高强度聚焦超声作用下体模组织温度上升研究

为研究高强度聚焦超声(HIFU)作用下组织温度上升规律,建立了高强度聚焦声场和组织温度场有限元仿真模型,并通过体外辐照实验对仿真模型进行了验证。通过仿真对水和组织域中的聚焦声场进行建模,计算吸收声能并将其用作热源以计算组织内的温升。进一步制备仿生物组织凝胶体模,利用热电偶进行HIFU作用下体模组织焦点处的测温。结果表明:该模型可有效预测HIFU治疗时的温度上升,与实验所得温度误差不超过 3℃;体模组织受到超声辐照时温度会立即升高,起初温升速率较快,随着辐照时间延长,温升速率逐渐降低,停止辐照后温度立即下降。     

Integrated catheter for 3-D intracardiac echocardiography and ultrasound ablation

A catheter device with integrated ultrasound imaging array and ultrasound ablation transducer is introduced. This device has been designed for use in interventional cardiac procedures in which the cardiac anatomy is first imaged using real-time three-dimensional (3-D) ultrasound, then ablated to treat arrhythmias. The imaging array includes 112 elements operating at 5.4 MHz arranged in a 2-D matrix. Individual elements have a bandwidth of 21% and an insertion loss of 80 dB. The array has an azimuth resolution of 12 degrees and an elevation resolution of 8.7 degrees. The ablation transducer is a concentric piezoelectric transducer PZT-4 ring (outside diameter (O.D.), 4.5 mm, inside diameter (I.D.), 3.1 mm) operating at 10 MHz that surrounds the imaging array. It can produce a spatial-peak, temporal-average intensity up to 16 W/cm2. The entire device fits into a 9 Fr lumen with a 14 Fr tip to accommodate the ablation ring. With this device we have imaged, in realtime 3-D, a variety of targets including wire phantoms, fixed sheep hearts, and fresh bovine tissue. The ablation ring has been used to heat tissue-mimicking rubber 14 degrees C, as well as create lesions in fresh bovine tissue.     

Annular phased-array high-intensity focused ultrasound device for image-guided therapy of uterine fibroids

An ultrasound (US), image-guided high-intensity focused ultrasound (HIFU) device was developed for noninvasive ablation of uterine fibroids. The HIFU device was an annular phased array, with a focal depth range of 30-60 mm, a natural focus of 50 mm, and a resonant frequency of 3 MHz. The in-house control software was developed to operate the HIFU electronics drive system for inducing tissue coagulation at different distances from the array. A novel imaging algorithm was developed to minimize the HIFU-induced noise in the US images. The device was able to produce lesions in bovine serum albumin-embedded polyacrylamide gels and excised pig liver. The lesions could be seen on the US images as hyperechoic regions. Depths ranging from 30 to 60 mm were sonicated at acoustic intensities of 4100 and 6100 W/cm2 for 15 s each, with the latter producing average lesion volumes at least 63% larger than the former. Tissue sonication patterns that began distal to the transducer produced longer lesions than those that began proximally. The variation in lesion dimensions indicates the possible development of HIFU protocols that increase HIFU throughput and shorten tumor treatment times.     

The feasibility of using electrically focused ultrasound arrays to induce deep hyperthermia via body cavities

The results of a simulation study and subsequent experimental verification on the feasibility of using electrically focused arrays for intracavitary ultrasound hyperthermia are presented. The relative acoustic pressure fields from these cylindrical phased arrays were calculated for different dimensions and acoustic parameters to determine relevant design criteria. A thermal model based on the bioheat transfer equation was used to compute the resulting steady-state temperature distributions in tissue for various array configurations. This study has shown that cylindrical arrays of a practical size (75 mm long, 15 mm OD), resonating at 0.5 MHz with individual elements that are 1.5-mm wide, can preferentially heat regions that are between 20 and 50 mm from the surface of the array. In addition, it was shown that the temperature distribution can be further controlled by varying the focal position within the target volume, producing heated regions up to 40 mm wide. If practical constraints (i.e. number of amplifiers available or minimum element size attainable) become a limiting factor, arrays with wider elements would also be functional, but with certain restrictions applied to their flexible heating patterns. Thus, these electrically focused ultrasound arrays appear to offer a significant improvement over the existing intracavitary hyperthermia methods by producing a deeper and more controlled energy deposition.     

Theoretical study of steady-state temperature rise within the eye due to ultrasound insonation

The soft tissue thermal index (TIS), as defined in the AIUM/NEMA Output Display Standard, may not be relevant with respect to eye exposure, primarily because of differences in actual vs. assumed acoustic and thermal properties. Therefore, a theoretical study of temperature rise within the eye due to ultrasound insonation was undertaken to compare the TIS with more exact calculations. At each plane in the direction of propagation, the focused ultrasound beam was modeled as a disc of uniform intensity. Each disc becomes a heat source, and integration over all discs provides the total temperature rise at any axial position. Calculations were done assuming the ultrasound beam intersects the lens of the eye as well as for the case in which the beam does not intersect the lens. Results were found for frequencies of 7.0 MHZ to 40 MHZ, transducer diameters of 0.2 cm to 1.0 cm, and focal lengths ranging from 0.2 cm to 3.0 cm. Perfusion was assumed negligible and thermal and acoustic parameters were taken from reported studies. For every case, the ratio of maximum temperature rise to the TIS (assuming constant output power) was calculated. For the lens case, the ratio varied from 7.35 to 0.8. For the no-lens case, the ratio varied from 4.1 to 0.4. These results indicate that the TIS is not adequate to represent the temperature rise occurring within the eye upon insonation.     

Enhanced heat deposition using ultrasound contrast agent--modeling and experimental observations

Ultrasound contrast agents (UCA), created originally for visualization and diagnostic purposes, recently have been suggested as efficient enhancers of ultrasonic power deposition in tissue. The ultrasonic energy absorption by the contrast agents, considered as problematic in diagnostic imaging, might have beneficial impact in therapeutic applications such as targeted hyperthermia-based or ablation treatments. Introduction of gas microbubbles into the tissue to be treated can improve the effectiveness of current treatments by limiting the temperature rise to the treated site and minimizing the damage to the surrounding healthy tissues. To this end, proper assessment of the governing parameters of energy absorption by ultrasonically induced stabilized bubbles is important for both diagnostic and therapeutic ultrasound applications. The current study was designed to predict theoretically and measure experimentally the dissipation and heating effects of encapsulated UCA in a well-controlled and calibrated environment. The ultrasonic effects of the microbubble concentration, transmitted intensity, and frequency on power dissipation and stability of the UCA have been studied. The maximal temperature elevation obtained during 300 s experiments was 21 degrees C, in a 10 ml volume target containing UCA, insonifled by unfocused 3.2 MHz continuous wave (CW) at spatial average intensity of 1.1 W/cm2 (182 kPa). The results also suggest that higher frequencies are more efficiently absorbed by commonly used UCA. In particular, for spatial average intensity of 1.1 W/cm2 and concentration of 5 x 10(6) microspheres/cm3, no significant reduction of UCA absorption was noticed during the first 150 s for insonation at 3.2 MHz and the first 100 s for insonation at 1 MHz. In addition, when lower average intensity of 0.5 W/cm2 (160 kPa) at 3.2 MHz was used, the UCA absorptivity sustained for almost 200 s. Thus, when properly activated, UCA may be suitable for localized hyperthermic therapies.     

Quantitative modeling of the anisotropy of ultrasonic backscatterfrom canine myocardium

Reports extensions and new results of the First Time Domain Born approximation model used by Mottley and Miller (1982) to describe the anisotropy of ultrasonic backscatter measured in canine myocardium. The interaction of an ultrasonic plane wave impulse with a single cylindrical scatterer using time and frequency domain approaches is reviewed. Myocardial tissue is modeled as a suspension of aligned cylindrically shaped scatterers uniformly distributed in a homogeneous medium. The authors propose extensions to this model to deal with nonideal scatterer orientation, by introducing axial distribution functions and scatterer size distributions based on histology, modeled as a uniform distribution. The backscatter coefficient in the range 2.0-8.0 MHz is calculated. An algorithm to compute the average differential scattering cross section is presented. Ultrasonic elastic properties of myocardial tissue are discussed. Results of the anisotropy of the numerically computed backscatter parameters for model media having nominal mechanical and acoustic properties of canine myocardial tissue are presented and compared to available experimental data along with discussion of possible conclusions     

Multifrequency ultrasound transducers for conformal interstitial thermal therapy

Control over the pattern of thermal damage generated by interstitial ultrasound heating applicators can be enhanced by changing the ultrasound frequency during heating. The ability to change transmission frequency from a single transducer through the use of high impedance front layers was investigated in this study. The transmission spectrum of multifrequency transducers was calculated using the KLM equivalent circuit model and verified with experimental measurements on prototype transducers. The addition of a quarter-wavelength thick PZT (unpoled) front layer enabled the transmission of ultrasound at two discrete frequencies, 4.7 and 9.7 MHz, from a transducer with an original resonant frequency of 8.4 MHz. Three frequency transmission at 3.3, 8.4, and 10.8 MHz was possible for a transducer with a half-wavelength thick front layer. Calculations of the predicted thermal lesion size at each transmission frequency indicated that the depth of thermal lesion could be varied by a factor of 1.6 for the quarter-wavelength front layer. Heating experiments performed in excised liver tissue with a dual-frequency applicator confirmed this ability to control the shape of thermal lesions during heating to generate a desired geometry. Practical interstitial Designs that enable the generation of shaped thermal lesions are feasible.     

HIFU focusing efficiency and a twin annular array source for prostate treatment

A measure of focusing efficiency is introduced for high-intensity, focused ultrasound (HIFU). The measure consists of the fraction of the total acoustic power emitted that linearly propagates through a circle located at the focus. The medium is absorption-free water, and power is computed using pressure and the normal component of velocity. 3 MHz phased-array designs involving different element layouts and curvatures are placed in square apertures of length 2.2 cm. The acoustic fields of these devices then are propagated to on-axis foci. The resulting focal efficiencies then are calculated using a two wavelength (0.1 cm) radius circle. Among these array designs, an annular array with 27 wavelength-wide rings then is extended to be the basis of a twin phased-array device for prostate hyperthermia treatment. The two annular arrays are attached to door-like hinges to allow for joint two-dimensional focusing. The focusing efficiency of this device then is compared to rectangular element-array devices with the same 5.4 by 2.2 cm source extent. With the addition of absorption and finite-amplitude distortion, the heating rate and temperature rise produced by the twin annular device in prostate tissue is considered. As a final look at the potential of annular array-based designs, three larger 2 MHz devices are briefly considered for abdominal treatment.     

Lithium niobate transducers for MRI-guided ultrasonic microsurgery

Focused ultrasound surgery (FUS) is usually based on frequencies below 5 MHz-typically around 1 MHz. Although this allows good penetration into tissue, it limits the minimum lesion dimensions that can be achieved. In this study, we investigate devices to allow FUS at much higher frequencies, in principle, reducing the minimum lesion dimensions. Furthermore, FUS can produce deep-sub-millimeter demarcation between viable and necrosed tissue; high-frequency devices may allow this to be exploited in superficial applications which may include dermatology, ophthalmology, treatment of the vascular system, and treatment of early dysplasia in epithelial tissue. In this paper, we explain the methodology we have used to build high-frequency high-intensity transducers using Y-36°-cut lithium niobate. This material was chosen because its low losses give it the potential to allow very-high-frequency operation at harmonics of the fundamental operating frequency. A range of single-element transducers with center frequencies between 6.6 and 20.0 MHz were built and the transducers' efficiency and acoustic power output were measured. A focused 6.6-MHz transducer was built with multiple elements operating together and tested using an ultrasound phantom and MRI scans. It was shown to increase phantom temperature by 32°C in a localized area of 2.5 x 3.4 mm in the plane of the MRI scan. Ex vivo tests on poultry tissue were also performed and shown to create lesions of similar dimensions. This study, therefore, demonstrates that it is feasible to produce high-frequency transducers capable of high-resolution FUS using lithium niobate.     

The combined concentric-ring and sector-vortex phased array for MRIguided ultrasound surgery

MRI guided ultrasound surgery requires small surgical equipment volumes to facilitate the treatment of larger patients in the limited space of a conventional MRI magnet. In addition, large focal volumes are required to reduce the treatment time of large tumors. The concentric-ring array is capable of moving the focus in one dimension, and previous studies have shown that a circular array composed of radial sectors is capable of producing enlarged focal volumes. These two array designs may be combined to create an array that is capable of both enlarging the focus and moving the focus along the axis of the array. Simulations were performed to predict the performance and capabilities of various combined array designs by using numerical routines to, calculate the acoustic power field, temperature distribution, and accumulated thermal dose. The results shown predict that the combined array can create necrosed tissue volumes over 30 times larger than the concentric-ring array while maintaining focal range. The simulation results were verified with an experimental array consisting of 13 rings and 4 sectors. In addition, simulations were performed where multiple focal patterns were cycled in the time domain to create an optimized heating pattern characterized by uniform thermal dose over the volume of the lesion. Such heating patterns resulted in a 40°C lower maximum temperature compared to single mode sonications while producing the same necrosed tissue volume, and yielded a rate of necrosis of 26.4 cm³ /h     

Sparse random ultrasound phased array for focal surgery

Ultrasound phased arrays offer several advantages over single focused transducer technology, enabling electronically programmable synthesis of focal size and shape, as well as position. While phased arrays have been employed for medical diagnostic and therapeutic (hyperthermia) applications, there remain fundamental problems associated with their use for surgery. These problems stem largely from the small size of each array element dictated by the wavelength employed at surgical application frequencies (2-4 MHz), the array aperture size required for the desired focal characteristics, and the number of array elements and electronic drive channels required to provide RF energy to the entire array. The present work involves the theoretical and experimental examination of novel ultrasound phased arrays consisting of array elements larger than one wavelength, minimizing the number of elements in an aperture through a combination of geometric focusing, directive beams, and sparse random placement of array elements, for tissue ablation applications. A hexagonally packed array consisting of 108 8-mm-diameter circular elements mounted on a spherical shell was modeled theoretically and a prototype array was constructed to examine the feasibility of sparse random array configurations for focal surgery. A randomly selected subset of elements of the prototype test array (64 of 108 available channels) was driven at 2.1 MHz with a 64-channel digitally controlled RF drive system. The performance of the prototype array was evaluated by comparing field data obtained from theoretical modeling to that obtained experimentally via hydrophone scanning. The results of that comparison, along with total acoustic power measurements, suggest that the use of sparse random phased arrays for focal surgery is feasible, and that the nature of array packing is an important determinant to observed performance     

Soft tissue temperature rise caused by scanned, diagnostic ultrasound

An acoustic-thermal model was developed for scanned diagnostic ultrasound in soft tissue. An adiabatic surface between the transducer and the skin was justified, and the model accounted for attenuation and focusing. The temperature along the central plane of the temporally averaged acoustic field was calculated by integration of line sources of heat that result from the tissue's absorption of ultrasound. The temperature profiles were calculated for 1400 transducers. The results show that current diagnostic transducers heat more significantly at the transducer-tissue interface than at the focus. The temperature rise in the focal region is typically less than 25% of that at the surface. The acoustic power per scan length that results in a 1 degrees C temperature rise at the surface is calculated as (210 mW-MHz/cm)/f. These results apply to both linear arrays and sectorlike scan formats. The temperature rises for simultaneous multimode scanned beams are additive as the peak temperatures of each mode will occur on the surface. Consideration was given to the surface boundary condition for such models. This boundary is considered adiabatic for calculation of heating due to acoustic absorption alone. Additional heating or cooling resulting from the transducer can then be superimposed on this solution.     

On the thermal effects associated with radiation force imaging of soft tissue

Several laboratories are investigating the use of acoustic radiation force to image the mechanical properties of tissue. Acoustic Radiation Force Impulse (ARFI) imaging is one approach that uses brief, high-intensity, focused ultrasound pulses to generate radiation force in tissue. This radiation force generates tissue displacements that are tracked using conventional correlation-based ultrasound methods. The tissue response provides a mechanism to discern mechanical properties of the tissue. The acoustic energy that is absorbed by tissue generates radiation force and tissue heating. A finite element methods model of acoustic heating has been developed that models the thermal response of different tissues during short duration radiation force application. The beam sequences and focal configurations used during ARFI imaging are modeled herein; the results of these thermal models can be extended to the heating due to absorption associated with other radiation force-based imaging modalities. ARFI-induced thermal diffusivity patterns are functions of the transducer f-number, the tissue absorption, and the temporal and spatial spacing of adjacent ARFI interrogations. Cooling time constants are on the order of several seconds. Tissue displacement due to thermal expansion is negligible for ARFI imaging. Changes in sound speed due to temperature changes can be appreciable. These thermal models demonstrate that ARFI imaging of soft tissue is safe, although thermal response must be monitored when ARFI beam sequences are being developed.     

Microbubble-enhanced cavitation for noninvasive ultrasound surgery

Experiments were conducted to explore the potential of stabilized microbubbles for aiding tissue ablation during ultrasound therapy. Surgically exteriorized canine kidneys were irradiated in situ using single exposures of focused ultrasound. In each experiment, tip to eight separate exposures were placed in the left kidney. The right kidney was then similarly exposed, but while an ultrasound contrast agent was continually infused. Kidneys were sectioned and examined for gross observable tissue damage. Tissue damage was produced more frequently, by lower intensity and shorter duration exposures, in kidneys irradiated with the contrast agent present. Using 250-ms exposures, the minimum intensity that produced damage was lower in kidneys with microbubbles than those without (controls) in 10 of 11 (91%) animals. In a separate study using /spl sim/3200 W/cm/sup 2/ exposures, the minimum duration that produced damage was shorter after microbubbles were introduced in 11 of 12 (92%) animals. With microbubbles, gross observable tissue damage was produced with exposure intensity /spl ges//spl sim/800 W/cm/sup 2/ and exposure duration /spl ges/10 /spl mu/s. The overall intensity and duration tissue damage thresholds were reduced by /spl sim/2/spl times/ and /spl sim/100/spl times/, respectively. Results indicate that acoustic cavitation is a primary damage mechanism. Lowering in vivo tissue damage thresholds with stabilized microbubbles acting as cavitation nuclei may make acoustic cavitation a more predictable, and thus practical, mechanism for noninvasive ultrasound surgery.     

Thresholds for nonlinear effects in high- intensity focused ultrasound propagation and tissue heating

For a variety of reasons, including their simplicity and ability to capitalize upon superposition, linear acoustic propagation models are preferable to nonlinear ones in modeling the propagation of high-intensity focused ultrasound (HIFU) beams. However, under certain conditions, nonlinear models are necessary to accurately model the beam propagation and heating. In analyzing the performance of a HIFU system, it is advantageous to know before the analysis whether a linear model suffices. This paper examines the problem of determining the thresholds at which nonlinear effects become important. It is demonstrated that nonlinear interaction has different effects on different physical and derived quantities, such as compressional pressure, rarefactional pressure, intensity, heat rate, temperature rise, and thermal lesion volume. Thresholds are determined as a function of the dimensionless gain, nonlinearity, and absorption parameters. The relative difference between linear and nonlinear predictions is plotted as a series of contours, enabling practitioners to locate their system in parameter space and determine whether nonlinearity significantly affects the quantities of interest.     

Multifunctional catheters combining intracardiac ultrasound imaging and electrophysiology sensing

A family of 3 multifunctional intracardiac imaging and electrophysiology (EP) mapping catheters has been in development to help guide diagnostic and therapeutic intracardiac EP procedures. The catheter tip on the first device includes a 7.5 MHz, 64-element, side-looking phased array for high resolution sector scanning. The second device is a forward-looking catheter with a 24-element 14 MHz phased array. Both of these catheters operate on a commercial imaging system with standard software. Multiple EP mapping sensors were mounted as ring electrodes near the arrays for electrocardiographic synchronization of ultrasound images and used for unique integration with EP mapping technologies. To help establish the catheters' ability for integration with EP interventional procedures, tests were performed in vivo in a porcine animal model to demonstrate both useful intracardiac echocardiographic (ICE) visualization and simultaneous 3-D positional information using integrated electroanatomical mapping techniques. The catheters also performed well in high frame rate imaging, color flow imaging, and strain rate imaging of atrial and ventricular structures. The companion paper of this work discusses the catheter design of the side-looking catheter with special attention to acoustic lens design. The third device in development is a 10 MHz forward-looking ring array that is to be mounted at the distal tip of a 9F catheter to permit use of the available catheter lumen for adjunctive therapy tools.     

In vivo acceleration of ultrasonic tissue heating by microbubble agent

The ultrasonic power absorbed by a microbubble in its continuous wave response is estimated through numerically solving a version of the Rayleigh-Plesset equation. At an ultrasonic frequency of 3 MHz, a resonant microbubble, approximately 1.1 microm in radius, showed an absorption cross section of about 0.005 mm2 in its low power response. This estimation predicts that the tissue ultrasonic absorption will be doubled when such microbubbles are delivered to the tissue at a concentration of about eight bubbles/mm3 in tissue. An exteriorized murine kidney was exposed to focused ultrasound at 3.2 MHz in degassed saline, and the tissue temperature change was measured. With an intravenous bolus administration of a microbubble agent, the ultrasonically induced temperature elevation was multiplied by up to five times. The enhancement in temperature elevation gradually decreased as the microbubble agent was eliminated from the body. The experimental results agreed with the prediction in the order of magnitude. This effect may have a potential use to enhance the throughput as well as the selectivity of focused ultrasound treatment.     

Tissue ultrasound absorption measurement with MRI calorimetry

The renewed interest in the use of high intensity focused ultrasound (US) for minimally invasive magnetic resonance imaging (MRI)-guided thermal therapy has stimulated a review of the interaction mechanisms of US with tissue. Although the study of tissue US properties has been conducted extensively, agreements on the measured values of tissue US absorption are poor. We propose a noninvasive approach to measure tissue US absorption based on a form of MRI calorimetry. US absorption is measured in a small tissue sample through a knowledge of the US intensity distribution incident on the tissue and an MRI measurement of total absorbed energy arising from US exposure. US absorption measurements were conducted at room temperature for ex-vivo bovine liver tissue at 1 MHz, which led to a measured US absorption coefficient of 0.058 Np/cm or 0.504 dB/cm. Because this approach is noninvasive, the experimental complications exhibited in earlier studies are not present. Furthermore, this approach can be applied over a range of frequencies, tissues, and temperatures, which will aid in understanding of biothermal effects of high intensity US to improve thermal therapy.     

The monopole-source solution for estimating tissue temperatureincreases for focused ultrasound fields

The monopole-source solution to the problem of estimating tissue temperature rise generated by a focused ultrasound beam is presented. The acoustic pressure field generated by a focused, continuous-wave ultrasound source using the acoustic monopole-source method is developed. The point-source solution to the linear bio-heat transfer equation is used to calculate the axial, steady-state temperature increase for both circular and rectangular apertures. The results of the circular aperture are compared with the temperature increase calculated using the heated-disc method and are shown to be in substantial agreement. Finally, the temperature increase generated by the circular aperture is compared to that of the rectangular aperture for the same source power, aperture surface area, operating frequency, and medium properties, and it is shown that the rectangular source generates temperature increases less than those of the circular source under these conditions