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。     

牙齿组织光热动态特性仿真与试验研究

调制激光作用牙齿组织发生散射形成光子密度波, 而由于光热效应产生热波, 基于一维介质辐射传输漫射近似方程与一维热传导方程建立了调制激光作用牙齿组织半透明混合介质的一维热波数学模型. 利用该模型仿真分析了牙齿龋损特性参数(牙釉质龋损层光吸收系数、散射系数、热扩散系数及龋损深度)对光热辐射动态响应特性的影响与规律. 利用红外探测器(HgCdTe, 2–12 μm)记录808 nm半导体激光激发牙齿组织产生的热波信号, 由锁相放大器计算热波信号的幅值与相位. 通过频率扫描试验获得了牙齿组织的光热动态响应, 利用多参数最佳统计拟合方法得到了牙齿组织特性参数. 结果表明光热辐射测量对牙齿组织不均匀性和龋损特性均具有较高敏感性与特异性.     

基于电阻抗层析成像的高强度聚焦超声温度监测技术

作为一种对正常组织无损伤且不易引起癌细胞转移的非入侵肿瘤治疗手段,高强度聚焦超声(HIFU)治疗过程中焦域的温度监测是实现剂量精准控制的关键.本文基于生物组织的温度-电阻抗的关系,将电阻抗层析成像(EIT)和HIFU治疗相结合,提出了一种利用组织焦平面的表面电压实现电阻抗重构的检测技术.建立了HIFU治疗和EIT综合系统模型,在考虑组织的声吸收条件下,对三维Helmholtz方程在柱坐标下的声场计算进行了二维简化,并引入Pennes生物热传导方程来计算HIFU焦域的声压和温升分布特性;引入生物组织的温度-电阻抗关系,基于麦克斯韦电磁场理论,建立了具有温度分布HIFU焦域的电流和电压计算模型,利用恒流注入的边界条件实现电场计算,获得焦平面的表面电压分布.在数值计算中,利用实验聚焦换能器参数,模拟了在固定声功率下组织焦域的声场和温度场分布,以及中心和偏心聚焦条件下不同治疗时刻的电导率分布;然后通过对称电极的循环电流注入,计算了组织模型焦平面内的电流密度和电势分布,获得了焦平面圆周分布的表面电极电压;进一步采用修正的牛顿-拉夫逊算法,利用32×32的表面电极电压实现了焦平面内电导率分布的重建.结果表明,基于温度-电阻抗关系的EIT电导率重建技术不但能准确定位HIFU焦域中心,还能恢复HIFU治疗中焦域的温度分布,证明了EIT用于HIFU治疗中温度监测的可行性,为其疗效评估和剂量控制提供了一种无创电阻抗测量和成像新方法.     

高强度聚焦超声经颅脑肿瘤治疗焦域的仿真研究*

为了研究脑组织和脑肿瘤组织在HIFU治疗时形成焦域的特性及坏死肿瘤组织、不同治疗剂量参数以及多次治疗时焦点间距和时间间隔对HIFU形成焦域的影响,本文以脑胶质瘤患者为例,利用患者头颅CT图像数据建立HIFU经颅治疗的仿真模型,基于Westervelt声波非线性传播方程和Pennes生物热传导方程进行HIFU经颅治疗的仿真研究。结果表明,脑组织和脑肿瘤组织内形成HIFU焦域的差异较小,坏死肿瘤组织对HIFU温度场分布有较小影响;辐照声强越大,焦点温升达到同一温度所用时间越短,焦域长短轴越短,颅骨处温升越低;当焦点间距在一定范围内时,第一次辐照形成的温度场分布对第二个焦点温升达到同一温度所需时间影响较大;两次辐照时间间隔对颅骨处温升和两次聚焦形成60?C以上温度分布影响较小。     

基于分数导数研究高强度聚焦超声的非线性声场

在高强度聚焦超声(high intensity focused ultrasound, HIFU) 的研究中, 生物组织的衰减和色散性质会对声能量的空间分布产生影响. 本文提出应用分数导数修正非线性Khokhlov-Zabolotskaya-Kuznetsov (KZK)方程, 研究生物组织中非线性HIFU声场. 对三种生物仿体的衰减和声速色散的理论实验研究表明分数导数应用的可行性, 在此基础上通过数值仿真分析研究了衰减及声速随频率的变化对HIFU焦域分布的影响. 研究结果表明, 在计算强非线性聚焦超声时, 由于高次谐波的强色散作用, 引入分数导数来解决生物组织特殊的衰减以及色散问题可进一步提高HIFU治疗的安全性. 关键词： 分数导数 声衰减 色散 高强度聚焦超声     

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。     

激光超声中首达纵波脉冲的一种新解释

当脉冲激光辐射到样品物体上时,会产生脉冲超声波(包括体波和表面波)。利用脉冲激光作为激励源,可避免与样品的机械接触,可对样品实行远距离的非接触式无损检测。 传统的光声理论利用了经典热弹耦合方程(CTE)该理论假设热扩散的速度为无限大,它的热传导方程是一个抛物型方程。人们利用这个方程在解释实验上     

固体中激光热弹超声的光穿透效应

本文从热弹性基本方程出发，理论上研究了非金属固体材料受激光热弹激励超声时，光穿透效应对所产生声波的影响。在一维模型中，通过求解热扩散方程和热弹性位移方程，得到弹性位移的一般表达式，分析了材料的光叩收性质与声波位移振幅的关系。在二维模型中，对于轴对称分布的情况，忽略热扩散的影响，采用积分变换法求解热弹性运动方程，推导出远场区中的位移解析表达式。给出了纵波和横波的指向性图案，讨论了光穿透效应对声源指向性的影响。     

激光医学中热响应的遥测技术研究

采用辐射温度测量技术实现了激光与生物组织热响应的无损监测.便携式红外辐射监测仪内置LD红光指示和对准音提示,在距离红外透镜25 mm处最小物面孔径为2.5 mm.靶点组织的温升变化是激光输出参量和被测生物组织自身的光、热物理特性的综合反映,与可能产生的疗效密切相关.实验记录了单个红宝石激光脉冲、连续CO2激光作用下多种组织的热响应过程,从辐照时间、温升峰值、上升时间等角度讨论了不同组织、不同条件下组织热响应的差异.     

激光诱导间质热疗中生物组织的温度场研究

激光诱导间质热疗疗效评估的前提是必须获得准确的激光在不同功率、不同照射时间的生物组织温度场分布.利用多物理场直接耦合分析软件COMSOL Multiphysics构建了在组织光学参量不变情况下的三维有限元传热模型.该模型基于Pennes生物传热方程和轴对称高斯形状的激光光束热源方程,参量针对离体猪肝组织,考虑到了生物组织热物性密度、比热和热导率随温度变化的情况.仿真获得激光功率为0.77 W、0.95 W、1.23 W,照射时间为10~90 s,径向距离0~2 mm范围和轴向距离0~4 mm范围的温度场数据集.利用拟合算法,获得了自变量为激光功率、照射时间、径向距离和轴向距离的生物组织温度场分布模型.将功率为0.88 W和1.05 W时的结果与Pennes方程结果相比较,两者误差在5%以内.     

Influence of dynamic tissue properties on temperature elevation and lesions during HIFU scanning therapy: Numerical simulation

When large tumors are treated,ablation of the entire volume of tumors requires multiple treatment spots formed by high intensity-focused ultrasound(HIFU)scanning therapy.The heating effect of HIFU on biological tissue is mainly reflected in temperature elevation and tissue lesions.Tissue property parameters vary with temperature and,in turn,the distribution of temperature as well as the heating effects change accordingly.In this study,an HIFU scanning therapy model considering dynamic tissue properties is provided.The acoustic fields and temperature fields are solved combining the Helmholtz wave equation with Pennes bio-heat transfer equation based on the finite element method(FEM)to investigate the effects of various tissue properties(i.e.,the attenuation coefficient,acoustic velocity,thermal conductivity,specific heat capacity,density,and blood perfusion rate)on heating performance.Comparisons of the temperature distribution and thermal lesions under static and dynamic properties are made based on the data of tissue property parameters varying with temperature.The results show that the dynamic changes of thermal conductivity,specific heat capacity,and acoustic velocity may account for the decrease of temperature elevation in HIFU treatment,while the dynamic changes of attenuation coefficient,density,and blood perfusion rate aggravate the increase of temperature on treatment spots.Compared with other properties,the dynamic change of attenuation coefficient has a greater impact on tissue temperature elevation.During HIFU scanning therapy,the temperature elevation and tissue lesions of the first treatment spot are smaller than those of the subsequent treatment spots,but the temperature on the last treatment spot drops faster during the cooling period.The ellipsoidal tissue lesion is not symmetrical;specifically,the part facing toward the previous treatment spot tends to be larger.Under the condition of the same doses,the temperature elevation and the size of tissue lesions under dynamic properties present significant growth in comparison to static properties.Besides,the tissue lesion begins to form earlier with a more unsymmetrical shape and is connected to the tissue lesion around the previous treatment spot.As a result,lesions around all the treatment spots are connected with each other to form a closed lesion region.The findings in this study reveal the influence of dynamic tissue properties on temperature elevation and lesions during HIFU scanning therapy,providing useful support for the optimization of treatment programs to guarantee higher efficacy and safety.     

Control of the dynamics of a boiling vapour bubble using pressure-modulated high intensity focused ultrasound without the shock scattering effect: A first proof-of-concept study

Boiling histotripsy is a promising High-Intensity Focused Ultrasound (HIFU) technique that can be used to induce mechanical tissue fractionation at the HIFU focus via cavitation. Two different types of cavitation produced during boiling histotripsy exposure can contribute towards mechanical tissue destruction: (1) a boiling vapour bubble at the HIFU focus and (2) cavitation clouds in between the boiling bubble and the HIFU source. Control of the extent and degree of mechanical damage produced by boiling histotripsy is necessary when treating a solid tumour adjacent to normal tissue or major blood vessels. This is, however, difficult to achieve with boiling histotripsy due to the stochastic formation of the shock scattering-induced inertial cavitation clouds. In the present study, a new histotripsy method termed pressure-modulated shockwave histotripsy is proposed as an alternative to or in addition to boiling histotripsy without inducing the shock scattering effect. The proposed concept is (a) to generate a boiling vapour bubble via localised shockwave heating and (b) subsequently control its extent and lifetime through manipulating peak pressure magnitudes and a HIFU pulse length. To demonstrate the feasibility of the proposed method, bubble dynamics induced at the HIFU focus in an optically transparent liver tissue phantom were investigated using a high speed camera and a passive cavitation detection systems under a single 10, 50 or 100 ms-long 2, 3.5 or 5 MHz pressure-modulated HIFU pulse with varying peak positive and negative pressure amplitudes from 5 to 89 MPa and −3.7 to −14.6 MPa at the focus. Furthermore, a numerical simulation of 2D nonlinear wave propagation with the presence of a boiling bubble at the focus of a HIFU field was conducted by numerically solving the generalised Westervelt equation. The high speed camera experimental results showed that, with the proposed pressure-modulated shockwave histotripsy, boiling bubbles generated by shockwave heating merged together, forming a larger bubble (of the order of a few hundred micron) at the HIFU focus. This coalesced boiling bubble then persisted and maintained within the HIFU focal zone until the end of the exposure (10, 50, or 100 ms). Furthermore, and most importantly, no violent cavitation clouds which typically appear in boiling histotripsy occurred during the proposed histotripsy excitation (i.e. no shock scattering effect). This was likely because that the peak negative pressure magnitude of the backscattered acoustic field by the boiling bubble was below the cavitation cloud intrinsic threshold. The size of the coalesced boiling bubble gradually increased with the peak pressure magnitudes. In addition, with the proposed method, an oval shaped lesion with a length of 0.6 mm and a width of 0.1 mm appeared at the HIFU focus in the tissue phantom, whereas a larger lesion in the form of a tadpole (length: 2.7 mm, width: 0.3 mm) was produced by boiling histotripsy. Taken together, these results suggest that the proposed pressure-modulated shockwave histotripsy could potentially be used to induce a more spatially localised tissue destruction with a desired degree of mechanical damage through controlling the size and lifetime of a boiling bubble without the shock scattering effect.     

球形集声器在生物组织中形成的组织损伤

球形集声器可在亚波长焦域内形成高强度声压,在高强度聚焦超声治疗中具有潜在应用前景.本文结合非线性声传播理论及生物传热学理论,研究球形集声器在生物组织中形成的组织损伤.实验中采用430 kHz,内径为240 mm的球形集声器对肝组织作用,结果表明:集声器表面声压为53 kPa时作用2 s,可以形成小于波长尺度的组织损伤.理论计算结果与实验结果符合得较好,并且理论模型可优化球形集声器的开口孔径.研究结果表明,球形集声器可应用于肿瘤的精细超声治疗.     

Impact of cavitation on lesion formation induced by high intensity focused ultrasound

High intensity focused ultrasound(HIFU) has shown a great promise in noninvasive cancer therapy. The impact of acoustic cavitation on the lesion formation induced by HIFU is investigated both experimentally and theoretically in transparent protein-containing gel and ex vivo liver tissue samples. A numerical model that accounts for nonlinear acoustic propagation and heat transfer is used to simulate the lesion formation induced by the thermal effect. The results showed that lesions could be induced in the samples exposed to HIFU with various acoustic pressures and pulse lengths. The measured areas of lesions formed in the lateral direction were comparable to the simulated results, while much larger discrepancy was observed between the experimental and simulated data for the areas of longitudinal lesion cross-section. Meanwhile,a series of stripe-wiped-off B-mode pictures were obtained by using a special imaging processing method so that HIFUinduced cavitation bubble activities could be monitored in real-time and quantitatively analyzed as the functions of acoustic pressure and pulse length. The results indicated that, unlike the lateral area of HIFU-induced lesion that was less affected by the cavitation activity, the longitudinal cross-section of HIFU-induced lesion was significantly influenced by the generation of cavitation bubbles through the temperature elevation resulting from HIFU exposures. Therefore, considering the clinical safety in HIFU treatments, more attention should be paid on the lesion formation in the longitudinal direction to avoid uncontrollable variation resulting from HIFU-induced cavitation activity.     

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.     

The interaction of shockwaves with a vapour bubble in boiling histotripsy: The shock scattering effect

Boiling histotripsy is a High Intensity Focused Ultrasound (HIFU) technique which uses a number of short pulses with high acoustic pressures at the HIFU focus to induce mechanical tissue fractionation. In boiling histotripsy, two different types of acoustic cavitation contribute towards mechanical tissue destruction: a boiling vapour bubble and cavitation clouds. An understanding of the mechanisms underpinning these phenomena and their dynamics is therefore paramount to predicting and controlling the overall size of a lesion produced for a given boiling histotripsy exposure condition. A number of studies have shown the effects of shockwave heating in generating a boiling bubble at the HIFU focus and have studied its dynamics under boiling histotripsy insonation. However, not much is known about the subsequent production of cavitation clouds that form between the HIFU transducer and the boiling bubble. The main objective of the present study is to examine what causes this bubble cluster formation after the generation of a boiling vapour bubble. A numerical simulation of 2D nonlinear wave propagation with the presence of a bubble at the focus of a HIFU field was performed using the k-Wave MATLAB toolbox for time domain ultrasound simulations, which numerically solves the generalised Westervelt equation. The numerical results clearly demonstrate the appearance of the constructive interference of a backscattered shockwave by a bubble with incoming incident shockwaves. This interaction (i.e., the reflected and inverted peak positive phase from the bubble with the incoming incident rarefactional phase) can eventually induce a greater peak negative pressure field compared to that without the bubble at the HIFU focus. In addition, the backscattered peak negative pressure magnitude gradually increased from 17.4 MPa to 31.6 MPa when increasing the bubble size from 0.2 mm to 1.5 mm. The latter value is above the intrinsic cavitation threshold of –28 MPa in soft tissue. Our results suggest that the formation of a cavitation cloud in boiling histotripsy is a threshold effect which primarily depends (a) the size and location of a boiling bubble, and (b) the sum of the incident field and that scattered by a bubble.     

时间反转方法用于高强度聚焦超声的焦点偏移补偿

传统的高强度聚焦超声(HIFU)治疗中实际焦点和预设焦点容易出现偏移,为考察时间反转方法对HIFU治疗中焦点偏移的补偿效果,采用时域有限差分方法求解Westervelt方程,建立高强度聚焦声场数值模型。数值计算得到在人体软组织中进行HIFU治疗时,采用时间反转方法后焦点偏移距离最大仅为1.6 mm。脂肪层厚度及声源强度改变对时间反转聚焦精度影响不大,F数(焦点距离同换能器孔径的比值)降低时,焦点偏移减小。研究表明在人体软组织吸收系数和非线性系数范围内,时间反转方法可有效补偿焦点偏移,达到更好的聚焦效果。      

Ultrasound line-by-line scanning method of spatial–temporal active cavitation mapping for high-intensity focused ultrasound

This paper presented an ultrasound line-by-line scanning method of spatial–temporal active cavitation mapping applicable in a liquid or liquid filled tissue cavities exposed by high-intensity focused ultrasound (HIFU). Scattered signals from cavitation bubbles were obtained in a scan line immediately after one HIFU exposure, and then there was a waiting time of 2 s long enough to make the liquid back to the original state. As this pattern extended, an image was built up by sequentially measuring a series of such lines. The acquisition of the beamformed radiofrequency (RF) signals for a scan line was synchronized with HIFU exposure. The duration of HIFU exposure, as well as the delay of the interrogating pulse relative to the moment while HIFU was turned off, could vary from microseconds to seconds. The feasibility of this method was demonstrated in tap-water and a tap-water filled cavity in the tissue-mimicking gelatin–agar phantom as capable of observing temporal evolutions of cavitation bubble cloud with temporal resolution of several microseconds, lateral and axial resolution of 0.50 mm and 0.29 mm respectively. The dissolution process of cavitation bubble cloud and spatial distribution affected by cavitation previously generated were also investigated. Although the application is limited by the requirement for a gassy fluid (e.g. tap water, etc.) that allows replenishment of nuclei between HIFU exposures, the technique may be a useful tool in spatial–temporal cavitation mapping for HIFU with high precision and resolution, providing a reference for clinical therapy.