Enhanced heat deposition using ultrasound contrast agent--modeling and experimental observations

Ultrasound contrast agents (UCA), created originally for visualization and diagnostic purposes, recently have been suggested as efficient enhancers of ultrasonic power deposition in tissue. The ultrasonic energy absorption by the contrast agents, considered as problematic in diagnostic imaging, might have beneficial impact in therapeutic applications such as targeted hyperthermia-based or ablation treatments. Introduction of gas microbubbles into the tissue to be treated can improve the effectiveness of current treatments by limiting the temperature rise to the treated site and minimizing the damage to the surrounding healthy tissues. To this end, proper assessment of the governing parameters of energy absorption by ultrasonically induced stabilized bubbles is important for both diagnostic and therapeutic ultrasound applications. The current study was designed to predict theoretically and measure experimentally the dissipation and heating effects of encapsulated UCA in a well-controlled and calibrated environment. The ultrasonic effects of the microbubble concentration, transmitted intensity, and frequency on power dissipation and stability of the UCA have been studied. The maximal temperature elevation obtained during 300 s experiments was 21 degrees C, in a 10 ml volume target containing UCA, insonifled by unfocused 3.2 MHz continuous wave (CW) at spatial average intensity of 1.1 W/cm2 (182 kPa). The results also suggest that higher frequencies are more efficiently absorbed by commonly used UCA. In particular, for spatial average intensity of 1.1 W/cm2 and concentration of 5 x 10(6) microspheres/cm3, no significant reduction of UCA absorption was noticed during the first 150 s for insonation at 3.2 MHz and the first 100 s for insonation at 1 MHz. In addition, when lower average intensity of 0.5 W/cm2 (160 kPa) at 3.2 MHz was used, the UCA absorptivity sustained for almost 200 s. Thus, when properly activated, UCA may be suitable for localized hyperthermic therapies.     

Reduction of cavitation using pseudorandom signals [therapeutic US]

It is known that the scattering of ultrasound by cavitation bubbles reduces the efficiency of treatment by high-intensity focused ultrasound. In the authors' experiments striving to reduce grating lobe levels of annular arrays they observed less microbubble formation at the focus of the transducer when pseudorandom phase-modulated CW signals were used rather than single-frequency CW signals. To confirm this unexpected result, the authors performed an experiment in a solution of luminol which is known to be a cavitation detector. A 5-cm diameter spherical transducer (1.1 MHz center frequency and 0.6 MHz bandwidth), focused at 197 mm was used. The ratio of the sonoluminescence intensity produced by a single-frequency signal to that produced by a pseudorandom phase-modulated signal increased with the intensity of the applied held and attained a value of nearly 50 for an intensity of 4.6 W cm^-2      

Design of focused ultrasound surgery transducers

High-intensity focused ultrasound surgery (FUS) has been developed for the extracorporeal treatment of various benign and malignant soft tissue tumors. The system developed at the Institute of Cancer Research/Royal Marsden (ICR/RM) National Health Service (NHS) Trust incorporates a 150 mm focal length focused bowl transducer operated at 1.7 MHz, and is currently undergoing Phase 1 clinical trials for the treatment of benign prostatic hyperplasia and superficial bladder cancer. However, the application of this transducer is limited by its focal length to a maximum depth of 100 mm, and by power absorption in the skin to a minimum depth of 40 mm. A computer model of acoustic fields, which assumes uniform excitation of the transducer over its entire surface, has previously been published. This has been used both to calculate the intensity in nonattenuating media, and to estimate the absorbed power per unit volume in homogeneous tissues in order to allow determination of the transducer configurations (frequency, focal length, and diameter) necessary for the treatment of both deep (~150 mm) and shallow (~20 mm) soft tissue tumors. These depths encompass the typical range for human tissues which are likely to be treated. Calculations cover the frequency range 0.5-4.5 MHz, focal lengths from 70 to 200 mm, and transducer diameters from 30 to 190 mm. The results show that appropriate transducers can be designed for the noninvasive treatment of tumors in specific organs     

Parametric Studies of Laser Generated Ultrasonic Signals in Ablative Regime: Time and Frequency Domains

A laser pulse incident on a material may generate ultrasound by means of two different phenomena: thermoelastic effect at low power density and ablation effect at high power density. Ablative generation of ultrasound is necessary for some critical applications such as on-line weld quality monitoring in which strong signals are required to compensate the elevated temperature and the long path length. While the waveform in time domain has been discussed extensively in the literature, there is little knowledge about the frequency components of laser ultrasound, although this information is necessary for practical applications. In this paper, analytical results from both thermoelastic and ablative regimes are reviewed. Laser ultrasonic signals (longitudinal waves and surfaces waves) generated by laser ablation are measured in a number of metal samples (2024 A1, 6061 A1, 7075 A1, mild steel, and copper) with a broadband laser interferometer. The frequency spectra are analyzed and compared for different thicknesses (50.8 mm, 25.4 mm, 12.7 mm, and 6.4 mm) and for different power densities. Hanning windowing is applied to the longitudinal pulses in time domain before frequency analysis is performed. The experimental data match the theoretical predictions very well. The results show that the frequency spectrum extends from 0 to 15 MHz, while the center frequency occurs near 2 MHz. The detailed distribution of the spectrum is dependent on the material, thickness, and laser power density.     

High-temperature and broadband immersion ultrasonic probes

Immersion ultrasonic probes for measurements and imaging at high temperature are presented. The probes consist of sol-gel-sprayed thick films as piezoelectric ultrasonic transducers (UTs) directly deposited onto steel buffer rods. They operate in pulse-echo mode at temperatures up to 500/spl deg/C. The operating ultrasonic frequency is between 5 MHz and 20 MHz, controlled by the film thickness. The ultrasonic thickness measurement of a steel plate with the probe fully immersed in molten zinc at 450/spl deg/C was demonstrated using ultrasonic plane waves. For imaging purposes, the probing end of the steel buffer rod was machined into a semispherical concave shape to form an ultrasonic lens and achieve high spatial resolution with focused ultrasound in liquids. Ultrasonic surface and subsurface imaging using a mechanical raster scan of the focused probe in silicone oil at 200/spl deg/C was also carried out. The importance of the signal-to-noise ratio (SNR) in the pulse-echo measurement is discussed.     

Lithium niobate transducers for MRI-guided ultrasonic microsurgery

Focused ultrasound surgery (FUS) is usually based on frequencies below 5 MHz-typically around 1 MHz. Although this allows good penetration into tissue, it limits the minimum lesion dimensions that can be achieved. In this study, we investigate devices to allow FUS at much higher frequencies, in principle, reducing the minimum lesion dimensions. Furthermore, FUS can produce deep-sub-millimeter demarcation between viable and necrosed tissue; high-frequency devices may allow this to be exploited in superficial applications which may include dermatology, ophthalmology, treatment of the vascular system, and treatment of early dysplasia in epithelial tissue. In this paper, we explain the methodology we have used to build high-frequency high-intensity transducers using Y-36°-cut lithium niobate. This material was chosen because its low losses give it the potential to allow very-high-frequency operation at harmonics of the fundamental operating frequency. A range of single-element transducers with center frequencies between 6.6 and 20.0 MHz were built and the transducers' efficiency and acoustic power output were measured. A focused 6.6-MHz transducer was built with multiple elements operating together and tested using an ultrasound phantom and MRI scans. It was shown to increase phantom temperature by 32°C in a localized area of 2.5 x 3.4 mm in the plane of the MRI scan. Ex vivo tests on poultry tissue were also performed and shown to create lesions of similar dimensions. This study, therefore, demonstrates that it is feasible to produce high-frequency transducers capable of high-resolution FUS using lithium niobate.     

Simulation of noninvasive blood pressure estimation using ultrasound contrast agent microbubbles

The microbubble ultrasound contrast agent (UCA) has been widely recognized as a potential noninvasive tool for blood pressure measurement. However, UCA indices such as the shift in the resonance frequency and echo amplitude have problems of low resolution, nonlinear relationship with blood pressure, etc. In this paper, a novel UCA index, the shift in the subharmonic optimal driving frequency (SSODF) of microbubbles, is proposed. The effectiveness of the index for estimating blood pressure was evaluated by performing a microbubble acoustic response simulation. The behavior of commercial UCA microbubbles was investigated as a function of the driving acoustic pressure (in kilopascals) and ambient overpressure (in millimeters of mercury). Simulation results showed that for a 1.6-μm-diameter microbubble, SSODF increased linearly with the overpressure in a range of 0 to 200 mmHg and was maximum (2.07 MHz) at 380 kPa. Changes of the overpressure as small as 5 mmHg can be detected using SSODF. For a population of microbubbles with a Gaussian size distribution (mean diameter: 1.6 μm, standard deviation: 0.2 μm), SSODF was 1.7 MHz at 280 kPa. With further experimental validation, the proposed method may be developed as a novel noninvasive technique for accurate blood pressure measurement.     

High-frequency, nonlinear flow imaging of microbubble contrast agents

It has been shown that nonlinear scattering can be stimulated from microbubble contrast agents at high-transmit frequencies (14-32 MHz). This work was extended to demonstrate the feasibility of nonlinear contrast imaging through modifications of existing ultrasound biomicroscopy linear B-scan imaging instrumentation. In this study, we describe the development and evaluation of prototype coherent flow imaging instrumentation for nonlinear microbubble imaging using transmit frequencies from 10 to 50 MHz. Phantom validation experiments were conducted to demonstrate color and power flow imaging using nonlinear 10 MHz (subharmonic) scattering induced by a 20 MHz transmit frequency. In vivo flow imaging of a rabbit ear microvessel was successfully performed. This work indicates the feasibility of performing flow imaging at high frequencies using nonlinear scattering from microbubbles.     

Two-dimensional ultrasound receive array using an angle-tuned Fabry-Perot polymer film sensor for transducer field characterization and transmission ultrasound imaging

A 2-D optical ultrasound receive array has been investigated. The transduction mechanism is based upon the detection of acoustically induced changes in the optical thickness of a thin polymer film acting as a Fabry-Perot sensing interferometer (FPI). By illuminating the sensor with a large-area laser beam and mechanically scanning a photodiode across the reflected output beam, while using a novel angle-tuned phase bias control system to optimally set the FPI working point, a notional 2-D ultrasound array was synthesized. To demonstrate the concept, 1-D and 2-D ultrasound field distributions produced by planar 3.5-MHz and focused 5-MHz PZT ultrasound transducers were mapped. The system was also evaluated by performing transmission ultrasound imaging of a spatially calibrated target. The "array" aperture, defined by the dimensions of the incident optical field, was elliptical, of dimensions 16 x 12 mm and spatially sampled in steps of 0.1 mm or 0.2 mm. Element sizes, defined by the photodiode aperture, of 0.8, 0.4, and 0.2 mm were variously used for these experiments. Two types of sensor were evaluated. One was a discrete 75-microm-thick polyethylene terephthalate FPI bonded to a polymer backing stub which had a wideband peak noise-equivalent pressure of 6.5 kPa and an acoustic bandwidth 12 MHz. The other was a 40-microm Parylene film FPI which was directly vacuum-deposited onto a glass backing stub and had an NEP of 8 kPa and an acoustic bandwidth of 17.5 MHz. It is considered that this approach offers an alternative to piezoelectric ultrasound arrays for transducer field characterization, transmission medical and industrial ultrasound imaging, biomedical photoacoustic imaging, and ultrasonic nondestructive testing.     

Broadband ultrasound field mapping system using a wavelength tuned, optically scanned focused laser beam to address a Fabry Perot polymer film sensor

An optical system for rapidly mapping broad-band ultrasound fields with high spatial resolution has been developed. The transduction mechanism is based upon the detection of acoustically induced changes in the optical thickness of a thin polymer film acting as a Fabry Perot sensing interferometer (FPI). By using a PC-controlled galvanometer mirror to line-scan a focused laser beam over the surface of the FPI, and a wavelength-tuned phase bias control system to optimally set the FPI working point, a notional 1D ultrasound array was synthesized. This system enabled ultrasound fields to be mapped over an aperture of 40 mm, in 50-microm steps with an optically defined element size of 50 microm and an acquisition time of 50 ms per step. The sensor comprised a 38-microm polymer film FPI which was directly vacuum-deposited onto an impedance-matched polycarbonate backing stub. The -3 dB acoustic bandwidth of the sensor was 300 kHz to 28 MHz and the peak noise-equivalent-pressure was 10 kPa over a 20-MHz measurement bandwidth. To demonstrate the system, the outputs of various planar and focused pulsed ultrasound transducers with operating frequencies in the range 3.5 to 20 MHz were mapped. It is considered that this approach offers a practical and inexpensive alternative to piezoelectric-based arrays and scanning systems for rapid transducer field characterization and biomedical and industrial ultrasonic imaging applications.     

Ultrasonic and Viscoelastic Properties of Small-Volume Mesogen Samples at the Phase Transition

The ultrasonic method is very informative for research of viscoelastic properties of mesogens at changing thermodynamic parameters of state. At phase transitions, anomalies of the velocity of propagation and coefficient of absorption of ultrasound waves as well as of viscoelastic properties are observed. These anomalies for liquid crystals are most pronounced at frequencies lower that 1 MHz. Up to now acoustic resonators with volumes of about 5 cm³ have been used, which considerably prevents the application of this method for science-based newly synthesized mesogenic compounds. This article presents experimental results obtained by means of a new resonator method with samples with volumes of 0.06 cm³ to 0.15 cm³. The velocity and coefficient of absorption of ultrasound were measured at frequencies from 0.68 MHz to 1.63 MHz for four mesogens: esters of alkyloxyphenylcyclo-hexane-2-carbonic acid and n-amylphenol. It has been shown that temperature dependencies of ultrasonic parameters obtained in small-volume cells correspond to those established previously by traditional methods using measuring cells with larger volumes. It is also shown that the temperature dependencies of the bulk viscosity and the bulk elasticity modulus derived from our ultrasonic measurements, in general features, duplicate the corresponding dependencies obtained by standard methods. It confirms that the proposed acoustic method is suitable for routine investigations of viscoelastic properties of small-volume samples of mesogenic compounds.     

Ultrasonic techniques for imaging and measurements in molten aluminum

In order to achieve net shape forming, processing of aluminum (Al) in the molten state is often necessary. However, few sensors and techniques have been reported in the literature due to difficulties associated with molten Al, such as high temperature, corrosiveness, and opaqueness. In this paper, development of ultrasonic techniques for imaging and measurements in molten Al using buffer rods operated at 10 MHz is presented. The probing end of the buffer rod, having a flat surface or an ultrasonic lens, was immersed into molten Al while the other end with an ultrasonic transducer was air-cooled to room temperature. An ultrasonic image of a character "N", engraved on a stainless steel plate immersed in molten Al, and its corrosion have been observed at 780 degrees C using the focused probe in ultrasonic pulse-echo mode. Because cleanliness of molten Al is crucial for part manufacturing and recycling in Al processing, inclusion detection experiments also were carried out using the nonfocused probe in pitch-catch and pulse-echo modes. Backscattered ultrasonic signals from manually added silicon carbide particles, with an average diameter of 50 microm, in molten Al have been successfully observed at 780 degrees C. For optimal image quality, the spatial resolution of the focused probe was crucial, and the high signal-to-noise ratio of the nonfocused probe was the prime factor responsible for the inclusion detection sensitivity using backscattered ultrasonic signals. In addition, it was found that ultrasound could provide an alternative method for evaluating the degree of wetting between a solid material and a molten metal. Our experimental results showed that there was no ultrasonic coupling at the interface between an alumina rod and molten Al up to 1000 degrees C; therefore, no wetting existed at this interface. Also because ultrasonic velocity in alumina is temperature dependent, this rod proved to be able to be used as an in-line temperature monitoring sensor under 1000 degrees C in molten Al.     

Golay pulse encoding for microbubble contrast imaging in ultrasound

We present a technique that uses Golay phase encoding, pulse inversion, and amplitude modulation (GPIAM) for microbubble contrast agent imaging with ultrasound. This technique improves the contrast-to-tissue ratio (CTR) by increasing the time-bandwidth product of the insonating waveforms. A nonlinear pulse compression algorithm is used to compress the signal energy upon receive. A 6.5-dB improvement in CTR was observed using an 8-chip GPIAM sequence compared to a conventional pulse-inversion amplitude-modulation sequence. The CTR improvement comes at the cost of a reduction in frame rate: GPIAM coding uses four input pulses whereas most contrast imaging sequences require two or three pulses. Our results showed that the microbubble response can be phase encoded and subsequently compressed using a nonlinear matched-filtering algorithm, in order to enhance the signal from the contrast agent, while maintaining resolution and suppressing the tissue signal.     

Characterization of cell membrane response to ultrasound activated microbubbles

Contrast agents for ultrasound imaging, composed of tiny gas microbubbles, have become a reality in clinical routine. They are extensively used in radiology for detection and characterization of various tumors and in cardiology for left ventricular opacification. Recent experimental studies showed that ultrasound waves in combination with contrast agent microbubbles increase transiently cell membrane permeability in a process known as sonoporation. This effect is thought to allow foreign molecules to enter the cell. In that context, we explored the cell membrane's responses to microbubbles' oscillations as the mechanism is not completely understood. Breast cancer cell line in combination with contrast microbubbles were used. Ultrasound was applied using a transducer of 1 MHz center frequency transmitting a 10-cycle burst of different acoustic pressures repeated every 100 mus. Patch-clamp technique in whole cell configuration was used to explore transmembrane ion exchange through the variations in membrane potential. To characterize the activated ion channels, the variations of the intracellular calcium (Ca(2+)) concentration were explored using a fluorescent marker. The results revealed that ultrasound stimulation induces a rapid hyperpolarization of cell membrane potential when the microbubble is in direct contact with the cell, but the potential returned to its initial value when ultrasound stimulation stopped. The change in cell membrane potential indicates the activation of specific ion channels and depends on the quality of microbubble adhesion to the cell membrane. Microbubbles were shown to induce a mechanical stretch activating BKca channels. Simultaneous Ca(2+) measurements indicate a slow and progressive Ca(2+) increase that is likely a consequence of BKca channels opening not a cause. These results demonstrate that microbubbles' oscillations under ultrasound activation entail modulation of cellular function and signaling by t- riggering the modulation of ionic transports through the cell membrane. Cells response to the mechanical stretch caused by gentle microbubble oscillations is characterized by the opening of BKca stretch channels and a Ca(2+) flux, which might potentially trigger other cellular responses responsible for membrane sonopermeabilization.     

Nanosized Phase‐Changeable “Sonocyte” for Promoting Ultrasound Assessment

Despite the ability of microbubble contrast agents to improve ultrasound diagnostic performance, their application potential is limited due to low stability, fast clearance, and poor tissue permeation. This study presents a promising nanosized phase‐changeable erythrocyte (Sonocyte), composed of liposomal dodecafluoropentane coated with multilayered red blood cell membranes (RBCm), for improving ultrasound assessments. Sonocyte is the first RBCm‐functionalized ultrasound contrast agent with uniform nanosized morphology, and exhibits good stability, systemic circulation, target‐tissue accumulation, and even ultrasound‐responsive phase transition, thereby satisfying the inherent requirement of ultrasound imaging. It is identified that Sonocyte displays similar sensitivity as microbubble SonoVue, a clinical ultrasound contrast agent, for effectively detecting normal parenchyma and hepatic necrosis. Importantly, compared with SonoVue lacking of ability to detect tumors, Sonocyte can identify tumors with high sensitivity and specificity due to superior tumor accumulation and penetration. Therefore, Sonocyte exhibits superior capabilities over SonoVue, endowing with a great clinical application potential.     

A wireless batteryless deep-seated implantable ultrasonic pulser-receiver powered by magnetic coupling

This study tests a deep-seated implantable ultrasonic pulser-receiver, powered wirelessly by magnetic coupling. A 30-cm energy-transmitting coil was designed to wrap around the body, and was driven by a current of 1.2 A rms at a frequency of 5.7 MHz to generate a magnetic field. A 2-cm receiving coil was positioned at the center of the primary coil for receiving the magnetic energy and powering the implantable device. A capacitor-diode voltage multiplier in the implantable circuit was used to step-up the receiving coil voltage from 12.5 to 50 V to operate an ultrasonic pulser. FEA magnetic field simulations, bench-top, and ex vivo rabbit measurements showed that the magnetic energy absorption in body tissue is negligible and that the magnetic coupling is not sensitive to receiving coil placement. The receiving coil and the power conditioning circuits in the implantable device do not contain ferromagnetic material, so a magnetic-resonance-compatible device can be achieved. A 5-MHz ultrasound transducer was used to test the implantable circuit, operating in pulse-echo mode. The received echo was amplified, envelope-detected, frequency-modulated, and transmitted out of the rabbit body by a radio wave. The modulated echo envelope signal was received by an external receiver located about 10 cm away from the primary coil. The study concludes that operation of a batteryless and wireless deep-seated implantable ultrasonic pulser-receiver powered by coplanar magnetic coupling is feasible.     

Characteristics of acoustic streaming created and measured bypulsed Doppler ultrasound

Self measurement of acoustic streaming by Doppler ultrasound could be used to evaluate properties of fluids such as viscosity or the coagulation of blood. To characterize acoustic streaming caused by pulsed ultrasonic beams, Doppler signal processing was used to measure streaming velocity under a variety of conditions in vitro using blood and water. Velocities as high as 5 mm/s were measured in blood at the diagnostic power levels (3.5 mW) used in 20 MHz catheter velocimetry. It was found that streaming decreases with distance due to absorption and beam spreading, increases with applied acoustic power, and decreases with increased viscosity during blood coagulation. However, the increase in velocity with acoustic power is nonlinear with an exponent of 0.67 for water and 1.42 for blood even though the radiation force as measured by deflection of a suspended transducer is linear with power. The time constant of streaming to a step change in acoustic power is 80 ms in blood and 200 ms in water. It is concluded that streaming is measurable in pulsed Doppler beams, that it could produce artifacts or unintended effects, and that it could be used to characterize fluid properties and to detect coagulation of whole blood     

Tissue ultrasound absorption measurement with MRI calorimetry

The renewed interest in the use of high intensity focused ultrasound (US) for minimally invasive magnetic resonance imaging (MRI)-guided thermal therapy has stimulated a review of the interaction mechanisms of US with tissue. Although the study of tissue US properties has been conducted extensively, agreements on the measured values of tissue US absorption are poor. We propose a noninvasive approach to measure tissue US absorption based on a form of MRI calorimetry. US absorption is measured in a small tissue sample through a knowledge of the US intensity distribution incident on the tissue and an MRI measurement of total absorbed energy arising from US exposure. US absorption measurements were conducted at room temperature for ex-vivo bovine liver tissue at 1 MHz, which led to a measured US absorption coefficient of 0.058 Np/cm or 0.504 dB/cm. Because this approach is noninvasive, the experimental complications exhibited in earlier studies are not present. Furthermore, this approach can be applied over a range of frequencies, tissues, and temperatures, which will aid in understanding of biothermal effects of high intensity US to improve thermal therapy.     

Acoustic radiation force enhances targeted delivery of ultrasound contrast microbubbles: in vitro verification

Recent research has shown that targeted ultrasound contrast microbubbles achieve specific adhesion to regions of intravascular pathology, but not in areas of high flow. It has been suggested that acoustic radiation can be used to force free-stream microbubbles toward the target, but this has not been verified for actual targeted contrast agents. We present evidence that acoustic radiation indeed increases the specific targeted accumulation of microbubbles. Lipid microbubbles bearing an antibody as a targeting ligand were infused through a microcapillary flow chamber coated with P-selectin as the target protein. A 2.0 MHz ultrasonic pulse was applied perpendicular to the flow direction. Microbubble accumulation was observed on the flow chamber surface opposite the transducer. An acoustic pressure of 122 kPa enhanced microbubble adhesion up to 60-fold in a microbubble concentration range of 0.25 x 10(6) to 75 x 106) ml(-1). Acoustic pressure mediated the greatest adhesion enhancement at concentrations within the clinical dosing range. Acoustic pressure enhanced targeting nearly 80-fold at a wall shear rate of 1244 s(-1), suggesting that this mechanism is appropriate for achieving targeted microbubble delivery in high-flow vessels. Microbubble adhesion increased with the square of acoustic pressure between 25 and 122 kPa, and decreased substantially at higher pressures.     

Detection of magnetic nanoparticles in tissue using magneto-motive ultrasound

The purpose of this study was to demonstrate the magneto-motive ultrasonic detection of superparamagnetic iron oxide (SPIO) nanoparticles as a marker of macrophage recruitment in tissue. The capability of ultrasound to detect SPIO nanoparticles (core diameter ～20?nm) taken up by murine liver macrophages was investigated. Eight mice were sacrificed two days after the intravenous administration of four SPIO doses (1.5, 1.0, 0.5, and 0.1?mmol Fe/kg body weight). In the iron-laden livers, ultrasound Doppler measurements showed a frequency shift in response to an applied time-varying magnetic field. M-mode scan and colour power Doppler images of the iron-laden livers also demonstrated nanoparticle movement under focused magnetic field excitation. In the livers of two saline injected control mice, no movement was observed using any ultrasound imaging modes. The results of our experiments indicate that ultrasound imaging of magneto-motive excitation is a candidate imaging modality to identify tissue-based macrophages containing SPIO nanoparticles.