the stresses surrounding the small bubble increase as the ultrasound amplitude and the initial radius of the large bubble increase, whereas they decrease with the inter-bubble distance increasing. Moreover, increasing the tissue viscoelasticity will reduce the suppression effects of the nearby bubble, except in instances where the compressive stress and tensile stress first increase and then decrease with the tissue elasticity and viscosity increasing respectively. This study can provide a further understanding of the mechanisms of cavitation-associated mechanical damage to the adjacent tissues or cells.

Dui Qin,1,2,* Lei Zhang,1,* Hongrui Zhu,1 Junjie Chen,1 Daocheng Wu,1 Ayache Bouakaz,3 Mingxi Wan,1 Yi Feng1 1The Key Laboratory of Biomedical Information Engineering of Ministry of Education, Department of Biomedical Engineering, School of Life Science and Technology, Xi’an Jiaotong University, Xi’an, People’s Republic of China; 2Department of Biomedical Engineering, School of Bioinformatics, Chongqing University of Posts and Telecommunications, Chongqing, People’s Republic of China; 3UMR 1253, iBrain, Université de Tours, Inserm, Tours, F-37032, France*These authors contributed equally to this workCorrespondence: Mingxi Wan; Yi FengThe Key Laboratory of Biomedical Information Engineering of Ministry of Education, Department of Biomedical Engineering, School of Life Science and Technology, Xi’ an Jiaotong University, Xi’ An, 710049, People’s Republic of ChinaTel +86 29 82667924Fax +86 29 82668668Email mxwan@mail.xjtu.edu.cn; fengyi@mail.xjtu.edu.cnBackground: Photothermal therapy (PTT) has attracted considerable attention for cancer treatment as it is highly controllable and minimally invasive. Various multifunctional nanosystems have been fabricated in an “all-in-one” form to guide and enhance PTT by integrating imaging and therapeutic functions. However, the complex fabrication of nanosystems and their high cost limit its clinical translation.Materials and Methods: Herein, a high efficient “one-for-all” nanodroplet with a simple composition but owning multiple capabilities was developed to achieve ultrasound (US) imaging-guided and cavitation-enhanced PTT. Perfluoropentane (PFP) nanodroplet with a polypyrrole (PPy) shell (PFP@PPy nanodroplet) was synthesized via ultrasonic emulsification and in situ oxidative polymerization. After characterization of the morphology, its photothermal effect, phase transition performance, as well as its capabilities of enhancing US imaging and acoustic cavitation were examined. Moreover, the antitumor efficacy of the combined therapy with PTT and acoustic cavitation via the PFP@PPy nanodroplets was studied both in vitro and in vivo.Results: The nanodroplets exhibited good stability, high biocompatibility, broad optical absorption over the visible and near-infrared (NIR) range, excellent photothermal conversion with an efficiency of 60.1% and activatable liquid-gas phase transition performance. Upon NIR laser and US irradiation, the phase transition of PFP cores into microbubbles significantly enhanced US imaging and acoustic cavitation both in vitro and in vivo. More importantly, the acoustic cavitation enhanced significantly the antitumor efficacy of PTT as compared to PTT alone thanks to the cavitation-mediated cell destruction, which demonstrated a substantial increase in cell detachment, 81.1% cell death in vitro and 99.5% tumor inhibition in vivo.Conclusion: The PFP@PPy nanodroplet as a “one-for-all” theranostic agent achieved highly efficient US imaging-guided and cavitation-enhanced cancer therapy, and has considerable potential to provide cancer theranostics in the future.Keywords: one-for-all nanodroplet, theranostics, photothermal therapy, acoustic cavitation, ultrasound imaging

Highlights • Initial bubble nucleation in a metastable PFP nanodroplet during ADV was described. • The modified CNT combined the phase-change thermodynamics of PFP. • The thermodynamics was exactly predicted by the Redlich–Kwong equation of state. • The modified CNT eliminated the intrinsic limitations of the CNT. • Nanodroplet properties exerted strong influences on the ADV nucleation threshold., Acoustic droplet vaporization (ADV) capable of converting liquid perfluorocarbon (PFC) micro/nanodroplets into gaseous microbubbles has gained much attention due to its medical potentials. However, its physical mechanisms for nanodroplets have not been well understood due to the disappeared superharmonic focusing effect and the prominent Laplace pressure compared to microdroplets, especially for the initial ADV nucleation occurring in a metastable PFC nanodroplet. The classical nucleation theory (CNT) was modified to describe the ADV nucleation via combining the phase-change thermodynamics of perfluoropentane (PFP) and the Laplace pressure effect on PFP nanodroplets. The thermodynamics was exactly predicted by the Redlich–Kwong equation of state (EoS) rather than the van der Waals EoS, based on which the surface tension of the vapor nucleus as a crucial parameter in the CNT was successfully obtained to modify the CNT. Compared to the CNT, the modified CNT eliminated the intrinsic limitations of the CNT, and it predicted a larger nucleation rate and a lower ADV nucleation threshold, which agree much better with experimental results. Furthermore, it indicated that the nanodroplet properties exert very strong influences on the nucleation threshold instead of the acoustic parameters, providing a potential strategy with an appropriate droplet design to reduce the ADV nucleation threshold. This study may contribute to further understanding the ADV mechanism for PFC nanodroplets and promoting its potential theranostic applications in clinical practice.

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.

Highlights • The radial and translational motions of two interacting bubbles are studied. • Bubble dynamics is analyzed by bifurcation structures and acoustic emission spectra. • Small bubble is remarkably suppressed, while large bubble is slightly enlarged. • Bubble−bubble interaction reduces the nonlinear dynamics and acoustic emissions. • Viscoelasticity of the medium reduces the radial and translational bubble motions., The cavitation-mediated bioeffects are primarily associated with the dynamic behaviors of bubbles in viscoelastic tissues, which involves complex interactions of cavitation bubbles with surrounding bubbles and tissues. The radial and translational motions, as well as the resultant acoustic emissions of two interacting cavitation bubbles in viscoelastic tissues were numerically investigated. Due to the bubble–bubble interactions, a remarkable suppression effect on the small bubble, whereas a slight enhancement effect on the large one were observed within the acoustic exposure parameters and the initial radii of the bubbles examined in this paper. Moreover, as the initial distance between bubbles increases, the strong suppression effect is reduced gradually and it could effectively enhance the nonlinear dynamics of bubbles, exactly as the bifurcation diagrams exhibit a similar mode of successive period doubling to chaos. Correspondingly, the resultant acoustic emissions present a progressive evolution of harmonics, subharmonics, ultraharmonics and broadband components in the frequency spectra. In addition, with the elasticity and/or viscosity of the surrounding medium increasing, both the nonlinear dynamics and translational motions of bubbles were reduced prominently. This study provides a comprehensive insight into the nonlinear behaviors and acoustic emissions of two interacting cavitation bubbles in viscoelastic media, it may contribute to optimizing and monitoring the cavitation-mediated biomedical applications.

Laser-activated bioprobes with high photothermal conversion efficiency (IRPDA@PFH NDs) based on biocompatible IR-780 doped polydopamine perfluorocarbon nanodroplets (NDs) were developed. When protected by gelatin microspheres, their near-spherical morphologies can be easily observed with transmission electron microscope. Doping IR-780 (3 w/w % of added dopamine hydrochloride) can significantly enhance near-infrared (NIR) absorption and photothermal conversion efficiency to 57.7%. The enhanced NIR absorption and nonradiative relaxation are preferred to stronger photoacoustic (PA) signals and higher PA imaging definition; ultrasound (US) signals also increase more than 2.5 times because of easier phase change of NDs. These bioprobes had sensitive PA/US imaging capability with highly effective substitute utilizations, in which polydopamine was used either as a PA contrast or a photothermal agent. Perfluorocarbon can be used as an US contrast agent and temperature indicator. More importantly, the gray value increments of US increase with temperature in a general range from 35 to 55 °C. Especially, an approximate linear increasing of gray value in the optimized photothermal therapy (PTT) range from 35 °C to 50 °C could be used for the temperature monitoring and control of PTT. During PTT, the heated regions and the extent of photothermal heating can be visualized by US imaging. These findings indicate their great potential for biosensing and PTT monitoring.

Inertial cavitation is crucial for the therapeutic effects of sonodynamic. Therefore, approaches that can induce highly efficient inertial cavitation should be of benefit for sonodynamic effect. Our previous study demonstrated that highly efficient inertial cavitation activity can be achieved through the combinatorial use of a short-pulsed focused ultrasound (SPFU) sequence and perfluorohexane (PFH) nanodroplets. Herein, we applied the SPFU sequence and PFH nanodroplets in sonodynamic. A hydrophobic sonosensitizer, IR780 iodine, was loaded inside denatured bovine serum albumin-shelled PFH (PFH@BSA-IR780) nanodroplets. The sonodynamic efficacy was validated by treating HeLa cervical cancer cells. Under SPFU exposure, PFH@BSA-IR780 nanodroplets were highly effective in promoting reactive oxygen species generation and inducing cancer cell death. A significant decrease in cell viability was achieved within just 10 s. Besides the cytotoxicity of ROS, the mechanical bioeffects of inertial cavitation also led to severe cell death resulting from higher acoustic power or the longer treatment time. The application of the SPFU sequence coupled with PFH@BSA-IR780 nanodroplets is a promising strategy for efficient sonodynamic.

Purpose of the study The aim of this study was to perform a meta-analysis to derive precise estimation of the association of interleukin-23 receptor (IL-23R), IL-1 receptor 2 (IL-1R2), IL-12 beta (IL-12B), IL-10 and tumour necrosis factor (TNF)-α polymorphisms with ankylosing spondylitis (AS) susceptibility. Study design A systematic literature search was conducted to identify the relevant studies. Pooled OR with 95% CI was calculated to assess the strength of the association in a fixed or random-effects model. Results A total of 13 917 cases and 19 849 controls in 43 eligible studies were included in the meta-analysis. Seventeen single-nucleotide polymorphisms (SNPs) in the abovementioned five cytokine genes were evaluated. The results indicate that the nine SNPs (rs11209026, rs1004819, rs10489629, rs11465804, rs1343151, rs11209032, rs1495965, rs7517847, rs2201841) of IL-23R are associated with AS susceptibility in all study subjects in the allelic model. Moreover, stratification by ethnicity identified a significant association between seven SNPs of IL-23R and AS susceptibility in Europeans and Americans, but not in Asians. In addition, the IL-10–819 C/T and TNF-α−857 C/T polymorphisms also confer susceptibility to AS, especially in Asian population. Conclusion The results suggested that the genetic susceptibility for AS is associated with the nine SNPs of IL-23R in overall population. In the subgroup analysis, significant associations were shown in European and American population, but not in Asian population. Our results also suggest that IL-10–819 C/T and TNF-α−857 C/T polymorphism might be associated with AS risk, especially in Asian population.

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 Kashchiev's 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.

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.

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.

Acoustic droplet vaporization (ADV) has shown a great potential in extravascular tumor-targeting theranostics. The mechanical perturbations produced during ADV process (e.g. initial volume expansion, cavitation, and movement of the bubble) on the nearby cells could cause cell dysfunction with irreversible cell membrane damage or facilitate drug delivery due to sonoporation. A confocal acousto-optical microscopic system was used to investigate the bioeffects of ADV on nearby cells in real time with high-speed microscopic imaging and fluorescence imaging. A 5 MHz single-element transducer driven by a high power pulser was focused confocally with the microscopy to induce ADV nearby the cells. Calcein-AM and propidium iodide (PI) were added for real-time evaluating cells viability and tracking cell membrane integrity after ADV, respectively. HeLa cervical cancer cells were cultured in the Opticell chamber and perfluoropentane (PFP) nanodroplets were added prior to experiments. Upon ultrasound exposure, the rapid vaporization of PFP nanodroplets into gaseous bubbles and subsequent ADV bubble-cell interactions were observed by high-speed imaging, including the bubble growth, aggregation, coalescence and translational motion above the apical cell membrane layer or near the cells. A pronounced and continuous increase in the intracellular PI fluorescence intensity in the cells near ADV was observed in the fluorescence images post-ADV. It indicated the loss of cell membrane integrity, which was also confirmed by a complete leakage of Calcein. It revealed that the rapid ADV event and formed ADV bubbles forced by ultrasound pulses can cause the irreversible pores on the cell membrane, which results in significant cell damage and eventually cell death. Understanding the real-time characteristics of ADV-mediated bioeffects on cells is significant to develop this approach in vivo and then in clinic.

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. Nanodroplet phase transition was performed in a confocal microscopic system where the ultrasound and focused laser were co-focused in a 200 μm inner diameter cellulose tube in vitro. The perfluoropentane (PFP) droplets were perfused by a syringe. The phase transition process was monitored by both high speed microphotography and acoustic detection. The acoustic signals were converted to the frequency domain and compared with ADV. Microscopic images revealed the distinct patterns of phase transition by ADV and PAC in the cellulose tube. Acoustic signals from PAC showed distinct photoacoustic characteristics with wide-band low frequency components and harmonic components. Compared with ADV, both patterns showed the distinct advantage for predetermining the exact spatial and temporal occurrence of phase transition by the additional focused laser. The energy threshold, although relevant with droplet diameter, was also significantly reduced.

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 paramount importance for developing and applying this approach in clinical practice.

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.

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.

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 stable cavitation. Due to the reduced energy threshold of phase transition, the proposed method enables the theranostic applications of PFC nanodroplets at lower and safer laser/ultrasound energies in tissues or cells. Detection of high amplitude signals also revealed the potential of this method to generate strong photoacoustic signals for the photoacoustic imaging.

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.