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Deep abdominal images suffer from poor diffraction-limited lateral resolution. Extending the aperture size can improve resolution. However, phase distortion and clutter can limit the benefits of larger arrays. Previous studies have explored these effects using numerical simulations, multiple transducers, and mechanically swept arrays. In this work, we used an 8.8-cm linear array transducer to investigate the effects of aperture size when imaging through the abdominal wall. We acquired channel data in fundamental and harmonic modes using five aperture sizes. To avoid motion and increase the parameter sampling, we decoded the full-synthetic aperture data and retrospectively synthesized nine apertures (2.9-8.8 cm). We imaged a wire target and a phantom through ex vivo porcine abdominal samples and scanned the livers of 13 healthy subjects. We applied bulk sound speed correction to the wire target data. Although point resolution improved from 2.12 to 0.74 mm at 10.5 cm depth, contrast resolution often degraded with aperture size. In subjects, larger apertures resulted in an average maximum contrast degradation of 5.5 dB at 9-11 cm depth. However, larger apertures often led to visual detection of vascular targets unseen with conventional apertures. An average 3.7-dB contrast improvement over fundamental mode in subjects showed that the known benefits of tissue-harmonic imaging extend to larger arrays.

As the applications of ultrasonic thermal therapies expand, the design of the high-intensity array must address both the energy delivery of the main beam and the character and relevance of off-target beam energy. We simulate the acoustic field performance of a selected set of circular arrays organized by array format, including flat versus curved arrays, periodic versus random arrays, and center void diameter variations. Performance metrics are based on the -3-dB focal main lobe (FML) positioning range, axial grating lobe (AGL) temperatures, and side lobe levels. Using finite-element analysis, we evaluate the relative heating of the FML and the AGLs. All arrays have a maximum diameter of 100λ, with element count ranging from 64 to 1024 and continuous wave frequency of 1.5 MHz. First, we show that a 50% spherical annulus produces focus beam side lobes which decay as a function of lateral distance at nearly 87% of the exponential rate of a full aperture. Second, for the arrays studied, the efficiency of power delivery over the -3-dB focus positioning range for spherical arrays is at least 2-fold greater than for flat arrays; the 256-element case shows a 5-fold advantage for the spherical array. Third, AGL heating can be significant as the focal target is moved to its distal half-intensity depth from the natural focus. Increasing the element count of a randomized array to 256 elements decreases the AGL-to-FML heating ratio to 0.12 at the distal half-intensity depth. Further increases in element count yield modest improvements. A 49% improvement in the AGL-to-peak heating ratio is predicted by using the Sumanaweera spiral element pattern with randomization.

Ultrasound contrast agent microbubbles are intravascular agents that can be used to estimate blood perfusion. Blood perfusion may be estimated by destroying the bubbles in a vascular bed and observing the refresh of contrast agents back into the vascular bed. Contrast agents can be readily destroyed by traditional imaging techniques. The design of a nondestructive imaging technique is necessary for the accurate quantification of contrast agent refresh. In this work, subharmonic imaging is investigated as a method for nondestructive imaging with the contrast agent microbubble MP1950 (Mallinckrodt, Inc., St. Louis, MO). Optical observation during insonation, in conjunction with a modified Rayleigh-Plesset (R-P) analysis, provides insight into the mechanisms of and parameters required for subharmonic frequency generation. Subharmonic imaging with a transmission frequency that is the same as the resonant frequency of the bubble is shown to require a minimum pressure of insonation that is greater than the experimentally-observed bubble destruction threshold. Subharmonic imaging with a transmission frequency that is twice the resonant frequency of the bubble produces a subharmonic frequency response while minimizing bubble instability. Optimization is performed using optical experimental analysis and R-P analysis.

Ultrasound contrast agents are encapsulated microbubbles, filled either with air or a higher weight molecular gas, ranging in size from 1 to 10 microns in diameter. The agents are modeled as air-filled spherical elastic shells of variable thickness and material properties. The scattered acoustic field is computed from a modal series solution, and reflectivity and angular scattering are then determined from the computed fields for agents of various properties. We show that contrast agents also support shell resonance responses in addition to the monopole response, which has been the focus of previous contrast agent studies. Lamb waves appear to be the source of these additional responses. A shell or curvature Lamb wave generates dipole peaks in the 1- to 40-MHz range for 2.5 to 3.5 microns radius agents with elastic properties approximating those of albumin protein. The inclusion of damping affects the lower frequency dipole peaks but is less important for responses occurring above approximately 30 MHz. Moreover, these responses hold untapped potential for clinical ultrasound applications such as tissue perfusion studies and high frequency contrast agent imaging.

Various applications of contrast-assisted ultrasound, including blood vessel detection, perfusion estimation, and drug delivery, require controlled destruction of contrast agent microbubbles. The lifetime of a bubble depends on properties of the bubble shell, the gas core, and the acoustic waveform impinging on the bubble. Three mechanisms of microbubble destruction are considered: fragmentation, acoustically driven diffusion, and static diffusion. Fragmentation is responsible for rapid destruction of contrast agents on a time scale of microseconds. The primary characteristics of fragmentation are a very large expansion and subsequent contraction, resulting in instability of the bubble. Optical studies using a novel pulsed-laser optical system show the expansion and contraction of ultrasound contrast agent microbubbles with the ratio of maximum diameter to minimum diameter greater than 10. Fragmentation is dependent on the transmission pressure, occurring in over 55% of bubbles insonified with a peak negative transmission pressure of 2.4 MPa and in less than 10% of bubbles insonified with a peak negative transmission pressure of 0.8 MPa. The echo received from a bubble decorrelates significantly within two pulses when the bubble is fragmented, creating an opportunity for rapid detection of bubbles via a decorrelation-based analysis. Preliminary findings with a mouse tumor model verify the occurrence of fragmentation in vivo. A much slower mechanism of bubble destruction is diffusion, which is driven by both a concentration gradient between the concentration of gas in the bubble compared with the concentration of gas in the liquid, as well as convective effects of motion of the gas-liquid interface. The rate of diffusion increases during insonation, because of acoustically driven diffusion, producing changes in diameter on the time scale of the acoustic pulse length, thus, on the order of microseconds. Gas bubbles diffuse while they are not being insonified, termed static diffusion. An air bubble with initial diameter of 2 microns in water at 37 degrees C is predicted to fully dissolve within 25 ms. Clinical ultrasound contrast agents are often designed with a high molecular weight core in an attempt to decrease the diffusion rate. C3F8 and C4F10 gas bubbles of the same size are predicted to fully dissolve within 400 ms and 4000 ms, respectively. Optical experiments involving gas diffusion of a contrast agent support the theoretical predictions; however, shelled agents diffuse at a much slower rate without insonation, on the order of minutes to hours. Shell properties play a significant role in the rate of static diffusion by blocking the gas-liquid interface and decreasing the transport of gas into the surrounding liquid. Static diffusion decreases the diameter of albumin-shelled agents to a greater extent than lipid-shelled agents after insonation.

Ultrasound contrast agents provide new opportunities to image vascular volume and flow rate directly. To accomplish this goal, new pulse sequences can be developed to detect specifically the presence of a microbubble or group of microbubbles. We consider a new scheme to detect the presence of contrast agents in the body by examining the effect of transmitted phase on the received echoes from single bubbles. In this study, three tools are uniquely combined to aid in the understanding of the effects of transmission parameters and bubble radius on the received echo. These tools allow for optical measurement of radial oscillations of single bubbles during insonation, acoustical study of echoes from single contrast agent bubbles, and the comparison of these experimental observations with theoretical predictions. A modified Herring equation with shell terms is solved for the time-dependent bubble radius and wall velocity, and these outputs are used to formulate the predicted echo from a single encapsulated bubble. The model is validated by direct comparison of the predicted radial oscillations with those measured optically. The transient bubble response is evaluated with a transducer excitation consisting of one-cycle pulses with a center frequency of 2.4-MHz. The experimental and theoretical results are in good agreement and predict that the transmission of two pulses with opposite polarity will yield similar time domain echoes with the first significant portion of the echo generated when the rarefactional half-cycle reaches the bubble.

Optimal use of encapsulated microbubbles for ultrasound contrast agents and drug delivery requires an understanding of the complex set of phenomena that affect the contrast agent echo and persistence. With the use of a video microscopy system coupled to either an ultrasound flow phantom or a chamber for insonifying stationary bubbles, we show that ultrasound has significant effects on encapsulated microbubbles. In vitro studies show that a train of ultrasound pulses can alter the structure of an albumin-shelled bubble, initiate various mechanisms of bubble destruction or produce aggregation that changes the echo spectrum. In this analysis, changes observed optically are compared with those observed acoustically for both albumin and lipid-shelled agents. We show that, when insonified with a narrowband pulse at an acoustic pressure of several hundred kPa, a phospholipid-shelled bubble can undergo net radius fluctuations of at least 15%; and an albumin-shelled bubble initially demonstrates constrained expansion and contraction. If the albumin shell contains air, the shell may not initially experience surface tension; therefore, the echo changes more significantly with repeated pulsing. A set of observations of contrast agent destruction is presented, which includes the slow diffusion of gas through the shell and formation of a shell defect followed by rapid diffusion of gas into the surrounding liquid. These observations demonstrate that the low-solubility gas used in these agents can persist for several hundred milliseconds in solution. With the transmission of a high-pulse repetition rate and a low pressure, the echoes from, contrast agents can be affected by secondary radiation force. Secondary radiation force is an attractive force for these experimental conditions, creating aggregates with distinct echo characteristics and extended persistence. The scattered echo from an aggregate is several times stronger and more narrowband than echoes from individual bubbles.

In contrast to previous systems in which an ultrasonic pulse was repeatedly directed to a discrete line of sight, a new method has been developed to continuously scan over a region in order to rapidly assess blood velocities in superficial small blood vessels. Using this technique, which we call swept-scan, a high frequency transducer can rapidly translate across a region of interest, and sensitive maps of blood velocity in small blood vessels can be constructed. This system has been applied to flow mapping in the anterior segment of the eye, which is clinically significant in cases of trauma and glaucoma. No previous imaging technique has been capable of estimating blood velocities within this region in a clinically useful manner. With this new technique, each 2-D scan of the eye can be obtained in an interval on the order of 1 second, and blood flow through the iris and ciliary body can be detected in vessels as small as 40 microns. A major implication of this new technique is that a wall filter can be applied continuously to the return from all regions, thus eliminating the transient response that occurs along each line of sight in traditional Doppler systems.

Ultrasound contrast agents consist of a gas bubble, encapsulated by a shell for stabilization. The shell dampens the fluctuations in the bubble radius when insonified. The detection of contrast microbubbles during a medical examination can indicate whether a region is perfused with blood. Here, the authors consider the effect of the phase of sonification signal on the backscatter by the bubble echo. By transmitting two short pulses of ultrasound with opposite phases, the authors demonstrate that a unique pair of echoes can be generated by a single microbubble, and that the properties of these echoes may be useful in the discrimination of bubble and tissue echoes. Specifically, the significant echo amplitude begins coincident with each transmitted rarefactional half-cycle, and the mean frequency of this echo depends on the transmitted phase. When rarefaction is transmitted first for a 2.25 MHz signal, the mean frequency is 0.8 MHz higher for an albumin-shelled bubble and 0.9 MHz higher for a lipid-shelled bubble. The experimental results agree with the predictions of the Gilmore-Akulichev equation.

Current harmonic imaging scanners transmit a narrowband signal that limits spatial resolution in order to differentiate the echoes from tissue from the echoes from microbubbles. Because spatial resolution is particularly important in applications, including mapping vessel density in tumors, we explore the use of wideband signals in contrast imaging. It is first demonstrated that microspheres can be destroyed using one or two pulses of ultrasound. Thus, temporal signal processing strategies that use the change in the echo over time can be used to differentiate echoes from bubbles and echoes from tissue. Echo parameters, including intensity and spectral shape for narrowband and wideband transmission, are then evaluated. Through these experiments, the echo intensity received from bubbles after wideband transmission is shown to be at least as large as that for narrowband transmission, and can be larger. In each case, the echo intensity increases in a nonlinear fashion in comparison with the transmitted signal intensity. Although the echo intensity at harmonic multiples of the transmitted wave center frequency can be larger for narrowband insonation, echoes received after wideband insonation demonstrate a broadband spectrum with significant amplitude over a very wide range of frequencies.

A comprehensive theoretical performance comparison of the wideband maximum-likelihood (WMLE) and cross-correlation strategies, previously proposed and evaluated for the estimation of blood velocity using ultrasound is presented. It is based on evaluation of the bias, local and global accuracy, and signal-to-noise ratio (SNR) performance. The results show that the intervening medium does not bias either wideband estimation, due to the effect of tracking the scattering target. The presence of intervening tissue actually improves the global accuracy of both wideband estimators, without a significant change in the local accuracy of either wideband estimator. After the transmission of P pulses, a comparison of the performance of the two strategies shows that the cross-correlation estimator requires P(2 ) correlations to achieve performance similar to that of the WMLE with P operations. In addition, the WMLE can increase the effective SNR in comparison with cross correlation.

For pt.I see ibid., vol.38, p.1-16, Jan. 1991. The signal models and performance of the estimation strategies described in pt.I are tested with experimental ultrasonic data. The ultrasonic data analyzed verify the theoretical model and predicted performance. The averaged correlation, verified experimentally, confirms that the correlation envelope can be used to estimate the velocity of scatterers and that the shape of the correlation function conveys information regarding the velocity profile within the sample volume. For both the wideband point and range spread estimators, the predicted improvement in velocity resolution and the reduction in height of subsidiary velocity peaks are demonstrated. Through the use of these estimation strategies, information regarding the mean velocity and velocity variation are available for each spatial location within the vessel. This information is presented using a three-dimensional spatial velocity profile display, which appears to offer a number of advantages in the rapid identification of pathology.

The derivation and theoretical evaluation of new wideband maximum-likelihood strategies for the estimation of blood velocity using acoustic signals are presented. A model for the received signal from blood scatterers, using a train of short wideband pulses, is described. Evaluation of the autocorrelation of the signal based on this model shows that the magnitude, periodicity, and phase of the autocorrelation are affected by the mean scatterer velocity and the presence of a velocity spread target. New velocity estimators are then derived that exploit the effect of the scatterer velocity on both the signal delay and the shift in frequency. The wideband range spread estimator is derived using a statistical model of the target. Based on the point target assumption, a simpler wideband maximum-likelihood estimator is also obtained. These new estimation strategies are analyzed for their local and global performance. Evaluation of the Cramer-Rao bound shows that the bound on the estimator variance is reduced using these estimators, in comparison with narrowband strategies. In order to study global accuracy, the expected estimator output is evaluated, and it is determined that the width of the mainlobe is reduced. In addition, it is shown that the height of subsidiary velocity peaks is reduced through the use of these new estimators.