Jeffrey A. Ketterling

Radiation-force technique to monitor lesions during ultrasonic therapy.

This report describes a monitoring technique for high-intensity focused ultrasound (US), or HIFU, lesions, including protein-denaturing lesions (PDLs) and those made for noninvasive cardiac therapy and tumor treatment in the eye, liver and other organs. Designed to sense the increased stiffness of a HIFU lesion, this technique uniquely utilizes the radiation force of the therapeutic US beam as an elastographic push to detect relative stiffness changes. Feasibility was demonstrated with computer simulations (treating acoustically induced displacements, concomitant heating, and US displacement-estimation algorithms) and pilot in vitro experimental studies, which agree qualitatively in differentiating HIFU lesions from normal tissue. Detectable motion can be induced by a single 5 ms push with temperatures well below those needed to form a lesion. Conversely, because the characteristic heat diffusion time is much longer than the characteristic relaxation time following a push, properly timed multiple therapy pulses will form lesions while providing precise control during therapy.

Design and fabrication of a 40-MHz annular array transducer

This paper investigates the feasibility of fabricating a five-ring, focused annular array transducer operating at 40 MHz. The active piezoelectric material of the transducer was a 9-/spl mu/m thick polyvinylidene fluoride (PVDF) film. One side of the PVDF was metallized with gold and forms the ground plane of the transducer. The array pattern of the transducer and electrical traces to each annulus were formed on a copper-clad polyimide film. The PVDF and polyimide were bonded with a thin layer of epoxy, pressed into a spherically curved shape, then back filled with epoxy. A five-ring transducer with equal area elements and 100 /spl mu/m kerfs between annuli was fabricated and tested. The transducer had a total aperture of 6 mm and a geometric focus of 12 mm. The pulse/echo response from a quartz plate located at the geometric focus, two-way insertion loss (IL), complex impedance, electrical crosstalk, and lateral beamwidth all were measured for each annulus. The complex impedance data from each element were used to perform electrical matching, and the measurements were repeated. After impedance matching, f/sub c/ /spl sim/ 36 MHz and -6-dB bandwidths ranged from 31 to 39%. The ILs for the matched annuli ranged from -28 to -38 dB.

Recent developments in tissue-type imaging (TTI) for planning and monitoring treatment of prostate cancer.

Because current methods of imaging prostate cancer are inadequate, biopsies cannot be effectively guided and treatment cannot be effectively planned and targeted. Therefore, our research is aimed at ultrasonically characterizing cancerous prostate tissue so that we can image it more effectively and thereby provide improved means of detecting, treating and monitoring prostate cancer. We base our characterization methods on spectrum analysis of radiofrequency (rf) echo signals combined with clinical variables such as prostate-specific antigen (PSA). Tissue typing using these parameters is performed by artificial neural networks. We employed and evaluated different approaches to data partitioning into training, validation, and test sets and different neural network configuration options. In this manner, we sought to determine what neural network configuration is optimal for these data and also to assess possible bias that might exist due to correlations among different data entries among the data for a given patient. The classification efficacy of each neural network configuration and data-partitioning method was measured using relative-operating-characteristic (ROC) methods. Neural network classification based on spectral parameters combined with clinical data generally produced ROC-curve areas of 0.80 compared to curve areas of 0.64 for conventional transrectal ultrasound imaging combined with clinical data. We then used the optimal neural network configuration to generate lookup tables that translate local spectral parameter values and global clinical-variable values into pixel values in tissue-type images (TTIs). TTIs continue to show cancerous regions successfully, and may prove to be particularly useful clinically in combination with other ultrasonic and nonultrasonic methods, e.g., magnetic-resonance spectroscopy.

Operational verification of a 40-MHz annular array transducer

An experimental system to take advantage of the imaging capabilities of a 5-ring polyvinylidene fluoride (PVDF)-based annular array is presented. The array has a 6-mm total aperture and a 12-mm geometric focus. The experimental system is designed to pulse a single element of the array and then digitize the received data of all array channels simultaneously. All transmit/receive pairs are digitized and then the data are post-processed with a synthetic-focusing technique to achieve an enhanced depth of field (DOF). The performance of the array is experimentally tested with a wire phantom consisting of 25-mum diameter wires diagonally spaced at 1-mm by 1-mm intervals. The phantom permitted the efficacy of the synthetic-focusing algorithm to be tested and was also used for two-way beam characterization. Experimental results are compared to a spatial impulse response method beam simulation. After synthetic focusing, the two-way echo amplitude was enhanced over the range of 8 to 19 mm and the 6-dB DOF spanned from 9 to 15 mm. For a wire at a fixed axial depth, the relative time delays between transmit/receive ring pairs agreed with theoretical predictions to within plusmn2 ns. To further test the system, B-mode images of an excised bovine eye were rendered

Chirp-coded excitation imaging with a high-frequency ultrasound annular array

High-frequency ultrasound (HFU, > 15 MHz) is an effective means of obtaining fine-resolution images of biological tissues for applications such as opthalmologic, dermatologic, and small animal imaging. HFU has two inherent drawbacks. First, HFU images have a limited depth of field (DOF) because of the short wavelength and the low fixed F-number of conventional HFU transducers. Second, HFU can be used to image only a few millimeters deep into a tissue because attenuation increases with frequency. In this study, a five-element annular array was used in conjunction with a synthetic-focusing algorithm to extend the DOF. The annular array had an aperture of 10 mm, a focal length of 31 mm, and a center frequency of 17 MHz. To increase penetration depth, 8-mus, chirp-coded signals were designed, input into an arbitrary waveform generator, and used to excite each array element. After data acquisition, the received signals were linearly filtered to restore axial resolution and increase the SNR. To compare the chirp-coded imaging method with conventional impulse imaging in terms of resolution, a 25-mum diameter wire was scanned and the -6-dB axial and lateral resolutions were computed at depths ranging from 20.5 to 40.5 mm. The results demonstrated that chirp-coded excitation did not degrade axial or lateral resolution. A tissue-mimicking phantom containing 10-mum glass beads was scanned, and backscattered signals were analyzed to evaluate SNR and penetration depth. Finally, ex vivo ophthalmic images were formed and chirp-coded images showed features that were not visible in conventional impulse images.

HIGH-FREQUENCY CHIRP ULTRASOUND IMAGING WITH AN ANNULAR ARRAY FOR OPHTHALMOLOGIC AND SMALL-ANIMAL IMAGING

High-frequency ultrasound (HFU, >20 MHz) is an attractive means of obtaining fine-resolution images of biological tissues for ophthalmologic, dermatological and small-animal imaging applications. Even with current improvements in circuit designs and high-frequency equipment, HFU has two inherent limitations. First, HFU images have a limited depth-of-field (DOF) because of the short wavelength and the low fixed F-number of conventional HFU transducers. Second, HFU is usually limited to shallow imaging because of the significant attenuation in most tissues. In a previous study, a five-element annular array with a 17-MHz center frequency was excited using chirp-coded signals, and a synthetic-focusing algorithm was used to extend the DOF and increase penetration depth. In the present study, a similar approach with two different five-element annular arrays operating near a center frequency of 35 MHz is implemented and validated. Following validation studies, the chirp-imaging methods were applied to imaging vitreous-hemorrhage-mimicking phantoms and mouse embryos. Images of the vitreous phantom showed increased sensitivity using the chirp method compared with a standard monocycle imaging method, and blood droplets could be visualized 4mm deeper into the phantom. Three-dimensional datasets of 12.5-day-old mouse embryo heads were acquired in utero using chirp and conventional excitations. Images were formed and brain ventricles were segmented and reconstructed in three dimensions. The brain ventricle volumes for the monocycle excitation exhibited artifacts that were not apparent on the chirp-based dataset reconstruction.

Direct observation of microbubble oscillations

The study of microbubble oscillations is important for the understanding of sonoluminescence phenomena. Bubble dynamic behavior is conventionally detected with light scattering techniques. This method generally gives little information about the shapes of a bubble during its oscillation. In order to observe the bubble shapes, a direct imaging system was set up. The shape of a bubble levitated in a liquid is magnified and displayed on a TV screen. The bubble is illuminated with an LED lamp which is strobed at a frequency slightly different from the driving sound field. This technique can slow the moving image of the bubble, allowing one to observe the shape of a bubble oscillating between 5 to 100 μm in diameter. Experiments show that when a bubble oscillates with sonoluminescence, it keeps a closely spherical shape during the entire oscillation period. However, with the increase of gas concentration in the host liquid, sonoluminescence disappears and higher mode shapes are developed during the bubble’s sh...

Excitation of polymer-shelled contrast agents with high-frequency ultrasound

Few experimental and complementary theoretical studies have investigated high-frequency (>20 MHz) nonlinear responses from polymer-shelled ultrasound contrast agents. Three polymer agents with different shell properties were examined for their single-bubble backscatter when excited with a 40 MHz tone burst. Higher-order harmonic responses were observed for the three agents; however, their occurrence was at least partly due to nonlinear propagation. Only one of the agents (1.1 microm mean diameter) showed a subharmonic response for longer excitations (approximately 10-15 cycles) and midlevel pressure excitations ( 2.5 MPa). Theoretical calculations of the backscattered spectrum revealed behavior similar to the experimental results in specific parameter regimes.

Improved High-Resolution Ultrasonic Imaging of the Eye

Currently, virtually all clinical diagnostic ultrasound systems used in ophthalmology are based on fixed-focus, single-element transducers. High-frequency (> or = 20-MHz) transducers introduced to ophthalmology during the last decade have led to improved resolution and diagnostic capabilities for assessment of the anterior segment and the retina. However, single-element transducers are restricted to a small depth of field, limiting their capacity to image the eye as a whole. We fabricated a 20-MHz annular array probe prototype consisting of 5 concentric transducer elements and scanned an ex vivo human eye. Synthetically focused images of the bank eye showed improved depth of field and sensitivity, allowing simultaneous display of the anterior and posterior segments and the full lens contour. This capability may be useful in assessment of vitreoretinal pathologies and investigation of the accommodative mechanism.

Characterization of the spatial resolution of different high-frequency imaging systems using a novel anechoic-sphere phantom

The spatial resolution of high-frequency ultrasound (HFU, >;20 MHz) imaging systems is usually determined using wires perpendicular to the beam. Recently, two tissue-mimicking phantoms (TMPs) were developed to estimate three-dimensional (3-D) resolution. Each TMP consists of nine 1-cm-wide slabs of tissue-mimicking material containing randomly distributed anechoic spheres. All anechoic spheres in one slab have the same dimensions, and their diameter is increased from 0.1 mm in the first slab to 1.09 mm in the last. The scattering background for one set of slabs was fabricated using 3.5-μm glass beads; the second set used 6.4-μm glass beads. The ability of a HFU system to detect these spheres against a speckle background provides a realistic estimation of its 3-D spatial resolution. In the present study, these TMPs were used with HFU systems using single-element transducers, linear arrays, and annular arrays. The TMPs were immersed in water and each slab was scanned using two commercial imaging systems and a custom HFU system based on a 5-element annular array. The annular array had a nominal center frequency of 40 MHz, a focal length of 12 mm, and a total aperture of 6 mm. A synthetic-focusing algorithm was used to form images with an increased depth-of-field. The penetration depth was increased by using a linear-chirp signal spanning 15 to 65 MHz over 4 μs. Results obtained with the custom system were compared with those of the commercial systems (40-MHz probes) in terms of sphere detection, i.e., 3-D spatial resolution, and contrast-to-noise ratio (CNR). Resulting B-mode images indicated that only the linear-array transducer failed to clearly resolve the 0.2-mm spheres, which showed that the 3-D spatial resolution of the single-element and annulararray transducers was superior to that of the linear array. The single-element transducer could only detect these spheres over a narrow 1.5 mm depth-of-field, whereas the annular array was able to detect them to depths of at least 7 mm. For any size of the anechoic spheres, the annular array excited by a chirp-coded signal provided images of the highest contrast, with a maximum CNR of 1.8 at the focus, compared with 1.3 when using impulse excitation and 1.6 with the single-element transducer and linear array. This imaging configuration also provided CNRs above 1.2 over a wide depth range of 8 mm, whereas CNRs would quickly drop below 1 outside the focal zone of the other configurations.The spatial resolution of high-frequency ultrasound (HFU, >;20 MHz) imaging systems is usually determined using wires perpendicular to the beam. Recently, two tissue-mimicking phantoms (TMPs) were developed to estimate three-dimensional (3-D) resolution. Each TMP consists of nine 1-cm-wide slabs of tissue-mimicking material containing randomly distributed anechoic spheres. All anechoic spheres in one slab have the same dimensions, and their diameter is increased from 0.1 mm in the first slab to 1.09 mm in the last. The scattering background for one set of slabs was fabricated using 3.5-μm glass beads; the second set used 6.4-μm glass beads. The ability of a HFU system to detect these spheres against a speckle background provides a realistic estimation of its 3-D spatial resolution. In the present study, these TMPs were used with HFU systems using single-element transducers, linear arrays, and annular arrays. The TMPs were immersed in water and each slab was scanned using two commercial imaging systems and a custom HFU system based on a 5-element annular array. The annular array had a nominal center frequency of 40 MHz, a focal length of 12 mm, and a total aperture of 6 mm. A synthetic-focusing algorithm was used to form images with an increased depth-of-field. The penetration depth was increased by using a linear-chirp signal spanning 15 to 65 MHz over 4 μs. Results obtained with the custom system were compared with those of the commercial systems (40-MHz probes) in terms of sphere detection, i.e., 3-D spatial resolution, and contrast-to-noise ratio (CNR). Resulting B-mode images indicated that only the linear-array transducer failed to clearly resolve the 0.2-mm spheres, which showed that the 3-D spatial resolution of the single-element and annulararray transducers was superior to that of the linear array. The single-element transducer could only detect these spheres over a narrow 1.5 mm depth-of-field, whereas the annular array was able to detect them to depths of at least 7 mm. For any size of the anechoic spheres, the annular array excited by a chirp-coded signal provided images of the highest contrast, with a maximum CNR of 1.8 at the focus, compared with 1.3 when using impulse excitation and 1.6 with the single-element transducer and linear array. This imaging configuration also provided CNRs above 1.2 over a wide depth range of 8 mm, whereas CNRs would quickly drop below 1 outside the focal zone of the other configurations.