Randall R. Kinnick

Shearwave dispersion ultrasound vibrometry (SDUV) for measuring tissue elasticity and viscosity

Characterization of tissue elasticity (stiffness) and viscosity has important medical applications because these properties are closely related to pathological changes. Quantitative measurement is more suitable than qualitative measurement (i.e., mapping with a relative scale) of tissue viscoelasticity for diagnosis of diffuse diseases where abnormality is not confined to a local region and there is no normal background tissue to provide contrast. Shearwave dispersion ultrasound vibrometry (SDUV) uses shear wave propagation speed measured in tissue at multiple frequencies (typically in the range of hundreds of Hertz) to solve quantitatively for both tissue elasticity and viscosity. A shear wave is stimulated within the tissue by an ultrasound push beam and monitored by a separate ultrasound detect beam. The phase difference of the shear wave between 2 locations along its propagation path is used to calculate shear wave speed within the tissue. In vitro SDUV measurements along and across bovine striated muscle fibers show results of tissue elasticity and viscosity close to literature values. An intermittent pulse sequence is developed to allow one array transducer for both push and detect function. Feasibility of this pulse sequence is demonstrated by in vivo SDUV measurements in swine liver using a dual transducer prototype simulating the operation of a single array transducer.

Optimization of ultrasound-mediated gene transfer: comparison of contrast agents and ultrasound modalities

AIMS Ultrasound (US)-enhanced gene transfer for cardiovascular disease is an emerging technique with translational relevance. Prior to pre-clinical applications, optimization of gene transfer using various US contrast agents and parameters is required. In order to do so, two clinically relevant contrast agents (Optison and PESDA), and two US modalities (dedicated continuous wave system and diagnostic scanner) were tested in vitro and in vivo. METHODS AND RESULTS In vitro, luciferase activity was measured after exposure of primary vascular cells to combinations of luciferase plasmid, contrast agents, and US exposures. US gene transfer was consistently superior to controls. PESDA was better than Optison; there was no significant difference between US modalities. In vivo, luciferase activity in skeletal muscle of rats was measured after injection of plasmid or adenovirus, expressing luciferase with or without US exposure. Diagnostic US was superior to continuous wave. US plasmid gene transfer was highly localized, and was superior to all controls except adenovirus which lacked spatial specificity. To deliver a secreted transgene product, US gene transfer of a plasmid expressing tissue factor pathway inhibitor (TFPI) to skeletal muscle resulted in a dose-related increase in plasma activity for up to 5 days after delivery. CONCLUSION US-enhanced plasmid gene transfer is capable of transducing skeletal muscle in vivo either directly or via an intravascular route. This enhanced nonviral method is an alternative to plasmid DNA alone or viral vectors.

Detection of tissue harmonic motion induced by ultrasonic radiation force using pulse-echo ultrasound and kalman filter

A method using pulse echo ultrasound and the Kalman filter is developed for detecting submicron harmonic motion induced by ultrasonic radiation force. The method estimates the amplitude and phase of the motion at desired locations within a tissue region with high sensitivity. The harmonic motion generated by the ultrasound radiation force is expressed as extremely small oscillatory Doppler frequency shifts in the fast time (A-line) of ultrasound echoes, which are difficult to estimate. In slow time (repetitive ultrasound echoes) of the echoes, the motion also is presented as oscillatory phase shifts, from which the amplitude and phase of the harmonic motion can be estimated with the least mean squared error by Kalman filter. This technique can be used to estimate the traveling speed of a harmonic shear wave by tracking its phase changes during propagation. The shear wave propagation speed can be used to solve for the elasticity and viscosity of tissue as reported in our earlier study. Validation and in vitro experiments indicate that the method provides excellent estimations for very small (submicron) harmonic vibrations and has potential for noninvasive and quantitative stiffness measurements of tissues such as artery

Acoustic shear-wave imaging using echo ultrasound compared to magnetic resonance elastography

We compare a previously developed phase contrast-based magnetic resonance imaging technique (MRE) to a phase-based ultrasound (US) method for measuring small cyclic displacements (submicrometer level) caused by propagating acoustic shear waves in tissue-like media. Our preliminary experiments with gelatin phantoms show that acoustic shear-wave propagation can be measured with US, and we speculate that this technique could find applications in medical imaging.

BIAS OBSERVED IN TIME-OF-FLIGHT SHEAR WAVE SPEED MEASUREMENTS USING RADIATION FORCE OF A FOCUSED ULTRASOUND BEAM

Measurement of shear wave propagation speed has important clinical applications because it is related to tissue stiffness and health state. Shear waves can be generated in tissues by the radiation force of a focused ultrasound beam (push beam). Shear wave speed can be measured by tracking its propagation laterally from the push beam focus using the time-of-flight principle. This study shows that shear wave speed measurements with such methods can be transducer, depth and lateral tracking range dependent. Three homogeneous phantoms with different stiffness were studied using curvilinear and linear array transducer. Shear wave speed measurements were made at different depths, using different aperture sizes for push and at different lateral distance ranges from the push beam. The curvilinear transducer shows a relatively large measurement bias that is depth dependent. The possible causes of the bias and options for correction are discussed. These bias errors must be taken into account to provide accurate and precise time-of-flight shear wave speed measurements for clinical use.

Improved Shear Wave Motion Detection Using Pulse-Inversion Harmonic Imaging With a Phased Array Transducer

Ultrasound tissue harmonic imaging is widely used to improve ultrasound B-mode imaging quality thanks to its effectiveness in suppressing imaging artifacts associated with ultrasound reverberation, phase aberration, and clutter noise. In ultrasound shear wave elastography (SWE), because the shear wave motion signal is extracted from the ultrasound signal, these noise sources can significantly deteriorate the shear wave motion tracking process and consequently result in noisy and biased shear wave motion detection. This situation is exacerbated in in vivo SWE applications such as heart, liver, and kidney. This paper, therefore, investigated the possibility of implementing harmonic imaging, specifically pulse-inversion harmonic imaging, in shear wave tracking, with the hypothesis that harmonic imaging can improve shear wave motion detection based on the same principles that apply to general harmonic B-mode imaging. We first designed an experiment with a gelatin phantom covered by an excised piece of pork belly and show that harmonic imaging can significantly improve shear wave motion detection by producing less underestimated shear wave motion and more consistent shear wave speed measurements than fundamental imaging. Then, a transthoracic heart experiment on a freshly sacrificed pig showed that harmonic imaging could robustly track the shear wave motion and give consistent shear wave speed measurements of the left ventricular myocardium while fundamental imaging could not. Finally, an in vivo transthoracic study of seven healthy volunteers showed that the proposed harmonic imaging tracking sequence could provide consistent estimates of the left ventricular myocardium stiffness in end-diastole with a general success rate of 80% and a success rate of 93.3% when excluding the subject with Body Mass Index higher than 25. These promising results indicate that pulse-inversion harmonic imaging can significantly improve shear wave motion tracking and thus potentially facilitate more robust assessment of tissue elasticity by SWE.

In vitro and in vivo real-time imaging with ultrasonic limited diffraction beams

Recently, there has been great interest in a new class of solutions to the isotropic/homogeneous scaler wave equation which represents localized waves or limited diffraction beams in electromagnetics, optics, and acoustics. Applications of these solutions to ultrasonic medical imaging, tissue characterization, and nondestructive evaluation of materials have also been reported. The authors report a real-time medical imager which uses limited diffraction Bessel beams, X-waves, Axicons, or conventional beams. Results (in vitro and in vivo) show that the images obtained with limited diffraction beams have higher resolution and good contrast over larger depth of field compared to images obtained with conventional focused beams. These results suggest the potential clinical usefulness of limited diffraction beams.

Implementation of vibro-acoustography on a clinical ultrasound system

Vibro-acoustography (VA) is an ultrasound-based imaging modality that uses two ultrasound beams of slightly different frequencies to produce images based on the acoustic response due to harmonic ultrasound radiation force excitation at the difference frequency between the two ultrasound frequencies. VA has demonstrated feasibility and usefulness in imaging of breast and prostate tissue. However, previous studies have been performed either in controlled water tank settings or using a prototype breast scanner equipped with a water tank. In order to make VA more accessible and relevant to clinical use, we report here on the implementation of VA on a General Electric Vivid 7 ultrasound scanner. In this paper, we will describe software and hardware modifications that were performed to make VA functional on this system. We will discuss aperture definition for the two ultrasound beams and beamforming using a linear array transducer. Experimental results from beam measurements and phantom imaging studies will be shown. The implementation of VA provides a step towards clinical translation of this imaging modality for applications in various organs including breast and prostate.

In Vivo Vibroacoustography of Large Peripheral Arteries

Objective:Vibroacoustography allows imaging of objects on the basis of their acoustic signal emitted during low-frequency (kHz) vibrations produced by 2 intersecting ultrasound beams at slightly different frequencies. This study tested the feasibility of using vibroacoustography to distinguish between normal and calcified femoral arteries in a pig model. Materials and Methods:Thirteen normal porcine femoral arteries, 7 with experimentally induced arterial calcifications, and 1 control artery injected with saline only were scanned in vivo. Images were obtained at 45 kHz using a 3 MHz confocal transducer. The acoustic emission signal was detected with a hydrophone placed on the animals limb. Images were reconstructed on the basis of the amplitude of the acoustic emission signal. Vessel patency, vessel dimensions, and the extent of calcified plaques were confirmed in vivo by angiography and conventional ultrasound. Excised arteries were reexamined with vibroacoustography, X-ray radiography, and histology. Results:In vivo, vibroacoustography produced high-resolution, speckle-free images with a high level of anatomic detail. Measurements of femoral artery diameter were similar by vibroacoustography and conventional ultrasound (mean difference ± SD, 0.1 ± 0.4 mm). Calcified plaque area measured by different methods was comparable (vibroacoustography, in vivo: 1.0 ± 0.9 cm2; vibroacoustography in vitro: 1.1 ± 0.6 cm2; X-ray radiography: 0.9 ± 0.6 cm2). The reproducibility of measurements was high. Sensitivity and specificity for detecting calcifications were 100% and 86%, respectively, and positive and negative predictive values were 77% and 100%, respectively. Conclusions:Vibroacoustography provides accurate and reproducible measurements of femoral arteries and vascular calcifications in living animals.

Quantitative assessment of scleroderma by surface wave technique

Scleroderma is a multisystem disease characterized by cutaneous and visceral fibrosis. Skin disease is both a disabling feature of scleroderma and a predictor of visceral involvement. The established method of skin assessment is the modified Rodnan skin score (MRSS) which uses semi-quantitative manual skin scoring. However, the Rodnan method is subjective. We have developed a technique and system for assessing skin health by producing and analyzing surface waves in the skin to determine the skin viscoelastic properties. Viscoelasticity of human skin is measured on 30 healthy volunteers and 10 scleroderma patients at six anatomic sites. A small force, monitored by a force transducer, is applied to the skin using a ball-tipped device attached to a mechanical shaker. The skin motion is measured by a scanning laser vibrometer. The surface wave speed is measured by the phase gradient method. The viscoelasticity is inversely estimated by the wave speed dispersion. A typical measurement of the surface wave speed is 3.25±0.19 m/s on the forearm of a volunteer at 200 Hz. With the wave speed dispersion from 100 Hz to 400 Hz, the shear elasticity μ(1) and shear viscosity μ(2) are estimated, respectively, 7.86±1.86 kPa and 5.03±0.60 Pa on the forearm. Statistical analyses suggest that there are significant differences of viscoelasticity between scleroderma patients and healthy subjects. Scleroderma can be effectively and quantitatively evaluated based on human skin viscoelasticity.