Application Of Radiation Force Research Articles

Fun with levitators

The acoustic radiation force is enjoying something of a comeback on the celebrity circuit these days. Current applications are seen, for example, in elasticity imaging in biomedical ultrasound, and separation technologies in the biomedical and petroleum arenas. But of course the application of radiation force to acoustic levitation has a long history, and in this talk, we will explore levitation to illustrate the principles of radiation force in standing waves with sample inclusions. With a little luck, both large bubbles in water and liquid drops in air will be demonstrated.

GPU-based real-time small displacement estimation with ultrasound

General purpose computing on graphics processing units (GPUs) has been previously shown to speed up computationally intensive data processing and image reconstruction algorithms for computed tomography (CT), magnetic resonance (MR), and ultrasound images. Although some algorithms in ultrasound have been converted to GPU processing, many investigative ultrasound research systems still use serial processing on a single CPU. One such ultrasound modality is acoustic radiation force impulse (ARFI) imaging, which investigates the mechanical properties of soft tissue. Traditionally, the raw data are processed offline to estimate the displacement of the tissue after the application of radiation force. It is highly advantageous to process the data in real-time to assess their quality and make modifications during a study. In this paper, we present algorithms for efficient GPU parallel processing of two widely used tools in ultrasound: cubic spline interpolation and Loupas' two-dimensional autocorrelator for displacement estimation. It is shown that a commercially available graphics card can be used for these computations, achieving speed increases up to 40x compared with single CPU processing. Thus, we conclude that the GPU-based data processing approach facilitates real-time (i.e., <1 second) display of ARFI data and is a promising approach for ultrasonic research systems.

Dual Frequency Method for Simultaneous Translation and Real-Time Imaging of Ultrasound Contrast Agents Within Large Blood Vessels

A dual frequency excitation method for simultaneous translation and selective real-time imaging of microbubbles is presented. The method can distinguish signals originating from free flowing and static microbubbles. This method is implemented on a programmable scanner with a broadband linear array. The programmable interface allows for dynamic variations in the acoustic parameters and aperture attributes, enabling application of this method to large blood vessels located at varying depths. The performance of the method was evaluated in vitro (vessel diameter 2mm) by quantifying the sensitivity of the method to various acoustic, microbubble, and fluid flow parameters. It was observed that the static microbubble response maximized at the approximate resonance frequency of the microbubble population (estimated from a coulter counter measurement), thus, signifying the need for dual frequency excitation. The static microbubble signal declined from 25 to 12 dB with increasing centerline flow velocities (2.65–15.9cm/s); indicating the applicable range of flow velocities. The maximum intensity of the static microbubbles signal scaled with variations in the microbubble concentration. The rate of increment of static microbubble signal was independent of microbubble concentration. It was deduced that the rate of increment of the static microbubble signal is primarily a function of the pulse frequency, whereas the maximum static microbubble signal intensity is dependent on three parameters: (a) the pulse frequency, (b) the flow velocity and (c) the microbubble concentration. The proposed dual frequency sequence may enable the application of radiation force for optimizing the effect of targeted imaging and modulating drug delivery in large blood vessels with high flow velocities. (E-mail: avp2b@virginia.edu)

Biomedical applications of radiation force generated in standing ultrasonic waves

This talk presents an overview of physical basis for the action of acoustic radiation force on particles in standing waves in relation to biomedical applications. The effect itself is known since the 19th century (Kundt, 1974) and its biomedical significance was demonstrated in 1971 by Dyson et al. However, despite a long history, extensive studies of particle behavior in standing ultrasonic waves have started only during the last decade due to numerous emerging biomedical applications. The range of currently explored applications is broad: targeted drug and gene delivery, increasing sensitivity of biosensors and immunochemical tests, manipulating cells in suspensions, microstirring, and others. The presentation will focus on theoretical analysis and applications of radiation force acting on particles and bubbles in the standing ultrasonic fields. Dynamics of particle motion induced by ultrasonic radiation force as a function of frequency, intensity, and other variables will be considered. The principal difference in interaction of ultrasonic standing wave field with solid particles and with bubbles due to resonant properties and high compressibility of the latter will be quantitatively analyzed. Several specific biomedical applications of the analyzed phenomena will be discussed.

Impulsive acoustic radiation force: imaging approaches and clinical applications

Focused acoustic radiation force can be used to locally mechanically excite tissue, and the tissue response can be monitored with conventional ultrasonic displacement estimation methods. Many groups are currently exploring the potential for radiation force based methods to derive information about tissue stiffness associated with different pathologies. These techniques can be implemented on a modified diagnostic ultrasound scanner, using the same transducer for both generating the radiation force excitation and monitoring the tissue response. Multiple locations within an imaging field of view can be interrogated sequentially, by electronically controlling the push and track apertures and beam locations. A variety of data processing and imaging approaches are under investigation. Images are generated of the tissue displacement magnitude within the region of excitation at a given time after radiation force application. These images portray relative differences in tissue stiffness, and provide interesting structural information that is well correlated with, and often exhibits improved contrast over, matched B‐mode images. Methods for quantifying tissue stiffness through monitoring shear wave propagation, as originally proposed by Sarvazyan, are also under investigation. Results from ongoing clinical studies using these methods in a variety of organs (e.g., liver, prostate, breast, and heart) will be presented.

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.

A new targeted drug delivery method using ultrasound and acoustically active lipospheres

The goal is to create a strategy for localized drug delivery using engineered delivery vehicles and ultrasound energy. These drug delivery vehicles, referred to as acoustically active lipospheres (AALs), consist of small gas bubbles surrounded by thick oil shells (where drugs can be carried) and are enclosed by an outermost lipid layer. Ultrasound radiation force can be used to displace these vehicles near the blood vessel wall, after which a higher intensity pulse can fragment the vehicle and transfer its contents to the endothelium. Blood velocity ranges from 1 to 10 mm/s in the microvasculature. Therefore, agents in capillaries insonified by a transducer with a 1 mm focal beam width for 0.1 to 1 seconds can be displaced of 1 to 2 mm. Delivery vehicles containing various fluorescent dyes within the oil layer are exposed to ultrasound in cell chambers or flowing vessels. Fluorescence intensity increases more than 10-fold with application of radiation force and fragmentation, both over no exposure and over fragmentation pulses alone (both P&amp;lt;0.001). This implies radiation force is necessary to bring AALs into proximity of the cell monolayer before their destruction in order for drug delivery to occur.

Acoustic radiation force impulse imaging of the mechanical properties of arteries: In vivo and ex vivo results

We present results of a pilot study of ex vivo and in vivo acoustic radiation force impulse (ARFI) imaging demonstrating measurements of the mechanical properties of the carotid and popliteal arteries. The results were obtained on a modified commercial scanner, providing coregistered B-mode and color Doppler images. 2D and 1D through time images are formed from the measurements of tissues’ response to very brief and localized applications of radiation force. The images show good correlation with B-mode and, in ex vivo studies, pathology-based characterizations of vessel geometry and plaque stiffness. In vivo measurements of arterial response during both systole and diastole are presented. We address implementation issues and discuss potential applications of this new vascular imaging method. (E-mail: gregg.trahey@duke.edu

On the thermal effects associated with radiation force imaging of soft tissue

Several laboratories are investigating the use of acoustic radiation force to image the mechanical properties of tissue. Acoustic Radiation Force Impulse (ARFI) imaging is one approach that rises brief, high-intensity, focused ultrasound pulses to generate radiation force in tissue. This radiation force generates tissue displacements that are tracked using conventional correlation-based ultrasound methods. The tissue response provides a mechanism to discern mechanical properties of the tissue. The acoustic energy that is absorbed by tissue generates radiation force and tissue heating. A finite element methods model of acoustic heating has been developed that models the thermal response of different tissues during short duration radiation force application. The beam sequences and focal configurations used during ARFI imaging are modeled herein; the results of these thermal models can be extended to the heating due to absorption associated with other radiation force-based imaging modalities. ARFI-induced thermal diffusivity patterns are functions of the transducer f-number, the tissue absorption, and the temporal and spatial spacing of adjacent ARFI interrogations. Cooling time constants are on the order of several seconds. Tissue displacement due to thermal expansion is negligible for ARFI imaging. Changes in sound speed due to temperature changes call be appreciable. These thermal models demonstrate that ARFI imaging of soft tissue is safe, although thermal response must be monitored when ARFI beam sequences are being developed.

On the thermal effects associated with radiation force imaging of soft tissue

Several laboratories are investigating the use of acoustic radiation force to image the mechanical properties of tissue. Acoustic Radiation Force Impulse (ARFI) imaging is one approach that uses brief, high-intensity, focused ultrasound pulses to generate radiation force in tissue. This radiation force generates tissue displacements that are tracked using conventional correlation-based ultrasound methods. The tissue response provides a mechanism to discern mechanical properties of the tissue. The acoustic energy that is absorbed by tissue generates radiation force and tissue heating. A finite element methods model of acoustic heating has been developed that models the thermal response of different tissues during short duration radiation force application. The beam sequences and focal configurations used during ARFI imaging are modeled herein; the results of these thermal models can be extended to the heating due to absorption associated with other radiation force-based imaging modalities. ARFI-induced thermal diffusivity patterns are functions of the transducer f-number, the tissue absorption, and the temporal and spatial spacing of adjacent ARFI interrogations. Cooling time constants are on the order of several seconds. Tissue displacement due to thermal expansion is negligible for ARFI imaging. Changes in sound speed due to temperature changes can be appreciable. These thermal models demonstrate that ARFI imaging of soft tissue is safe, although thermal response must be monitored when ARFI beam sequences are being developed.

Estimating localized oscillatory tissue motion for assessment of the underlying mechanical modulus

The technique of harmonic motion imaging (HMI) uses the localized stimulus of the oscillatory ultrasonic radiation force as produced by two overlapping beams of distinct frequencies, and estimates the resulting harmonic displacement in the tissue in order to assess its underlying mechanical properties. In this paper, we studied the relationship between measured displacement and stiffness in gels and tissues in vitro. Two focused ultrasound transducers with a 100 mm focal length were used at frequencies of 3.7500 MHz and either 3.7502 (or 3.7508 MHz), respectively, in order to produce an oscillatory motion at 200 Hz in the gel or tissue. A 1.1 MHz diagnostic transducer (Imasonics, Inc.) was also focused at 100 mm and acquired 5 ms RF signals (pulse repetition frequency (PRF)=3.5 kHz) at 100 MHz sampling frequency during radiation force application. First, three 50 × 50 mm 2 acrylamide gels were prepared at concentrations of 4%, 8% and 16%. The resulting displacement was estimated using crosscorrelation techniques between successively acquired RF signals with a 2 mm window and 80% window overlap at 1260 W/cm 2. A normal 1-D indentation instrument (TeMPeST) applied oscillatory loads at 0.1–200 Hz with a 5 mm-diameter flat indenter. Then, 12 displacement measurements in 6 porcine muscle specimens (two measurements/case, as above) were made in vitro, before and after ablation which was performed for 10 s at 1260 W/cm 2. In all gel cases, the harmonic displacement was found to linearly increase with intensity and exponentially decrease with gel concentration. The TeMPeST measurements showed that the elastic moduli for the 4%, 8% and 16% gels equaled 3.93 ± 0.06, 17.1 ± 0.2 and 75 ± 2 kPa, respectively, demonstrating that the HMI displacement estimate depends directly on the gel stiffness. Finally, in the tissues samples, the mean displacement amplitude showed a twofold decrease between non-ablated and ablated tissue, demonstrating a correspondence between the HMI response and an increase in stiffness measured with the TeMPeST instrument.