In vitro measurement of attenuation and nonlinear scattering from echogenic liposomes

Echogenic liposomes (ELIP) are an excellent candidate for concurrent imaging and drug delivery applications. They combine the advantages of liposomes-biocompatibility and ability to encapsulate both hydrophobic and hydrophilic drugs-with strong reflections of ultrasound. The objective of this study is to perform a detailed in vitro acoustic characterization - including nonlinear scattering that has not been studied before - along with an investigation of the primary mechanism of echogenicity. Both components are critical for developing viable clinical applications of ELIP. Mannitol, a cryoprotectant, added during the preparation of ELIP is commonly believed to be critical in making them echogenic. Accordingly, here ELIP prepared with varying amount of mannitol concentration are investigated for their pressure dependent linear and non-linear scattered responses. The average diameter of these liposomes is measured to be 125-185 nm. But they have a broad size distribution including liposomes with diameters over a micro-meter as observed by TEM and AFM. These larger liposomes are critical for the overall echogenicity. Attenuation through liposomal solution is measured with four different transducers (central frequencies 2.25, 3.5, 5, 10 MHz). Measured attenuation increases linearly with liposome concentration indicating absence of acoustic interactions between liposomes. Due to the broad size distribution, the attenuation shows a flat response without a distinct peak in the range of frequencies (1-12 MHz) investigated. A 15-20 dB enhancement with 1.67 μg/ml of lipids is observed both for the scattered fundamental and the second harmonic responses at 3.5 MHz excitation frequency and 50-800 kPa amplitude. It demonstrates the efficacy of ELIP for fundamental as well as harmonic ultrasound imaging. The scattered response however does not show any distinct subharmonic peak for the acoustic excitation parameters studied. Small amount of mannitol proves critical for echogenicity. However, mannitol concentration above 100 mM shows no effect.     

Properties and characteristics of P(VDF/TrFE) transducers manufactured by a solution casting method for use in the MHz-range ultrasound in air

Highly effective piezoelectric polymer transducers operating in air at high frequencies have been successfully made by casting a solution of ferroelectric poly(vinylidene fluoride-co-trifluoroethylene) P(VDF/TrFE) directly on a backing metal plate, and their performance has been evaluated. By utilizing this method, it has been possible to develop the three kinds of transducers that operate respectively at 4, 6 and 10 MHz in air. For precise evaluation of the performance of the P(VDF/TrFE) transducers, the absorption loss in air was measured up to 10 MHz. It was confirmed that the empirical formula obtained from the measured absorption values in air at high frequencies was in alignment with its theoretical value. In addition, a high lateral resolution acoustic image of a ROM-Chip (amplitude-image) at 6 MHz in air was successfully displayed using an air coupled concave type P(VDF/TrFE) transducer by bonding an epoxy adhesive.     

Analysis of 2-D motion tracking in ultrasound with dual transducers

We study displacement and strain measurement error of dual transducers (two linear arrays, aligned orthogonally and coplanar). Displacements along the beam of each transducer are used to obtain measurements in two-dimensions. Simulations (5 MHz) and experiments (10 MHz) are compared to measurements with a single linear array, with and without angular compounding. Translation simulations demonstrate factors of 1.07 larger and 8.0 smaller biases in the axial and lateral directions respectively, for dual transducers compared to angular compounding. As the angle between dual transducers decreases from 90° to 40°, for 1% compression simulations, the lateral RMS error ranges from 2.1 to 3.9 μm compared to 9 μm with angular compounding. Simulation of dual transducer misalignment of 1 mm and 2° result in errors of less than 9 μm. Experiments demonstrate factors of 3.0 and 5.2 lower biases for dual transducers in the axial and lateral directions respectively compared to angular compounding.     

Bipolar-power-transistor-based limiter for high frequency ultrasound imaging systems

High performance limiters are described in this paper for applications in high frequency ultrasound imaging systems. Limiters protect the ultrasound receiver from the high voltage (HV) spikes produced by the transmitter. We present a new bipolar power transistor (BPT) configuration and compare its design and performance to a diode limiter used in traditional ultrasound research and one commercially available limiter. Limiter performance depends greatly on the insertion loss (IL), total harmonic distortion (THD) and response time (RT), each of which will be evaluated in all the limiters. The results indicated that, compared with commercial limiter, BPT-based limiter had less IL (−7.7 dB), THD (−74.6 dB) and lower RT (43 ns) at 100 MHz. To evaluate the capability of these limiters, they were connected to a 100 MHz single element transducer and a two-way pulse-echo test was performed. It was found that the −6 dB bandwidth and sensitivity of the transducer using BPT-based limiter were better than those of the commercial limiter by 22% and 140%, respectively. Compared to the commercial limiter, BPT-based limiter is shown to be capable of minimizing signal attenuation, RT and THD at high frequencies and is thus suited for high frequency ultrasound applications.     

Large GMI effect in Co-rich amorphous wire by tensile stress

Quality Co₆₈Fe_4.5Si₁₅B_12.5 amorphous wires are fabricated and their giant magneto impedance (GMI) effect are investigated at frequencies ranging from 0.1 to 20 MHz with or without tensile stress applied. Experimental results indicate that the GMI effect of these wires can be effectively improved by applying a small axial tensile stress. There is a pronounced increase from 1.3% to 47.3% in impedance ratio at 0.6 MHz when a stress of 103 MPa is applied. The GMI response is further increased to 261% by doing so at 15 MHz. The field sensitivity of these wires is optimized and it increases from 0.55 to 2.73%/(A/m) at 0.6 MHz and it is proved that the most sensitive field response is obtained by applying a tensile stress of 84.5 MPa below 1 MHz. With reference to the stress evolution of sensitivity at varying frequencies, the maximum field sensitivity shifts to a lower stress with increasing frequency. Quantitatively, a stress as small as 18.4 MPa is enough to yield a field sensitivity as high as 6.7%/(A/m) at 15 MHz. This demonstrates the possibility of achieving small stress (<100 MPa) induced large enhancement of GMI effect and field sensitivity at frequencies of several tens of MHz that are of much technical interest in sensor applications.     

Acoustic characterization of a new trisacryl contrast agent. Part I: In vitro study

The objective of the study was to acoustically characterize trisacryl polymeric microparticles (TMP), which are derived from biocompatible embolic agents.With significant acoustic properties, these polymeric particles could be potentially used as targeted ultrasound contrast agents, directed towards a specific site, with ligands conjugation on the polymeric network surface. In the in vitro study, a pulser/receiver (PRF of 1 kHz), associated to different transducers (5, 10 and 15 MHz), was used to measure the acoustic properties of the TMP inserted in a Couette flow device. Acoustic characterization according to TMP concentration (0.12-15.63 mg/ml), frequency (4.5-17 MHz, defined by each transducer bandwidth), ultrasound pressure (137-378 kPa) and exposure time (0-30 min) was conducted. Particle attenuation was also evaluated according to TMP concentration and emission frequency. Backscattering increased non linearly with concentration and maximum enhancement was of 16.4 dB ± 0.89 dB above 7.8 mg/ml. This parameter was found non-linear with increasing applied pressure and no harmonic oscillation could be noticed. Attenuation reached approximately 1.4 dB/cm at 15 MHz and for the 15.6 mg/ml suspension.The TMP have revealed in vitro ultrasound properties comparable to those observed with known contrast agents, studied in similar in vitro systems. However, such set-ups combined with a rather aqueous suspending medium, have some limitations and further investigations need now to be conducted to approach in vivo conditions in terms of flow and blood environment.     

Ultrasound generation with high power and coil only EMAT concepts

Electro-magnetic acoustic transducers (EMATs) are intended as non-contact and non-destructive ultrasound transducers for metallic material. The transmitted intensities from EMATS are modest, particularly at notable lift off distances. Some time ago a concept for a “coil only EMAT” was presented, without static magnetic field. In this contribution, such compact “coil only EMATs” with effective areas of 1–5 cm² were driven to excessive power levels at MHz frequencies, using pulsed power technologies. RF induction currents of 10 kA and tens of Megawatts are applied. With increasing power the electroacoustic conversion efficiency also increases. The total effect is of second order or quadratic, therefore non-linear and progressive, and yields strong ultrasound signals up to kW/cm² at MHz frequencies in the metal. Even at considerable lift off distances (cm) the ultrasound can be readily detected. Test materials are aluminum, ferromagnetic steel and stainless steel (non-ferromagnetic). Thereby, most metal types are represented. The technique is compared experimentally with other non-contact methods: laser pulse induced ultrasound and spark induced ultrasound, both damaging to the test object’s surface. At small lift off distances, the intensity from this EMAT concept clearly outperforms the laser pulses or heavy spark impacts.     

10 GHz passive harmonic mode-locking in Er-Yb double-clad fiber laser

In this paper we report passive harmonic mode-locking of an Erbium/Ytterbium-doped double-clad fiber laser with repetition rates up to 10 GHz. The modes synchronization was obtained using Nonlinear Polarization Rotation mechanism. The stable operation at 634th harmonic of the fundamental (15.8 MHz) repetition frequency was achieved. Soliton pulses with the duration of less than 900 fs and 300 mW average output power were obtained.     

Electromagnetic wave absorption properties of flaky Fe-Ti-Si-Al nanocrystalline composites

Nanocrystalline Fe-Ti-Si-Al flaky powders with large aspect ratio have been fabricated by high-energy planetary milling melt-spun ribbons. Magnetic composites made of thermally annealed Fe-Ti-Si-Al flaky powders embedded in epoxy resin exhibit excellent electromagnetic wave absorption properties in a wide frequency range from 100 MHz to 2.65 GHz. Ti additions can enhance the electrical resistivity of Fe-Si-Al alloy without changing the crystallographic structure, resulting in the reduction of eddy current loss at high frequencies. Moreover, the substitution of Ti for Fe enhances the cut-off frequency of flaky powder-polymer composites. Meanwhile, compared to the Ti-free composites, reflection loss of the Ti-doped composites (3 mm in thickness) is lower than −10 dB in the frequency range from 593 MHz to 1.83 GHz, indicating that the composites can effectively work in a wider frequency bandwidth.     

Bonding and impedance matching of acoustic transducers using silver epoxy

Silver epoxy was selected to bond transducer plates on glass substrates. The properties and thickness of the bonding medium affect the electrical input impedance of the transducer. Thus, the thickness of the silver epoxy bonding layer was used as a design parameter to optimize the structure for the transducer input impedance to match the 50 Ω output impedance of most radio frequency (RF) generators. Simulation and experimental results show that nearly perfect matching is achieved without using any matching circuit. At the matching condition, the transducer operates at a frequency band a little bit below the half-wavelength resonant frequency of the piezoelectric plate. In experiments, lead titanate (PT) piezoelectric plates were employed. Both full-size, 11.5 mm × 2 mm × 0.4 mm, and half-size, 5.75 mm × 2 mm × 0.4 mm, can be well matched using optimal silver epoxy thickness. The transducer assemblies demonstrate high efficiency. The conversion loss from electrical power to acoustic power in soda-lime glass is 4.3 dB. This loss is low considering the fact that the transducers operate at off-resonance by 12%. With proper choice of silver epoxy thickness, the transducer can be matched at the fundamental, the 3rd and 5th harmonic frequencies. This leads to the possible realization of triple-band transducers. Reliability was assessed with thermal cycling test according to Telcordia GR-468-Core recommendation. Of the 30 transducer assemblies tested, none broke until 2900 cycles and 27 have sustained beyond 4050 cycles.     

Ultrasonic properties of water/sorbitol solutions

Ultrasonic longitudinal velocity and attenuation were measured for aqueous solutions of sorbitol at approximately 5 MHz. For pure sorbitol, the ultrasonic velocity reached 3200 m s⁻¹, consequently leading to a high acoustical impedance (around 5 × 10⁶ Rayleigh) and good matching between the ultrasonic transducers and material samples.     

Ultrasound phase rotation beamforming on multi-core DSP

Phase rotation beamforming (PRBF) is a commonly-used digital receive beamforming technique. However, due to its high computational requirement, it has traditionally been supported by hardwired architectures, e.g., application-specific integrated circuits (ASICs) or more recently field-programmable gate arrays (FPGAs). In this study, we investigated the feasibility of supporting software-based PRBF on a multi-core DSP. To alleviate the high computing requirement, the analog front-end (AFE) chips integrating quadrature demodulation in addition to analog-to-digital conversion were defined and used. With these new AFE chips, only delay alignment and phase rotation need to be performed by DSP, substantially reducing the computational load. We implemented the delay alignment and phase rotation modules on a Texas Instruments C6678 DSP with 8 cores. We found it takes 200 μs to beamform 2048 samples from 64 channels using 2 cores. With 4 cores, 20 million samples can be beamformed in one second. Therefore, ADC frequencies up to 40 MHz with 2:1 decimation in AFE chips or up to 20 MHz with no decimation can be supported as long as the ADC-to-DSP I/O requirement can be met. The remaining 4 cores can work on back-end processing tasks and applications, e.g., color Doppler or ultrasound elastography. One DSP being able to handle both beamforming and back-end processing could lead to low-power and low-cost ultrasound machines, benefiting ultrasound imaging in general, particularly portable ultrasound machines.     

Development of calibration techniques for ultrasonic hydrophone probes in the frequency range from 1 to 100 MHz

The primary objective of this work was to develop and optimize the calibration techniques for ultrasonic hydrophone probes used in acoustic field measurements up to 100 MHz. A dependable, 100 MHz calibration method was necessary to examine the behavior of a sub-millimeter spatial resolution fiber optic (FO) sensor and assess the need for such a sensor as an alternative tool for high frequency characterization of ultrasound fields. Also, it was of interest to investigate the feasibility of using FO probes in high intensity fields such as those employed in HIFU (high intensity focused ultrasound) applications. In addition to the development and validation of a novel, 100 MHz calibration technique the innovative elements of this research include implementation and testing of a prototype FO sensor with an active diameter of about 10 μm that exhibits uniform sensitivity over the considered frequency range and does not require any spatial averaging corrections up to about 75 MHz. The results of the calibration measurements are presented and it is shown that the optimized calibration technique allows the sensitivity of the hydrophone probes to be determined as a virtually continuous function of frequency and is also well suited to verify the uniformity of the FO sensor frequency response. As anticipated, the overall uncertainty of the calibration was dependent on frequency and determined to be about ±12% (±1 dB) up to 40 MHz, ±20% (±1.5 dB) from 40 to 60 MHz and ±25% (±2 dB) from 60 to 100 MHz. The outcome of this research indicates that once fully developed and calibrated, the combined acousto-optic system will constitute a universal reference tool in the wide, 100 MHz bandwidth.     

Effect of dual-frequency clutter suppression in harmonic Doppler detection

Background

High-frequency Doppler imaging is highly potential for detection of blood flow in microcirculation. In a swept-scan system, however, the spectral broadening of tissue clutter limits the detectability of low-velocity flow signal. Conventionally, the scanning speed of transducer has to be reduced to alleviate the clutter interference but at the cost of imaging frame rate. For example, the blood velocity of 0.5 mm/s becomes detectable only with a scanning speed lower than 1 mm/s. In this study, an alternative method is examined by suppressing the clutter magnitude to reduce the interference to flow signal without sacrificing scanning speed.

Methods

The method of third harmonic (3f₀) transmit phasing can suppress the tissue harmonic clutter by transmitting at the fundamental and the additional 3f₀ frequencies to achieve mutual cancellation between the frequency-sum and the frequency-difference components of the second harmonic signal. With 3f₀ transmit phasing, the cut-off frequency of wall filtering can be reduced to preserve low-velocity flow without compromising the frame rate.

Results

Our results indicate that the 3f₀ transmit phasing effectively reduces the harmonic clutter magnitude and thus improves the flow signal-to-clutter ratio. Compared to the conventional counterpart, the clutter-suppressed color flow and power Doppler images show fewer clutter artifacts and is capable of detecting more low-velocity flow of microbubbles. The resultant color-pixel-density also improves with clutter suppression.

Conclusion

For the swept-scan high-frequency (>20 MHz) system, 3f₀ transmit phasing is capable of providing effective clutter suppression. With the same achievable scanning speed, the resultant Doppler image has higher sensitivity for low-velocity flow and is less susceptible to clutter artifacts.     

A study on the control of dye solution temperature on the line-width and wavelength stability of a copper vapour laser pumped single mode dye laser

This paper presents a study on the line-width and wavelength stability of a single mode narrow line-width (≈ 100 MHz) dye laser pumped by a copper vapour laser, with and without precision temperature control of dye solution. The single mode dye laser system was based on a specially designed SS metal dye cell and grazing incidence grating (GIG) dye resonator with intra-cavity double prism beam expander and etalon. A high precision wavelength-meter was used to record the line-width and frequency stability data. With the coarse dye solution temperature control of 23 ± 2 °C, dye laser line-width varied in a periodic fashion (in every 30 s) between 100 and 770 MHz. Frequency stability was ± 215 MHz (1 min). This is attributed to switching from single to double mode due to temperature induced cavity length change. For the precise dye solution control of 23 ± 0.1 °C, the periodic variation of the line-width was removed completely and the line-width was always ≤ 100 MHz. The frequency stability also improved to ± 42 MHz (1 min). It is established that the dye temperature control is very crucial for achieving, highly frequency stable single axial mode operation.     

Effect of annealing on magnetoimpedance of Co68Fe4Zr10Cu2B16 ribbons

Magnetoimpedance (MI) in Co₆₈Fe₄Zr₁₀Cu₂B₁₆ alloy has been investigated in the frequency range 500 kHz–5 MHz and with the application of external steady magnetic field in the longitudinal direction, up to 100 Oe. MI measurements were carried out on as-cast ribbons and also on conventionally annealed and Joule-annealed ribbons. In as cast ribbons, the maximum MI observed is 13% at a frequency of 500 kHz and it decreases to 5% and 4% with conventional annealing at 100 °C and 150 °C, respectively. On the other hand, MI decreases to 8% and 6% with Joule annealing employing currents of 100 mA and 200 mA, respectively. However, Joule annealing with the application of a magnetic field of 5–10 Oe in the transverse direction causes the MI to decrease to 12% and 11% for currents of 100 mA and 200 mA, respectively. In the as-cast ribbons, double peak behavior is observed in all the frequencies whereas, in the annealed ribbons, double peak behavior in general is observed only at high frequencies.     

Development of low loss Mn–Zn ferrite working at frequency higher than 3 MHz

With the advance of modern electronic technology, there has been a critical need for Mn–Zn ferrites with even higher permeability and even lower power loss at higher frequencies. In this study, ferrite with extremely low losses than conventional ferrite materials at high frequency was developed employing a conventional ceramic powder processing technique. As a result, the core loss at 3 MHz, 10 mT and 100 °C is around 300 kW/m³, and its cutoff frequency is 4 MHz. Furthermore, the electromagnetic characteristics and the microstructure of this new DMR50 material are also discussed.     

Cytotoxicity and GMI bio-sensor detection of maghemite nanoparticles internalized into cells

In this work we determine conditions to produce cell samples for imaging with detection of the modification of the magnetic field by maghemite (Fe₂O₃) nanoparticles acting as a high sensitivity magnetic bio-sensor based on the giant magneto-impedance (GMI) effect. Mat Ly Lu cells are grown for 24 h with various maghemite nanoparticles concentrations (from 0 to 6 mg/ml). The percentage of viable cells is determined by counting labeled cells with trypan blue under an optical microscope. The quantity of nanoparticles internalized into the cells is evaluated by X-ray fluorescence analysis and expressed in iron moles per cell. The GMI bio-sensor was tested with the various samples. We observed that the best sensitivity of the GMI bio-sensor was obtained at a frequency of 1 MHz. To confirm these results in the presence of cell samples, four measurement frequencies were pre-selected (from 1 to 100 MHz) and tested. Cell growth conditions compatible with an acceptable percentage of cell viability for various concentrations of nanoparticles were also determined. These experiments allow us to conclude that cell growth with 0.1 mg/ml of nanoparticles for 24 h shows modifications of the magnetic field detectable optimally at 1 MHz frequency.     

Reflector-based phase calibration of ultrasound transducers

Recently, the measurement of phase transfer functions (PTFs) of piezoelectric transducers has received more attention. These PTFs are useful for e.g. coding and interference based imaging methods, and ultrasound contrast microbubble research. Several optical and acoustic methods to measure a transducer’s PTF have been reported in literature. The optical methods require a setup to which not all ultrasound laboratories have access to. The acoustic methods require accurate distance and acoustic wave speed measurements. A small error in these leads to a large error in phase, e.g. an accuracy of 0.1% on an axial distance of 10 cm leads to an uncertainty in the PTF measurement of ±97° at 4 MHz. In this paper we present an acoustic pulse-echo method to measure the PTF of a transducer, which is based on linear wave propagation and only requires an estimate of the wave travel distance and the acoustic wave speed. In our method the transducer is excited by a monofrequency sine burst with a rectangular envelope. The transducer initially vibrates at resonance (transient regime) prior to the forcing frequency response (steady state regime). The PTF value of the system is the difference between the phases deduced from the transient and the steady state regimes. Good agreement, to within 7°, was obtained between KLM simulations and measurements on two transducers in a 1-8 MHz frequency range. The reproducibility of the method was ±10°, with a systematic error of 2° at 1 MHz increasing to 16° at 8 MHz. This work demonstrates that the PTF of a transducer can be measured in a simple laboratory setting.     

Nanocomposite cerium oxide polymer matching layers with adjustable acoustic impedance between 4 MRayl and 7 MRayl

A new class of materials for ultrasonic matching layers is presented. The materials consist of nanoscale cerium oxide particles in an epoxy functionalized organic inorganic hybrid polymer matrix. The cerium oxide agglomerates to particles with 20 nm diameters. The content of particles in the polymer matrix could be increased to 75 wt.% which corresponds to 37 vol.%. The most technical important piezoelectrical ceramics have an acoustic impedance of about 30 MRayl, to improve coupling into water or biological tissue with an acoustic impedance of about 1.5 MRayl a matching layer should have an acoustic impedance of about 6.8 MRayl. With a filling degree of 75 wt.% the new composite material reaches an acoustic impedance of 7 MRayl. The materials are synthesized by a hydrolytic condensation combined with polymerization. This way of synthesis allows the use of organic solvents to adjust the viscosity of the sol and the application of different coating techniques. Ultrasound transducers (100 MHz) were built to test the new matching layers and an increase of the voltage signal amplitude of about 100% could be detected.