Subharmonic generation from ultrasonic contrast agents.

Ultrasonic contrast agents are used to enhance backscatter from blood and thus aid in delineating blood from surrounding tissue. However, behaviour of contrast agents in an acoustic field is nonlinear and leads to harmonic components in the backscattered signal. Various research groups have investigated second-harmonic emissions. In this work, the subharmonic emission from contrast agents is investigated with a view towards potential use in imaging. It is shown that the microbubbles with various surface properties, such as contrast agents, generate significant subharmonics under various insonating conditions. Theoretical results as well as experimental results using Optison indicate the generation of strong subharmonics with burst insonation at twice the resonant frequency of the microbubble. It is suggested that subharmonic imaging may provide a better modality than second-harmonic imaging to delineate blood from tissue and will be of significant importance for imaging deep vessels, such as in echocardiography and vascular diseases, due to the high signal-to-clutter ratio of the subharmonic imaging.

In vitro Doppler detection of axisymmetric stenoses from transverse velocity measurements.

Results are presented on Doppler flow measurements distal to models of arterial stenosis under steady and pulsatile flow conditions. The models simulate mild to moderate stenoses. Emphasis is placed on flow structure determination (vortex shedding or coherent eddies) which might be the distinguishing characteristic of a mild stenosis (less than or equal to 50%). A new approach is taken by making the measurements with the ultrasonic beam normal to the axial flow direction. The transverse velocity measurements avoid detecting the superposed axial flow component so that flow structure can be determined, and also provide clinical advantages of the ease of localization. A pulsed RF directional Doppler system is used together with high resolution temporal autoregressive spectral analysis. Vortex shedding and coherent structures are detected under steady and pulsatile flow conditions. The influence of the frequency parameter on the flow pattern is also studied.

Second harmonic ultrasonic blood perfusion measurement.

In vitro and in vivo testing of a recently introduced method of evaluating blood perfusion is presented, where the Doppler shift of the second harmonic component of the backscattered echo is measured. Central to this measurement is the administration of a galactose-based contrast agent (Schering AG, Berlin, Germany, SHU-508 or derivative) which has been shown in vitro to exhibit extraordinary nonlinear backscattering properties. Two types of experiments are described: in vitro studies on excised sheep kidneys and in vivo studies on living rabbits. In the animal model, blood perfusion was manipulated by various mechanisms to obtain some indication of the quantitative ability of the measurement. Comparisons between measurements made at the fundamental component of the backscattered echo and at the second harmonic show that use of the second harmonic measurement results in a much improved ratio of blood echo intensity to tissue echo intensity (signal-to-clutter ratio), allowing detection of blood flowing in smaller vessels and opening up the potential for real-time determination of blood volume fluctuations in tissue.

Estimation of axial blood velocity using the Doppler equation corrected for broadening.

To estimate axial velocity for vessels that are so narrow that their width is comparable to the minimum length of the range cell, it has been customary to substitute the maximum Doppler frequency fmax into the classical Doppler equation [eqn (1)]. It was shown here that this ignores transit time broadening, which can lead to significant errors at large beam-to-flow angles. We use a relation [eqn (2)], which does take this broadening into account, and give in vivo experimental proof of this allows accurate estimation of the axial velocity even when the range cell extends across the whole vessel lumen. It may be concluded, therefore, that, by using the above procedure for taking transit time spectral broadening into account, more accurate velocity estimates can be obtained for laminar flow than is possible with the current method using the classical Doppler equation uncorrected for broadening.

Second harmonic characteristics of the ultrasound contrast agents albunex and FSO69.

Techniques necessary for measurement of the second harmonic of the insonifying frequency backscattered from ultrasonic contrast agents are described, and used to determine this characteristic for the agents Albunex and FSO69. The results confirm theoretical predictions that scattered second harmonic pressure is proportional to the square of the incident pressure. Because contrast agents of the type investigated improve discrimination of blood echoes against tissue echoes by means of the second harmonic of the insonifying frequency, these results allow a comparison of the relative merits of Albunex and FSO69 for harmonic imaging.

Onset delay of acoustic second harmonic backscatter from bubbles or microspheres.

A well-known method of enhancing blood detectability in ultrasound imaging of tissues detects the second harmonic of the incident radiation, which is generated by ultrasound contrast agents in the form of bubbles or microspheres that may have been injected into the blood. We report here a delay in the onset of the backscattered second harmonic with respect to the backscattered first harmonic for these agents. This effect, which should limit the axial resolution attainable with harmonic imaging, is investigated by simulation as well as experiment, and its dependence on the incident ultrasonic amplitude and microsphere parameters is established.

Doppler spectral characterization of flow disturbances in the carotid with the Doppler probe at right angles to the vessel axis.

This paper reports on a new method intended to detect early flow disturbances generated by small lesions, using conventional clinical instrumentation. In vitro experiments on models of stenotic vessels are presented which prove that ultrasound Doppler, with the beam directed at right angles to the vessel axis can detect vortices and other flow disturbances caused by wall irregularities. These disturbances characterized by small velocity components first toward and then away from the transducer correlate with the spectrum of vortices caused by small artificial lesions. We found these disturbances in flow to be too small to cause detectable broadening in the Doppler spectrum acquired in the traditional way (i.e. with the beam at an angle less than 90 degrees). The detected flow disturbances were found to depend on the surface roughness, the profile of the obstructive lesion and the narrowing of the vessel. Similar flow disturbances to those detected in vitro were demonstrated in vivo for this new beam orientation in regions of the carotid, such as the bulb and the beginning of the common carotid, where vortex-like flows are expected.

Improved blood velocity estimation using the maximum Doppler frequency.

In vessels whose diameter is smaller than the length of the range cell or measurement volume, the maximum blood velocity is often calculated from the maximum frequency of the Doppler spectrum, using the classical Doppler equation. It is shown that the accuracy of this procedure is significantly improved at large beam-to-flow angles, if a correction for transit time broadening is made. This finding is based on the demonstration that the maximum frequency of the Doppler spectrum depends only on the maximum velocity passing through the measurement volume, but in a manner which is a function both of the Doppler shift frequency as well as the transit time broadening associated with the passage of scatterers through the beam width.

Demonstration of three-dimensional vector flow estimation using bandwidth and two transducers on a flow phantom.

A method of performing three-dimensional (3-D) velocity vector estimation with two transducers is demonstrated on a flow phantom using the Doppler spectra's mean frequencies and bandwidths. The results are compared with 3-D vector estimates computed from Doppler mean frequencies obtained with a five-transducer system. It is shown that the two-transducer vector Doppler system which uses bandwidth can improve on the accuracy of a three-transducer vector Doppler system which relies only on Doppler mean frequencies.

Advantages of subharmonic over second harmonic backscatter for contrast-to-tissue echo enhancement.

It is shown experimentally that backscatter from two ultrasonic contrast agents suspended in water or saline contains subharmonics of the incident frequency that are stronger than those backscattered at the same incident pressure from chicken breast. It is also shown that the ratio of subharmonic backscattered from contrast to that backscattered from tissue, is stronger than the ratio of backscattered second harmonic. In consequence, blood that contains contrast should be more easily detectable with respect to tissue if the subharmonic, rather than the second harmonic, is used for imaging.

On the spectral properties of Doppler thread phantoms.

It is shown that some of the threads used in Doppler phantoms have a repetitive structure which leads to peaks in the angular distribution of the backscattered power at beam axis-to-flow angles of theta = 90 degrees and approximately theta = 70 degrees. This nonuniform scattering does not significantly interfere with modelling the Doppler spectrum peak as a function of velocity and beam-to-thread angle, but makes it impossible to model the spectral width as a function of these parameters. A new plaited structure is described which has a periodicity too small to lead to subsidiary reflection peaks, and which has a more uniform backscattering profile than the other threads studied.

Invariance of the Doppler bandwidth with range cell size above a critical beam-to-flow angle.

For a sound beam impinging on a blood vessel, with a range cell much smaller than the vessel diameter, it is known that the breadth of the echo Doppler spectrum is proportional to the velocity of the flow through the range cell. As the range cell is lengthened to include a greater range of velocities, the spectrum is expected to widen proportionately. It is shown theoretically, and confirmed experimentally, that if the beam-to-flow angle is greater than a critical value, the Doppler spectrum bandwidth is independent of the length of the range cell, and depends only on the maximum velocity encompassed by it. This happens because for angles greater than the critical, the narrow spectra produced by lower velocity flows near the vessel walls are contained within the broader spectrum produced by the higher speed flow near the vessel axis. The critical angle is the angle at which the flow axis is normal to one of the beam edges.

Split-spectrum processing: analysis of polarity threshold algorithm for improvement of signal-to-noise ratio and detectability in ultrasonic signals.

A polarity thresholding algorithm that has recently been developed for split-spectrum processing for ultrasonic coherent noise reduction is theoretically analyzed to evaluate its performance. The probability density function (PDF) of the output of the algorithm is derived and used to calculate the theoretical signal-to-noise ratio (SNR) enhancement and the receiver operating characteristics. The performance limits of the algorithm are also established. Some experimental results of SNR enhancement obtained with the polarity thresholding algorithm are presented.

Bubble sizing with high spatial resolution.

The authors propose a technique that allows them to size bubbles with the same accuracy as with the double-frequency method and to locate them with the same range resolution as with the pulsed Doppler velocimeter. They demonstrate that the signal scattered by the bubble insonified by a high-frequency pulsed ultrasonic field and a low-frequency pumping field is a low-frequency signal sampled at the repetition frequency rate and in which the amplitude is maximum when the bubble resonates. However using a conventional Doppler flowmeter, the maximum amplitude is not detectable when the repetition frequency is a multiple of the pump frequency. The modifications of the signal processing needed to overcome this drawback are discussed and implemented in the conventional Doppler flowmeter. Using this modified setup the lateral and the longitudinal range resolution are the same as in conventional Doppler flowmeters. The resonance frequency thus obtained is also compared to the resonance frequency measured by the double Doppler frequency method. Some practical improvements are proposed to make the system easy to use. Using this latest version, the resonant requencies for ten different bubble sizes are measured and compared. The case in which the nonlinearity effect (due to a bubble at resonance) generates out-of-phase upper and lower sidebands is discussed, and it is demonstrated that this effect is so feeble that it is negligible.

Experimental proof of Doppler bandwidth invariance.

A line flow of scatterers crossing the sound field produced by a focused circular transducer at uniform velocity originates a quasi-triangular Doppler spectrum. It is known that the spectrum shape and width depend on the line flow to beam axis angle, as well as on the transducer geometry. It has recently been theoretically predicted that this spectrum width is independent of the flow line location in the sound field. Experimental verification of the new theorem, based on the use of a thread phantom operated at various orientations, ranges, and offsets, with respect to the ultrasound transducer, is presented. The tests were made with a computerized pulsed Doppler system designed to perform optimal real-time spectral analysis of data obtained in this application. The prototype system and the experimental procedure adopted for demonstrating in vitro the invariance of the Doppler spectral bandwidth are described.

Doppler ultrasound technique for measuring capillary-speed flow velocities with strong stationary echoes.

Ultrasound Doppler is widely used for low measurement in both medicine and industry, having the advantages of being non-invasive and comparatively simple and therefore inexpensive. The technique has not however been used for capillary blood flow measurement, because of the relatively low velocities encountered and because of the presence of strong interfering signals from the encompassing tissue. An ultrasound Doppler system capable of measuring flow velocities of one millimetre per second in the presence of one thousand times stronger interfering signals is described, as well as test results using both thread and flow phantoms.

Velocity magnitude estimation with linear arrays using Doppler bandwidth.

The dependence of pulsed wave Doppler bandwidth on parameters typical of linear transducer arrays used in commercial Duplex and color flow mapping systems is investigated experimentally. For a single flow line it is observed that this bandwidth generally depends not only on the scatterer velocity and the beam-to-flow angle, but also on the flow line range and orientation. This is due to the fact that in Duplex and color flow systems the transducer is differently focused in the scan and elevation planes and its aperture and focal lengths are often made to vary, depending on the distance of the flow line from the transducer. It is however experimentally demonstrated that, at points where the ultrasound beamwidths in the scan and elevation planes are both comparable to the sample volume length, the Doppler bandwidth is independent of the beam-to-flow angle. It is also shown that this invariance can be extended to other ranges by appropriately modifying the array aperture. Finally, as an application of this independence, the flow-line velocity magnitude in these beam regions is estimated with better than 5% uncertainty through a simple bandwidth measurement.