Design of efficient, broadband single-element (20-80 MHz) ultrasonic transducers for medical imaging applications

This paper discusses the design, fabrication, and testing of sensitive broadband lithium niobate (LiNbO/sub 3/) single-element ultrasonic transducers in the 20-80 MHz frequency range. Transducers of varying dimensions were built for an f# range of 2.0-3.1. The desired focal depths were achieved by either casting an acoustic lens on the transducer face or press-focusing the piezoelectric into a spherical curvature. For designs that required electrical impedance matching, a low impedance transmission line coaxial cable was used. All transducers were tested in a pulse-echo arrangement, whereby the center frequency, bandwidth, insertion loss, and focal depth were measured. Several transducers were fabricated with center frequencies in the 20-80 MHz range with the measured -6 dB bandwidths and two-way insertion loss values ranging from 57 to 74% and 9.6 to 21.3 dB, respectively. Both transducer focusing techniques proved successful in producing highly sensitive, high-frequency, single-element, ultrasonic-imaging transducers. In vivo and in vitro ultrasonic backscatter microscope (UBM) images of human eyes were obtained with the 50 MHz transducers. The high sensitivity of these devices could possibly allow for an increase in depth of penetration, higher image signal-to-noise ratio (SNR), and improved image contrast at high frequencies when compared to previously reported results.     

A 100-200 MHz ultrasound biomicroscope

The development of higher frequency ultrasound imaging systems affords a unique opportunity to visualize living tissue at the microscopic level. This work was undertaken to assess the potential of ultrasound imaging in vivo using the 100-200 MHz range. Spherically focused lithium niobate transducers were fabricated. The properties of a 200 MHz center frequency device are described in detail. This transducer showed good sensitivity with an insertion loss of 18 dB at 200 MHz. Resolution of 14 /spl mu/m in the lateral direction and 12 /spl mu/m in the axial direction was achieved with f/1.14 focusing. A linear mechanical scan system and a scan converter were used to generate B-scan images at a frame rate up to 12 frames per second. System performance in B-mode imaging is limited by frequency dependent attenuation in tissues. An alternative technique, zone-focus image collection, was investigated to extend depth of field. Images of coronary arteries, the eye, and skin are presented along with some preliminary correlations with histology. These results demonstrate the feasibility of ultrasound biomicroscopy In the 100-200 MHz range. Further development of ultrasound backscatter imaging at frequencies up to and above 200 MHz will contribute valuable information about tissue microstructure.     

SPUDT filters for the 2.45 GHz ISM band

Filters based on using single-phase, unidirectional transducers (SPUDT) consisting of lambda/4 and wider electrodes are presented. The design variants exploit the significant difference between the reflectivity of short-circuited lambda/4 electrodes and that of floating wide electrodes on 128 degree lithium niobate (LiNbO3). The surface acoustic wave (SAW) devices operating at 2.45 GHz have critical dimensions of about 0.3-0.4 microm, accessible to standard optical lithography. When matched, the fabricated SPUDT filters exhibit minimum insertion losses of 5.5-7.9 dB together with 3 dB passbands of 89-102 MHz. The majority of the insertion loss can be attributed to the attenuation on free surface and inside the grating, and to the resistivity of the electrodes.     

Characterization of high-frequency, single-element focused transducers with wire target and hydrophone

In this paper, a wire-target technique was used for lateral beam profile measurements for a single-element, focused transducers in the very high-frequency range (35-60 MHz). Two wire targets made from 9-cm long tungsten wires with diameters of 8 microm and 20 microm were used as the pulse-echo targets to measure the lateral beam profiles at the focal plane of two single-element, focused transducers, a spherically focused 40 MHz transducer and a lens-focused in-house lithium niobate (LiNbO3) 60 MHz transducer. For comparison, measurements on the same transducers were performed by three small-aperture hydrophones with geometrical diameters varying from 37 microm to 150 microm. Tomographic reconstruction of the acoustic field from the spherically focused transducer also was conducted. Results obtained with the wire-target technique are comparable to those obtained with small-aperture hydrophones in characterizing lateral radiation patterns of a single-element, focused transducer in the high-frequency range (35-60 MHz). However, the wire-target method may overestimate pulse length because of the additional attenuation caused by the return path. Compared to small-aperture hydrophones, the wire-target technique is simpler and more cost effective. Its major advantage, however, is in the frequency range above 100 MHz in which commercial hydrophones are not yet available.     

Half-thickness inversion layer high-frequency ultrasonic transducers using LiNbO3 single crystal.

Half-thickness inversion layer high-frequency ultrasonic transducers were fabricated using lithium niobate (LiNbO3) single crystal plate. The transducers developed for this study used a 36 degrees rotated Y-cut LiNbO3 thin plate with an active element thickness of 115 microm. The designed center frequency was in the range of 30 to 60 MHz. Half-thickness inversion layer was formed after the sample was annealed at a high temperature, and it is shown that the inversion layer thickness can be controlled by the temperature. Silver powder/epoxy composite and parylene were used as acoustic matching layers. A lossy silver epoxy was used as the backing material. Using an analytical method, the electrical impedance for different inversion layer ratios was determined. The measured resonant frequency was consistent with the modeled data. Even-order higher frequency broadband ultrasonic transducers with a center frequency at 60 MHz was obtained using half-thickness inversion layer of LiNbO3 single crystal.     

Half-thickness inversion layer high-frequency ultrasonic transducers using LiNbO/sub 3/ single crystal

Half-thickness inversion layer high-frequency ultrasonic transducers were fabricated using lithium niobate (LiNbO₃) single crystal plate. The transducers developed for this study used a 36deg rotated Y-cut LiNbO₃ thin plate with an active element thickness of 115 mum. The designed center frequency was in the range of 30 to 60 MHz. Half-thickness inversion layer was formed after the sample was annealed at a high temperature, and it is shown that the inversion layer thickness can be controlled by the temperature. Silver powder/epoxy composite and parylene were used as acoustic matching layers. A lossy silver epoxy was used as the backing material. Using an analytical method, the electrical impedance for different inversion layer ratios was determined. The measured resonant frequency was consistent with the modeled data. Even-order higher frequency broadband ultrasonic transducers with a center frequency at 60 MHz were obtained using half-thickness inversion layer of LiNbO₃ single crystal     

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.     

44-MHz LiNbO3 transducers for UBM-guided Doppler ultrasound

In the post genome-sequencing era, physiological phenotyping of genetically engineered mice is critical to further our understanding of the functional consequences of specific genetic defects. We have developed a 40-50 MHz ultrasound biomicroscopy-(UBM) guided, pulsed Doppler system for the sensitive detection of in vivo blood velocity waveforms in the mouse embryonic cardiovascular system. Our approach uses separate transducers for simultaneous imaging and Doppler blood flow measurements. To this end, unfocused, air-backed lithium niobate (LiNbO/sub 3/) transducers provide sensitive Doppler detection and the flexibility of adjusting the axial position of the pulsed Doppler sample volume over many millimeters depth range of the collimated ultrasound beam. In this paper we describe the fabrication and characterization of the electromechanical and ultrasonic beam properties of 44-MHz LiNbO/sub 3/ Doppler transducers. We further demonstrate the utility of these Doppler transducers for interrogating blood vessels such as the dorsal aorta over a range of mouse embryonic stages and axial range-gate depths.     

Focused Ultrasound Preconditioning for Augmented Nanoparticle Penetration and Efficacy in the Central Nervous System

Microbubble activation with focused ultrasound (FUS) facilitates the noninvasive and spatially‐targeted delivery of systemically administered therapeutics across the blood–brain barrier (BBB). FUS also augments the penetration of nanoscale therapeutics through brain tissue; however, this secondary effect has not been leveraged. Here, 1 MHz FUS sequences that increase the volume of transfected brain tissue after convection‐enhanced delivery of gene‐vector “brain‐penetrating” nanoparticles were first identified. Next, FUS preconditioning is applied prior to trans‐BBB nanoparticle delivery, yielding up to a fivefold increase in subsequent transgene expression. Magnetic resonance imaging (MRI) analyses of tissue temperature and K_trans confirm that augmented transfection occurs through modulation of parenchymal tissue with FUS. FUS preconditioning represents a simple and effective strategy for markedly improving the efficacy of gene vector nanoparticles in the central nervous system.     

Silicon-on-insulator based nanoresonators for mechanical mixing at radio frequencies

Nanomechanical resonators now allow operating frequencies approaching the range of several 100 MHz. Thus, nanomechanical devices become interesting for applications in signal processing. The main advantage of these devices is their high robustness against thermal and electrical shocks. Therefore, they can be used as very sensitive detectors or frequency selective components in communication electronics. Driving the resonators into nonlinear response increases the sensitivities further. Most importantly, such resonators can be used for a novel kind of mechanical mixing. Here, the mechanical oscillations of tiny bridges and oscillators can be used to realize such novel devices for high-frequency signal processing. We present measurements on mechanical mixing in a nanomechanical resonator operated at 100 MHz.     

Anechoic sphere phantoms for estimating 3-D resolution of very-high-frequency ultrasound scanners

Two phantoms have been constructed for assessing performance of high-frequency ultrasound imagers. They also allow for periodic quality assurance tests and training technicians in the use of higher-frequency scanners. The phantoms contain eight blocks of tissue-mimicking material; each block contains a spatially random distribution of suitably small anechoic spheres having a small distribution of diameters. The eight mean sphere diameters are distributed from 0.10 to 1.09 mm. The two phantoms differ primarily in terms of the frequency dependence of the backscatter coefficient of the background material. Because spheres have no preferred orientation, all three (spatial) dimensions of resolution contribute to sphere detection on an equal basis; thus, the resolution is termed 3-D. Two high-frequency scanners are compared. One employs single-element (fixed focus) transducers (25 and 55 MHz), and the other employs variable focus linear arrays (20, 30, and 40 MHz). The depth range for detection of spheres of each size is determined corresponding to determination of 3-D resolution as a function of depth. As expected, the single-element transducers are severely limited in useful imaging depth ranges compared with the linear arrays. In this preliminary report, only one human observer analyzed images.     

Quantitative ultrasound estimates from populations of scatterers with continuous size distributions

Although quantitative ultrasound imaging based on backscattering coefficients has proven potential for tissue characterization, the scattering models used in most studies assume distributions of identical scatterers. However, actual tissues may exhibit multiple levels of spatial scales. Therefore, the objective of the present study is to analyze the effects of scatterer size distributions when using a fluid-sphere model for estimating values of effective scatterer diameter (ESD) through both simulations and experiments. For simulations, ESD estimates were obtained at several analysis frequencies between 1 and 40 MHz from populations of scatterers with diameters ranging between 25 and 100 μm, 25 and 50 μm, 50 and 100 μm, and 50 and 75 μm. For sufficiently high analysis frequencies, the ESD estimates obtained through simulations were approximately inversely proportional to frequency and mostly independent of the underlying scatterer size distribution. Asymptotic expressions for the expected ESD estimates at low- and high-frequency limits were derived. Experiments were conducted using two gelatin phantoms with contrast agent spheres ranging in diameter from 30 to 140 μm and 70 to 140 μm, and 5-, 7.5-, 10-, and 13-MHz focused transducers. Not only was the asymptotic behavior of ESD versus frequency estimates observed experimentally, but also the experimental ESD estimates using the 10- and 13-MHz transducers were lower than the smallest scatterers present in the second phantom. These results may have a direct impact on how scatterer size estimates corresponding to specimens with different subresolution spatial scales should be interpreted.     

Unit-delay focusing architecture and integrated-circuit implementation for high-frequency ultrasound

High-frequency ultrasound (above 10 MHz) has been used successfully in many medical applications, including eye, skin, gastrointestinal, intravascular, and Doppler flow imaging. Most of these applications use single-element transducers, thereby imposing a tradeoff between resolution and depth of field. Fabrication difficulties and the need for high-speed electronic beamformers have prevented widespread use of arrays at high frequencies. In this paper, a unit-delay focusing architecture suitable for use with high-frequency ultrasound annular arrays is described. It uses a collection of identical, active delay cells that may be simultaneously varied to accomplish focusing. Results are presented for an analog integrated circuit intended for use with a five-element, 50-MHz planar annular array. Focusing is possible over an axial range for which the ratio of maximum to minimum f-number is 2.1. Unit-delay architectures also are described for curved annular arrays and linear arrays.     

Design of focused ultrasound surgery transducers

High-intensity focused ultrasound surgery (FUS) has been developed for the extracorporeal treatment of various benign and malignant soft tissue tumors. The system developed at the Institute of Cancer Research/Royal Marsden (ICR/RM) National Health Service (NHS) Trust incorporates a 150 mm focal length focused bowl transducer operated at 1.7 MHz, and is currently undergoing Phase 1 clinical trials for the treatment of benign prostatic hyperplasia and superficial bladder cancer. However, the application of this transducer is limited by its focal length to a maximum depth of 100 mm, and by power absorption in the skin to a minimum depth of 40 mm. A computer model of acoustic fields, which assumes uniform excitation of the transducer over its entire surface, has previously been published. This has been used both to calculate the intensity in nonattenuating media, and to estimate the absorbed power per unit volume in homogeneous tissues in order to allow determination of the transducer configurations (frequency, focal length, and diameter) necessary for the treatment of both deep (~150 mm) and shallow (~20 mm) soft tissue tumors. These depths encompass the typical range for human tissues which are likely to be treated. Calculations cover the frequency range 0.5-4.5 MHz, focal lengths from 70 to 200 mm, and transducer diameters from 30 to 190 mm. The results show that appropriate transducers can be designed for the noninvasive treatment of tumors in specific organs     

Evaluation of polyvinyl alcohol cryogel as an acoustic coupling medium for low‐intensity transcranial focused ultrasound

Transcranial focused ultrasound (FUS) has emerged as a noninvasive neuromodulatory modality with exquisite depth penetration and spatial selectivity. Liquids, such as degassed water or mineral oil, are used as acoustic coupling media between the ultrasound‐generating transducer and the brain; however, they require a separate container that limits the spatial orientation of the transducers with respect to the sonication target. Nonliquid, gel‐like materials that do not require a housing container have been sought after as coupling media to overcome such limitations. Polyvinyl alcohol (PVA), when dissolved in water and undergone freeze–thaw cycle(s), forms a flexible hydrogel having a high level of acoustic transmission. To examine the feasibility of the PVA cryogel as the coupling material for transcranial FUS, the mechanical properties (in terms of its Young's modulus) and acoustic attenuation of the PVA cryogel were examined using different concentrations and number of freeze–thaw cycles. The cryogel with 6 or 7% (w/v) concentrations and two freeze–thaw cycles showed minimum pressure attenuation (on the order of 1%) across the different ultrasound frequencies (250–650 kHz). The cryogel was molded to fit around a single‐element FUS transducer and was applied to a head phantom, showing the flexibility in orienting the sonication paths at different angles and depths. The use of the cryogel did not alter the location and shape of acoustic focal profile compared to the one measured in the degassed water. The present work suggests that PVA cryogel may be used as an alternative acoustic coupling medium for low‐intensity FUS applications.     

A single-element transducer with nonuniform thickness for high-frequency broadband applications

The design, fabrication, and evaluation of a high-frequency single-element transducer are described. The transducer has an annular geometry, with the thickness of the piezoelectric material increasing from the center to the outside. This single-element annular transducer (SEAT) can provide a broader frequency range than a conventional single-element transducer with a uniform thickness (single-element uniform transducer, or SEUT). We compared the characteristics of a SEAT and a SEUT. Both transducers used 36deg-rotated, Y-cut lithium niobate (LiNbO₃) material. The SEAT had a diameter of 6 mm and comprised 6 subelements of equal area (electrically connected by a single electrode on each side) whose thickness ranged from 60 mum (center) to 110 mum (outside), which resulted in the center frequency of the subelements varying from 59.8 MHz to 25 MHz. The overall center frequency was 42.4 MHz. The annular pattern was constructed using an ultrasonic sculpturing machine that reduced the root-mean-square value of the surface roughness to 454.47 nm. The bandwidth of the SEAT was 19% larger than that of the SEUT. However, compared with the SEUT, the 2-way insertion loss of the SEAT was increased by 3.1 dB. The acoustic beam pattern of the SEAT was also evaluated numerically by finite-element simulations and experimentally by an ultrasound beam analyzer. At the focus (10.5 mm from the transducer surface), the -6 dB beam width was 108 mum. There was reasonable agreement between the data from simulations and experiments. The SEAT can be used for imaging applications that require a wider transducer bandwidth, such as harmonic imaging, and can be manufactured using the same techniques used to produce transducers with multiple frequency bands.     

Shear-horizontal acoustic waves in piezoelectric plates bordered with conductive liquid

The influence of a conductive liquid on the characteristics of shear-horizontal acoustic waves of zeroth order (SH0 mode) propagating in thin piezoelectric plates of lithium tantalate, lithium niobate, and potassium niobate was investigated. Experimental results obtained for SH0 mode devices fabricated on lithium niobate plates are found to be in good agreement with theory. The data presented in this paper is useful for a proper design of various acoustic wave sensors operating in contact with conductive liquids.     

An integrated circuit with transmit beamforming flip-chip bonded to a 2-D CMUT array for 3-D ultrasound imaging

State-of-the-art 3-D medical ultrasound imaging requires transmitting and receiving ultrasound using a 2-D array of ultrasound transducers with hundreds or thousands of elements. A tight combination of the transducer array with integrated circuitry eliminates bulky cables connecting the elements of the transducer array to a separate system of electronics. Furthermore, preamplifiers located close to the array can lead to improved receive sensitivity. A combined IC and transducer array can lead to a portable, high-performance, and inexpensive 3-D ultrasound imaging system. This paper presents an IC flip-chip bonded to a 16 x 16-element capacitive micromachined ultrasonic transducer (CMUT) array for 3-D ultrasound imaging. The IC includes a transmit beamformer that generates 25-V unipolar pulses with programmable focusing delays to 224 of the 256 transducer elements. One-shot circuits allow adjustment of the pulse widths for different ultrasound transducer center frequencies. For receiving reflected ultrasound signals, the IC uses the 32-elements along the array diagonals. The IC provides each receiving element with a low-noise 25-MHz-bandwidth transimpedance amplifier. Using a field-programmable gate array (FPGA) clocked at 100 MHz to operate the IC, the IC generated properly timed transmit pulses with 5-ns accuracy. With the IC flip-chip bonded to a CMUT array, we show that the IC can produce steered and focused ultrasound beams. We present 2-D and 3-D images of a wire phantom and 2-D orthogonal cross-sectional images (Bscans) of a latex heart phantom.     

Wideband linear power amplifier for high-frequency ultrasonic coded excitation imaging

Linear power amplifiers are critical components in ultrasonic imaging systems that implement chirp-coded excitation. Bench-top commercial power amplifiers are usually used in academic laboratories for high-frequency ultrasound imaging, and the imaging performance depends greatly on these general-purpose instruments. To achieve a wide dynamic range, a power amplifier consisting of two stages is developed for chirp-coded ultrasound imaging applications through the implementation of custom-designed broadband 1:1 transformers and the optimization of feedback circuits. The amplifier has broad bandwidth (5 to 135 MHz), maintaining a linearity up to the 1-dB gain compression point (P1dB) of 41.5 dBm, allowing 16 dBm input power level at 60 MHz. The mean and the maximum values of output third-order intercept points (OIP3) are 51.8 and 53.5 dBm, respectively, between 20 and 110 MHz. With 12 dBm input power, the gain of the amplifier varies between 24 and 29 dB, offering a uniformity which would allow excitation of a 70-MHz single-element transducer with windowed chirp-coded bursts sweeping from 40 to 100 MHz. The performance in high-frequency ultrasound imaging is evaluated with a wire phantom. Echo signal-to-noise ratio (eSNR) of the designed amplifier is 7 dB better than a commercial amplifier, and spatial resolution is maintained.     

Microelastic imaging of bone

Several high-frequency ultrasound techniques have been developed during the last decade with the intention of assessing elastic properties of bone at the tissue level. The basic measurement principles can be divided into: 1) measurement of the compressional wave velocity in thin tissue sections; 2) measurement of surface acoustic wave velocities in thick sections; and 3) derivation of the acoustic impedance from the confocal reflection amplitude in thick sections. In this paper, the 3 principles are described with example measurements given in the frequency range from 50 MHz to 1.2 GHz. The measurements were made with 2 microscopes operating in the pulse-echo mode, either with frequencies up to 200 MHz and time-resolved detection or between 100 MHz and 2 GHz and amplitude detection. The methods are compared and their application potentials and limitations are discussed with respect to the hierarchical structure of cortical bone. Mapping of the confocal reflection amplitude has superior capabilities for deriving quantitative elastic and structural parameters in the heterogeneous bone material. Even at low frequencies (50 MHz), the mineralized tissue matrix can be separated from the larger pores (Haversian canals), and the elastic coefficient in the probing direction can be measured in 2 dimensions. Depending on the type of sample surface preparation (flat or cylindrically shaped), local distribution of a single elastic coefficient or the average transverse isotropic stiffness tensor can be derived. With frequencies in the GHz range, the lamellar bone structure can be analyzed. However, at one GHz, the acoustic wavelength is still one order of magnitude larger than the individual mineralized collagen fibrils. Although the thickness of a lamellar unit can easily be assessed from the acoustic image, the derivation of the anisotropic elastic properties of the mineralized collagen fibrils as well as the detailed structure of a lamella can only be accomplished with further model assumptions.