An in vitro feasibility study of controlled drug release from encapsulated nanometer liposomes using high intensity focused ultrasound

A liposome with a diameter ranging from 150 to 200 nm has been considered to be one of the optimal vehicles for targeted drug delivery in vivo since it is able to encapsulate drug and also circulate in the blood stream stably. Its small size, however, makes controlled release of its encapsulated content difficult. A feasibility study for applications of high intensity focused ultrasound (HIFU) of the mega-hertz frequency to induce controlled release of its content was carried out. This study, using the dynamic light scattering and transmission electron microscopic observation, demonstrated 21.2% of encapsulated fluorescent materials (FITC) could be released from liposomes with an average diameter of 210 nm when exposed to continuous (cw) ultrasound at 1.1 MHz (I_SPTA = 900 W/cm²) for 10 s and the percentage release efficiency can reach to 70% after 60 s irradiation. This result also reveals that rupture of relatively large liposomes (>100 nm) and generation of pore-like defects in the membrane of small liposomes (<100 nm) due to HIFU excitation might be the main causes of the release; the inertial cavitation took place during the irradiation. The controlled drug release from liposomes by HIFU may be proven to be a potential useful modality for clinical applications.     

Analytical and numerical calculations of optimum design frequency for focused ultrasound therapy and acoustic radiation force

Focused ultrasound therapy relies on acoustic power absorption by tissue. The stronger the absorption the higher the temperature increase is. However, strong acoustic absorption also means faster attenuation and limited penetration depth. Hence, there is a trade-off between heat generation efficacy and penetration depth. In this paper, we formulated the acoustic power absorption as a function of frequency and attenuation coefficient, and defined two figures of merit to measure the power absorption: spatial peak of the acoustic power absorption density, and the acoustic power absorbed within the focal area. Then, we derived “rule of thumb” expressions for the optimum frequencies that maximized these figures of merit given the target depth and homogeneous tissue type. We also formulated a method to calculate the optimum frequency for inhomogeneous tissue given the tissue composition for situations where the tissue structure can be assumed to be made of parallel layers of homogeneous tissue. We checked the validity of the rules using linear acoustic field simulations. For a one-dimensional array of 4 cm acoustic aperture, and for a two-dimensional array of 4 × 4 cm² acoustic aperture, we found that the power absorbed within the focal area is maximized at 0.86 MHz, and 0.79 MHz, respectively, when the target depth is 4 cm in muscle tissue. The rules on the other hand predicted the optimum frequencies for acoustic power absorption as 0.9 MHz and 0.86 MHz, respectively for the 1D and 2D array case, which are within 6% and 9% of the field simulation results. Because radiation force generated by an acoustic wave in a lossy propagation medium is approximately proportional to the acoustic power absorption, these rules can be used to maximize acoustic radiation force generated in tissue as well.     

高强聚焦超声(HIFU)加热活体组织中的温度分布

在高强聚焦超声(HIFU)加热的情况下,利用多针射频(RF)测温装置测量活体组织内的温度分布,结果表明,温度梯度依赖于局部温度,温度越高,梯度越大。此外,本文还研究了血流对温度梯度的影响,结果似乎证实了理论预测,即血流(或血液灌注)减缓了温度(梯度)的变化。     

高强聚焦超声(HIFU)无创外科─21世纪治疗肿瘤的新技术

本文从简要回顾超声治疗的发展历史开始,重要介绍了90年代初在国际上兴起的HIFU无创外科技术及我国在该领域中的成就。文章继而对HIFU“切除”肿瘤的机理,治疗质量及其发展前景做了讨论。     

高强聚焦超声(HIFU)无创外科─21世纪治疗肿瘤的新技术

本文从简要回顾超声治疗的发展历史开始,重点介绍了９０年代初在国际上兴起的ＨＩＦＵ无创外科技术及我国在该领域中的成就．文章继而对ＨＩＦＵ“切除”肿瘤的机理,治疗质量及其及发展前景做了讨论．     

超声场的光纤探测

在高强度聚焦的超声场检测中,与一般的传感器相比,光纤在这一领域有着其特有的优势。本文从光纤的角度详细分析了各种可能的方法,比如端面法,声光衍射法,光纤光栅法等。     

高强度聚焦超声在医学超声领域中的发展与应用

高强度聚焦超声(high intensity focused ultrasound,简称HIFU)作为一种非侵入性、无毒副作用、具有巨大潜力的治疗肿瘤的手段,近年来已经越来越受到国内外学者的广泛关注。HIFU技术能将超声能量聚焦到人体组织的肿瘤内,产生高温,使肿瘤组织温度迅速上升至65℃以上,而发生不可逆转的凝固性坏死,从而达到消融肿瘤组织的目的。目前中国的HIFU肿瘤治疗技术和临床居国际领先。文章对HIFU在医学超声领域中的发展历史、现状和前景进行了探讨。     

高强度聚焦超声在医学超声领域中的发展与应用

高强度聚焦超声（high intensity focused ultrasound,简称HIFU）作为一种非侵入性、无毒副作用、具有巨大潜力的治疗肿瘤的手段,近年来已经越来越受到国内外学者的广泛关注。HIFU技术能将超声能量聚焦到人体组织的肿瘤内,产生高温,使肿瘤组织温度迅速上升至65℃以上,而发生不可逆转的凝固性坏死,从而达到消融肿瘤组织的目的。目前中国的HIFU肿瘤治疗技术和临床居国际领先。文章对HIFU在医学超声领域中的发展历史、现状和前景进行了探讨。     

液体中高强度聚焦超声场及其测量

基于已知文献,文章介绍了液体中高强度聚焦超声场的基本性质,包括传播、频谱、吸收、聚焦、辐射力等特性,描述了它的物理图景和测量方法。     

高强度聚焦超声(HIFU)——一门多学科的研究课题

高强度聚焦超声(high intensity focused ultrasound,简称HIFU)已作为一种无创外科工具而应用于门诊治疗肿瘤。文章介绍了它的基本原理、有关的研究现状和存在的问题,以及对今后研究工作的建议。文章特别强调高强度聚焦超声是一门多学科的综合研究课题,需要各方面的科学工作者通力协作。     

高强度聚焦超声（HIFU）——一门多学科的研究课题

高强度聚焦超声(high intensity focused ultrasound, 简称HIFU)已作为一种无创外科工具而应用于门诊治疗肿瘤。文章介绍了它的基本原理、有关的研究现状和存在的问题,以及对今后研究工作的建议。文章特别强调高强度聚焦超声是一门多学科的综合研究课题,需要各方面的科学工作者通力协作。     

Modulation of luciferase activity using high intensity focused ultrasound in combination with bioluminescence imaging, magnetic resonance imaging and histological analysis in muscle tissue

This study investigates the effect of high intensity focused ultrasound (HIFU) to muscle tissue transfected with a luciferase reporter gene under the control of a CMV-promoter. HIFU was applied to the transfected muscle tissue using a dual HIFU system. In a first group four different intensities (802 W/cm², 1401 W/cm², 2117 W/cm², 3067 W/cm²) of continuous HIFU were applied 20 s every other week for four times. In a second group two different intensities (802 W/cm², 1401 W/cm²) were applied 20 s every fourth day for 20 times. The luciferase activity was determined by bioluminescence imaging. The effect of HIFU to the muscle tissue was assessed by T1-weighted ± Gd-DTPA, T2-weighted and a diffusion-weighted STEAM sequence obtained on a 1.5-T GE-MRI scanner. Histology of the treated tissue was done at the end. In the first group the photon emission was at 3067.6 W/cm² 1.28 × 10⁷ ± 3.1 × 10⁶ photon/s (5.5 ± 1.2-fold), of 2157.9 W/cm² 8.1 ± 2.7 × 10⁶ photon/s (3.2 ± 1.1-fold), of 1401.9 W/cm² 9.3 ± 1.3 × 10⁶ photon/s (4.9 ± 0.4-fold) and of 802.0 W/cm² 8.6x ± 1.2 × 10⁶ photon/s (4.5 ± 0.6-fold) compared to baseline. In the second group the photon emission was at 1401.9 W/cm² and 802.0 W/cm² 14.1 ± 3.6 × 10⁶ photon/s (6.1 ± 1.5-fold), respectively, 5.1 ± 4.7 × 10⁶ photon/s (6.5 ± 2.0-fold). HIFU can enhance the luciferase activity controlled by a CMV-promoter.     

相控阵高强度聚焦超声的研究进展

相控阵高强度聚焦超声（high Intensity focused ultrasound,HIFU）技术可以通过电子调相自由控制聚焦区域中焦点的形状、位置、个数等,实现高精度、高效率的治疗。文章主要介绍了相控聚焦超声的原理、阵型设计、声场优化、控制算法、电路设计以及换能器材料等几个方面。     

微泡对高强度聚焦超声焦域影响的研究*

微泡对高强度聚焦超声(HIFU)治疗具有增效作用,而HIFU治疗中不同声学条件下微泡对HIFU治疗焦域的影响尚不清楚。本文基于声传播方程、Yang-Church气泡运动方程、生物热传导方程、时域有限差分法(FDTD)、龙格-库塔(RK)法数值仿真研究输入功率、激励频率和气泡初始半径对HIFU在含气泡体模中形成焦域的影响,并利用含Sono Vue造影剂的仿组织体模研究进行实验验证。结果表明,增大输入功率、气泡初始半径和升高激励频率均可增大焦域,随着输入功率的增大,焦域形状可能发生变化,而随着激励频率升高和气泡初始半径的增大,焦域会向远离换能器的方向移动。     

高强度聚焦超声治疗子宫肌瘤中水囊耦合的影响评估*

水囊作为一种特殊的辅助器件在高强度聚焦超声治疗子宫肌瘤的过程中发挥着重要作用,但它同时也会让声通道变得更加复杂,对超声治疗效率和超声引导影像均造成负面影响。基于实际临床场景,利用k-Wave声学仿真软件建立高强度聚焦超声辐照靶组织及其超声引导过程的仿真模型,在有无水囊两个场景下,对治疗效率和监控影像质量进行定量评估。结果表明,加入水囊后,声波的聚焦性变差,焦域处的最高温度降低;通过分析超声图像的分辨率、对比度、对比噪声以及背景信噪比,发现加入水囊后超声图像的质量降低。建立的数值仿真模型能够初步评估水囊对治疗效率和监控影像质量的影响,可作为一种评估体系用于优化水囊参数,如水囊材料、厚度、形状、内部溶液成分等,为下一步实验探索对治疗效率和影像质量影响最小的水囊耦合方式提供评估手段。     

HIFU治疗中换能器驱动电功率变化机制及规律*

高强度聚焦超声(HIFU)治疗中的驱动电功率对治疗效率起着非常关键的作用,驱动电功率控制的精准性势必会影响治疗的效率和安全性。前期研究表明：HIFU治疗过程中焦域瞬态物理特性的变化会导致换能器的负载阻抗发生变化,进而影响HIFU驱动电功率,但驱动电功率与焦域瞬态物理特性之间的影响关系及规律尚不明确。该文基于电压、电流传感器、空化检测探头和温度传感器等器件,构建了一种HIFU治疗中驱动电功率实时监测及焦域声空化、温度检测系统。基于该实验研究系统,以离体牛心组织作为HIFU辐照对象,分别研究了HIFU焦域温度变化、声空化及组织损伤与驱动电功率之间的变化关系及规律。研究结果表明：当焦域温度升高时,驱动电功率缓慢上升,驱动电功率与温度变化有良好的相关性;当空化产生时,驱动电功率出现明显的波动;当组织出现损伤时,驱动电功率呈陡然下降的变化。三种情景下,驱动电功率变化有明显区别,这有望为区分HIFU治疗过程中焦域处发生损伤和空化以及实时监测靶组织损伤程度提供一种新的解决方案。     

高强度聚焦超声用于肿瘤治疗的研究

高强度聚焦超声（ＨＩＦＵ）能在短时间内使病变组织的温度升至７０℃以上,导致病变组织凝固坏死,是一种具有巨大潜力的、非侵入的、有效的肿瘤治疗手段。本文对ＨＩＦＵ的动物试验、临床应用及治疗装置的研究情况进行了总结,分析了该技术尚存在的问题,最后展望了其应用前景。