The potential of transskull ultrasound therapy and surgery using the maximum available skull surface area

Based on previous studies, the transskull ultrasound field is re-examined by utilizing the maximum available skull surface area. The source is assumed to be in direct contact with the skull outer surface, and phase correction is adopted to obtain a sharp focus at a desired location. A digitized skull profile was obtained from Magnetic Resonance (MR) scan images of a volunteer. Two driving frequencies (0.5 and 1.0 MHz) within the appropriate frequency range for transskull ultrasound therapy and surgery are investigated. With no phase correction, there is no apparent transskull focus. With phase correction, a sharp transskull focus is obtained at the desired location. Both pressure and specific absorption rate (SAR) gains (ratios of pressure amplitude and SAR at the focal point compared to those on the outer skull surface) are examined, and it is shown that the skull heating problem can be overcome by utilizing the maximum available skull surface area. By specifying the phase correction for different locations, the focus can be successfully moved inside the deep brain volume without significantly compromising the pressure and SAR gains; however, the sidelobes may be of concern at superficial sites.     

Effects of an implant on temperature distribution in tissue during ultrasound diathermy

The effects of an implant on temperature distribution in a tissue-mimicking hydrogel phantom during the application of therapeutic ultrasound were investigated. In vitro experiments were conducted to compare the influences of plastic and metal implants on ultrasound diathermy and to calibrate parameters in finite element simulation models. The temperature histories and characteristics of the opaque (denatured) areas in the hydrogel phantoms predicted by the numerical simulations show good correlation with those observed in the in vitro experiments. This study provides an insight into the temperature profile in the vicinity of an implant by therapeutic ultrasound heating typically used for physiotherapy. A parametric study was conducted through numerical simulations to investigate the effects of several factors, such as implant material type, ultrasound operation frequency, implant thickness and tissue thickness on the temperature distribution in the hydrogel phantom. The results indicate that the implant material type and implant thickness are the main parameters influencing the temperature distribution. In addition, once the implant material and ultrasound operation frequency are chosen, an optimal implant thickness can be obtained so as to avoid overheating injuries in tissue.     

Transient temperature rise due to ultrasound absorption at a bone/soft-tissue interface

Thermal effects due to high ultrasound absorption in bone pose an ongoing safety issue. Of considerable concern is the heating of the soft tissue adjacent to the bone surface. Mathematical models can be useful in predicting the transient temperature near the interface during insonation. This paper develops a model that provides the temperature field in terms of simple expressions that convey the functional dependence of the material properties, and are easily incorporated into standards and ultrasound machine software, yet are able to incorporate the material properties of both bone and soft tissue. The model contains an asymptotic theory based upon a "high-attenuation" assumption: the distance diffused by heat over the time of interest is large compared to the ultrasound attenuation length. Model predictions of temperature rise and location of maximum temperature were in close agreement with finite-element calculations, using parameters appropriate for radiation-force imaging and focused-ultrasound surgery.     

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.     

Ultrasonic heating of the skull

Comparatively simple analysis shows that diagnostic ultrasound devices, in some cases, may approach output levels that can produce significant heating of tissues, particularly if the propagation path includes bone. Experimental tests of these predictions using rodents show that temperature increments of the order of 3 degrees C/W/cm2 are produced in skull bone with sharply focused fields at medically relevant frequencies.     

Temperature rise induced by an annular focused transducer with a wide aperture angle in multi-layer tissue

In order to improve the operability and accuracy of high-intensity focused ultrasound(HIFU), an annular focused transducer, whereby a B-ultrasound probe is placed in its center, is used to realize the real time monitoring and control of the treatment. In this paper, the spheroidal beam equation(SBE) was used to calculate the sound field by an annular focused transducer with a wide aperture angle to first derive the heat deposition and the Pennes equation was used to calculate the temperature field in multi-layer tissue. We studied the effect of different parameters on the temperature of the tissues. The result shows that the focal length has a significant influence on both maximum liver temperature rise and skin temperature rise, and both increase with the increase in the focal length. When the frequency increases, the temperature rise first undergoes a rapid increase before gradually reaching a maximum, and then finally decreasing. The temperature rise increases while the inner radius decreases or the sound pressure increases. By choosing suitable parameters, the proper temperature rise both on the target tissue and skin via an annular focused transducer with a wide aperture angle can be obtained.     

On the possibility of using multi-element phased arrays for shock-wave action on deep brain structures

A noninvasive ultrasound surgery method that relies on using multi-element focused phased arrays is being successfully used to destroy tumors and perform neurosurgical operations in deep structures of the human brain. However, several drawbacks that limit the possibilities of the existing systems in their clinical use have been revealed: a large size of the hemispherical array, impossibility of its mechanical movement relative to the patient’s head, limited volume of dynamic focusing around the center of curvature of the array, and side effect of overheating skull. Here we evaluate the possibility of using arrays of smaller size and aperture angles to achieve shock-wave formation at the focus for thermal and mechanical ablation (histotripsy) of brain tissue taking into account current intensity limitations at the array elements. The proposed approach has potential advantages to mitigate the existing limitations and expand the possibilities of transcranial ultrasound surgery.     

Sound scattering and localized heat deposition of pulse-driven microbubbles

The sound scattering of free microbubbles released from strongly driven ultrasound contrast agents with brittle shell (e.g., Sonovist) is studied numerically. At high peak pressure of the driving pulses, the bubbles respond nonlinearly with cross sections pronouncedly larger than in the linear case; a large portion of the energy is radiated into high frequency ultrasound. Subsequent absorption of these high frequencies in the surrounding liquid (blood) diminishes the effective scattering cross section drastically. The absorption results in highly localized heating, with a substantial temperature rise within the first few microm from the bubble surface. The maximum heating in 1 microm distance is strongly dependent on driving pressure. Temperature elevations of more than 100 K can be achieved for amplitudes of Pa approximately 30 atm, which coincides with the highest pressures used in ultrasound diagnostics. The perfectly spherical collapses assumed here occur rarely, and the heating is highly localized and transient (approximately 10 micros). Therefore, a thermal hazard would only be expected at driving pressures beyond the diagnostic range.     

Increased heating by diagnostic ultrasound due to nonlinear propagation

The heating of tissues by the absorption of ultrasound is an important safety consideration in the use of diagnostic ultrasound. This paper shows that models of ultrasonic heating for this situation need to take account of nonlinear propagation. Measurements were made of the temperature rise in a sample of tissue-mimicking gel, caused by the application of 3.6-MHz focused ultrasonic beams for 3 min. The propagation path to the focus was in water, to mimic the situation where the fetus is scanned through the full bladder. The effect of nonlinear propagation was seen by changing the pressure amplitude of the pulse, while altering the pulsing regime to preserve a constant spatial-peak temporal-average intensity of 1 W cm-2. When nonlinear distortion was present, an enhancement in the temperature rise was observed, which correlated with the value of the shock parameter. The enhancement ratio was typically up to a factor of 3, and the maximum temperature rise observed was 2 degrees C. This enhanced heating was seen both at the surface of the tissue-mimicking gel and after propagation through 23 mm of the material. Under conditions of nonlinear propagation, the maximum heating usually occurs in the prefocal region, rather than at the focus.     

The effect of temperature and viscoelasticity on cavitation dynamics during ultrasonic ablation

Inertial cavitation has been shown to enhance heating rates during high intensity focused ultrasound treatments. Cavitation dynamics will be affected by heating and by the changes in mechanical properties of tissue resultant from thermal denaturation; however, the nature of the change is not known and forms the focus of the current study. A Keller-Miksis equation is used to find the variation in inertial cavitation threshold with temperature in water and, when coupled with a Kelvin-Voigt viscoelastic model, in biological tissue. Simulated thermal ablation treatments in liver and muscle are used to explore the changes in cavitation dynamics, and the resultant frequency spectra of secondary acoustic emissions, due to tissue denaturation. Results indicate that viscosity is the key parameter controlling cavitation dynamics in biological tissues. The increase in viscosity during denaturation is predicted to increase inertial cavitation thresholds, leading to a substantial decrease in the higher harmonic content of the emitted pressure signal across a wide range of bubble radii. Experimental validation of these observations could offer improved methods to monitor therapeutic ultrasound treatments.     

Effects of electron levels broadening and electron temperature in tunnel structures based on metal nanoclusters

We study the influence of energy levels broadening and electron subsystem overheating in island electrode (cluster) on current-voltage characteristics of three-electrode structure. A calculation scheme for broadening effect in one-dimensional case is suggested. Estimation of broadening is performed for electron levels in disc-like and spherical gold clusters. Within the two-temperature model of metallic cluster and by using a size dependence of the Debye frequency the effective electron temperature as a function of bias voltage is found approximately. For helium temperature of ion subsystem, the heating temperature of electrons in a quantum disc is almost one order of magnitude higher than that in a sphere; it achieves thousands of Kelvin. We suggest that the effects of broadening and electron overheating are responsible for the smoothing of current-voltage curves, which is observed experimentally at low temperatures in structures based on clusters consisting of accountable number of atoms. However, a role of the broadening is much more significant.     

Subharmonic imaging of contrast agents

Ultrasound contrast agents promise to improve the sensitivity and specificity of diagnostic ultrasound imaging. It is of great importance to adapt ultrasound equipment for optimal use with contrast agents e.g., by exploiting the nonlinear properties of the contrast microbubbles. Harmonic imaging is one technique that has been extensively studied and is commercially available. However, harmonic imaging is associated with problems, due to second harmonic generation and accumulation within the tissue itself. Given the lack of subharmonic generation in tissue, one alternative is the creation of subharmonic images by transmitting at the fundamental frequency (fo) and receiving at the subharmonic (fo/2). Subharmonic imaging should have a much better lateral resolution and may be suitable for scanning deep-lying structures owing to the higher transmit frequency and the much smaller attenuation of scattered subharmonic signals. In this paper, we will review different aspects of subharmonic imaging including implementation, in-vitro gray-scale imaging and subharmonic aided pressure estimation.     

The finite element method for micro-scale modeling of ultrasound propagation in cancellous bone

Quantitative ultrasound for bone assessment is based on the correlations between ultrasonic parameters and the properties (mechanical and physical) of cancellous bone. To elucidate the correlations, understanding the physics of ultrasound in cancellous bone is demanded. Micro-scale modeling of ultrasound propagation in cancellous bone using the finite-difference time-domain (FDTD) method has been so far utilized as one of the approaches in this regard. However, the FDTD method accompanies two disadvantages: staircase sampling of cancellous bone by finite difference grids leads to generation of wave artifacts at the solid–fluid interface inside the bone; additionally, this method cannot explicitly satisfy the needed perfect-slip conditions at the interface. To overcome these disadvantages, the finite element method (FEM) is proposed in this study. Three-dimensional finite element models of six water-saturated cancellous bone samples with different bone volume were created. The values of speed of sound (SOS) and broadband ultrasound attenuation (BUA) were calculated through the finite element simulations of ultrasound propagation in each sample. Comparing the results with other experimental and simulation studies demonstrated the capabilities of the FEM for micro-scale modeling of ultrasound in water-saturated cancellous bone.     

Design and modeling of inversion layer ultrasonic transducers using LiNbO3 single crystal

Using inversion domain engineering controlled by heating temperature, the LiNbO(3) (LNO) piezoelectric plate with both odd and even-order thickness-extensional modes can be excited simultaneously. Therefore, the inversion layer ultrasound transducer is expected to be capable of operating over a wider frequency range. In this paper, the electrical impedance and the acoustic characteristics of LiNbO(3) (LNO) inversion layer transducer have been studied by finite element modeling (FEM). The transducer designed for this study uses a 36 degrees rotated Y-cut LiNbO(3) thin plate with an active element thickness of approximately 100 microm. First the electrical and elastic properties of the 36 degrees rotated Y-cut LNO were obtained by transforming a basic piezoelectric matrix for Z-cut LNO. In order to validate the FEM using the transformed properties several pieces of pure and 50% inversion layer LNO were tested on the electrical impedance analyzer. The modeled impedance characteristics were consistent with the measured data. Next the model was used to design 50-60 MHz transducers using pure and 30% inversion LNO. Two lambda/4 matching layers and a Tungsten loaded epoxy backing were used in these designs. The modeled results show that an over 90% bandwidth transducer can be made with proper matching and 30% inversion layer.     

超声激发声信号幅值实时监测HIFU焦域组织损伤*

聚焦超声消融肿瘤过程中的损伤实时监测是临床治疗面临的一个关键难题,双频聚焦超声不仅能提高治疗效率,且能在共焦区域激发出声信号,该声信号的幅值、频率等信息与焦域组织的机械和声学特性紧密相关。本文构建了一种双频聚焦超声治疗及组织损伤实时监测系统。该系统在聚焦超声辐照离体组织过程中,通过外部水听器接收双频激发的组织声发射信号,并通过上位机进行高速数据采集、数字滤波、时频处理等,分析声发射信号幅值与离体组织损伤之间的变化规律。实验研究结果表明：随着焦域组织损伤的形成,其弹性等声学特征发生改变,导致声发射信号幅值逐渐降低,表明声发射信号幅值的变化可较好地反映靶组织声学特征和结构的变化,从而实现聚焦超声治疗中靶组织损伤的实时监测。本文提出的监测方案相比传统超声影像监控更灵敏,有望为聚焦超声临床治疗中的组织损伤监控提供一种新的实时监测方案和手段。     

Thermal induced EPR signals in tooth enamel

Electron paramagnetic resonance (EPR) spectroscopy was used to detect the effects of temperature on powdered human tooth enamel, not irradiated in the laboratory. Samples were heated at temperature between 350 and 450, at 600 and at 1000°C, for different heating times, between 6 min and 39 h. Changes in the EPR spectra were detected, with the formation of new signals. Possible correlation between the changes in EPR spectra and modifications in the enamel and in the mineral phase of bone detected with other techniques is discussed. The implications for dosimetric applications of signals induced by overheating due to mechanical friction during sample preparation are underlined.     

Keyhole acceleration for magnetic resonance acoustic radiation force imaging (MR ARFI)

MR ARFI measures the displacement induced by the ultrasonic radiation force and provides the location of the focal spot without significant heating effects. Displacements maps obtained with MR ARFI provide an indirect estimation of the acoustic beam intensity at the target. This measure is essential for dose estimation prior to focused ultrasound treatments (FUS) and adaptive focusing procedures of MR-guided transcranial and transribs FUS. In the latter case, the beam correction is achieved by maximizing the displacement at focus. A significant number of serial MR ARFI images are required and thus, a partial k-space updating method, such as keyhole appears as a method of choice. The purpose of this work is to demonstrate via simulations and experiments the efficiency of the keyhole technique combined with a two-dimensional spin-echo MR ARFI pulse sequence. The method was implemented in an ex vivo calf brain taking advantage of the a priori knowledge of the focal spot profile. The coincidence of the phase-encoding axis with the longest axis of the focal spot makes the best use of the technique. Our approach rapidly provides the focal spot localization with accuracy, and with a substantial increase to the signal-to-noise ratio, while reducing ultrasound energy needed during MR-guided adaptive focusing procedures.     

Effects of nonlinear propagation, cavitation, and boiling in lesion formation by high intensity focused ultrasound in a gel phantom

The importance of nonlinear acoustic wave propagation and ultrasound-induced cavitation in the acceleration of thermal lesion production by high intensity focused ultrasound was investigated experimentally and theoretically in a transparent protein-containing gel. A numerical model that accounted for nonlinear acoustic propagation was used to simulate experimental conditions. Various exposure regimes with equal total ultrasound energy but variable peak acoustic pressure were studied for single lesions and lesion stripes obtained by moving the transducer. Static overpressure was applied to suppress cavitation. Strong enhancement of lesion production was observed for high amplitude waves and was supported by modeling. Through overpressure experiments it was shown that both nonlinear propagation and cavitation mechanisms participate in accelerating lesion inception and growth. Using B-mode ultrasound, cavitation was observed at normal ambient pressure as weakly enhanced echogenicity in the focal region, but was not detected with overpressure. Formation of tadpole-shaped lesions, shifted toward the transducer, was always observed to be due to boiling. Boiling bubbles were visible in the gel and were evident as strongly echogenic regions in B-mode images. These experiments indicate that nonlinear propagation and cavitation accelerate heating, but no lesion displacement or distortion was observed in the absence of boiling.     

低频加热合成金刚石的时间温场

 在高温高压下合成金刚石，工频加热与低频加热合成效果不同。工频加热是向腔体恒热量输入，在腔体中形成空间温场；低频加热是脉冲式向腔体输入热量，在腔体中既形成空间温场又形成时间温场。用时间温场解释了一些实验现象和结果。     

Efficiency of sound field focusing in an oceanic waveguide with background internal waves

The efficiency of focusing a reversed wave and the possibility of scanning the focal point in a shallow sea in the presence of an anisotropic field of background internal waves are theoretically considered. The localized fields are controlled by varying the transmission frequency without a change in the distribution of the reversed field over the array aperture. The effect of the periodically repeated focal spots is analyzed. Numerical calculations are performed for the longitudinal and transverse orientations of acoustic path relative to the propagation direction of internal waves.