组织凝固性坏死对基于纵向弛豫时间的磁共振测温的影响

高强度聚焦超声（High Intensity Focused Ultrasound,HIFU）治疗肿瘤时,为了保证治疗的安全性和有效性,需要对组织温度分布进行实时监测.磁共振成像（Magnetic Resonance Imaging,MRI）具有对温度敏感的成像参数,可以无创检测组织温度.本文结合组织相变对测温的影响,探讨了磁共振测温（Magnetic Resonance Thermometry,MRT）技术能否用于实时监控HIFU治疗.利用两态快速交换模型,提出在组织凝固性坏死的相变前后,MRI的纵向弛豫时间（T₁）参数与组织温度之间具有不同关系.并通过实验验证了上述假设.相对于传统的磁共振测温方法模型,本文考虑了HIFU治疗过程中组织相变对检测温度的影响,对利用磁共振测温引导HIFU治疗具有重要的参考价值.     

A flexible 9-channel coil array for fast 3D MR thermometry in MR-guided high-intensity focused ultrasound (HIFU) studies on rabbits at 3 T

Signal-to-noise ratio (SNR) is a critical factor in MR-guided high-intensity focused ultrasound (HIFU) for local heating, which can affect the accuracy of temperature measurement. In order to achieve high SNR and higher temporal resolution, dedicated coil arrays for MR-guided HIFU applications need to be developed. In this work, a flexible 9-channel coil array was designed, and constructed at 3 T to achieve fast temperature mapping for MR-guided HIFU applications on rabbit leg muscle. Coil performance was evaluated for SNR, and parallel imaging capability by in-vivo studies. Compared to a commercially available 4-channel flexible coil array, the dedicated 9-channel coil array has a much higher SNR, with at least a 2.6-fold increment in the region of interest (ROI). The inverse g-factors maps demonstrated that the dedicated 9-channel coil array has a better parallel imaging capability than the Flex Small 4. With accelerations normal to the array direction, both coil arrays showed much higher g-factors than those of accelerations along the array direction. Room temperature mapping was implemented to evaluate the temperature measurement accuracy by in-vivo experiments. The precisions of the 9-channel coil, ±0.18 °C for un-acceleration and ± 0.56 °C for acceleration at R = 2 × 2, both improved by an order of magnitude than these of the 4-channel coil, which were ± 1.45 °C for un-acceleration and ± 3.52 °C for acceleration at R = 2 × 2. In the fast temperature imaging on the rabbit leg muscle with heating, a high temporal resolution of 3.3 s with a temperature measurement precision of ±0.56 °C has been achieved using the dedicated 9-channel coil. This study demonstrates that the dedicated 9-channel coil array for rabbit leg imaging provides improved performance in SNR, parallel imaging capability, and the accuracy of temperature measurement compared to a commercial 4-channel coil, and it also achieves fast temperature mapping in practical MR-guided HIFU applications.     

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。     

The Relationship of Cavitation to the Negative Acoustic Pressure Amplitude in Ultrasonic Therapy

The relationship between the cavitation and acoustic peak negative pressure in the high-intensity focused ultrasound(HIFU)Held is analyzed in water and tissue phantom.The peak negative pressure at the focus is determined by a hybrid approach combining the measurement with the simulation.The spheroidal beam equation is utilized to describe the nonlinear acoustic propagation.The waveform at the focus is measured by a fiber optic probe hydrophone in water.The relationship between the source pressure amplitude and the excitation voltage is determined by fitting the measured ratio of the second harmonic to the fundamental component at the focus,based on the model simulation.Then the focal negative pressure is calculated for arbitrary voltage excitation in water and tissue phantom.A portable B-mode ultrasound scanner is applied to monitor HIFU-induced cavitation in real time,and a passive cavitation detection(PCD)system is used to acquire the bubble scattering signals in the HIFU focal volume for the cavitation quantification.The results show that:(1)unstable cavitation starts to appear in degassed water when the peak negative pressure of HIFU signals reaches 13.5 MPa;and(2)the cavitation activity can be detected in tissue phantom by B-mode images and in the PCD system with HIFU peak negative pressures of 9.0 MPa and 7.8 MPa,respectively,which suggests that real-time B-mode images could be used to monitor the cavitation activity in two dimensions,while PCD systems are more sensitive to detect scattering and emission signals from cavitation bubbles.     

Differential ultrasonic imaging for the characterization of lesions induced by high intensity focused ultrasound

High intensity focused ultrasound (HIFU) is an effective technique for noninvasive local creating coagulative necrotic lesions in deep target volumes without damage to the overlaying or surrounding tissues. It is very important to detect and evaluate lesions generated by HIFU during treatment procedures. This study describes the development of several differential ultrasonic imaging techniques to characterize lesions based on estimation of relative changes in tissue properties derived from backscattered RF data. A single, spherical HIFU transducer was used to produce lesions in soft tissues. The RF signals were recorded as outputs from a modified diagnostic ultrasound system. After some preprocessing, the integrated backscatter values, which can be used as an indicator of the microstructure and backscattering property of tissues, were calculated before and after HIFU treatment. The differential integrated backscatter values were subsequently used to form images revealing the lesion areas. The differential attenuation imaging with the same RF data was also performed, which has been proposed by a few researchers. The results of the differential integrated backscatter imaging were compared with that of the differential attenuation imaging and the former method offers some advantages over the latter method. The two methods above are both based on spectrum analysis and would spend much computational time. Therefore, some simple digital differential imaging methods, including absolute difference (AD), sum absolute differences (SAD), and sum squared differences (SSD) algorithms, were also proposed to detect HIFU-induced lesions. However, these methods cannot provide the information of the degree of tissue damage. Experiments in vitro bovine muscle and liver validated the method of differential integrated backscatter imaging for the characterization of HIFU-induced lesions. And the AD, SAD, and SSD algorithms can be implemented in real-time during HIFU therapy to visualize the lesions.     

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。      

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.     

MR monitoring of focused ultrasound surgery in a breast tissue model in vivo

The objective of this study was to investigate MRI methods for monitoring focused ultrasound surgery (FUS) of breast tumors. To this end, the mammary glands of sheep were used as tissue model. The tissue was treated in vivo with numerous single sonications which covered extended target volumes by employing a scanning technique. The ultrasound focus position was controlled by online temperature mapping based on the temperature dependence of the relaxation time T(1). This approach proved to be reliable and offers thus an alternative to proton resonance frequency methods, whose application is hampered in fatty tissues. FUS-induced tissue changes were visible on T(2)- as well as on pre- and post-contrast T(1)-weighted images. According to our initial experience, noninvasive MRI-guided FUS of breast tumors is feasible.     

Analysis of longitudinal relaxation rate constants from magnetization transfer MR images of human tissues at 0.1 T.

The human calf muscle was examined by using the magnetization transfer MR imaging technique. The time-dependent saturation transfer (TDST) method was applied at low magnetic field 0.1 T in order to measure the mobile water relaxation time T1w, the magnetization transfer rate Rwm from water to solid macromolecules, and the magnetization transfer contrast (MTC) of the human tissue. The magnetization transfer contrast of 0.67 was attained. The transfer rate Rwm was 4.5 sec-1 (+/- 0.3 sec-1) for the anterior tibial muscle and 5.0 sec-1 (+/- 0.4 sec-1) for the gastrocnemius muscles. The values of Rwm are considerably larger than the values of corresponding relaxation rates measured at high fields. The relaxation rate measurements of human tissues in vivo was shown to be possible at 0.1 T even within the framework of normal routine MR imaging. Magnetization transfer MR imaging is a very promising and practical method in order to assess the relaxation processes in heterogeneous human tissues in vivo, and it can improve the tissue characterization possibilities of MR imaging techniques.     

Noninvasive treatment efficacy monitoring and dose control for high-intensity focused ultrasound therapy using relative electrical impedance variation

As an effective therapeutic modality, high-intensity focused ultrasound(HIFU) can destroy tumour tissues by thermocoagulation with less metastasis, but it is still limited by inaccurate non-invasive temperature monitoring and efficacy evaluation. A model of electrical impedance measurement during HIFU therapy was established using the temperatureimpedance relationship. Based on the simulations of acoustic pressure, temperature, and electrical conductivity, the impedance of the phantom was calculated and experimentally demonstrated for different values of acoustic power values and treatment time. We proved that the relative impedance variation(RIV) increases linearly with the increasing treatment time at a fixed acoustic power, and the relative impedance variation rate shows a linear relationship with the acoustic power.The RIV and treatment time required for HIFU treatment efficacy are inversely proportional to the acoustic power and the square of acoustic power, respectively. The favourable results suggest that RIV can be used as an efficient indicator for noninvasive temperature monitoring and efficacy evaluation and may provide new strategy for accurate dose control of HIFU therapy.     

基于回波平移序列的快速三维磁共振温度成像方法

高强度聚焦超声（HIFU）是一种无创的热消融疗法，为保证其安全性和有效性，需要一种精度高、速度快的测温方法在其治疗过程中对温度进行监控.基于质子共振频率位移（PRFS）的磁共振温度成像（MRT）对温度具有较高的灵敏度，且与温度具有良好的线性关系，因此常被用于引导HIFU治疗.然而在实际应用中，HIFU治疗的最大隐患在于可能造成表皮灼伤，并且灼伤区域可能与焦点区域相隔较远.因此MRT的监控范围十分重要.本文基于三维回波平移成像序列，结合可控混叠的空间并行成像技术，实现了时间分辨率为3 s的快速三维温度成像.为了验证该方法的精度，本文首先设计了仿体降温实验，利用光纤温度计验证回波平移序列测温的准确度和精确度.然后在室温条件下扫描离体猪肉组织，对比加速前后的MRT的测温精确度.在HIFU加热条件下扫描离体猪肉组织，对比加速前后的MRT的测温准确度.结果显示，本文提出的方法可以在3 s内完成三维温度精准测量，对于HIFU治疗的安全监控具有重要意义.     

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.     

Impact of Treatment Trajectory on Temperature Field Uniformity in Biological Tissue Irradiated by Ultrasound Pulses with Shocks

High intensity focused ultrasound (HIFU) treatments typically involve the ablation of tissue volumes comprising multiple focal sites. One aspect of treatment planning involves the definition of a sequence of ultrasound pulses and corresponding focal sites as the sonication trajectory. Here, numerical simulations of the thermal effects of different trajectories are performed for HIFU exposures delivered to an ex vivo bovine liver sample by a clinical array (Sonalleve V2 3.0T system, Profound Medical Corp., Canada). Simulations consider boiling histotripsy regime with millisecond-long pulses that include shocks. Focusing of the ultrasound beam in tissue was modeled by the Westervelt equation, and the temperature field was modeled by the bioheat equation. To explore different treatment strategies, trajectories were considered with discrete foci located along two or four concentric circles with radii from 2 to 8 mm. Two approaches for traversing these focal sites were compared: In the first approach each discrete focus was sonicated by a sequence of 15 pulses before moving to the next site in the trajectory. In the second approach, each focus was sonicated once before moving to the next site, with sonications over the whole trajectory repeated 15 times. The influence of the trajectory’s size and the pulsing strategy on the temperature field was analyzed. It is shown that the structure of the temperature field is more uniform with a longer time interval between repeated irradiation of each focus, and the optimal time interval ranges from three to six pulse repetition periods.

     

B模式实时成像定量监控超声空化时空行为的研究

提出一种采用B超图像实现高强聚焦超声(HIFU)治疗时声空化的时空量化监控的方法。首先,采用B模式实时成像系统对不同声辐照能量下的HIFU在凝胶仿体中引发的超声空化进行实验监测;接着,利用二维数字图像处理算法消除高强聚焦超声(HIFU)在B超图像中产生的干涉条纹,并在此基础上,对B超成像中观察到的高亮区域的面积变化情况进行量化分析;最后,进一步讨论了驱动声压或脉冲宽度对超声空化产生的高亮区域的生成速度和面积大小的影响。结果显示该方法可以有效去除B超图像中的干涉条纹,并对HIFU引发的空化现象进行实时监测。实验结果还表明辐照声能量的提高将引发更强烈的声空化行为,并且显著缩短HIFU引发的空化泡群的初始生成时间。研究结果对进一步优化HIFU治疗有重要意义。      

Pulse compression technique for simultaneous HIFU surgery and ultrasonic imaging: a preliminary study

In an ultrasound image-guided High Intensity Focused Ultrasound (HIFU) surgery, reflected HIFU waves received by an imaging transducer should be suppressed for real-time simultaneous imaging and therapy. In this paper, we investigate the feasibility of pulse compression scheme combined with notch filtering in order to minimize these HIFU interference signals. A chirp signal modulated by the Dolph-Chebyshev window with 3-9 MHz frequency sweep range is used for B-mode imaging and 4 MHz continuous wave is used for HIFU. The second order infinite impulse response notch filters are employed to suppress reflected HIFU waves whose center frequencies are 4 MHz and 8 MHz. The prototype integrated HIFU/imaging transducer that composed of three rectangular elements with a spherically con-focused aperture was fabricated. The center element has the ability to transmit and receive 6 MHz imaging signals and two outer elements are only used for transmitting 4 MHz continuous HIFU wave. When the chirp signal and 4 MHz HIFU wave are simultaneously transmitted to the target, the reflected chirp signals mixed with 4 MHz and 8 MHz HIFU waves are detected by the imaging transducer. After the application of notch filtering with pulse compression process, HIFU interference waves in this mixed signal are significantly reduced while maintaining original imaging signal. In the single scanline test using a strong reflector, the amplitude of the reflected HIFU wave is reduced to −45 dB. In vitro test, with a sliced porcine muscle shows that the speckle pattern of the restored B-mode image is close to that of the original image. These preliminary results demonstrate the potential for the pulse compression scheme with notch filtering to achieve real-time ultrasound image-guided HIFU surgery.     

Two-point method for T1 estimation with optimized gradient-echo sequence

Relaxation times estimation methods play a central role in various problems, such as magnetic resonance (MR) hardware calibration, tissue characterization, or temperature measurement. Previous studies have proposed optimization criteria to estimate the relaxation time T1 faster than with a multipoint method leading to two-point methods. In this paper, the class of optimized two-point methods is extended to gradient-echo (GE) sequence offering new advantages over spin-echo (SE) or inversion recovery (IR) sequences. Two GE acquisitions, with optimal flip angles theta1 and theta2 minimizing both the total scan time and the variance in the computed T1 image were applied to estimate T1, and the results were compared with those of SE sequence with optimized paired repetition times T(R1) and T(R2). First, phantom studies were carried out with five tissue-like samples on a 0.5T scanner. Then in vivo, human brain T1 image were calculated using both optimized GE and SE two-point methods. More precise T1 GE estimates than those for SE were found thanks to high signal-to-noise ratio (SNR) per unit of time, but with a small bias. These results also concern the temperature variation measurement methods, based on T1 estimation. Preliminary experimental data for temperature measurement are given.     

Real-time volumetric MR thermometry using 3D echo-shifted sequence under an open source reconstruction platform

PurposeThe aim of this work is to implement real-time 3D MR thermometry for high intensity focused ultrasound (HIFU) monitoring.MethodsVolumetric MR thermometry was implemented based on a 3D echo-shifted sequence with short TR to improve temperature sensitivity. The 3D acquisition was accelerated in two phase encoding directions with controlled aliasing in volumetric parallel imaging (CAIPIRINHA). Image reconstruction was run in an open source reconstruction platform (Gadgetron).ResultsPhantom experiments showed the proposed volumetric thermometry was comparable to the fiber optical thermometer. In-vivo animal experiments in rabbit thigh showed that the temperature error before and after 4× acceleration was less than 0.65 °C. Finally, real-time 3D thermometry with temporal resolution ~3 s and spatial resolution 2 × 2 × 5 mm³ (spatial coverage 192 × 192 × 80 mm³) was achieved with Gadgetron reconstruction.ConclusionReal-time temperature monitoring was achieved in-vivo by using parallel imaging accelerated 3D echo-shifted sequence with Gadgetron reconstruction.     

Determination of Toxic Elements in Muscle Tissues of Five Fish Species Using Ultrasound‐Assisted Pseudodigestion by Electrothermal Atomic Absorption Spectrophotometry: Optimization Study

A simple and rapid method is described for the determination of As, Cd, and Pb in muscle tissue of five freshwater fish species by ultrasound‐assisted pseudodigestion (USD). A Plackett‐Burman experimental design was used as a multivariate strategy for the evaluation of the effects of varying several variables at once. The variables such as sonication time (ST), sample mass of muscle tissues (SM), temperature of ultrasonic bath (T), nitric acid (A1), and mixture of acid and oxidant (A2) have been studied. From these studies, some variables showed significant effect on % recovery, and they were further optimized by a 2³+star central composite design, which involved 16 experiments. Optimum values of the variables were selected for the development of USD to determine the contents of As, Cd, and Pb in muscle tissue of five fish species, used as bioindicators for Lake Manchar (Sindh, Pakistan) to know whether consumption of these fishes threatens human health. The determination of three toxic elements under study was carried out by electrothermal atomic absorption spectrometry (ETAAS). The accuracy of the optimized procedure was evaluated by analysis of certified reference materials DORM‐2 (Dogfish Muscle Certified Reference Material for Trace Elements) and by comparison with conventional wet acid digestion methodology. No significant differences were observed for p=0.05 when comparing the values obtained by the proposed USD method and conventional digestion method (CDM) (paired t‐test). The average relative standard deviation of the USD method varied between 4.05%, 7.53%, and 4.55% for As, Cd, and Pb, respectively (n=10).     

Nonlinear absorption in biological tissue for high intensity focused ultrasound

In recent years the propagation of the high intensity focused ultrasound (HIFU) in biological tissue is an interesting area due to its potential applications in non-invasive treatment of disease. The base principle of these applications is the heat effect generated by ultrasound absorption. In order to control therapeutic efficiency, it is important to evaluate the heat generation in biological tissue irradiated by ultrasound. In his paper, based on the Khokhlov-Zabolotkaya-Kuznetsov (KZK) equation in frequency-domain, the numerical simulations of nonlinear absorption in biological tissues for high intensity focused ultrasound are performed. We find that ultrasound thermal transfer effect will be enhanced with the increasing of initial acoustic intensity due to the high harmonic generation. The concept of extra absorption factor is introduced to describe nonlinear absorption in biological tissue for HIFU. The theoretical results show that the heat deposition induced by the nonlinear theory can be nearly two times as large as that predicated by linear theory. Then, the influence of the diffraction effect on the position of the focus in HIFU is investigated. It is shown that the sound focus moves toward the transducer compared with the geometry focus because of the diffraction of the sound wave. The position of the maximum heat deposition is shifted to the geometry focus with the increase of initial acoustic intensity because the high harmonics are less diffraction. Finally, the temperature in the porcine fat tissue changing with the time is predicated by Pennes' equation and the experimental results verify the nonlinear theoretical prediction.     

Targeted damage effects of high intensity focused ultrasound (HIFU) on liver tissues of Guizhou Province miniswine

HIFU can pass through tissues and accurately damage target tissues inside organisms. This article reports on the oriented damage effects of HIFU upon miniswine internal and external liver tissues, and suggests a new conception of the 'biological focal field'. The results revealed that: (1) HIFU can be used to damage accurately liver tissues under the guide of a B-modal ultrasound device; (2) the scope of the injury is connected with sound intensity and irradiation time; and (3) the different layers of tissue through which the ultrasound has passed remain undamaged.