Greenleaf, James F.

Vibro-acoustography is a method that uses the dynamic radiation force (stress) of ultrasound to locally excite an object at low frequency [Fatemi and Greenleaf, Science 280, 82]. A multifrequency vibro-acoustography method is proposed that uses a multifrequency radiation stress produced by an array transducer driven with N ultrasound frequencies. A multifrequency image at the different N(N−1)/2 frequencies is produced with one scan of the region of interest, increasing the information yield by a factor of N(N−1)/2. Image formation theory is presented for multifrequency vibro-acoustography using an annular array transducer. Simulations of the stress field were performed for a 20-element, 3.5-MHz annular array transducer. Four ultrasound frequencies produce six unique low-frequency components in the point spread function. Computer phantoms with small spheres are used to demonstrate the usefulness of multifrequency vibro-acoustography for microcalcification detection in breast imaging. The lateral and axial width of the main lobe at −6 dB is 0.68 and 6.47 mm, respectively. The lateral and axial sidelobe levels are −27.8 and −16.8 dB, respectively. The proposed method holds the potential for large gains of information with good spatial resolution and no increase in scanning time. [Work supported by Grant EB00535-03 from NIH.]

We have proposed generating a bending wave in the arterial wall using ultrasound radiation force and measuring the wave velocity along the arterial wall [Zhang et al., IEEE Trans. Ultrason. Ferroelectr. Freq. Control 52, 642–652 (2005)]. Here, we report the results of in vivo studies on pigs. The pig was anesthetized, and a micromanometer tip catheter was inserted into the femoral artery to measure luminal pressure. A water bath was created on the animal’s groin to allow unimpeded access of the ultrasound beams to the femoral artery. The femoral artery was first located using a 13-MHz linear-array transducer. Then, a vibro-acoustography image was obtained to ensure precise positioning of the excitation force relative to the artery. The artery was excited by the force transducer and the resulting vibration of the arterial wall was measured by a sensing Doppler transceiver. Measured wave velocity was 3.1 m/s at 300 Hz. With this new method wave velocity over a distance of 5 mm, and therefore stiffness of arteries, can be measured locally and non-invasively. Measurement time is short in a few tens of milliseconds, which allows pressure dependence and pharmacological effect on the wall properties to be measured at different cardiac times.

The head-gimbal assembly suspension is a cantilever-like structure that holds the heads on a hard drive. We will discuss a noncontact method for modal testing, of suspensions in air, that utilizes the radiation force at the difference frequency generated by two intersecting ultrasound beams. The resulting low-frequency excitations were measured using a scanning vibrometer. This excitation technique has been demonstrated for MEMS and other small devices. There are several unique advantages of the ultrasound radiation force relative to mechanical shakers. Since the ultrasound radiation force is noncontact, a specialized test fixture was not needed; the technique was relatively insensitive to distracting resonances of fixtures and support structures. Another advantage is broadband excitation; a 550-kHz confocal ultrasound transducer excited suspension resonance frequencies from under 1 kHz to over 50 kHz. Other advantages include the ability to selectively excite different modes. For example, the amplitude of the suspension’s 2.28-kHz transverse mode was suppressed by an order of magnitude by shifting the modulation phase between the two ultrasound beams by 90. In another test, the amplitude of the 6.01-kHz torsional mode was doubled by moving the ultrasound focus point from near the center to near the edge of the suspension.

Vibro-acoustography is based on audio-frequency harmonic vibrations induced in the object by the radiation force of focused ultrasound. The resulting object vibration produces a hydrophone detectable acoustic emission that is a function of regional dynamic properties of the object at the vibration frequency. The amplitude of the hydrophone signal is mapped into an image that represents the object’s vibro-acoustic response to the radiation force by scanning the focused ultrasound across the object. Contrast in Vibro-acoustography images represent several properties of the object, including the dynamic characteristics at the audio frequency and scattering and absorption properties at the ultrasound frequency. A Vibro-acoustography system has been combined with a stereo-tactic x-ray mammography system for in vivo breast imaging and has been tested on a number of volunteers. Resulting images show soft tissue structures and microcalcifications within breast with high contrast, high resolution, and no speckles. The results have been verified using x-ray mammograms of the breast. The encouraging results from in vitro and in vivo experiments suggest further development of vibro-acoustography may lead to a new clinical breast imaging modality. [Work supported in part by a grant from the Susan G. Komen Breast Cancer Foundation. Vibro-acoustography is patented by MF and JFG.]

The fact that modulated ultrasound at a pulse intensity of 160 mW/cm2 can induce fracture healing implies that cells that are sensitive to strain can feel and respond to this signal. A hypothesis that uses Nyborg inspired methods to investigate this effect will be presented along with data from a wide variety of simulations and experimental data. It appears that the response is mediated through the cytoskeleton and may be associated with interaction of the sound with focal adhesion complexes at one end of the skeletal fibers for high frequency responses and with the nuclear membrane at the other end of the fibers for low frequency responses. Although this hypothesis is nascent it is supported with experimental data from the literature.

In vitro studies have shown that treatment with 1.5 MHz ultrasound signal (160 mW/cm2) at a 200 μs tone burst repeating at 1 kHz increases proteoglycan synthesis in chondrocytes [J. Parvisi et al., J. Orthop. Res. 17, 488–494 (1999)]. It was hypothesized that a continuous 1 kHz signal would be similar to the pulsed 1.5 MHz signal in stimulating chondrocytes to produce proteoglycan, which may cause accelerated fracture healing. In vitro experiments were performed with ATDC5 cells, a chondrogenic clonal cell line, plated in 6-well plates for 3 to 7 days before receiving ultrasound treatments. Cells were treated with either 1.5 MHz pulsed signal or 1 kHz signal for 20 minutes per day for 9 to 11 days. The signals were calibrated so that the bottom of the 6-well plate moved 10 nm for each condition. After the final treatment, cell layers were stained with Alcian blue, which stains cartilage nodules providing a measure of chondrogenesis. Both 1.5 MHz and 1 kHz led to a highly significant increase in chondrogenesis compared to control. Quantitative image analysis of stained wells showed that treatments with either signal increased number of nodules 2.3-fold (p<0.02) and total area of nodules 3-fold (p<0.02) compared to controls.

With the advent of MEMS, modal analysis of small structures is increasingly important. However, conventional excitation techniques normally require contact, which may not be feasible for small objects. We present a non-contact method that uses interference of ultrasound frequencies in air to produce low-frequency excitation of structures. Objects studied included hard-drive HGA suspensions and MEMS devices. The vibration induced by the ultrasound radiation force was varied in a wide range from 0 Hz to 50 kHz. Object motion was detected using a laser vibrometer; measured frequencies agreed with expected values. Also demonstrated was the unique capability to selectively enhance or suppress modes independently. For example, the ratio of the vibrational amplitudes of the 175 Hz first-bending and 1.33 kHz torsional modes of a small cantilever could be changed from in excess of 10:1 to less than 1:10 by shifting the ultrasound modulation phase 90 degrees. Similar changes were obtained for a 3 mm square MEMS mirror in the ratios of vibration amplitude around its two separate axes. Torsional modes of a hard-drive suspension could be selectively enhanced by over a factor of two by moving the ultrasound focus point from near the center to near the edge of the suspension.

Vibro-acoustography is an imaging technique that maps the acoustic response of an object to a localized harmonic radiation force. This force is generated by two interfering continuous-wave ultrasound beams at slightly different frequencies f1 and f2. The system point-spread function (PSF) is related to the radiation force on a point-target. Imaging artifacts depend on the PSF sidelobes, which can be reduced by mismatching the sidelobes of each ultrasound beam. Here, we propose a beamforming approach based on an 8-element sector transducer with consecutive elements alternately driven at f1 and f2. The transducer generates two ultrasound beams skewed by 22.5° with respect to each other. The system PSF is analytically derived. The theory is validated by experiments using a small steel sphere (radius =0.2 mm) as a point-target. A laser vibrometer is used to measure the vibration of the sphere and evaluate the PSF of the system. Theoretically, the PSF sidelobes are under −15.8 dB in eight spots circularly distributed and separated by 22.5°, which agrees with the experimental results. Simulation shows that with 16 elements sidelobes are under −35.2 dB. In conclusion, sector transducers for vibro-acoustography may have lower sidelobes as the number of array elements is increased. [Work supported by Grant Nos. EB00535-01, EB2640, and IMG0100744.]

Vibro-acoustography is a technique that uses the radiation force of amplitude-modulated ultrasound to evaluate the dynamic response of an object at the modulation frequency. One potential application of this technique is to assess the reaction of the host tissue to the implant material by evaluating the mechanical properties of the tissue surrounding the implant. To do this, we use vibro-acoustography to measure the frequency response of the implant, and use this information to evaluate the mechanical parameters of the surrounding. Two theoretical models are developed to study the dynamic response of an implant in tissue. The first model is for an implant (1×25-mm steel beam) fully embedded in a viscoelastic medium (tissue). The second model is for a partially embedded implant with one part exposed to the open environment. The exposed end is rigidly connected to a base, and the other end is freely embedded in the viscoelastic medium. At the interface between the two media matching of boundary conditions is achieved to determine the force response. For both models eigenvalues and eigenfunctions are determined and transfer functions are evaluated. The first two natural frequencies compare well with available experimental and finite-element data.

Vibro-acoustography is a new noncontact imaging method based on the radiation force of ultrasound. We extend this technique for imaging of arterial vessels based on vibration resonance. The arterial vessel is excited remotely by ultrasound at a resonant frequency, at which the vibration of the vessel as well as its transmission to the body surface are large enough to be measured. By scanning the ultrasound beam across the vessel plane and measuring the vibration at one single point on the body or vessel surface, an image of the interior artery can be mapped. Theory is developed that predicts the measured velocity is proportional to the value of the mode shape at resonance. Experimental studies were carried out on a silicone tube embedded in a cylindrical gel phantom of large radius, which simulates a large artery and the surrounding body. The fundamental frequency was measured at which the ultrasound transducer scanned across the tube plane with velocity measurement at one single point on the tube or on the phantom by laser. The images obtained show clearly the interior tube and the modal shape of the tube. The present technique offers a new imaging method for arterial vessels.