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1.
于洁  郭霞生  屠娟  章东 《物理学报》2015,64(9):94306-094306
随着生命科学及现代医学的发展, 一体化无创精准诊疗已经日益成为人们关注的焦点问题, 而关于超声造影剂微泡的非线性效应的相关机理、动力学建模及其在超声医学领域中的应用研究也得到了极大的推动. 本文对下列课题进行了总结和讨论, 包括: 1)基于Mie散射技术和流式细胞仪对造影剂微泡参数进行定征的一体化解决方案; 2)通过对微泡包膜的黏弹特性进行非线性修正, 构建新的包膜微泡动力学模型; 3)探索造影剂惯性空化阈值与其包膜参数之间的相关性; 以及4)研究超声联合造影剂微泡促进基因/药物转染效率并有效降低其生物毒性的相关机理.  相似文献   

2.
The past several decades have witnessed great progress in “smart drug delivery”, an advance technology that can deliver genes or drugs into specific locations of patients’ body with enhanced delivery efficiency. Ultrasound-activated mechanical force induced by the interactions between microbubbles and cells, which can stimulate so-called “sonoporation” process, has been regarded as one of the most promising candidates to realize spatiotemporal-controllable drug delivery to selected regions. Both experimental and numerical studies were performed to get in-depth understanding on how the microbubbles interact with cells during sonoporation processes, under different impact parameters. The current work gives an overview of the general mechanism underlying microbubble-mediated sonoporation, and the possible impact factors (e.g., the properties of cavitation agents and cells, acoustical driving parameters and bubble/cell micro-environment) that could affect sonoporation outcomes. Finally, current progress and considerations of sonoporation in clinical applications are reviewed also.  相似文献   

3.
In this study, we investigated the effects of extracellular matrix rigidity, an important physical property of microenvironments regulating cell morphology and functions, on sonoporation facilitated by targeted microbubbles, highlighting the role of microbubbles. We conducted mechanistic studies at the cellular level on physiologically relevant soft and rigid substrates. By developing a unique imaging strategy, we first resolved details of the 3D attachment configurations between targeted microbubbles and cell membrane. High-speed video microscopy then unveiled bubble dynamics driven by a single ultrasound pulse. Finally, we evaluated the cell membrane permeabilization using a small molecule model drug. Our results demonstrate that: (1) stronger targeted microbubble attachment was formed for cells cultured on the rigid substrate, while six different attachment configurations were revealed in total; (2) more violent bubble oscillation was observed for cells cultured on the rigid substrate, while one third of bubbles attached to cells on the soft substrate exhibited deformation shortly after ultrasound was turned off; (3) higher acoustic pressure was needed to permeabilize the cell membrane for cells on the soft substrate, while under the same ultrasound condition, acoustically-activated microbubbles generated larger pores as compared to cells cultured on the soft substrate. The current findings provide new insights to understand the underlying mechanisms of sonoporation in a physiologically relevant context and may be useful for the clinical translation of sonoporation.  相似文献   

4.
A reinterpretation of existing theory for rectified diffusion, the process by which bubbles in a sound field may grow in radius, is presented in order to quantitate the effect of acoustic microstreaming on bubble growth rates. The 1/t term in the growth rate equation is defined as the "decay term" and t as the "decay time," the time required for the gas concentration in the liquid contacting the bubble to rise (or fall) from its initial to its final value. In the absence of microstreaming, t is the duration of sonification. In the presence of microstreaming, t may be calculated from the streaming velocity and the bubble radius. A comparison between theory and the experimental results of Eller [A. Eller, J. Acoust. Soc. Am. 46, 1246-1250 (1969)] and of Gould [R.K. Gould, J. Acoust. Soc. Am. 56, 1740-1746 (1974)] shows reasonable agreement in the low kHz range. Theoretical results in the frequency range of 1-10 MHz at 1 and 4 bar are also presented.  相似文献   

5.
A model system consisting of a thin layer of vacuum-deposited metallic aluminium on a glass microscope slide was developed to demonstrate the effectiveness of cavitational activity (occurring within the cooling water supply of a dental ultrasonic descaler operating at 25 kHz) in the removal of particulate matter from solid surfaces. The pattern of particulate matter removal using this model system demonstrated both the mechanism of bubble activity and the erosive nature of microbubbles.Non-resonant bubbles were formed by surface wave activity and adhered to the surface of the slide. There was some removal of the aluminium metal at the periphery of the bubble (probably by a microstreaming mechanism) giving a ‘ghost’ outline. The majority of aluminium removal was caused by numerous microbubbles of non-resonant sizes (typically 1 to 2 μm diameter) formed by surface wave induced fragmentation of the parent bubble.The damaging and erosive effects of transient cavitational activity appear to be the result of sub-resonant sized microbubble formation from larger parent bubbles.  相似文献   

6.
Sonoporation uses ultrasound, with the aid of ultrasound contrast agents (UCAs), to enhance cell permeabilization, thereby allowing delivery of therapeutic compounds noninvasively into specific target cells. The objective of this study was to determine if a computational model describing shear stress on a cell membrane due to microstreaming would successfully reflect sonoporation activity with respect to the peak rarefactional pressure. The theoretical models were compared to the sonoporation results from Chinese hamster ovary cells using Definity(?) at 0.9, 3.15, and 5.6 MHz and were found to accurately describe the maximum sonoporation activity, the pressure where a decrease in sonoporation activity occurs, and relative differences between maximum activity and the activity after that decrease. Therefore, the model supports the experimental findings that shear stress on cell membranes secondary to oscillating UCAs results in sonoporation.  相似文献   

7.
Coated microbubbles, unlike tissue are able to scatter sound subharmonically. Therefore, the subharmonic behavior of coated microbubbles can be used to enhance the contrast in ultrasound contrast imaging. Theoretically, a threshold amplitude of the driving pressure can be calculated above which subharmonic oscillations of microbubbles are initiated. Interestingly, earlier experimental studies on coated microbubbles demonstrated that the threshold for these bubbles is much lower than predicted by the traditional linear viscoelastic shell models. This paper presents an experimental study on the subharmonic behavior of differently sized individual phospholipid coated microbubbles. The radial subharmonic response of the microbubbles was recorded with the Brandaris ultra high-speed camera as a function of both the amplitude and the frequency of the driving pulse. Threshold pressures for subharmonic generation as low as 5 kPa were found near a driving frequency equal to twice the resonance frequency of the bubble. An explanation for this low threshold pressure is provided by the shell buckling model proposed by Marmottant et al. [J. Acoust. Soc. Am. 118, 3499-3505 (2005)]. It is shown that the change in the elasticity of the bubble shell as a function of bubble radius as proposed in this model, enhances the subharmonic behavior of the microbubbles.  相似文献   

8.
Radionuclide tumour therapy with ultrasound contrast microbubbles   总被引:6,自引:0,他引:6  
Radionuclides have shown to be effective in tumour therapy. However, the side effects determine the maximum deliverable dose. Recently, it has been demonstrated that cells can be permeabilised through sonoporation using ultrasound and contrast microbubbles. The use of sonoporation in treatment of tumours may increase the anti-tumour efficacy of radionuclide treatment. The mechanisms as well as the effects sonoporation in tumour treatment strategies are still not understood. The purpose of this study is to determine the effects of ultrasound and contrast microbubbles on the internalisation of the radionuclide (111)In-DOTA-Tyr(3)-octreotate in tumour cells. To optimize ultrasound settings for ultrasound adjunctive tumour therapy we incubated rat pancreatic CA20948 tumour cells with two dyes (MW 40 and 70 kDa). The uptake levels were compared with cells treated with ultrasound and contrast microbubbles for different ultrasound settings. The highest molecular uptake was found with addition of contrast microbubbles (ratio of 10 bubbles to 1 cell) and with the ultrasound setting: duty cycle 0.013%, mechanical index (MI) 0.42, and treatment times of 30 and 60 min. These settings were used to enhance the internalisation of (111)In-DOTA-Tyr(3)-octreotate. We found a 160% higher internalisation of (111)In-DOTA-Tyr(3)-octreotate by tumour cells adjunctively treated with ultrasound and contrast microbubbles compared to untreated cells. These results show that adjunctive tumour treatment with the radionuclide (111)In-DOTA-Tyr(3)-octreotate and ultrasound contrast microbubbles may be feasible. When using adjunctive ultrasound contrast microbubble treatment, a lower radionuclide doses are required to reach the same anti-tumour effect.  相似文献   

9.
A theoretical investigation of the forced linear oscillations of a gas microbubble in a blood capillary, whose radius is comparable in size to the bubble radius is presented. The natural frequency of oscillation, the thermal and viscous damping coefficients, the amplitude resonance, the energy resonance, as well as the average energy absorbed by the system, bubble plus vessel, have been computed for different kinds of gas microbubbles, containing air, octafluropropane, and perflurobutane as a function of the bubble radius and applied frequency. It has been found that the bubble behavior is isothermal at low frequencies and for small bubbles and between isothermal and adiabatic for larger bubbles and higher frequencies, with the viscous damping dominating over the thermal damping. Furthermore, the width of the energy resonance is strongly dependent on the bubble size and the natural frequency of oscillation is affected by the presence of the vessel wall and position of the bubble in the vessel. Therefore, the presence of the blood vessel affects the way in which the bubble absorbs energy from the ultrasonic field. The motivation of this study lies in the possibility of using gas microbubbles as an aid to therapeutic focused ultrasound treatments.  相似文献   

10.
Sonoporation—transient plasma membrane perforation elicited by the interaction of ultrasound waves with microbubbles—has shown great potential for drug delivery and gene therapy. However, the heterogeneity of sonoporation introduces complexities and challenges in the realization of controllable and predictable drug delivery. The aim of this investigation was to understand how non-acoustic parameters (bubble related and bubble-cell interaction parameters) affect sonoporation. Using a customized ultrasound-exposure and fluorescence-imaging platform, we observed sonoporation dynamics at the single-cell level and quantified exogenous molecular uptake levels to characterize the degree of sonoporation. Sonovue microbubbles were introduced to passively regulate microbubble-to-cell distance and number, and bubble size. 1 MHz ultrasound with 10-cycle pulse duration and 0.6 MPa peak negative pressure were applied to trigger the inertial collapse of microbubbles. Our data revealed the impact of non-acoustic parameters on the heterogeneity of sonoporation. (i) The localized collapse of relatively small bubbles (diameter, D < 5.5 μm) led to predictable sonoporation, the degree of which depended on the bubble-to-cell distance (d). No sonoporation was observed when d/D > 1, whereas reversible sonoporation occurred when d/D < 1. (ii) Large bubbles (D > 5.5 μm) exhibited translational movement over large distances, resulting in unpredictable sonoporation. Translation towards the cell surface led to variable reversible sonoporation or irreversible sonoporation, and translation away from the cell caused either no or reversible sonoporation. (iii) The number of bubbles correlated positively with the degree of sonoporation when D < 5.5 μm and d/D < 1. Localized collapse of two to three bubbles mainly resulted in reversible sonoporation, whereas irreversible sonoporation was more likely following the collapse of four or more bubbles. These findings offer useful insight into the relationship between non-acoustic parameters and the degree of sonoporation.  相似文献   

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