Design of chirp excitation waveform for dual-frequency harmonic contrast detection

Tissue background suppression is essential for harmonic detection of ultrasonic contrast microbubbles. To reduce the tissue harmonic amplitude for improvement of contrast-to-tissue ratio (CTR), the method of third harmonic (3f₀) transmit phasing uses an additional 3f₀ transmit signal to provide mutual cancellation between the frequency-sum component and the frequency-difference component of tissue harmonic signal. Chirp excitation can further improve the SNR in harmonic imaging without requiring an excessive transmit pressure and thus reduce potential bubble destruction. However, for effective suppression of tissue harmonic background in 3f₀ transmit phasing, the 3f₀ chirp waveform has to be carefully designed for the generation of spectrally matched cancellation pairs over the entire second harmonic band. In this study, we proposed a chirp waveform suitable for the method of 3f₀ transmit phasing, the different-bandwidth chirp signal (DBCS). With the DBCS waveform, the frequency-difference component of tissue harmonic signal becomes a chirp signal similar to its frequency-sum counterpart. Thus, the combination of the DBCS waveform with the 3f₀ transmit phasing can markedly suppress the tissue harmonic amplitude for CTR improvement together with effective SNR increase of contrast harmonic signal. Our results indicate that, as compared with the conventional Gaussian pulse, the DBCS waveform can provide 6-dB improvement of SNR in 3f₀ transmit phasing with a CTR increase of 3 dB. Nevertheless, the limitation of available transmit bandwidth and the frequency-dependent attenuation can degrade the performance of the DBCS waveform in tissue suppression. The design of the DBCS waveform is also applicable to other dual-frequency imaging techniques that rely on the harmonic generation at the difference frequency.     

Golay-encoded excitation for dual-frequency harmonic detection of ultrasonic contrast agents

Golay-encoded excitation in combination with the third harmonic (3f?) transmit phasing is examined for both signal-to-noise ratio (SNR) and contrast-to-tissue ratio (CTR) improvements in harmonic imaging of contrast microbubbles. To produce the cancellation pair of tissue harmonic signal in 3f? transmit phasing, the phase of the bit waveform is properly designed for both the fundamental and the 3f? transmit signals to provide the Golay encoding of the received harmonic responses. Results indicate that the proposed Golay excitation can effectively suppress the tissue harmonic amplitude to increase CTR. Meanwhile, the SNR of the contrast harmonic signal also improves because of the elongated waveform of Golay excitation. Nevertheless, the generation of marked range side-lobes of the bubble region would degrade the achievable SNR improvement and the image contrast, especially when the bit of Golay excitation increases. The range side-lobes could result from the nonlinear resonance of the microbubbles that interferes with the phase modulation of the Golay encoding.     

Impact of propagation through an aberrating medium on the linear effective apodization of a nonlinearly generated second harmonic field

Techniques based on the nonlinearly generated second harmonic signal (tissue harmonic imaging) have rapidly supplanted linear (fundamental) imaging methods as the standard in two-dimensional echocardiography. Enhancements to the compactness of the nonlinearly generated second harmonic (2f) field component with respect to the fundamental (1f) field component are widely considered to be among the factors contributing to the observed image quality improvements. The objective of this study was to measure the impact of phase and amplitude aberrations resulting from propagation through an inhomogeneous tissue, on the beamwidths associated with: the fundamental (1f); the nonlinearly generated second harmonic (2f); and the linearly propagated, effective apodization signal at the same (21) frequency. Modifications to the transmit characteristics of a phased-array imaging system were validated with hydrophone measurements. Results demonstrate that the characteristics of the diffraction pattern associated with the linear-propagation effective apodization transmit case were found to be in good agreement with the detailed spatial characteristics of the nonlinearly generated second harmonic field. The effects of the abdominal wall tissue aberrators are apparent for all three of the beam profiles studied. Consistent with the improved image quality associated with harmonic imaging, the aberrated nonlinearly generated second harmonic beam was shown to remain more compact than the corresponding aberrated fundamental beam patterns in the presence of the interposed aberrator.     

Suppression of propagating second harmonic in ultrasound contrast imaging

Contrast agents, such as bubbles, are used in ultrasound to enhance backscatter from blood. To increase contrast between these agents and tissue, nonlinear methods such as harmonic imaging can be used. Contrast is limited, however, by tissue second harmonic signals. We show that a major source of this signal is nonlinear propagation through tissue. In addition, we present methods to suppress this second harmonic generation. One simple approach is to decrease the f/number of the imaging system. Simulations show that doubling the size of the array, while keeping total power output constant, decreases propagating second harmonic generation. A second approach uses active noise cancellation to suppress second harmonic generation. A specific method, the harmonic cancellation system (HCS), is developed and presented as an example. In simulations, HCS decreased second harmonic generation by over 30 dB. Using such methods, contrast can be improved between tissue and bubbles in harmonic imaging.     

High frequency nonlinear B-scan imaging of microbubble contrast agents

It was previously shown that it is possible to produce nonlinear scattering from microbubble contrast agents using transmit frequencies in the 14-32 MHz range, suggesting the possibility of performing high-frequency, nonlinear microbubble imaging. In this study, we describe the development of nonlinear microbubble B-scan imaging instrumentation capable of operating at transmit center frequencies between 10 and 50 MHz. The system underwent validation experiments using transmit frequencies of 20 and 30 MHz. Agent characterization experiments demonstrate the presence of nonlinear scattering for the conditions used in this study. Using wall-less vessel phantoms, nonlinear B-scan imaging is performed using energy in one of the subharmonic, ultraharmonic, and second harmonic frequency regions for transmit frequencies of 20 and 30 MHz. Both subharmonic and ultraharmonic imaging modes achieved suppression of tissue signals to below the noise floor while achieving contrast to noise ratios of up to 26 and 17 dB, respectively. The performance of second harmonic imaging was compromised by nonlinear propagation and offered no significant contrast improvement over fundamental mode imaging. In vivo experiments using the subharmonic of a 20 MHz transmit pulse show the successful detection of microvessels in the rabbit ear and in the mouse heart. The results of this study demonstrate the feasibility of nonlinear microbubble imaging at high frequencies     

Spatial coherence of backscatter for the nonlinearly produced second harmonic for specific transmit apodizations

To be successful, correlation-based, phase-aberration correction requires a high correlation among backscattered signals. For harmonic imaging, the spatial coherence of backscatter for the second harmonic component is different than the spatial coherence of backscatter for the fundamental component. The purpose of this work was to determine the effect of changing the transmit apodization on the spatial coherence of backscatter for the nonlinearly generated second harmonic. Our approach was to determine the effective apodizations for the fundamental and second harmonic using both experimental measurements and simulations. Two-dimensional measurements of the transverse cross sections of the finite-amplitude ultrasonic fields generated by rectangular and circular apertures were acquired with a hydrophone. Three different one-dimensional transmit apodization functions were investigated: uniform, Riesz, and trapezoidal. An effective apodization was obtained for each transmit apodization by backpropagating the values measured from within the transmit focal zone using a linear angular spectrum approach. Predictions of the spatial coherence of backscatter were obtained using the pulse-echo Van Cittert-Zernike theorem. In all cases the effective apodization at 2f was narrower than the transmit apodization. We demonstrate that certain transmit apodizations result in a greater spatial coherence of backscatter at the second harmonic than at the fundamental.     

Acoustic signatures of submicron contrast agents

Previous studies have revealed that hard-shelled submicron contrast agents exhibit large relative expansions and strong acoustical echoes that can be observed experimentally, and predicted by theoretical simulations. In this paper, we study harmonic imaging and pulse-pair imaging techniques designed to assist in the differentiation of these contrast agents from tissue. For harmonic imaging, we apply a high-sensitivity, narrowband strategy that differentiates the microbubble from tissue based on the generation of strong harmonic echoes. For pulse-pair imaging, we apply high spatial resolution, wideband strategies using phase inversion, which relies on the frequency differences observed in response to phase-inverted pulses, and signal subtraction, which takes advantage of the amplitude differences in response to identical pulses. The bubble-to-phantom signal amplitude ratio in the absence of motion approaches 20 dB using phase inversion and 30 dB using signal subtraction; both techniques are robust for up to 50 microm of simulated motion. With the experience gained in these studies, we hope to advance the development of multi-pulse or shaped-pulse techniques that are optimized for specific clinical applications.     

Harmonic leakage and image quality degradation in tissue harmonic imaging

Image quality degradation caused by harmonic leakage was studied for finite amplitude distortion-based harmonic imaging. Various sources of harmonic leakage, including transmit waveform, signal bandwidth, and system nonlinearity, were investigated using both simulations and hydrophone measurements. Effects of harmonic leakage in the presence of sound velocity inhomogeneities were also considered. Results indicated that sidelobe levels of the harmonic beam pattern were directly affected by harmonic leakage when the harmonic signal was obtained by filtering out the fundamental signal. Because sidelobe levels also increase with the bandwidth of the transmitted signal, a trade-off exists between axial resolution and contrast resolution. It is concluded that accurate control of the frequency content of the waveform prior to propagation is necessary to optimize imaging performance of tissue harmonic imaging. The filtering technique was also compared with the pulse inversion technique. It was shown that the pulse inversion technique effectively suppresses harmonic leakage at the cost of imaging frame rate and potential motion artifacts     

Source prebiasing for improved second harmonic bubble-response imaging

The use of the second harmonic bandwidth in order to improve the contrast enhancement of vascular space provided by microbubble echo contrast is well established. A significant obstacle to improving on the contrast advantage of the second harmonic bandwidth arises from the linear response of tissue to the finite amplitude distortion produced second harmonic in the beam. A scheme in which the source wave contains a second harmonic component designed to cancel out the second harmonic produced by finite amplitude distortion in the focal region was computationally investigated. This prebiasing scheme was found to offer significant reductions in the amplitude of the second harmonic in the focal region. These reductions were found in both the homogeneous tissue path case and in the inhomogeneous tissue path case. The resulting clinical potential of source prebiasing is discussed. Also, it was observed that the inhomogeneous focusing of the finite amplitude distortion-produced second harmonic was significantly better than that of a same frequency fundamental with an identical homogeneous path focal profile.     

Precompensated excitation waveforms to suppress harmonic generation in MEMS electrostatic transducers

Microelectromechanical systems (MEMS) electrostatic-based transducers inherently produce harmonics as the electrostatic force generated in the transmit mode is approximately proportional to the square of the applied voltage signal. This characteristic precludes them from being effectively used for harmonic imaging (either with or without the addition of microbubble-based contrast agents). The harmonic signal that is nonlinearly generated by tissue (or contrast agent) cannot be distinguished from the inherent transmitted harmonic signal. We investigated two precompensation methods to cancel this inherent harmonic generation in electrostatic transducers. A combination of finite element analysis (FEA) and experimental results are presented. The first approach relies on a calculation, or measurement, of the transducer's linear transfer function, which is valid for small signal levels. Using this transfer function and a measurement of the undesired harmonic signal, a predistorted transmit signal was calculated to cancel the harmonic inherently generated by the transducer. Due to the lack of perfect linearity, the approach does hot work completely in a single iteration. However, with subsequent iterations, the problem becomes more linear and converges toward a very satisfactory result (a 18.6 dB harmonic reduction was achieved in FEA simulations and a 20.7 dB reduction was measured in a prototype experiment). The second approach tested involves defining a desired function [including a direct current (DC) offset], then taking the square root of this function to determine the shape of the required input function. A 5.5 dB reduction of transmitted harmonic was obtained in both FEA simulation and experimental prototypes test.     

Motion artifacts of pulse inversion-based tissue harmonic imaging

Motion artifacts of the pulse inversion technique were studied for finite amplitude distortion-based harmonic imaging. Motion in both the axial and the lateral directions was considered. Two performance issues were investigated. One is the harmonic signal intensity relative to the fundamental intensity and the other is the potential image quality degradation resulting from spectral leakage. A one-dimensional (1-D) correlation-based correction scheme also was used to compensate for motion artifacts. Results indicated that the tissue harmonic signal is significantly affected by tissue motion. For axial motion, the tissue harmonic intensity decreases much more rapidly than with lateral motion. The fundamental signal increases for both axial and lateral motion. Thus, filtering is still required to remove the fundamental signal, even if the pulse inversion technique is applied. The motion also potentially decreases contrast resolution because of the uncancelled spectral leakage. Also, it was indicated that 1-D motion correction is not adequate if nonaxial motion is present.     

Ultrasound speckle reduction using harmonic oscillator models

A speckle reduction algorithm called the harmonic imaging (HI) algorithm is presented. It is based on a multicomponent scattering model for medical ultrasonics. The backscattered ultrasound quadrature signal is modeled as the sum of three components after demodulation. The first component represents nonresolvable diffuse scatterers, while the second component represents subresolvable quasi-periodic scatterers. The third component represents resolvable quasi-periodic scatterers and mirroring surfaces. Since the second component gives rise to the most long range destructive interference effects it is eliminated in the HI algorithm to reduce speckle. Due to its slow spatial variation, it can be almost completely eliminated simply by differentiating the backscattered demodulated quadrature signal. Lissajous-like figures are observed in complex plots of the signals from ultrasound beams going through tissues with quasi-periodic components and sometimes in areas with only diffuse scatterers. Therefore the sum of the complex signals from the resolvable and nonresolvable scatterers within a resolution cell is modeled by two orthogonal and independent harmonic oscillators. The estimated, total energy of these two oscillators determines the gray level value of the HI image within the resolution cell. The HI images produced using radio frequency data from a phantom and from tissues in vivo are more blurred than ordinary envelope images, but the signal to noise ratio and tissue contrast were higher for the HI images     

Changes in the echoes from ultrasonic contrast agents with imaging parameters

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.     

Spatial coherence of the nonlinearly generated second harmonic portion of backscatter for a clinical imaging system

Correlation-based approaches to phase aberration correction rely on the spatial coherence of backscattered signals. The spatial coherence of backscatter from speckle-producing targets is predicted by the auto correlation of the transmit apodization (Van Cittert-Zernike theorem). Work by others indicates that the second harmonic beam has a wider mainlobe with lower sidelobes than a beam transmitted at 2f. The purpose of this paper is to demonstrate that the spatial coherence of backscatter for the second harmonic is different from that of the fundamental, as would be anticipated from applying the Van Cittert-Zernike theorem to the reported measurements of the second harmonic field. Another objective of this work is to introduce the concept of the effective apodization and to verify that the effective apodization of the second harmonic is narrower than the transmit apodization. The spatial coherence of backscatter was measured using three clinical arrays with a modified clinical imaging system. The spatial coherence results were verified using a pseudo-array scan in a transverse plane of the transmitted field with a hydrophone. An effective apodization was determined by backpropagating these values using a linear angular spectrum approach. The spatial coherence for the harmonic portion of backscatter differed systematically and significantly from the auto correlation of the transmit apodization.     

Optimization of a phased-array transducer for multiple harmonic imaging in medical applications: frequency and topology

Second-harmonic imaging is currently one of the standards in commercial echographic systems for diagnosis, because of its high spatial resolution and low sensitivity to clutter and near-field artifacts. The use of nonlinear phenomena mirrors is a great set of solutions to improve echographic image resolution. To further enhance the resolution and image quality, the combination of the 3rd to 5th harmonics--dubbed the superharmonics--could be used. However, this requires a bandwidth exceeding that of conventional transducers. A promising solution features a phased-array design with interleaved low- and high-frequency elements for transmission and reception, respectively. Because the amplitude of the backscattered higher harmonics at the transducer surface is relatively low, it is highly desirable to increase the sensitivity in reception. Therefore, we investigated the optimization of the number of elements in the receiving aperture as well as their arrangement (topology). A variety of configurations was considered, including one transmit element for each receive element (1/2) up to one transmit for 7 receive elements (1/8). The topologies are assessed based on the ratio of the harmonic peak pressures in the main and grating lobes. Further, the higher harmonic level is maximized by optimization of the center frequency of the transmitted pulse. The achievable SNR for a specific application is a compromise between the frequency-dependent attenuation and nonlinearity at a required penetration depth. To calculate the SNR of the complete imaging chain, we use an approach analogous to the sonar equation used in underwater acoustics. The generated harmonic pressure fields caused by nonlinear wave propagation were modeled with the iterative nonlinear contrast source (INCS) method, the KZK, or the Burger's equation. The optimal topology for superharmonic imaging was an interleaved design with 1 transmit element per 6 receive elements. It improves the SNR by ~5 dB compared with the interleaved (1/2) design reported in literature. The optimal transmit frequency for superharmonic echocardiography was found to be 1.0 to 1.2 MHz. For superharmonic abdominal imaging this frequency was found to be 1.7 to 1.9 MHz. For 2nd-harmonic echocardiography, the optimal transmit frequency of 1.8 MHz reported in the literature was corroborated with our simulation results.     

Intravascular ultrasound tissue harmonic imaging in vivo

Tissue harmonic imaging (THI) has been shown to increase image quality of medical ultrasound in the frequency range from 2 to 10 MHz and might, therefore, also be used to improve image quality in intravascular ultrasound (IVUS). In this study we constructed a prototype IVUS system that could operate in both fundamental frequency and second harmonic imaging modes. This system uses a conventional, continuously rotating, single-element IVUS catheter and was operated in fundamental 20 MHz, fundamental 40 MHz, and harmonic 40 MHz modes (transmit 20 MHz, receive 40 MHz). Hydrophone beam characterization measurements demonstrated the build-up of a second harmonic signal as a function of increasing pressure. Imaging experiments were conducted in both a tissue-mimicking phantom and in an atherosclerotic animal model in vivo. Acquisitions of fundamental 20 and 40 MHz and second harmonic acquisitions resulted in cross sections of the phantom and a rabbit aorta. The harmonic results of the imaging experiments showed the feasibility of intravascular THI with a conventional IVUS catheter both in a phantom and in vivo. The harmonic acquisitions also showed the potential of THI to reduce image artifacts compared to fundamental imaging.     

Adaptive resonator-based method for power system harmonic analysis

A simple algorithm for the harmonic estimation, in a wide range of frequency changes, with benefits in a reduced complexity and computational efforts is prescribed. This implementation is based on a recently introduced common structure for recursive discrete transforms and contemplated as an implementation of finite-impulse-response (FIR) and infinite-impulse-response (MR) filter transfer functions to reduce computational efforts. This structure consists of digital resonators in a common negative feedback loop. The structure of the estimation algorithm consists of two decoupled modules: the first one for an adaptive filter of input signal with harmonic amplitude and phase calculation, the second one for an external frequency estimation. A very suitable algorithm for frequency and harmonic phasor estimations is obtained. To demonstrate the performance of the developed algorithm, computer-simulated data records are processed. Simulation results show that this algorithm is applicable to detect the harmonic amplitudes of steady-state, varying and decaying sinusoidal signals. It has been found that the proposed method really meets the needs of online applications. This technique provides accurate amplitude estimates in about one period.     

A 120-MHz Bandwidth Linear Signal Transmission System Using Fiber Optics

A complete linear fiber-optic-signal transmission system with an upper frequency limit greater than 150 MHz is described. The transmitter accepts signals in the range of 1 to 15 mV and amplitude modulates an LED. The emitted light signal is carried via fiber optics to a receiver employing a silicon avalanche detector and an amplifier which increases the signal level to the hundreds of millivolts range. Sine-wave bandwidth is 30 kHz-120 MHz (voltage response down to 70 percent), and phase distortion is low, thus preserving pulseshapes. For a transmission path consisting of 15 m of low-cost fiber cable, the dynamic range is 30 dB with harmonic content 30 dB below signal.     

Second harmonic imaging and harmonic Doppler measurements withAlbunex

Gaseous ultrasound contrast agents, such as Albunex, have been shown to be valuable clinically for the better identification of certain anatomic structures and for quantitating organ perfusion. However, the application of a contrast agent sometimes also reduces the image contrast between the blood and the surrounding tissues. This paper presents experimental results to show that this problem may be alleviated by using harmonic signals generated by nonlinear backscattering of these microbubbles. The results show that the second harmonic signal produced by Albunex is significant and that harmonic images in which backscattered echoes from solid tissues were filtered out, but not those from Albunex, can be obtained. In addition, a continuous wave Doppler arrangement has been implemented. It permits quantitative harmonic Doppler measurements at different frequencies, concentrations, and transmitted acoustic pressures. When Albunex was compared to polystyrene microsphere suspensions which possess exclusively linear behavior, Doppler power at second and subharmonic frequencies could only be detected from these microbubbles. A comparison of results on Doppler powers measured at the first harmonic from polystyrene spheres and Albunex indicates that at a transmitting frequency of 2.5 MHz, the Doppler power from Albunex is 12 dB stronger than the polystyrene spheres, whereas at 5 MHz, the Doppler power from Albunex is 3 dB weaker than that from the polystyrene spheres     

频谱校正时谱线干涉的影响及判定方法

针对现代比例（内插）频谱校正法要求参与计算的两条谱线只包含单频率成分信号的特点，分析了包含有两个以上频率成分信号和负频率成分所产生的谱线干涉现象及由此带来的较大校正误差问题，推导并提出了离散频谱中谱干涉的相位和幅值综合判断方法以及校正的可信度，当可信度为１００％时，此离散谱峰为单频率成分，由此实现了单频率信号离散频谱的自动校正。仿真计算表明该方法简便易行、精度高