Ultrasonic Doppler measurements of blood flow velocity of rabbit retinal vessels using a 45-MHz needle transducer.

BACKGROUND: The purpose of this study is to measure blood flow velocity of rabbit retinal vessels using a 45-MHz ultrasonic Doppler system with a needle transducer. METHODS: A high-frequency pulsed Doppler system that utilizes a 45-MHz PMN-PT needle transducer was developed to measure retinal blood flow velocity in situ. The pulsed Doppler allowed the differentiation of retinal from choroidal blood flow velocity. The needle transducer was inserted into the vitreous cavity through a 20-gauge incision port to access the retinal vessels. The first phase of the experiment evaluated the reproducibility of the measurements. The second phase measured velocities at four positions from the optic disc edge to the distal part of each vessel in nine eyes for the temporal and six eyes for the nasal portions. The angle between the transducer and the retinal vessel at each site was measured in enucleated rabbit eyes to estimate and compensate for measurement errors. RESULTS: In the first phase, the average measurement error was 5.97 +/- 1.34%. There was no significant difference comparing all eyes. In the second phase, the velocities gradually slowed from the disc edge to the distal part, and temporal velocities were faster than nasal velocities at all measurement sites. CONCLUSION: This study demonstrated the feasibility of reliably measuring retinal blood flow velocity using a 45-MHz ultrasonic Doppler system with a needle transducer.

Realtime photoacoustic microscopy of murine cardiovascular dynamics.

Non-invasive visualization of cardiovascular dynamics in small animals is challenging due to their rapid heart-rates. We present a realtime photoacoustic imaging system consisting of a 30-MHz ultrasound array transducer, receive electronics, a high-repetition-rate laser, and a multicore-computer, and demonstrate its ability to image optically-absorbing structures of the beating hearts of young athymic nude mice at rates of approximately 50 frames per second with 100 microm x 25 microm spatial resolution. To our knowledge this is the first report of realtime photoacoustic imaging of physiological dynamics.

Piezoelectric PZT thick films on LaNiO(3) buffered stainless steel foils for flexible device applications.

In this paper, we report on 4.5µm piezoelectric Pb(Zr(0.52)Ti(0.48))O(3) (PZT) thick films deposited on flexible stainless steel (SS) foils with LaNiO(3) (LNO) buffer layers using a ceramic powder/sol-gel solution modified composite method. The polycrystalline thick films show a hysteresis loop at an applied electric field of 900 kV cm(-1) with remanent polarization and coercive electric field values of 27µC cm(-2) and 85 kV cm(-1), respectively. At 1 kHz, the dielectric constant is 653 and the dielectric loss is 0.052. The leakage current density of the film is lower than 1.55 × 10(-5) Acm(-2) over the range of 0 to ±150V. The conduction current shows ohmic behaviour at a low electric field and space-charge-limited current characteristics at a high electric field.

Nano-structured TiO(2) film fabricated at room temperature and its acoustic properties.

Nano-structured TiO(2) thin film has been successfully fabricated at room temperature. Using a quarter wavelength characterization method, we have measured the acoustic impedance of this porous film, which can be adjusted from 5.3 to 7.19 Mrayl by curing it at different temperatures. The uniform microstructure and easy fabrication at room temperature make this material an excellent candidate for matching layers of ultra-high frequency ultrasonic imaging transducers.

Temperature dependence of oriented growth of Pb[Yb(1/2)Nb(1/2)]O(3)-PbTiO(3) thin films deposited on LNO/Si substrates.

(1-x)Pb[Yb(1/2)Nb(1/2)]O(3)-xPbTiO(3) (PYbN-PT, x=0.5)(001) oriented thin films were deposited onto LaNiO3 (LNO)/Si(001) substrates by sol-gel processing. The crystallographic texture of the films was controlled by the annealing temperature and heating rate. Highly (001) oriented LNO thin films were prepared by a simple metal organic decomposition technique, and the samples were annealed at 700 °C and 750 °C using a rapid thermal annealing process and furnace, respectively. X-ray diffraction analysis revealed that the films of PYbN-PT were highly (001) oriented along LNO/Si substrates. The degree of PYbN-PT orientation is dependent on the heating rate and annealing temperature. Annealing heating rate of 10 °C/s and high annealing temperature near 750 °C produce the greatest degree of (001) orientation, which gives rise to improved dielectric properties.

Recent developments in diagnostic ultrasound.

Ultrasound is being used increasingly in clinical diagnosis throughout the world in many medical specialties. Its major advantages over other imaging modalities are that it is minimally invasive, less expansive, and portable. Its resolution rivals that of X-ray computerized tomography and magnetic resonant imaging. Its limitations are that certain organs, such as lung and bone, are inaccessible by ultrasound, and that certain organs such as heart can only be accessed through limited acoustic windows. In recent years, great advances have been achieved in ultrasound imaging technology that make it even more versatile. Color Doppler flow imaging, parallel processing, Duplex scanning, and transesophageal imaging are just a few examples. In this paper, those developments, among others, are reviewed and their implications in clinical practice are discussed.

Reverberation reduction in ultrasonic B-mode images via dual frequency image subtraction.

The authors demonstrate the feasibility of an approach, dual-frequency subtraction imaging, for suppressing artifacts produced by reverberation of strong echoes among specular reflectors. This method is based upon the principle that specularly reflected echoes from flat boundaries are frequency-independent whereas the diffusely scattered echoes from small scatterers are frequency-dependent. The approach was assessed on phantoms including one consisting of two parallel plastic plates between layers of foam sponges using a prototype experimental system. Preliminary results show that this method is superior to simple thresholding techniques or signal compression and holds great promise for suppressing reverberation artifacts in ultrasonic images.

Hydrogels with enhanced mass transfer for transdermal drug delivery.

The sonophoretic transport rates of monomeric insulin and vasopressin across human skin in vitro in the presence of a 20 kHz ultrasound field are shown to differ substantially depending on whether molecules enter the skin from a saline solution or from a viscous ultrasonic coupling medium (specifically, a methyl cellulose hydrogel or viscous sol). Theoretically, the reduction in sonophoretic transport caused by the hydrogels can be explained by boundary layers that form within the hydrogel owing to the relatively rapid rate of molecular transport across the (ultrasonically) permeated stratum corneum as well as poor diffusive mass transfer between the skin and gel. The results of in vitro experiments performed with an ac current accompanying the ultrasound show that the mass-transfer barrier posed by the hydrogel can be eliminated for both vasopressin and insulin by suppressing the diffusive boundary layers, indicating that relatively high rates of sonophoretic molecular transport across human skin are achievable when hydrogels are used as the ultrasound coupling medium as long as method is used to induce molecular mixing within the gel.

Analysis of ultrasonic scattering in blood via a continuum approach.

Since the pioneering work by Reid et al. on measuring ultrasonic scattering in blood, this phenomenon has been extensively studied both theoretically and experimentally. The knowledge on ultrasonic scattering properties of blood is needed for the design of ultrasonic methods for measuring blood flow, and a better interpretation of ultrasonic images. The development of high frequency intravascular or intracardiac imaging devices raises the possibility of measuring blood properties, e.g., erythrocyte aggregation and fibrinogen concentration, in situ. A number of theoretical approaches have been developed to analyze this phenomenon where in general ultrasound wavelength is much greater than the erythrocytes. These results show that the backscattering coefficient of blood, defined as power backscattered by a unit volume of blood per steradian per unit incident intensity, is proportional to variance of the erythrocyte number fluctuation and backscattering cross-section of a single erythrocyte. In this paper, we will show that similar results can also be obtained by taking a continuum approach.

Ultrasonic backscattering from porcine whole blood of varying hematocrit and shear rate under pulsatile flow.

It was shown previously that ultrasonic scattering from whole blood varies during a flow cycle under pulsatile flow both in vitro and in vivo. It has been postulated that this cyclic variation may be associated with the dynamics of red cell aggregation because the shearing force acting on the red cell aggregates across the lumen is a function of time during a flow cycle. In all studies, the local shear rate variation as a function of time is unknown. The effect of shear rate on the red cell aggregation and, thus, on ultrasonic scattering from blood can only be merely speculated. One solution to this problem is to estimate the shear rate in a flow conduit by finite element analysis (FEA). An FEA computational fluid dynamics (CFD) tool was used to calculate local shear rate in a series of experiments in which ultrasonic backscattering from porcine whole blood under pulsatile flow was measured as a function of hematocrit and shear rate intravascularly with a 10-MHz catheter-mounted transducer in a mock flow loop. The results show that, at 20 beats per min (BPM), the magnitudes of the cyclic variation for hematocrits at 30, 40, and 50% were approximately 4 dB. However, at 60 BPM, the magnitude of cyclic variation was found to be minimal. The results also confirm previous findings that the amplitude and the timing of the peak of ultrasonic backscattering from porcine whole blood under pulsatile flow during a flow cycle are dependent upon the shear rate and hematocrit in a complicated way.

Cyclic variation of Doppler power from whole blood under pulsatile flow.

The echogenicity and Doppler power from whole blood under pulsatile flow have been found to vary during the flow cycle in previous studies both in vitro and in vivo. The present study was undertaken to better understand this phenomenon. Doppler power from whole blood under pulsatile flow was measured with a pulsed Doppler flowmeter as a function of the flow cycle, radial position and compliance of the vessel in a mock flow loop. It was found that the cyclic variation is more pronounced if the stroke rate is less than 56 beats/min and that the peak of the Doppler power from whole blood flowing near the center stream coincided with the peak of the flow velocity. However, it began to lead the velocity peak as the measurement site was moved away from the center stream. The lead increased as the radial distance was increased. The results also show that the compliance of the vessel can affect, to a certain extent, the magnitude of the cyclic variation. Results from intravascular Doppler measurements rule out the possibility that the cyclic variation is primarily due to the variation in attenuation caused by vessel wall during a flow cycle.

A study of the relationship between mechanical and ultrasonic properties of dystrophic and normal skeletal muscle.

A study has been made of the application of radio frequency (RF) ultrasound to the detection of muscular dystrophy by monitoring passively stretched skeletal muscle. The tests included detection of integrated backscatter changes in response to both static loading, in which muscle samples were stretched and allowed to relax, and stress relaxation. In both static and step strain loading conditions, the dystrophic muscle was found to exhibit little change in backscatter power while normal muscle responded to loading with significant changes in integrated backscatter. The backscatter response is compared with mechanical properties of the tissue (time constants and stress-strain constants). Both mechanical and ultrasonic time constants of relaxation are not significantly different between normal and dystrophic tissue, but stress-strain constants do differ. The difference in response of dystrophic and normal tissue appears to be due to a repression of motion of the constituent anatomy of dystrophic muscle which is responsible for the change of echogenicity with passive stretch.

Time-domain ultrasonic contrast blood flowmetry.

Time-domain ultrasonic blood flow estimation methods have recently received considerable attention because of their advantages over conventional Doppler methods. Among them are that they may yield better spatial resolution and that methods based on frame-to-frame speckle tracking do not require a knowledge of the angle between directions of blood flow and the ultrasound beam. These methods, however, suffer from an intrinsic problem of poor signal-to-noise ratio, since the echoes scattered back by blood are much weaker than those of the surrounding structures. In addition, the maximal velocity that can be estimated by frame-to-frame tracking via conventional ultrasonic scanners is limited by the frame rate of the scanner. In this article, we will present experimental results to show that these problems may be alleviated by using a high frame rate scanner in conjunction with the injection of an ultrasonic contrast agent. In this study the contrast agent used was Albunex.

The effect of hemodynamics, vessel wall compliance and hematocrit on ultrasonic Doppler power: an in vitro study.

Previous in vitro studies in rigid tubes under pulsatile flow conditions have reported a lack of a cyclic variation in blood echogenicity that contradicts in vivo results. To investigate whether or not these variations can be attributed to the compliance of the vessel wall, a series of in vitro experiments with compliant tubes, under pulsatile flow conditions, was performed. Two important factors that may affect the Doppler power were investigated: 1. the dependence on hematocrit and 2. the effect of the vessel wall elasticity. In the present study, it is shown that, at the low beat rates, the peak of the mean Doppler power within the flow cycle depends on the vessel wall compliance. When the vessel becomes more compliant, the peak is shifted from the early to the late systole. Additionally, there is a correlation between the power peak and hematocrit that is more evident in compliant vessels. At a higher pulsation rate of 37 beats/min, a different variation is observed. A drop in the power occurs near peak systole in compliant tube experiments and is more pronounced as the vessel becomes more constricted. The observed power drop agrees with previously reported in vivo results, but is not seen in rigid tube experiments. The results of this study suggest that proper interpretation of cyclic variations in Doppler power requires a knowledge of hemodynamic parameters, such as the modulus of elasticity of the vessel wall, propagation velocity or, possibly, the phase angle of input impedance.

High-frequency backscatter and attenuation measurements of selected bovine tissues between 10 and 30 MHz.

There are now diagnostic ultrasonic imaging devices that operate at very high frequencies (VHF) of 20 MHz and beyond for clinical applications in ophthalmology, dermatology, vascular surgery, endoluminal imaging and small animal imaging. To be able to better interpret these images and to further the development of these devices, knowledge of ultrasonic attenuation and scattering of biological tissues in this frequency range is crucial. Attenuation and backscatter coefficients (BSCs) of bovine tissues in the frequency range of 10 to 30 MHz were measured, respectively, using a standard substitution method for attenuation measurements and a modified narrow-band substitution method for scattering measurements. A modified substitution method for scattering measurements has to be used at high frequencies because unfocused transducers due to their decreased sensitivity cannot be used in the simple substitution method. In the modified method, the flat reflector is substituted by a particulate reference medium whose BSC is well-known and documented; in this case, a red cell suspension. In this paper, experimental results on BSC and attenuation coefficient measured between 10 and 30 MHz are reported. The frequency dependence of backscatter of the selected bovine tissues ranges from 2.4 to 3.5, whereas attenuation is observed to be still approximately linearly proportional to frequency. The BSC measured with the modified method is in good agreement with those obtained with the standard method between 10 and 20 MHz.

A computer model for simulating ultrasonic scattering in biological tissues with high scatterer concentration.

Scattering of ultrasonic waves by biological tissues at different scatterer concentrations is investigated using one- and two-dimensional computer simulation models. The backscattered power as a function of scatterer concentrations is calculated using two types of incident waves, a Gaussian shaped pulse and a continuous wave (CW). The simulation results are in good agreement with the Percus-Yevick packing theory within the scatterer concentrations, from 0% to 100% in one-dimensional (1D) space, and 0% to 46% in two-dimensional (2D) space. In all cases, the simulation results from a pulsed incident wave show a much smaller standard deviation (SD) than those from an incident CW. The simulation can serve as a useful tool to verify scattering theories, simulate different experimental conditions, and to investigate the interaction between the scatterer properties and the scattering of ultrasonic waves. More importantly, the 2D simulation procedure serves as an initial step toward the final realization of a true three-dimensional (3D) simulation of ultrasonic scattering in biological tissues.

Doppler power variation from porcine blood under steady and pulsatile flow.

Although a number of recent studies have demonstrated that the echogenicity of blood varies as a function of time under pulsatile flow, the fundamental mechanisms responsible for it are still uncertain. To better understand this phenomenon, the Doppler power from porcine blood and polystyrene microsphere suspensions was measured at the center of the tube as functions of two crucial parameters, flow velocity and stroke rate (for pulsatile flow), under steady and pulsatile flow in a mock flow loop. In the present study, the experimental results were obtained with a 10-MHz pulsed Doppler system with a frequency response estimated more accurately by electronic injection, and validated by comparing to the radiofrequency (RF) signal acquired from the same Doppler instrument. The results show that the Doppler power from microspheres and porcine red blood cell (RBC) suspensions did not vary appreciably (< 2 dB), with either the speed or stroke rate (for pulsatile flow only) under steady and pulsatile flow. It was found that the Doppler power from porcine whole blood under steady flow decreased with the speed by approximately 13 dB from 3 to 33 cm/s and was only 3 dB higher than that from RBC suspension at 33 cm/s, suggesting minimal RBC aggregation in whole blood at this speed. The apparent cyclic variation from whole blood was observed at 20 and 40 beats/min (BPM). The cyclic variation became more obvious as the speed and stroke rate decreased. The mean Doppler power over a cycle increased as the peak speed decreased. The Doppler power reached a maximum near peak systole and a minimum at late diastole at the center of the tube. This pattern cannot be explained by RBC aggregation due to the shear rate alone, and may be attributed to acceleration and deceleration along with aggregation. The cyclic variation was not observed at 60 BPM, probably because of a lack of time for aggregation to occur.

Quantitative measurements of second harmonic Doppler using ultrasound contrast agents.

Quantitative measurements of second harmonic and first harmonic Doppler were carried out using two ultrasound contrast agents, Albunex and FS069. The RMS amplitudes of the Doppler shift spectra were measured as a function of the concentration of the agents, frequency and transmitted acoustic pressure. The results showed that, for a given lot of contrast agent investigated, FS069 was able to produce higher levels of first and, especially, second harmonic signals compared to Albunex. Under the same experimental conditions, the RMS Doppler amplitude (RDA) of FS069 was 3.8 +/- 0.8 dB higher than Albunex at first harmonic and 12.6 +/- 0.8 dB higher at second harmonic. The ratio of the second harmonic to first harmonic RDA, which we called R2/R1, decreases at a rate of 7 dB/MHz for both agents with increasing frequency. The difference in the value of R2/R1 between FS069 and Albunex at any frequency was approximately 4.5 dB. R2/R1 was found to increase linearly as a function of the transmitted acoustic pressure for both agents. Simulations using the Rayleigh-Plesset equation show a decrease of R2/R1 at a rate of 5 dB/MHz. Comparison of experimental results with theory indicates that the shell elasticity parameter may be an increasing function of the mean diameter of the bubbles.

In situ measurements of Doppler power vs. flow turbulence intensity in red cell suspensions.

Whereas previous studies have shown that ultrasonic backscatter and Doppler power from blood are affected by flow turbulence, turbulence level has only been inferred from the flow Reynolds number and not directly measured. In this study, both ultrasonic Doppler power and flow turbulence intensity were measured in situ to quantify the relationship between Doppler power and flow turbulence. Three grid meshes of different geometries were used in a steady-flow mock loop to generate controlled levels of flow turbulence in porcine red blood cell saline suspensions. Doppler power was measured by a 10-MHz PW Doppler flowmeter, and the turbulence intensity by using constant-temperature hot film anemometry. We showed that Doppler power is affected by turbulence and hematocrit in a complex way. At a fixed hematocrit, Doppler power increases nonlinearly with turbulence intensity and, at fixed turbulence intensity, Doppler power peaks at an optimal hematocrit level that increases with turbulence level. The shape factor, introduced by Lucas and Twersky (1987) to take into account effects of shape and orientation of the scatterers in a dense distribution of small and tenuous scatterers, was estimated by fitting the experimental data to the theoretical model. The results indicate that shape factor decreases with increasing turbulence intensity.

A feasibility study on quantitating myocardial perfusion with Albunex, an ultrasonic contrast agent.

Quantitating regional myocardial perfusion has been the much sought-after but still elusive goal of many intensive investigations over the years. Videodensitometry of the variation of myocardial echogenicity in two-dimensional (2-D) echocardiograms as a function of time in conjunction with the injection of a bolus of an ultrasound contrast agent has been used clinically as a tool for a direct assessment of regional myocardial perfusion, despite that the precise relationship between tissue echogenicity observed on an image and the echoes detected by the ultrasonic probe is unknown. A study was undertaken to determine whether ultrasonic backscatter calculated from unprocessed radio frequency (RF) echoes returned from myocardium could be used to quantitate regional myocardium perfusion. A real-time ultrasonic scanner has been modified and interfaced to a microcomputer to acquire RF data at a rate up to 10 frames per second. Preliminary experimental data were obtained from four open-chest dogs following intracoronary injection of a bolus of Albunex and two dogs following intravenous injection with this modified scanner. On one hand, these results indicate that the integrated backscatter measured from the region of myocardium perfused by the coronary artery where Albunex is injected and selected for monitoring initially increases, reaches a peak, and then decreases as the contrast agent is washed out and that the magnitude of the peak is approximately linearly proportional to the volume concentration of Albunex microspheres injected, clearly demonstrating the feasibility of this approach for quantitating region myocardial perfusion. On the other hand, intravenous injections did not result in any appreciable change in myocardial backscatter in the left ventricle although a response could be observed in the left ventricular blood pool.