Greenleaf, James F.

Vibro-acoustography is a new noncontact imaging method based on the radiation force of ultrasound. We extend this technique for tissue characterization of arterial tubes by vibration techniques. The arterial tube can be excited remotely by ultrasound at its resonant frequencies where the vibration and acoustic emission of the tube can be measurable. From these resonant frequencies, the material properties of the arterial tube can be found. A theory for a tube with tissue is formulated using first-order shear deformation theory to include the effects of transverse shear deformation and rotary inertia. A wave propagation approach is applied for easy handling of the boundary conditions. Experimental studies were carried out on a silicone tube embedded in a cylindrical gel phantom. A confocal transducer is used to produce the radiation force of ultrasound for exciting the tube–phantom structure. The vibration of the tube and the phantom are measured with a laser vibrometry system. The fundamental mode of a tube–phantom structure is well excited by the radiation force of ultrasound, and was measured to be 81.8 Hz, which is close to the theoretical prediction of 83.3 Hz. Both excitation and measurement are remote and noncontact, important attributes for future study of arteries.

Palpation is routinely used for detecting pathology using the stiffness of the tissue and is more than 2000 years old. Palpation is subjective and limited to individual experience and to the accessibility of the tissue region to touch. Noninvasive images of elastic modulus may be useful to distinguish tissues and pathologic processes based on mechanical properties such as elastic modulus. Static, quasistatic, or cyclic stresses have been applied while strains have been measured using ultrasound or MRI. The related elastic modulus has been estimated from visco-elastic models of tissue mechanics. Recently we have developed a new ultrasound technique that produces speckle free images related to both tissue stiffness and reflectivity. This method, termed Ultrasound Stimulated Vibro-acoustography [Science 280, 83–85 (1998); PNAS 96, 6603–6608 (1999)], uses ultrasound radiation pressure to produce sound vibrations from a small region of the tissue that depend on the scattering and elastic characteristics of the tissue. The method can detect microcalcification within breasts, and promises to provide high-quality images of calcification within the arteries. Vibro-acoustography can detect mechanical defects in prostheses such as artificial mitral and aortic valves. The method may also be used in nondestructive evaluation. [Work supported by HL 61451, DBI 7980-4.]

Ultrasound (US) enhancement of plasmid-based gene transfer is an emerging technique. Our hypothesis was that two contrast agents (Optison and PESDA), and two US exposure modalities (dedicated continuous wave system and diagnostic scanner) may have different effects. Luciferase plasmid with or without contrast agent was added to vascular smooth muscle cells and endothelial cells, followed by US exposure. Luciferase activity was measured 24 h later. US exposure consistently induced higher transfection rates than all controls. PESDA was superior to Optison in both cell lines. In vitro, continuous wave and diagnostic US were not significantly different. In vivo, Lux and PESDA were injected into skeletal muscles of rats (IM or intra-arterial) followed or not by US exposure. In separate animals, adenovirus encoding for luciferase was injected IM and was not followed by US exposure. Gene transfer efficacy was 8–10 fold higher with US and PESDA than with plasmid alone, but 2 fold lower than with adenovirus. However, as opposed to adenovirus, US-enhanced plasmid gene transfer was highly localized to the injected muscle, with no expression at distal sites. Our results support the hypothesis that contrast agents and exposure modalities are not equivalent with regard to gene transfer efficacy.

Elasticity imaging methods have been used to study tissue mechanical properties and have demonstrated that tissue elasticity changes with disease state. Quantitative mechanical properties can be measured in a model independent manner if both shear wave speed and attenuation are known. However, measuring shear wave speed attenuation is challenging in the field of elasticity imaging. Typically, only shear wave speed is measured and rheological models, such as Kelvin-Voigt, Maxwell and Standard Linear Solid, are used to solve for shear viscoelastic complex modulus. Acoustic radiation force has been used to study quasi-static viscoelastic properties of tissue during creep and relaxation conditions, however, as with shear wave propagation methods, a rheological model needs to be fit to the creep or relaxation experimental data to solve for viscoelastic parameters. This paper presents a method to quantify viscoelastic properties in a model-independent way by estimating complex shear elastic modulus over a wide frequency range using time-dependent creep response induced by acoustic radiation force. The acoustic radiation force induced creep (RFIC) method uses a conversion formula that is the analytic solution of the constitutive equation relating time dependent stress and time dependent strain. The RFIC method in combination with shear wave propagation is used to measure the complex shear modulus so that knowledge of the applied radiation force magnitude is not necessary. Numerical simulation of creep strain and compliance using the Kelvin-Voigt model shown that the conversion formula is sensitive to sampling frequency, the first reliable measure in time and the long term viscosity approximation. Experimental data are obtained in homogeneous tissue mimicking phantoms and excised swine kidneys.

The goal of this experiment was to excite and measure, in a noncontact manner, the vibrational modes of the reed from a reed organ pipe. To perform ultrasound stimulated excitation, two ultrasound beams in air of different frequencies were directed at the reed; the audio-range beat frequency between these ultrasound beams induced vibrations. The resulting vibrational deflection shapes were measured with a scanning vibrometer. The modes of any relatively small object can be studied in air using this technique. For a 36 mm by 7 mm clamped brass reed cantilever, displacements and velocites of 5 μ and 4 mm/s could be imparted at the fundamental frequency of 145 Hz. Using the same ultrasound transducer, excitation across the entire range of audio frequencies was obtained, which was not possible using audio excitation with a speaker. Since the beam was focused on the reed, ultrasound stimulated excitation eliminated background effects observed during mechanical shaker excitation, such as vibrations of clamps and supports. We will discuss the results obtained using single, dual, and confocal ultrasound transducers in AM and unmodulated CW modes, along with results obtained using a mechanical shaker and audio excitation using a speaker.

Characterization of the viscoelastic mechanical properties of skin is important for improving accurate medical examination and diagnosis of disorders involving cutaneous and subcutaneous tissues; more thoroughly understanding skin biophysical and physiological properties; identifying normal and abnormal skin aging and disease processes; developing and applying improved pharmacologic and other therapeutic interventions; as well as cosmetic applications. Several noninvasive methods have been developed for measurement of mechanical properties of skin [1]. However, most methods measure a stiffness parameter but not the material properties of skin. For example, the suction method measures the displacement of skin in response to suction. The measurement is dependent on the aperture and fixation of probes and also difficult to interpret.

Research in quantitative whole breast ultrasound imaging has been developing rapidly. Recently, we published results from 2D transmission inverse scattering algorithms, based on optimization, incorporating diffraction, refraction, and limited multiple scattering effects, using data collected from an early prototype, which showed the feasibility of high resolution quantitative imaging of the breast tissue speed and attenuation, and concomitant refraction corrected reflection imaging. However, artifact problems in speed and attenuation result from the 2D algorithms and the data characteristics. The reflection algorithm uses the speed map to model refractive effects of rays, so these artifacts are unacceptable. The 3D inverse scattering algorithm presented here, using data from a new prototype, overcomes most of these artifacts. We then use a 3D refraction corrected 360° compounded reflection algorithm for high resolution speckle free reflection images. We discuss the transmission and reflection algorithms and the advanced scanner used to collect the data, as well as initial clinical results from the Mayo Clinic, Breast Cancer Imaging Center, Orange County, and the University California, San Diego. We show examples of cysts, fibroadenomas, calcifications, cancers, and DCIS, in dense, fatty, and average breast tissue, and compare these with hand-held ultrasound, MRI, and mammography, where available.

Ultrasound-stimulated vibro-acoustic spectrography is a recently-developed method that employs the radiation force of two intersecting continuous ultrasound beams to remotely vibrate an object at an arbitrary low frequency. Object vibration produces a sound field (acoustic emission) in the medium, which is a function of object mechanical properties. By measuring the acoustic emission field, one can obtain information about the mechanical parameters of the object. In this paper, we use this method for remote (noncontact) measurement of the dynamic Young's modulus of a rod based on its fundamental resonance frequency. Experimental results on an aluminum rod agree with the published data.

Limited diffraction beams, such as Durnin's J 0 Bessel beam, are a class of nonspreading solutions to the isotropic/homogeneous scalar wave equation. These beams can be approximately produced with finite aperture and energy over a deep depth of field. In this paper, we report the application of a broadband J 0 Bessel beam to nondestructive evaluation (NDE) of materials. Pulse-echo images of a stainless steel block phantom were obtained with both the Jo Bessel beam and a conventional focused Gaussian beam. Results show that uniformly high resolutions were obtained with the J 0 Bessel beam over a large distance. In addition, the lateral resolution of the J 0 Bessel beam is almost independent of the speed of sound of the materials inspected. In contrast, the lateral resolution of images obtained with the conventional focused Gaussian beam changes dramatically with the distance and the focal length of the beam in water is greatly reduced by the steel block. Therefore, limited diffraction beams could be useful for nondestructive evaluation of materials of different speeds of sound. Restoration of pulse-echo images obtained with these beams could be simplified.

A method to obtain a good compromise between the depth of field and the lateral resolution of “X waves” is proposed. The original X waves are theoretically nondiffracting beams generated by a specially phased infinite transmit aperture. When generated by a finite aperture, X waves are diffracting beams but have a large depth of field, maintaining uniform lateral field profiles. The proposed modification of the wave equation solution for X waves replaces a constant parameter representing the propagation angle of ultrasound with a function of radial distance at the aperture surface, and results in modified X waves that have a larger depth of field than the original X waves. Computer simulations show that a proper choice of the modification function can produce a new beam with improved field properties compared with the original X waves, promising images with higher lateral resolution and increased contrast over a large depth of field in high frame rate medical imaging. Experimental results are presented to verify the simulation results of the proposed method.