Exploring the Post-activation Behavioral Patterns of Intratumorally-injected Theranostic Nanodroplets: An Ultrasound-only Extravascular Monitoring Technique.

Phase-change nanodroplets (PCNDs) are customizable and controllable theranostic agents of particular interest in extravascular therapies such as drug delivery and histotripsy. High-bulk-boiling-point (HBP) PCNDs are preferred for their enhanced thermal stability under physiological temperature to achieve on-demand therapeutic effects on target sites - mainly in tumor tissue. However, the behavioral patterns of high-concentration, heterogeneously distributed HBP PCNDs in vivo have rarely been explored - the foci of PCNDs-related therapies mostly fall on the final therapeutic effect rather than the detailed behaviors of PCNDs, which may hamper the development and improvement of in vivo treatments with PCNDs. To fill the gap, we demonstrate an ultrasound-only extravascular monitoring technique to analyze the underlying behavioral patterns of intratumorally-injected HBP PCNDs. In our hypothesis, recondensation and coalescence are the two predominant patterns influencing the trend of the post-activation signal of PCNDs. A "blink map" method was thus proposed to separate the two parts of the signal by recognizing the unique signal pattern of stochastic recondensation, and four derivative metrics were calculated for further analysis. The results revealed the post-activation patterns of PCNDs at different activation-pulse durations and activation stages throughout the activation-imaging period, and several general trends were observed and explained by existing theories, suggesting the feasibility of our extravascular monitoring technique. Overall, this work enriches the knowledge of the characteristics of HBP PCNDs as extravascular theranostic agents, and the monitoring results have the potential to provide timely feedback on PCNDs-related treatments underway, which may help adjust the treatment strategy and improve the therapeutic efficacy.

Underwater Wavelength Attack on Discrete Modulated Continuous-Variable Quantum Key Distribution.

The wavelength attack utilizes the dependence of beam splitters (BSs) on wavelength to cause legitimate users Alice and Bob to underestimate their excess noise so that Eve can steal more secret keys without being detected. Recently, the wavelength attack on Gaussian-modulated continuous-variable quantum key distribution (CV-QKD) has been researched in both fiber and atmospheric channels. However, the wavelength attack may also pose a threat to the case of ocean turbulent channels, which are vital for the secure communication of both ocean sensor networks and submarines. In this work, we propose two wavelength attack schemes on underwater discrete modulated (DM) CV-QKD protocol, which is effective for the case with and without local oscillator (LO) intensity monitor, respectively. In terms of the transmittance properties of the fused biconical taper (FBT) BS, two sets of wavelengths are determined for Eve's pulse manipulation, which are all located in the so-called blue-green band. The derived successful criterion shows that both attack schemes can control the estimated excess noise of Alice and Bob close to zero by selecting the corresponding condition parameters based on channel transmittance. Additionally, our numerical analysis shows that Eve can steal more bits when the wavelength attack controls the value of the estimated excess noise closer to zero.

Effect of tissue viscoelasticity and adjacent phase-changed microbubbles on vaporization process and direct growth threshold of nanodroplet in an ultrasonic field.

Understanding the behavior of nanodroplets converted into microbubbles with applied ultrasound is an important problem in tumor therapeutical and diagnostic applications. In this study, a comprehensive model is proposed to investigate the vaporization process and the direct growth threshold of the nanodroplet by following the vapor bubble growth, especially attention devoted to the effect of tissue viscoelasticity and adjacent phase-changed microbubbles (PCMBs). It is shown that the ultrasonic energy must be sufficiently strong to counterbalance the natural condensation of the vapor bubble and the tissue stiffness-inhibitory effect. The softer tissue with a lower shear modulus favors the vaporization process, and the nanodroplet has a lower direct growth threshold in the softer tissue. Moreover, the adjacent PCMBs show a suppression effect on the vaporization process due to the negative value of the secondary Bjerknes force, implying an attractive force, preventing the nanodroplet from escaping from the constraint of the adjacent PCMBs. However, according to the linear scattering theory, the attractive force signifies that the constraint is weak, causing the direct growth threshold to increase in the range of 0.09-0.24 MPa. The weak increase in threshold demonstrates that the direct growth threshold is relatively unaffected by the adjacent PCMBs. The prediction results of our model are in good agreement with the experiment results obtained by the echo enhancement method, in which the threshold is relatively independent of the intermediate concentration. The findings presented here provide physical insight that will be further helpful in understanding the complex behavior of the nanodroplet responses to ultrasound in practical medical applications.

Interaction between particles and bubbles driven by ultrasound: Acoustic radiation force on an elastic particle immersed in the ideal fluid near a bubble.

A theoretical model is proposed to investigate the acoustic radiation force on the elastic particle for coupled particle-bubble system. Based on the sound scattering theory, an analytical expression of the force function is obtained for the particle in plane wave sound field. Numerical simulations are presented for elastic particle of stainless steel, steel or brass. The results reveal that the presence of bubbles can affect the feature of radiation force curves of particles. The force curve fluctuates, and negative force emerges in the small kR1 region for certain distance between the bubble and particle. There are more sharp peaks and dips in the curves because of the resonance of the elasticity of the system and the resonant peaks of the acoustic radiation force transfer to low frequencies when the size of elastic particle is increased. The approximate positive flat region is shortened because of the presence of bubble, which may help to optimize the size ranges of particle for acoustic screening. This study provides for improvement of the acoustic manipulation theoretical model.