Application Of Acoustic Radiation Force Research Articles

Applications of acoustic radiation force for material characterization and imaging

Acoustic radiation force has been used in many interesting medical and industrial applications in the past two decades. The fact that radiation stress can be confined to a small focal area and exerted remotely inside or on an object allows one to use this phenomenon in a variety of ways to explore properties of the object. Vibro-acoustography is a material characterization and imaging method that uses harmonic or impulsive acoustic radiation force to stimulate the targeted material and receives the resulting acoustic response. The output acoustic signal is then used to extract important information about the object. Biomedical applications of vibro-acoustography and its closely related methods include imaging, flow detection, and tissue characterization. Other applications include non-destructive evaluation/testing of materials, modal analysis of small structures, and microscopy. This talk presents an overview of vibro-acoustography and its closely related techniques over the past 20 years. Various biomedical and industrial applications will be presented. The talk will conclude with a discussion on potential future applications of this technology.

臨床診断における音響放射力の応用(<小特集>非線形音響技術の最先端～医療から航空宇宙まで～)

臨床診断における音響放射力の応用(<小特集>非線形音響技術の最先端～医療から航空宇宙まで～)

Acoustic radiation force in biomedical applications: origin, past, present, and future

In this talk, an overview of history and physical basis of biomedical applications of acoustic radiation force with a further look into new developments in this field will be presented. In 1902, Lord Rayleigh published his classical work on the theory of sound, introducing the concept of acoustic radiation pressure. Experimental demonstration of radiation force acting on particles in the standing wave field was made by August Kundt (1874). Much later, Wood and Loomis built radiation force balance (1927). Detailed analysis of ultrasound radiation force related to biomedical applications was made in numerous reviews and original articles of Wes Nyborg in the 1960s and 1970s. In spite of over century-old history, most of the significant biomedical applications of acoustic radiation force became known and were extensively studied only during last couple of decades. We will present and discuss recent progress in numerous applications such as the elasticity imaging, assessing viscoelastic properties of biological tissue, monitoring lesions during therapy, the manipulation of cells in suspension, acoustical tweezers, targeted drug and gene delivery. In addition to well established applications, the acoustic radiation force has considerable potential in numerous new areas, which will be discussed in the talk. [NIH R21AR065024.]

Applications of acoustic radiation force for microvascular tissue engineering

We have developed a non-invasive ultrasound-based method to spatially pattern cells within three-dimensional (3D) hydrogels, and have demonstrated translation of this technology to microvascular tissue engineering. Acoustic radiation forces associated with an ultrasound standing wave field (USWF) can rapidly organize a variety of cell types into distinct spatial patterns within 3D hydrogels. USWF-induced patterning of endothelial cells into distinct multicellular planar bands can lead to the rapid formation of complex microvessel networks throughout the volume of the collagen hydrogel. Recent efforts have focused on optimizing acoustic exposure parameters to control resultant 3D microvessel morphology, producing multilayered composite constructs with complex, physiologically relevant vascular morphologies, and developing dual ultrasound transducer systems to noninvasively direct cell patterning within injectable collagen hydrogels in situ. Engineering microvessel networks that structurally and functionally mimic native microvasculature is critical for the fabrication and survival of a broad range of bioengineered tissues, and for the fabrication of small, vascularized tissue constructs for use as realistic cost-effective in vitro models for drug discovery and testing.

Applications of acoustic radiation force for quantitative elasticity evaluation of bladder, thyroid, and breast

Acoustic radiation force (ARF) provides a simple and yet non-invasive mechanism to induce a localized stress inside human body. The response to this excitation is used to estimate the mechanical properties of the targeted tissue in vivo. This talk covers an overview of three studies that use ARF for estimation of elastic properties of thyroid, breast, and the bladder in patients. The studies on thyroid and breast were aimed at differentiating between malignant and benign nodules. The study on the bladder was aimed at indirect evaluation of bladder compliance; hence, only a global measurement was needed. The study on breast showed that 16 out of 18 benign masses and 21 out of 25 malignant masses were correctly identified. The study on 9 thyroid patients with 7 benign and 2 malignant nodules showed all malignant nodules were correctly classified and only 2 of the 7 benign nodules were misclassified. The bladder compliance study revealed a high correlation between our method and independent clinical measurement of compliance (R-squared of 0.8–0.9). Further investigations on larger groups of patients are needed to fully evaluate the performances of the methods.

Contactless and non-invasive delivery of micro-particles lying on a non-customized rigid surface by using acoustic radiation force

In the existing acoustic micro-particle delivery methods, the micro-particles always lie and slide on the surface of platform in the whole delivery process. To avoid the damage and contamination of micro-particles caused by the sliding motion, this paper deals with a novel approach to trap micro-particles from non-customized rigid surfaces and freely manipulate them. The delivery process contains three procedures: detaching, transporting, and landing. Hence, the micro-particles no longer lie on the surface, but are levitated in the fluid, during the long range transporting procedure. It is very meaningful especially for the fragile and easily contaminated targets. To quantitatively analyze the delivery process, a theoretical model to calculate the acoustic radiation force exerting upon a micro-particle near the boundary in half space is built. An experimental device is also developed to validate the delivery method. A 100μm diameter micro-silica bead adopted as the delivery target is detached from the upper surface of an aluminum platform and levitated in the fluid. Then, it is transported along the designated path with high precision in horizontal plane. The maximum deviation is only about 3.3μm. During the horizontal transportation, the levitation of the micro-silica bead is stable, the maximum fluctuation is less than 1μm. The proposed method may extend the application of acoustic radiation force and provide a promising tool for microstructure or cell manipulation.

Intravascular ultrasound catheter to enhance microbubble-based drug delivery via acoustic radiation force

Previous research has demonstrated that acoustic radiation force enhances intravascular microbubble adhesion to blood vessels in the presence of flow for moleculartargeted ultrasound imaging and drug delivery. A prototype acoustic radiation force intravascular ultrasound (ARFIVUS) catheter was designed and fabricated to displace a microbubble contrast agent in flow representative of conditions encountered in the human carotid artery. The prototype ARFIVUS transducer was designed to match the resonance frequency of 1.4- to 2.6-μm-diameter microbubbles modeled by an experimentally verified 1-D microbubble acoustic radiation force translation model. The transducer element was an elongated Navy Type I (hard) lead zirconate titanate (PZT) ceramic designed to operate at 3 MHz. Fabricated devices operated with center frequencies of 3.3 and 3.6 MHz with -6-dB fractional bandwidths of 55% and 50%, respectively. Microbubble translation velocities as high as 0.86 m/s were measured using a high-speed streak camera when insonating with the ARFIVUS transducer. Finally, the prototype was used to displace microbubbles in a flow phantom while imaging with a commercial 45-MHz imaging IVUS transducer. A sustained increase of 31 dB in average video intensity was measured following insonation with the ARFIVUS, indicating microbubble accumulation resulting from the application of acoustic radiation force.

초음파 의료 영상에서 비집속 송신을 이용한 고속 음향 복사력 임펄스 영상법

In medical ultrasound imaging, elasticity imaging helps to diagnose tumors such as cancer. This paper is concerned with the application of acoustic radiation force to soft tissue of interest to implement elasticity imaging. In order to reduce the data acquisition time, instead of relying on transmit focusing, a plane wave of burst type is transmitted to apply the acoustic radiation force simultaneously to an entire imaging region to be observed. A homogeneous phantom experiment confirms that increasing the transmit excitation duration instead of employing transmit focusing generates a high enough acoustic radiation force to obtain elasticity images. It is found, however, that a different displacement versus time characteristic is observed unlike the case of using a conventional focused acoustic radiation force. Experimental results obtained through the use of an ultrasound phantom and a bovine liver show that lesions can be correctly differentiated.

An In Vivo Validation of the Application of Acoustic Radiation Force to Enhance the Diagnostic Utility of Molecular Imaging Using 3-D Ultrasound

For more than a decade, the application of acoustic radiation force (ARF) has been proposed as a mechanism to increase ultrasonic molecular imaging (MI) sensitivity in vivo. Presented herein is the first noninvasive in vivo validation of ARF-enhanced MI with an unmodified clinical system. First, an in vitro optical-acoustical setup was used to optimize system parameters and ensure sufficient microbubble translation when exposed to ARF. 3-D ARF-enhanced MI was then performed on 7 rat fibrosarcoma tumors using microbubbles targeted to αvβ3 and nontargeted microbubbles. Low-amplitude (<25 kPa) 3-D ARF pulse sequences were tested and compared with passive targeting studies in the same animal. Our results demonstrate that a 78% increase in image intensity from targeted microbubbles can be achieved when using ARF relative to the passive targeting studies. Furthermore, ARF did not significantly increase image contrast when applied to nontargeted agents, suggesting that ARF did not increase nonspecific adhesion.

An In Vivo Validation of the Application of Acoustic Radiation Force to Enhance the Diagnostic Utility of Molecular Imaging Using 3-D Ultrasound

An In Vivo Validation of the Application of Acoustic Radiation Force to Enhance the Diagnostic Utility of Molecular Imaging Using 3-D Ultrasound

The development and potential of acoustic radiation force impulse (ARFI) imaging for carotid artery plaque characterization

Stroke is the third leading cause of death and long-term disability in the USA. Currently, surgical intervention decisions in asymptomatic patients are based upon the degree of carotid artery stenosis. While there is a clear benefit of endarterectomy for patients with severe (> 70%) stenosis, in those with high/moderate (50-69%) stenosis the evidence is less clear. Evidence suggests ischemic stroke is associated less with calcified and fibrous plaques than with those containing softer tissue, especially when accompanied by a thin fibrous cap. A reliable mechanism for the identification of individuals with atherosclerotic plaques which confer the highest risk for stroke is fundamental to the selection of patients for vascular interventions. Acoustic radiation force impulse (ARFI) imaging is a new ultrasonic-based imaging method that characterizes the mechanical properties of tissue by measuring displacement resulting from the application of acoustic radiation force. These displacements provide information about the local stiffness of tissue and can differentiate between soft and hard areas. Because arterial walls, soft tissue, atheromas, and calcifications have a wide range in their stiffness properties, they represent excellent candidates for ARFI imaging. We present information from early phantom experiments and excised human limb studies to in vivo carotid artery scans and provide evidence for the ability of ARFI to provide high-quality images which highlight mechanical differences in tissue stiffness not readily apparent in matched B-mode images. This allows ARFI to identify soft from hard plaques and differentiate characteristics associated with plaque vulnerability or stability.

Visualization of a focused ultrasound beam to guide radiation force‐induced clearance of kidney stones.

The incidence of kidney stones within the US population is now 10%, and rising. Many patients present with small stones, primary or recurrent, do not indicate interventional stone removal. We previously described a new stone removal method employing selective application of acoustic radiation force, at diagnostic output levels, to reposition stones for passive clearance. In this method, an imaging array transducer transmits pulses for image guidance and focused pulses to reposition the stone. Here we propose a new flash imaging modality to visualize the focused pulse to confirm targeting on the stone. To visualize the focused beam, short pulses were phase‐delayed across the transducer aperture to transmit a focused wave, from which echo data were collected, beamformed, and overlaid on a B‐mode image. The beam profile is visible because echo amplitude is higher within the convergent, focal, and divergent regions. During experiment, a stone was placed within a tissue phantom simulating the kidney lower pole and ureter. Once identified with B‐mode imaging, focal delays were calculated, targeting was confirmed by the beam visualization modality, and the stone was repositioned. Flash imaging visualization of the focused beam could be similarly applied to high‐intensity focused ultrasound therapy. [Work supported by NIH DK43881 NSBRI‐SMST01601.]

Biomedical applications of acoustic radiation force based on somatosensory reception

We have previously shown that short pulses of focused ultrasound may be used to stimulate locally receptor neural structures and thereby induce sensations that humans can perceive through the skin (for example tactile, warmth and cold, tickling, pain, etc.). Furthermore, ultrasound modulated by sound signals (tone, speech, music, etc.) can induce sound sensations corresponding to the nature of the modulation in persons with normal hearing. The mechanism underlying these effects that have been used in clinical diagnostic practice is related to the radiation force. We also showed recently that the phenomenon of the radiation force could be used in perspective robotic systems, sensors, and automated control systems, based on the use of tactile sensations in the human‐machine interface, as well as in devices that may allow blind and visually impaired persons to perceive textual information presented on a tactile display. The research was supported by INTAS (05‐1000008‐7841) and RFBR (06‐02‐16079).

Physical and historical bases of biomedical applications of radiation force

Radiation force is a universal phenomenon in any wave motion, electromagnetic or acoustic. Radiation force is produced by a change in the density of energy of the propagating wave. The concept of radiation pressure follows from Maxwell’s equations (1871), while the idea of electromagnetic wave (light) pressure can be traced back to Johannes Kepler (1619). Acoustic radiation force was first experimentally demonstrated by August Kundt (1874) and its physical bases were analyzed in classical works of Lord Rayleigh (1902), L. Brillouin, and P. Langevin. Until recently, main biomedical application of acoustic radiation force was in measuring acoustic power of therapeutic devices, but during the last 15 years it became one of the hottest areas of biomedical ultrasonics with numerous new applications ranging from acoustical tweezers, targeted drug and gene delivery, manipulating of cells in suspension, increasing the sensitivity of biosensors and immunochemical tests, assessing viscoelastic properties of fluids and biological tissue, and monitoring lesions during therapy. The widest new area of applications of radiation force is related to medical imaging in general and elasticity imaging specifically. Remote excitation of shear stress in a given site in the body using radiation force of focused ultrasound offers numerous new possibilities for medical diagnostics.

The application of acoustic radiation force for molecular imaging and drug delivery

Acoustic radiation force is exerted on objects in an acoustic field. By optimizing acoustic parameters to maximize this force, ultrasound contrast agents can be manipulated and concentrated with an acoustic field. This technique can be used to enhance molecular imaging and drug delivery. Ultrasonic molecular imaging employs contrast agents such as microbubbles, nanoparticles, or liposomes coated with ligands specific for receptors expressed on cells at sites of angiogenesis, inflammation, or thrombus. Concentration of these highly echogenic contrast agents at a target site enhances the ultrasound signal received from that site, promoting ultrasonic detection and analysis of disease states. It is demonstrated that acoustic radiation force can be used to displace targeted contrast agents to a vessel wall, greatly increasing the number of agents binding to available surface receptors. Radiation force can also be used for microparticle-carrier based drug delivery. Acoustically active drug-carrier vehicles can be concentrated with radiation force, and then disrupted with high-intensity ultrasound bursts, resulting in local delivery of the therapeutic agent. This talk will discuss simulations and experimental results demonstrating these applications.

Acoustic radiation force and acoustical tweezers used in biomedical research

General analytical expressions for the acoustic radiation forces generated by focused and unfocused ultrasonic beams on a small compressible sphere [J. Wu and G. Du, J. Acoust. Soc. Am. 87, 997 (1990)] and a rigid cylinder [Wu etal., J. Acoust. Soc. Am. 87, 581 (1990)] are derived. A new tool for biomedical research, acoustic tweezers, is developed [J. Wu, J. Acoust. Soc. Am. 89, 2140 (1991)]. Several applications of acoustic radiation force at megahertz frequencies such as determination of the tensile strength of a single actin protein filament are discussed. [Work supported by NIH.]