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.     

Transurethral ultrasound array for prostate thermal therapy:initial studies

This study presents the initial evaluation of an applicator designed for transurethral ultrasound thermotherapy (TUST) of prostate tissue in the treatment of benign prostatic hyperplasia (BPH) and cancer. A tubular multitransducer applicator, consisting of four piezoceramic tubes (2.5 mm diameter, 6 mm long, 6.8 MHz) under separate power control, was designed to fit within a semiflexible water-cooled temperature-regulated delivery catheter to be placed within the prostatic urethra during therapy. Sonication patterns were tailored to produce power depositions which avoid nontargeted tissues, such as the rectum. Computer simulations have demonstrated that 1.4-2.0 cm radial therapeutic zones (temperatures ⩾50-55°C, thermal doses >300 EM₄₃) with concurrent sparing of the urethral mucosa can be produced within prostate tissue having blood perfusion as high as 10 kg m^-3 s^-1 within 15-30 min. Acoustic distributions and power output measurements of a prototype applicator have demonstrated acoustic power levels approaching 10 W per each sectored transducer segment are attainable, with beam profiles collimated within the transducer length and with desired circumferential distributions. In vivo thermal dosimetry characterizations of these transurethral applicators have indicated that therapeutic temperatures between 50 and 90°C are attainable, controllable in the longitudinal and circumferential directions, and have effective radial heating. These results clearly indicate that transurethral ultrasound applicators have potential to provide improved spatial localization and control of the heating distribution over existing transurethral thermal therapy techniques for both hyperthermia and thermal coagulative therapy of the prostate     

Ultrasound applicators for interstitial thermal coagulation

Direct-coupled (DC) and catheter-cooled (CC) ultrasound applicator configurations were evaluated for high-temperature ultrasound interstitial thermal therapy (USITT) using computer simulations, acoustic beam measurements, and in vivo temperature measurements. The DC devices consist of 2.2-mm diameter tubular ultrasound transducers encapsulated within a thin biocompatible plastic coating, which can be inserted directly into the tissue. The CC devices incorporate 1.5-mm diameter tubular transducers, which are inserted within 2.2to 2.4-mm diameter plastic implant catheters and require an integrated water-cooling scheme. Simulated transient temperature profiles and cumulative thermal dose distributions indicate that each of these applicator configurations can produce target temperatures greater than 50 degrees C and corresponding thermal doses greater than 300 to 600 equivalent minutes at 43 degrees C (EM(43 degrees C)) within 5 min at a radial depth of 1 to 1.5 cm in moderately perfused tissues. Theoretical investigations of air-cooling implemented within DC applicators demonstrated a significant enhancement of thermal penetration compared with non-cooled DC applicators, thus approaching performance attainable with CC devices. Temperature distributions achieved with DC and CC applicators in vivo were in agreement with theoretical calculations and further demonstrate that the devices are practical, sufficient power output levels can be obtained, and the angular heating profiles can be shaped or directed to protect non-targeted critical normal tissues. This preliminary study demonstrates that these interstitial ultrasound applicators have potential to provide controlled thermal coagulation and necrosis of small target regions and deserve further investigation and development for possible implementation in the treatment of benign and cancerous lesions in sites such as prostate, liver, and brain.     

Automatic ultrasound determination of thermal coagulation front during laser tissue heating

Thermal therapies using laser, microwaves, radio frequency radiation, and high intensity focused ultrasound have shown great promise for minimally invasive treatment of benign and malignant lesions. To treat tissue effectively and safely, techniques that could monitor the advancement of coagulation front during treatment are highly desirable. This paper presents a noninvasive ultrasound technique for automatically determining the propagation of coagulation damage front during laser tissue heating. The basic assumption underlying this technique is that when coagulation is taking place in a tissue, owing to thermally induced structure changes in tissue, the waveform of echo signal scattered from that treated region should be changing accordingly. We first track echoes scattered from many small tissue regions during heating using a cross-correlation echo-tracking technique. We then use the waveform-change information to determine the position of coagulation front via an automatic calculation procedure. To test our technique, we carried out 35 experiments in which we irradiated fresh canine liver samples with a Nd:YAG laser (1064-nm wavelength) at various light fluence (62 to 167 W/cm(2)) and exposure time (20 to 350 s). A 13-mm diameter 10-MHz broadband single-element spherical focused ultrasound transducer was used to detect the thermal coagulation front. The root mean square difference between ultrasonically and visually determined coagulation depths was 0.77 mm. This good agreement between visually inspected and ultrasonically determined coagulation depths shows the potential of our technique for monitoring coagulative tissue damage during thermal therapy.     

Water-cooled, high-intensity ultrasound surgical applicators with frequency tracking

High-intensity, focused ultrasound (HIFU) applicators have been developed for arresting bleeding with the ultimate intent of use in surgery. The design uses a tapered titanium component for transmission coupling of the ultrasound energy from a spherically curved transducer to biological tissues. The nominal operating frequency is 5.5 MHz, in a highly resonant mode (quality factor of 327 with water load). Liquid cooling is used to remove energy loss-important at net applied power greater than 18 W/cm/sup 2/ at the surface of the piezoelectric element. A downward resonance frequency shift (>20 kHz) occurs, even with cooling, as the applicator warms with normal operation. A feedback technique is used for maintaining the excitation near optimum resonance. Standing wave ratios of the applied power of 1.6 or less are thus sustained. The system and applicators have been found to be highly robust, effective in achieving hemostasis in the hemorrhaging liver, spleen, lung, or blood vessels in rabbit and pig experiments. One unit has been operated for over 1.7 hours in treating organ hemorrhage in blunt trauma experiments with nine swine with electrical net power of up to 158 W (31 W/cm/sup 2/ across the transducer) and intensity of 2560 W/cm/sup 2/ at focus.     

Analysis of a multielement ultrasound hyperthermia applicator

An unfocused multielement ultrasound applicator was developed for hyperthermia treatment of superficial tumors. The applicator contains sixteen 3.8-cm(2) individually controllable elements on a 15.2-cm(2) piezoelectric ceramic plate. The acoustical power output of each element can be independently applied to facilitate uniform heating throughout the treatment area while minimizing undesired heating in normal tissues. The performance of the applicator was examined by measuring acoustical power output and beam profiles. The results of this analysis indicated that the applicator is capable of producing required therapeutic output levels with excellent localization and control of the power deposition.     

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.     

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.     

In vitro and in vivo brain ablation created by high-intensity focused ultrasound and monitored by MRI

In this paper, magnetic resonance imaging (MRI) is investigated for monitoring small and large lesions created by high-intensity focused ultrasound (HIFU) in freshly excised lamb brain and in rabbit brain in vivo. A single-element spherically focused transducer of 5 cm diameter, focusing at 10 cm and operating at 1 MHz was used. A prototype MRI-compatible positioning device that is used to navigate the transducer is described. The effects of HIFU were investigated using T1-W and T2-W fast spin echo (FSE) and fluid-attenuated inversion recovery (FLAIR). T2-W FSE and FLAIR show better anatomical details within the brain than T1-W FSE, but with T1-W FSE, the contrast between lesion and brain is higher for both thermal and bubbly lesions. The best contrast between lesion and brain with T1-W FSE is obtained with TR above 500 ms, whereas with T2-W FSE, the best contrast is observed between 40 and 60 ms. The maximum contrast to noise ratio (CNR) measured with T1-W FSE was approximately 20. With T2-W FSE, the corresponding CNR was approximately 12. With this system, we were able to create large lesions (by producing overlapping lesions), and it was possible to monitor these lesions with MRI with excellent contrast. The length of the lesions in vivo brain was much higher than the length in vitro, indicating that the penetration in the in vitro brain is limited, possibly by reflection due to trapped bubbles in the blood vessels. This paper demonstrates that HIFU has the potential to treat brain tumors in humans. This could be done either using a single-element transducer with a frequency around 1 MHZ or using a multi-element transducer.     

Acoustical evaluation of a prototype sector-vortex phased-array applicator

A prototype sector-vortex phased-array applicator for ultrasound hyperthermia was constructed and acoustically evaluated. The array transducer consists of special lead-titanate ceramic elements of 16 sectors and two tracks attached on a element is driven by a complementary pair of power MOSFETs at 750 kHz. An annular focal field approximated by the Mth order Bessel function is theoretically predicted to be formed when the array elements are driven with a phase distribution that rotates M (相似文献   

A new high intensity focused ultrasound applicator for surgical applications

Improved high-intensity focused ultrasound (HIFU) surgical applicators are required for use in a surgical environment. We report on the performance and characteristics of a new solid-cone HIFU applicator. Previous HIFU devices used a water-filled stand-off to couple the ultrasonic energy from the transducer to the treatment area. The new applicator uses a spherically-focused element and a solid aluminum cone to guide and couple the ultrasound to the tissue. Compared with the water-filled applicators, this new applicator is simpler to set up and manipulate, cannot leak, prevents the possibility of cavitation within the coupling device, and is much easier to sterilize and maintain during surgery. The design minimizes losses caused by shear wave conversion found in tapered solid acoustic velocity transformers operated at high frequencies. Computer simulations predicted good transfer of longitudinal waves. Impedance measurements, beam plots, Schlieren images, and force balance measurements verified strong focusing and suitable transfer of acoustic energy into water. At the focus, the -3 dB beam dimensions are 1.2 mm (axial)×0.3 mm (transverse). Radiation force balance measurements indicate a power transfer efficiency of 40%. In vitro and in vivo tissue experiments confirmed the applicator's ability to produce hemostasis     

Dual-mode IVUS catheter for intracranial image-guided hyperthermia: feasibility study

In this study, we investigated the feasibility of modifying 3-Fr IVUS catheters in several designs to potentially achieve minimally-invasive, endovascular access for image-guided ultrasound hyperthermia treatment of tumors in the brain. Using a plane wave approximation, target frequencies of 8.7 and 3.5 MHz were considered optimal for heating at depths (tumor sizes) of 1 and 2.5 cm, respectively. First, a 3.5-Fr IVUS catheter with a 0.7-mm diameter transducer (30 MHz nominal frequency) was driven at 8.6 MHz. Second, for a low-frequency design, a 220-μm-thick, 0.35 x 0.35-mm PZT-4 transducer--driven at width-mode resonance of 3.85 MHz--replaced a 40-MHz element in a 3.5-Fr coronary imaging catheter. Third, a 5 x 0.5-mm PZT-4 transducer was evaluated as the largest aperture geometry possible for a flexible 3-Fr IVUS catheter. Beam plots and on-axis heating profiles were simulated for each aperture, and test transducers were fabricated. The electrical impedance, impulse response, frequency response, maximum intensity, and mechanical index were measured to assess performance. For the 5 x 0.5-mm transducer, this testing also included mechanically scanning and reconstructing an image of a 2.5-cm-diameter cyst phantom as a preliminary measure of imaging potential.     

Ultrasonic waveguide applicator arrays for interstitial heating: a model study

In this paper we describe an ultrasonic waveguide multiapplicator array for interstitial heating. We first discuss the heat generation term common for this type of applicator and show that the radius of the applicator is the limiting factor in the pattern of heat deposition. We carry out finite element analysis simulations of temperature profiles for three- and four-applicator array, and we test the simulations by measurements in a large volume tissue phantom. With the positive result of this test, we use the simulations to evaluate the size of the heated volume for several applicators (three to six) and for various geometries of their positioning. We do the simulations for a range of the effective thermal conductivity and for two applicator diameters. The volume of the medium with temperatures above 42 degrees C was in the 25 to 73 cm(5 ) range. This volume increased linearly with the diameter of the boundary at the basal temperature. Power required to produce preselected temperature elevation increased monotonically with the effective thermal conductivity. With the 24 mm between the applicators, the array could elevate the temperature to the required value up to the 0.030 W/cm/K effective thermal conductivity.     

Feasibility of noncontact intracardiac ultrasound ablation and imaging catheter for treatment of atrial fibrillation

Atrial fibrillation (AF) affects 1% of the population and results in a cost of 2.8 billion dollars from hospitalizations alone. Treatments that electrically isolate portions of the atria are clinically effective in curing AF. However, such minimally invasive catheter treatments face difficulties in mechanically positioning the catheter tip and visualizing the anatomy of the region. We propose a noncontact, intracardiac transducer that can ablate tissue and provide rudimentary imaging to guide therapy. Our design consists of a high-power, 20 mm by 2 mm, 128-element, transducer array placed on the side of 7-French catheter. The transducer will be used in imaging mode to locate the atrial wall; then, by focusing at that location, a lesion can be formed. Imaging of previously formed lesions could potentially guide placement of subsequent lesions. Successive rotations of the catheter will potentially enable a contiguous circular lesion to be created around the pulmonary vein. The challenge of intracardiac-sized transducers is achieving high intensities (300-5000 W/cm2) needed to raise the temperature of the tissue above 43 degrees C. In this paper, we demonstrate the feasibility of an intracardiac-sized transducer for treatment of atrial fibrillation. In simulations and proof-of-concept experiments, we show a 37 degrees C temperature rise in the lesion location and demonstrate the possibility of lesion imaging.     

Noninvasive transesophageal cardiac thermal ablation using a 2-D focused, ultrasound phased array: a simulation study

This simulation study proposes a noninvasive, transesophageal cardiac-thermal ablation using a planar ultrasound phased array (1 MHz, 60 x 10 mm2, 0.525 mm interelement spacing, 114 x 20 elements). Thirty-nine foci in cardiac muscle were defined at 20, 40, and 60-mm distances and at various angles from the transducer surface to simulate the accessible posterior left atrial wall through the esophageal wall window. The ultrasound pressure distribution and the resulting thermal effect in a volume of 60 x 80 x 80 mm3, including esophagus and cardiac muscle, were simulated for each focus. For 1, 10, and 20-s sonications with 60 degrees C and 70 degrees C peak temperatures in cardiac muscle and without thermal damage in esophageal wall, the transducer acoustic powers were 105-727, 28-117, 21-79 W and 151-1044, 40-167, 30-114 W, respectively. The simulated lesions (thermal dose in equivalent minutes at 43 degrees C > or = 240 minutes) at these foci had lengths of 1-6, 3-11, 3-13 mm and 3-15, 5-19, 6-23 mm, respectively, and widths of 1-4, 2-7, 3-9 mm and 3-9, 4-13, 4-17 mm, respectively. As a first step toward feasibility, controllable tissue coagulation in cardiac tissue without damage to the esophagus was demonstrated numerically.     

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.     

Hybrid multi/single layer array transducers for increased signal-to-noise ratio

In medical ultrasound imaging, two-dimensional (2-D) array transducers are necessary to implement dynamic focusing in two dimensions, phase correction in two dimensions and high speed volumetric imaging. However, the small size of a 2-D array element results in a small clamped capacitance and a large electrical impedance, which decreases the transducer signal-to-noise ratio (SNR). We have previously shown that SNR is improved using transducers made from multi-layer PZT, due to their lower electrical impedance. In this work, we hypothesize that SNR is further increased using a hybrid array configuration: in the transmit mode, a 10 Omega electronic transmitter excites a 10 Omega multi-layer array element; in the receive mode, a single layer element drives a high impedance preamplifier located in the transducer handle. The preamplifier drives the coaxial cable connected to the ultrasound scanner. For comparison, the following control configuration was used: in the transmit mode, a 50 Omega source excites a single layer element, and in the receive mode, a single layer element drives a coaxial cable load. For a 5x102 hybrid array operating at 7.5 MHz, maximum transmit output power was obtained with 9 PZT layers according to the KLM transmission line model. In this case, the simulated pulse-echo SNR was improved by 23.7 dB for the hybrid configuration compared to the control. With such dramatic improvement in pulse-echo SNR, low voltage transmitters can be used. These can be fabricated on integrated circuits and incorporated into the transducer handle.     

Real-time 3-D ultrasound guidance of interventional devices

We have previously developed 2-D array transducers for many real-time volumetric imaging applications. These applications include transducers operating up to 7 MHz for transthoracic imaging, up to 15 MHz for intracardiac echocardiography (ICE), 5 MHz for transesophageal echocardiography (TEE) and intracranial imaging, and 7 MHz for laparoscopic ultrasound imaging (LUS). Now we have developed a new generation of miniature ring-array transducers integrated into the catheter deployment kits of interventional devices to enable real-time 3-D ultrasound scanning for improved guidance of minimally invasive procedures. We have constructed 3 new ring transducers. The first consists of 54 elements operating at 5 MHz. Typical measured transducer element bandwidth was 25%, and the 50 Ohm round trip insertion loss was -65 dB. Average nearest neighbor cross talk was -23.8 dB. The second is a prototype 108-element transducer operating at 5 MHz. The third is a prototype 108-element ring array with a transducer center frequency of 8.9 MHz and a -6 dB bandwidth of 25%. All transducers were integrated with an 8.5 French catheter sheath of a Cook Medical, Inc. vena cava filter deployment device.     

Lateral mode coupling to reduce the electrical impedance of small elements required for high power ultrasound therapy phased arrays

A method that uses lateral coupling to reduce the electrical impedance of small transducer elements in generating ultrasound waves was tested. Cylindrical, radially polled transducer elements were driven at their length resonance frequency. Computer simulation and experimental studies showed that the electrical impedance of the transducer element could be controlled by the cylinder wall thickness, while the operation frequency was determined by the cylinder length. Acoustic intensity (averaged over the cylinder diameter) over 10 W/cm² (a therapeutically relevant intensity) was measured from these elements.     

Transducer design for a portable ultrasound enhanced transdermal drug-delivery system

For application in a portable transdermal drug-delivery system, novel transducers have been designed to enhance insulin transmission across skin using ultrasound. Previous research has shown transdermal delivery of insulin across skin using commercial sonicators operating at 20 kHz with intensities ranging from 12.5 to 225 mW/cm/sup 2/. The goal of this research was to design and construct a small, lightweight transducer or array that could operate with a similar frequency and intensity range as a commercial sonicator used in previous transdermal ultrasound insulin experiments, but without the weight and mass of a sonicator probe. To obtain this intensity range, a cymbal transducer design was chosen because of its light, compact structure and low resonance frequency in water. To increase the spatial ultrasound field for drug delivery across skin, two arrays, each comprising of four cymbal transducers, were constructed. The first array, designated the standard array, used four cymbals transducer elements in parallel. A second array (named the stack array) used four cymbal transducers that used stacked piezoelectric discs to drive the titanium flextensional caps. Under similar driving conditions, the standard array produced intensities comparable to those achieved using a commercial sonicator.