Harmonic chirp imaging method for ultrasound contrast agent

Coded excitation is currently used in medical ultrasound to increase signal-to-noise ratio (SNR) and penetration depth. We propose a chirp excitation method for contrast agents using the second harmonic component of the response. This method is based on a compression filter that selectively compresses and extracts the second harmonic component from the received echo signal. Simulations have shown a clear increase in response for chirp excitation over pulse excitation with the same peak amplitude. This was confirmed by two-dimensional (2-D) optical observations of bubble response with a fast framing camera. To evaluate the harmonic compression method, we applied it to simulated bubble echoes, to measured propagation harmonics, and to B-mode scans of a flow phantom and compared it to regular pulse excitation imaging. An increase of approximately 10 dB in SNR was found for chirp excitation. The compression method was found to perform well in terms of resolution. Axial resolution was in all cases within 10% of the axial resolution from pulse excitation. Range side-lobe levels were 30 dB below the main lobe for the simulated bubble echoes and measured propagation harmonics. However, side-lobes were visible in the B-mode contrast 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.     

Observation of contrast agent response to chirp insonation with a simultaneous optical-acoustical system

Rayleigh-Plesset analysis, ultra-high speed photography, and single bubble acoustical recordings previously were applied independently to characterize the radial oscillation and resulting echoes from a microbubble in response to an ultrasonic pulse. In addition, high-speed photography has shown that microbubbles are destroyed over a single pulse or pulse train by diffusion and fragmentation. In order to develop a single model to characterize microbubble echoes based on oscillatory and destructive characteristics, an optical-acoustical system was developed to simultaneously record the optical image and backscattered echo from each microbubble. Combined observation provides the opportunity to compare predictions for oscillation and echoes with experimental results and identify discrepancies due to diffusion or fragmentation. Optimization of agents and insonating pulse parameters may be facilitated with this system. The mean correlation of the predicted and experimental radius-time curves and echoes exceeds 0.7 for the parameters studied here. An important application of this new system is to record and analyze microbubble response to a long pulse in which diffusion is shown to occur over the pulse duration. The microbubble response to an increasing or decreasing chirp is evaluated using this new tool. For chirp insonation beginning with the lower center frequency, low-frequency modulation of the oscillation envelope was obvious. However, low-frequency modulation was not observed in the radial oscillation produced by decreasing chirp insonation. Comparison of the echoes from similar sized microbubbles following increasing and decreasing chirp insonation demonstrated that the echoes were not time-reversed replicas. Using a transmission pressure of 620 kPa, the -6 dB echo length was 0.9 and 1.1 micros for increasing and decreasing chirp insonation, respectively (P = 0.02). The mean power in the low-frequency portion of the echoes was 8 (mV)2 and 13 (mV)2 for increasing and decreasing chirp insonation, respectively (P = 0.01).     

High-frequency dynamics of ultrasound contrast agents

Ultrasound contrast agents enhance echoes from the microvasculature and enable the visualization of flow in smaller vessels. Here, we optically and acoustically investigate microbubble oscillation and echoes following insonation with a 10 MHz center frequency pulse. A high-speed camera system with a temporal resolution of 10 ns, which provides two-dimensional (2-D) frame images and streak images, is used in optical experiments. Two confocally aligned transducers, transmitting at 10 MHz and receiving at 5 MHz, are used in acoustical experiments in order to detect subharmonic components. Results of a numerical evaluation of the modified Rayleigh-Plesset equation are used to predict the dynamics of a microbubble and are compared to results of in vitro experiments. From the optical observations of a single microbubble, nonlinear oscillation, destruction, and radiation force are observed. The maximum bubble expansion, resulting from insonation with a 20-cycle, 10-MHz linear chirp with a peak negative pressure of 3.5 MPa, has been evaluated. For an initial diameter ranging from 1.5 to 5 microm, a maximum diameter less than 8 microm is produced during insonation. Optical and acoustical experiments provide insight into the mechanisms of destruction, including fragmentation and active diffusion. High-frequency pulse transmission may provide the opportunity to detect contrast echoes resulting from a single pulse, may be robust in the presence of tissue motion, and may provide the opportunity to incorporate high-frequency ultrasound into destruction-replenishment techniques.     

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.     

Pulse subtraction time delay imaging method for ultrasound contrast agent detection

Detection of contrast agent in perfused tissues has been an important research topic for many years. Currently available methods are mostly based on the strong nonlinear scattering of contrast agent microbubbles. These methods selectively extract those parts of the spectrum that show the largest difference in nonlinearity between contrast agent and tissue. The method introduced in this paper expands this extraction approach in that it additionally exploits differences in system behavior between tissue and contrast bubbles. The resonant nature of contrast bubbles implies that the response of a contrast bubble is stateful, i.e., the response not only depends on the current input, but also on all previous inputs. Tissue does not show this dependence on previous inputs. Our method is based on a 3 pulse design in which the echoes from 2 nonoverlapping pulses are subtracted from a third pulse. With this method we aim to separate and suppress those parts in an echo signal that originate from tissue while leaving the part originating from contrast bubbles relatively undisturbed. Simulation results show increases up to 30 dB in contrast-to-tissue ratio (CTR) with this method relative to single pulse echoes. This was confirmed in an in vitro experiment that showed an increase of approximately 12 dB in CTR.     

Coded pulse excitation for ultrasonic strain imaging

Decorrelation strain noise can be significantly reduced in low echo-signal-to-noise (eSNR) conditions using coded excitation. Large time-bandwidth-product (>30) pulses are transmitted into tissue mimicking phantoms with 2.5-mm diameter inclusions that mimic the elastic properties of breast lesions. We observed a 5-10 dB improvement in eSNR that led to a doubling of the depth of focus for strain images with no reduction of spatial resolution. In high eSNR conditions, coded excitation permits the use of higher carrier frequencies and shorter correlation windows to improve the attainable spatial resolution for strain relative to that obtained with conventional short pulses. This paper summarizes comparative studies of strain imaging in noise-limited conditions obtained by short pulses and four common aperiodic codes (chirp, Barker, suboptimal, and Golay) as a function of attenuation, eSNR and applied strain. Imaging performance is quantified using SNR for displacement (SNRd), local modulation transfer function (LMTF), and contrast-to-noise ratio for strain (CNRepsilon). We found that chirp and Golay codes are the most robust for imaging soft tissue deformation using matched filter decoding. Their superior performance is obtained by balancing the need for low-range lobes, large eSNR improvement, and short-code duration.     

Broadband radio-frequency spectrum analysis in spectral-hole-burning media

We demonstrate a 20 GHz spectrum analyzer with 1 MHz resolution and >40 dB dynamic range using spectral-hole-burning (SHB) crystals, which are cryogenically cooled crystal hosts lightly doped with rare-earth ions. We modulate a rf signal onto an optical carrier using an electro-optic intensity modulator to produce a signal beam modulated with upper and lower rf sidebands. Illuminating SHB crystals with modulated beams excites only those ions resonant with corresponding modulation frequencies, leaving holes in the crystal's absorption profile that mimic the modulation power spectrum and persist for up to 10 ms. We determine the spectral hole locations by probing the crystal with a chirped laser and detecting the transmitted intensity. The transmitted intensity is a blurred-out copy of the power spectrum of the original illumination as mapped into a time-varying signal. Scaling the time series associated with the transmitted intensity by the instantaneous chirp rate yields the modulated beam's rf power spectrum. The homogeneous linewidth of the rare-earth ions, which can be <100 kHz at cryogenic temperatures, limits the fundamental spectral resolution, while the medium's inhomogeneous linewidth, which can be >20 GHz, determines the spectral bandwidth.     

Spatial encoding using a code division technique for fast ultrasound imaging

This paper describes a method for spatial encoding in synthetic transmit aperture ultrasound imaging. This allows several ultrasonic sources to be active simultaneously. The method is based on transmitting pseudorandom sequences to spatially encode the transmitters. The data can be decoded after only one transmission using the knowledge of the transmitted code sequences as opposed to other spatial encoding techniques, such as Hadamard or Golay encoding. This makes the method less sensitive to motion, and data can be acquired using fewer transmissions. The aim of this paper is to analyze the underlying theory and to test the feasibility in a physical system. The method has been evaluated in simulations using Field II in which the point-spread functions were simulated for different depths for a 7 MHz linear array transducer. A signal-to-noise ratio (SNR) simulation also was included in the study in which an improvement in SNR of approximately 1.5 dB was attained compared to the standard synthetic transmit aperture (STA) firing scheme. Considering the amount of energy transmitted, this value is low. A plausible explanation is given that is verified in simulation. The method also was tested in an experimental ultrasound scanner and compared to a synthetic transmit aperture ultrasound imaging scheme using a sinusoidal excitation. The performance of the proposed method was comparable to the reference with respect to axial and lateral resolution, but it displayed poorer contrast with sidelobe levels at approximately - 40 dB compared to the mainlobe.     

线性调频信号激励超声换能器的方法研究

针对超声换能器的特性,研究等幅及包络调制线性调频波的换能器激励响应。通过对比激励前后脉冲压缩的主瓣峰值、?3d B主瓣带宽和峰值旁瓣水平,探讨通过换能器后其信噪比和分辨率的性能。理论分析和仿真实验结果表明,两种调频信号通过换能器后信噪比和分辨率都减少,峰值旁瓣有所提高。包络调制线性调频信号激励换能器脉冲压缩的信噪比和分辨率高于等幅线性调频信号,但能量损失比等幅线性调频信号大。     

Experimental and theoretical evaluation of microbubble behavior: effect of transmitted phase and bubble size

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.     

Techniques for perfusion imaging with microbubble contrast agents

The acoustic properties of ultrasound contrast agents vary widely with agent composition and insonation conditions. For contrast imaging, methods are required to match RF and Doppler processing to each combination of transmission parameters and agent and tissue properties. We propose a method that uses the measured or modeled echoes from agent and tissue to specify directly the characteristics of RF and Doppler filters for contrast imaging. The proposed method is sufficiently general to cover most common imaging techniques including harmonic greyscale, Doppler, and pulse inversion imaging. Using this method, sample filters were designed to detect myocardial perfusion with the contrast agent Optison^TM (Mallinckrodt Medical, St. Louis, MO) under selected imaging conditions. Simplified power Doppler filtering, using a weighted sum of the Doppler samples, matched the performance of more complicated matrix filters. By coordinating the selection of RF and Doppler filters rather than designing these filters sequentially, agent-to-tissue contrast was increased by up to 3.9 dB. Under some conditions, fundamental RF filtering outperformed harmonic filtering for intermittent Doppler imaging     

Orthogonal quadratic chirp signals for simultaneous multi-zone focusing in medical ultrasound imaging

In medical ultrasound imaging, multi-zone focusing on transmission is used to enhance the lateral resolution at the expense of frame rate. As an alternative, this paper proposes a simultaneous multi-zone focusing method using orthogonal quadratic chirp signals to improve lateral resolution without sacrificing frame rate. In the proposed method, two weighted quadratic chirp signals with different spectra are simultaneously transmitted with different transmit time delays for multi-zone focusing. Because the two weighted quadratic chirps can be designed to have a desired level of cross-correlation after compression, the degradation of axial resolution resulting from the division of a spectrum is minimized. Through simulation, the performances of the proposed method were evaluated and compared with those of two-cycle pulsed excitation as a gold standard and two sub-band weighted linear chirps. In the simulation, the proposed method improved -6-dB and -20-dB lateral beam widths by factors of 1.67 and 1.84, respectively, compared with the pulsed excitation. The degradation of axial resolution in the proposed method was maximally 43% less than that in the linear chirp case. The results demonstrate that the proposed method is useful in the improvement of overall ultrasound image quality because the axial resolution of conventional ultrasound images is generally a few times higher than the lateral resolution.     

A new ultrasound contrast imaging approach based on the combination of multiple imaging pulses and a separate release burst

A new ultrasound contrast imaging technique is described that optimally employs the rupture of the contrast agent. It is based on a combination of multiple high frequency, broadband, imaging pulses and a separate release burst. The imaging pulses are used to survey the target before and after the rupture and release of free gas bubbles. In this way, both processes (imaging and release) can be optimized separately. The presence of the contrast agent is simply detected by correlating or subtracting the signal responses of the imaging pulses. Because the time delay between the imaging pulses can be very short, the subtraction is less affected by tissue motion and can be done in real time. In vitro measurements showed that by using a release burst, the detection sensitivity increased 12 to 43 dB for different types of contrast agents. In the presence of a moving phantom, the increase in sensitivity was 22 dB. This new method is very sensitive for contrast agent detection in fundamental imaging mode and, therefore, non-linear propagation effects do not limit the maximum obtainable agent-to-tissue ratio. However, because of the inherent destruction of the contrast agent, it has to operate in an intermittent way. Through experiments, we have demonstrated the potential of the method to achieve simultaneous high sensitivity for contrast detection, i.e., high agent-to-tissue ratio, and high spatial resolution performance for different types of contrast agents     

Pulse inversion Doppler: a new method for detecting nonlinear echoes from microbubble contrast agents

A novel technique for the selective detection of ultrasound contrast agents, called pulse inversion Doppler, has been developed. In this technique, a conventional Doppler or color Doppler pulse sequence is modified by inverting every second transmit pulse. Either conventional or harmonic Doppler processing is then performed on the received echoes. In the resulting Doppler spectra, Doppler shifts from linear and nonlinear scattering are separated into two distinct regions that can be analyzed separately or combined to estimate the ratio of nonlinear to linear scattering from a region of tissue. The maximum Doppler shift that can be detected is 1/2 the normal Nyquist limit. This has the advantage over conventional harmonic Doppler that it can function over the entire bandwidth of the echo signal, thus achieving superior spatial resolution in the Doppler image. In vitro measurements comparing flowing agent and cellulose particles suggest that pulse inversion Doppler can provide 3 to 10 dB more agent to tissue contrast than harmonic imaging with similar pulses. Similar measurements suggest that broadband pulse inversion Doppler can provide up to 16 dB more contrast than broadband conventional Doppler. Nonlinear propagation effects limit the maximum contrast obtainable with both harmonic and pulse inversion Doppler techniques.     

Characterization of strong fiber Bragg gratings using an applied thermal chirp and iterative algorithm

Coupling coefficients of various grating types and strengths are calculated from measurements of the complex reflectivity using an applied thermal chirp and optical frequency domain reflectometry (OFDR). The complex reflectivity is then utilized by a layer peeling algorithm to determine the coupling coefficient of the thermally chirped grating. A guess of the temperature profile enables the coupling coefficient of the unchirped grating to be estimated. An iterative algorithm is then used to converge on the exact coupling coefficient, employing an error minimization method applied to the reflectivity spectra. This technique removes the need for a reference grating while preserving the spatial resolution obtained with the initial OFDR measurement. Successful reconstruction of gratings with integrated |κ|L ~ 9.0 are demonstrated with a spatial resolution of less than 100 μm.     

Use of modulated excitation signals in medical ultrasound. Part II: Design and performance for medical imaging applications

In the first paper, the superiority of linear FM signals was shown in terms of signal-to-noise ratio and robustness to tissue attenuation. This second paper in the series of three papers on the application of coded excitation signals in medical ultrasound presents design methods of linear FM signals and mismatched filters, in order to meet the higher demands on resolution in ultrasound imaging. It is shown that for the small time-bandwidth (TB) products available in ultrasound, the rectangular spectrum approximation is not valid, which reduces the effectiveness of weighting. Additionally, the distant range sidelobes are associated with the ripples of the spectrum amplitude and, thus, cannot be removed by weighting. Ripple reduction is achieved through amplitude or phase predistortion of the transmitted signals. Mismatched filters are designed to efficiently use the available bandwidth and at the same time to be insensitive to the transducer's impulse response. With these techniques, temporal sidelobes are kept below 60 to 100 dB, image contrast is improved by reducing the energy within the sidelobe region, and axial resolution is preserved. The method is evaluated first for resolution performance and axial sidelobes through simulations with the program Field II. A coded excitation ultrasound imaging system based on a commercial scanner and a 4 MHz probe driven by coded sequences is presented and used for the clinical evaluation of the coded excitation/compression scheme. The clinical images show a significant improvement in penetration depth and contrast, while they preserve both axial and lateral resolution. At the maximum acquisition depth of 15 cm, there is an improvement of more than 10 dB in the signal-to-noise ratio of the images. The paper also presents acquired images, using complementary Golay codes, that show the deleterious effects of attenuation on binary codes when processed with a matched filter, also confirmed by presented simulated images.     

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.     

Contrast agent response to chirp reversal: simulations, optical observations, and acoustical verification

Active response of a microbubble is characterized by its resonance behavior where the microbubble might oscillate after the excitation waveform has been turned off. We investigate in this paper an excitation approach based on this resonance phenomenon using chirps. The technique, called chirp reversal, consists in transmitting a first excitation signal, the up-sweep chirp (UPF) of increasing frequency with time, and a second excitation signal, the down-sweep (DNF) that is a replica of the first signal, but time reversed with a sweep of decreasing frequency with time. Simulations using a modified Rayleigh-Plesset equation were carried out to determine bubble response to chirp reversal. In addition, optical observations and acoustical measurements were carried out to corroborate the theoretical findings. Results of simulations show differences between bubblesiquest oscillations in response to up-sweep and down-sweep chirps mainly for transmitted center frequencies above the bubbles resonance frequency. Bubbles that are at resonance or far away from resonance engender identical responses. From the optical data, the larger bubbles showed different dynamics when up-sweep or down-sweep chirps were transmitted. Smaller bubbles (< 2 mum diameter) appear to be less sensitive to frequency sweep at 1.7 MHz center frequency. However, driven at a higher center frequency, smaller bubbles tend to be more sensitive. These results were confirmed through the acoustical measurements. We concluded that simulations and experimental data show that significant differences might be observed between bubblesiquest responses to UPF and DNF chirps. We demonstrate in this study that, for an optimal use of chirp reversal, the transmit frequency should be higher than the resonance frequency of the contrast microbubbles.     

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.