生物组织成像中用反相位脉冲技术提高二次谐波信噪比的研究

本文基于有限振幅声波在介质中的非线性传播理论,分析了反相位脉冲技术对生物组织中二次谐波增强的原理.实验中利用反相位脉冲激发超声换能器,对生物组织中传播的非线性信号相加分析.结果表明反相位脉冲技术可有效抑制基波及奇次谐波信号,而可增强偶次谐波信号6dB.与滤波器滤波法相比,反相位脉冲技术在抑制基波信号的同时,可有效地提高二次谐波的信噪比,因而在生物组织的二次谐波成像中具有广阔的应用前景.     

Comparison of fundamental, second harmonic, and superharmonic imaging: a simulation study

In medical ultrasound, fundamental imaging (FI) uses the reflected echoes from the same spectral band as that of the emitted pulse. The transmission frequency determines the trade-off between penetration depth and spatial resolution. Tissue harmonic imaging (THI) employs the second harmonic of the emitted frequency band to construct images. Recently, superharmonic imaging (SHI) has been introduced, which uses the third to the fifth (super) harmonics. The harmonic level is determined by two competing phenomena: nonlinear propagation and frequency dependent attenuation. Thus, the transmission frequency yielding the optimal trade-off between the spatial resolution and the penetration depth differs for THI and SHI. This paper quantitatively compares the concepts of fundamental, second harmonic, and superharmonic echocardiography at their optimal transmission frequencies. Forward propagation is modeled using a 3D-KZK implementation and the iterative nonlinear contrast source (INCS) method. Backpropagation is assumed to be linear. Results show that the fundamental lateral beamwidth is the narrowest at focus, while the superharmonic one is narrower outside the focus. The lateral superharmonic roll-off exceeds the fundamental and second harmonic roll-off. Also, the axial resolution of SHI exceeds that of FI and THI. The far-field pulse-echo superharmonic pressure is lower than that of the fundamental and second harmonic. SHI appears suited for echocardiography and is expected to improve its image quality at the cost of a slight reduction in depth-of-field.     

The feasibility of pulse compression by nonlinear effective bandwidth extension

Chirp-encoded excitation has been utilized for increased signal-to-noise ratio (SNR) in both linear and harmonic imaging. In either case, it is necessary to isolate the relevant frequency band to avoid artifacts. In contrast, the present study isolates and then combines the fundamental and the higher harmonics, treating them as a single, extended bandwidth. Pulse-inverted sum and difference signals are first used to isolate even and odd harmonics. Matched filters specific to the source geometry and the transmit signal are then separately applied to each harmonic band. Verification experiments are performed using up to the third harmonic resulting from an underwater chirp excitation. Analysis of signal peaks after scattering from a series of steel and nylon wires indicates increased compression using the extended bandwidth, as compared to well-established methods for fundamental and second harmonic chirp compression. Using third harmonic bands, a mean pulse width of 56% relative to fundamental compression and 48% relative to second harmonic compression was observed. Further optimization of the compression by altering the transmission indicated 17% additional reduction in the pulse width and a 47% increase in peak-to-sidelobe ratio. Overall, results establish the feasibility of extended bandwidth signal compression for simultaneously increasing SNR and signal resolution.     

Third harmonic transmit phasing for SNR improvement in tissue harmonic imaging with Golay-encoded excitation

Background

Ultrasound tissue harmonic signal generally provides superior image quality as compared to the linear signal. However, since the generation of the tissue harmonic signal is based on finite amplitude distortion of the propagating waveform, the penetration and the sensitivity in tissue harmonic imaging are markedly limited because of the low signal-to-noise ratio (SNR).

Methods

The method of third harmonic (3f₀) transmit phasing can improve the tissue harmonic SNR by transmitting at both the fundamental (2.25 MHz) and the 3f₀ (6.75 MHz) frequencies to achieve mutual enhancement between the frequency-sum and the frequency-difference components of the second harmonic signal. To further increase the SNR without excessive transmit pressure, coded excitation can be incorporated in 3f₀ transmit phasing to boost the tissue harmonic generation.

Results

Our analyses indicate that the phase-encoded Golay excitation is suitable in 3f₀ transmit phasing due to its superior transmit bandwidth efficiency. The resultant frequency-sum and frequency-difference components of tissue harmonic signal can be simultaneously Golay-encoded for SNR improvement. The increase of the main-lobe signal with the Golay excitation in 3f₀ transmit phasing are consistent between the tissue harmonic measurements and the simulations. B-mode images of the speckle generating phantom also demonstrate the increases of tissue harmonic SNR for about 11 dB without noticeable compression artifacts.

Conclusion

For tissue harmonic imaging in combination with the 3f₀ transmit phasing method, the Golay excitation can provide further SNR improvement. Meanwhile, the axial resolution can be effectively restored by pulse compression while the lateral resolution remains unchanged.     

A simulation study on tissue harmonic imaging with a single-element intravascular ultrasound catheter

Recently, in vivo feasibility of tissue harmonic imaging with a mechanically rotated intravascular ultrasound (IVUS) catheter was experimentally demonstrated. To isolate the second harmonic signal content, a combination of pulse inversion and analog filtering was used. In this paper the development of a simulation tool to investigate nonlinear IVUS beams is reported, and the influence of transducer rotation and axial catheter-to-tissue motion on the efficiency of PI signal processing is evaluated. Nonlinear beams were simulated in homogeneous tissue-mimicking media at a transmit frequency of 20 MHz, which resulted in second harmonic pressure fields at 40 MHz. The competing effects of averaging and decorrelation between neighboring rf lines on the signal-to-noise ratio (SNR) were studied for a single point scatterer. An optimal SNR was achieved when lines were combined over 3 degrees - 3.75 degrees. When the transducer was rotated with respect to point scatterers, simulating the acoustic response of tissue, the fundamental frequency suppression using PI degraded rapidly with increasing interpulse angles. The effect of axial catheter-to-tissue motion on the efficiency of pulse inversion seemed to be of less influence for realistic motion values. The results of this study will aid in the optimization of harmonic IVUS imaging systems.     

Coded excitation for ultrasound tissue harmonic imaging

Coded excitation can improve the signal-to-noise ratio (SNR) in ultrasound tissue harmonic imaging (THI). However, it could suffer from the increased sidelobe artifact caused by incomplete pulse compression due to the spectral overlap between the fundamental and harmonic components of ultrasound signal after nonlinear propagation in tissues. In this paper, three coded tissue harmonic imaging (CTHI) techniques based on bandpass filtering, power modulation and pulse inversion (i.e., CTHI-BF, CTHI-PM, and CTHI-PI) were evaluated by measuring the peak range sidelobe level (PRSL) with varying frequency bandwidths. From simulation and in vitro studies, the CTHI-PI outperforms the CTHI-BF and CTHI-PM methods in terms of the PRSL, e.g., −43.5 dB vs. −24.8 dB and −23.0 dB, respectively.     

Coded excitation using biphase-coded pulse with mismatched filters for high-frequency ultrasound imaging

A scheme of using phase-coded excitation and mismatched filter compression for high-frequency ultrasound imaging is presented in this paper. Biphase-coded pulses were constructed to excite the transducer. Received signals were compressed with mismatched filters optimized by minimizing peak-sidelobe-level (PSL). Both simulation and experiments were carried out to demonstrate the advantage of this technique. The simulation results demonstrated a possible sidelobe reduction (<-90 dB) with a slightly decrease of the signal-to-noise ratio of less than 1 dB compared with the compression using matched filters alone. The experimental results showed about 14 dB SNR improvement as well as -40 dB sidelobe level when the Barker-13 code excitation with 3-cycle sinusoidal wave carrier was used.     

Experimental investigation of the pulse inversion technique for imaging ultrasound contrast agents

The application of ultrasound contrast agents aims to detect low velocity blood flow in the microcirculation. To enhance discrimination between tissue and blood containing the contrast agent, harmonic imaging is used. Harmonic imaging requires the application of narrow-band signals and is obscured by high levels of native harmonics generated in an intervening medium. To improve discrimination between contrast agent and native harmonics, a pulse inversion technique has been proposed. Pulse inversion allows wide-band signals, thus preserving the axial resolution. The present study examines the interference of native harmonics and discusses the practical difficulties of wide-band pulse inversion measurements of harmonics by a single transducer. Native harmonics are not eliminated by pulse inversion. Furthermore, only even harmonics remain and are amplified by 6 dB, alleviating the requirement for selective filtering. Finally, it is shown that the contaminating third harmonic contained in the square wave activation signal leaks through in the emitted signal. The spectral location of the contaminating third harmonic is governed by the transducer spectral characteristics while the location of the native and contrast agent second harmonics is not. Thus the contaminating third harmonic and the native and contrast agent second harmonics may overlap and interfere. Optimal discrimination requires a balance between maximal sensitivity for the second harmonic at reception and minimal interference from the contaminating third harmonic.     

Fast simulation of second harmonic ultrasound field using a quasi-linear method

Nonlinear propagation of sound has been exploited in the last 15 years in medical ultrasound imaging through tissue harmonic imaging (THI). THI creates an image by filtering the received ultrasound echo around the second harmonic frequency band. This technique produces images of enhanced quality due to reduced body wall reverberation, lower perturbations from off-axis echoes, and multiple scattering of reduced amplitude. In order to optimize the image quality it is essential to be able to predict the amplitude level and spatial distribution of the propagating ultrasound pulse. A method based on the quasi-linear approximation has been developed to quickly provide an estimate of the ultrasound pulse. This method does not need to propagate the pulse stepwise from the source plane to the desired depth; it directly computes a transverse profile at any depth from the definitions of the transducer and the pulse. The computation handles three spatial dimensions which allows for any transducer geometry. A comparison of pulse forms, transverse profiles, as well as axial profiles obtained by this method and state-of-the-art simulators, the KZKTexas code, and Abersim, shows a satisfactory match. The computation time for the quasi-linear method is also smaller than the time required by the other methods.     

Feasibility of 3D harmonic contrast imaging

Improved endocardial border delineation with the application of contrast agents should allow for less complex and faster tracing algorithms for left ventricular volume analysis. We developed a fast rotating phased array transducer for 3D imaging of the heart with harmonic capabilities making it suitable for contrast imaging. In this study the feasibility of 3D harmonic contrast imaging is evaluated in vitro. A commercially available tissue mimicking flow phantom was used in combination with Sonovue. Backscatter power spectra from a tissue and contrast region of interest were calculated from recorded radio frequency data. The spectra and the extracted contrast to tissue ratio from these spectra were used to optimize the excitation frequency, the pulse length and the receive filter settings of the transducer. Frequencies ranging from 1.66 to 2.35 MHz and pulse lengths of 1.5, 2 and 2.5 cycles were explored. An increase of more than 15 dB in the contrast to tissue ratio was found around the second harmonic compared with the fundamental level at an optimal excitation frequency of 1.74 MHz and a pulse length of 2.5 cycles. Using the optimal settings for 3D harmonic contrast recordings volume measurements of a left ventricular shaped agar phantom were performed. Without contrast the extracted volume data resulted in a volume error of 1.5%, with contrast an accuracy of 3.8% was achieved. The results show the feasibility of accurate volume measurements from 3D harmonic contrast images. Further investigations will include the clinical evaluation of the presented technique for improved assessment of the heart.     

Resonant third harmonic generation of a short pulse laser in plasma by applying a wiggler magnetic field

We examine the effect of wiggler magnetic field on pulse slippage of short pulse laser-induced third harmonic generation in plasma. The process of third harmonic generation of an intense short pulse laser in plasma is resonantly enhanced by the application of a magnetic wiggler. The laser exerts a ponderomotive force at second harmonic driving density oscillations. The second harmonic oscillations coupled with electron velocity at the laser frequency, produces a non-linear current, driving the third harmonic. Third harmonic pulse generates in the fundamental pulse domain. However, the group velocity of the third harmonic wave is greater than the fundamental wave. Hence, the third harmonic pulse saturates strongly and moves forward from the fundamental pulse at shorter distance than the second harmonic pulse.     

Fundamental study on subharmonic imaging by irradiation of amplitude-modulated ultrasound waves

The second harmonic and subharmonic components, the frequencies of which are twice and one half the fundamental frequency, are included in echoes from contrast agents. An imaging method, which employs a second harmonic (second harmonic imaging), is widely used in medical diagnoses. On the other hand, subharmonic is expected to provide a higher contrast between biological tissues and blood flow because echo signals are generated only from blood containing the contrast agents. However, the subharmonic component echo signal power from contrast agents is relatively low. This has resulted in little progress in the field of subharmonic imaging. In this study, a new imaging method is proposed using amplitude-modulated waves as transmitted waves combined with the pulse inversion method to enhance subharmonic echo signals. Two optimal frequencies are set, including the modulated waves, F(1) and F(2), so that the subharmonic frequency of F(1) and the second harmonic frequency of F(2) may result in the same value. This allows a more powerful signal at the frequency band because the second harmonic and subharmonic components are integrated. Furthermore, a B-mode ultrasound image of an agar phantom that imitated biological tissue and showed the effectiveness of our method was reconstructed. As a result, the echo power of the subharmonic component was enhanced by approximately 11.8 dB more than the conventional method and the signal to noise ratio showed an improvement of 7.6 dB.     

Evidence for ultrasonic finite-amplitude distortion in muscle using medical equipment

Finite-amplitude distortion of ultrasonic waves from medical equipment has been observed to occur following transmission through calf muscle in human volunteers. Measurements were made using both dynamic pulse-echo imaging equipment and physiotherapy equipment. In both cases irradiation was carried out under operating conditions commonly used clinically. Pressure waveforms were measured at the skin surface using a broadband polyvinylidene difluoride membrane hydrophone. Using a pulsed, weakly focused 2.5-MHz beam with input peak pressure of 0.8 MPa and a pressure gain of 5.3 at the focus, the mean second harmonic peak magnitude (16 measurements) was 17 dB below the fundamental peak. A 1.1-MHz continuous wave therapy set with input peak pressure of 0.5 MPa showed mean second harmonic magnitude 23 dB below the fundamental.     

Second harmonic generation from thick leaves using the two-photon laser scanning microscope

A laser-scanning microscope using second harmonic generation (SHG) as a probe is shown to produce high-resolution images of duckweed Lemna minuta leaves. These leaves are multi-cell layer thick. Second harmonic light is generated by a tightly focused short pulse laser beam and is collected by two objectives yielding forward and backward second harmonic digital images. This measurement shows that the signal of the second harmonic imaging in the forward and backward directions depends on the thickness of the chloroplast and that the forward-SH image was brighter than the backward-SH image. The image intensity also depended on the orientation of the chloroplast in relation to the illuminating polarization direction. Their light-induced re-orientation which was affected by the intensity of the illumination could be observed during the experiments.The novelty of this work is to establish new compact technique in which one can use the SH imaging to investigate the true architecture of the sensitive samples, the unknown samples and the samples which is not producing auto-fluorescence. Moreover, investigation of new or unknown samples needs a long time for looking at details of the sample. Thereby the sample will be exposed for long time to the laser radiation that will cause photobleaching and photodamage. Since the SHG does not undergo photobleaching and photodamage this will be the promising technique for investigating the sensitive and new unknown samples. Then one can move to acquire fluorescence images after complete investigation of the true architecture of the sample. The other advantage of SHG is that it has the ability to image highly ordered structural proteins without any exogenous labels. The SHG is an intrinsic and a coherent process. Imaging of intrinsic compounds avoids the complications of slicing and labeling, and samples can be investigated under physiological conditions.     

Investigation of transmit and receive performance at the fundamental and third harmonic resonance frequency of a medical ultrasound transducer

In this study, the phenomenon of higher harmonic thickness resonance of a piezoelectric transducer was used to investigate potentially additional sensitivity at the third harmonic frequency for conventional medical transducers. The motivation for this research is that some applications in medical ultrasound (e.g. third harmonic transmit phasing and contrast imaging) need probes which are sensitive around both the fundamental and third harmonic frequencies, and that these higher harmonic thickness modes, although often considered as undesired, might be used beneficially. The novelty aspect in this study is the presented transmit and receive potential at both the fundamental and third harmonic of a conventional cardiac probe with modified electrical tuning. Elements of an experimental PZT-based phased-array probe (f_c = 3 MHz, 64 elements, element width = 0.3 mm, elevation aperture = 13 mm) were electrically retuned with series inductors around the third harmonic resonance frequency at 10 MHz. Hydrophone measurements with 10-MHz-tuned elements showed that, as compared to a conventionally tuned element, the transmit transfer function at the third harmonic increased more than 23 dB, while the sensitivity at the fundamental frequency was only 6 dB lower. Pulse-echo measurements showed that the two-way transfer function of a 10-MHz-tuned element resulted in 20 dB increased sensitivity around the third harmonic as compared to an untuned element. Simulated transfer functions, from both a 1D KLM and 2D finite element model of an element of the experimental array transducer, confirmed the measured sensitivity peaks at the fundamental and third harmonic. In conclusion, this study demonstrated the effect of changing the electrical tuning on a conventional array transducer which increased the sensitivity around the third harmonic resonance frequency, while maintaining good sensitivity at the fundamental frequency.     

Chirp-coded robust synthetic aperture technique for medical endoscopic ultrasonography

A chirp-coded robust synthetic aperture(CRSA) technique for medical endoscopic ultrasonography is presented.The technique uses chirp-coded excitation and pulse compression to enhance the robustness of synthetic aperture technique.The effect of resolution enhancement by the CRSA technique is demonstrated by both Field II simulation and practical experiment. Data for 6 point targets is simulated and the performance of CRSA is compared with that of conventional barker-coded synthetic aperture technique(BSA).Nylon ropes are examined by a single element transducer centered at 8 MHz.Both simulation and experimental results indicated that CRSA can improve resolution of ultrasound images with good robustness as compared with the conventional BSA technique.The lateral resolution is upgraded to 1.4 mm from 1.8 mm.The main-lobe broadening and SNR degradation are 0.04 mm and 0.2 dB respectively,which are 0.95 mm and 3.6 dB lower than those of BSA,when the sound speed error is 6%of the true value 1540 m/s.It therefore can be concluded that CRSA has more robustness than BSA against the disturbance caused by sound speed errors.     

Investigation of superharmonic sound propagation and imaging in biological tissues in vitro

This article presents both theoretical and experimental studies on the superharmonic generation and its imaging in biological tissues. A superharmonic component is defined as a summation of the third-, fourth-, and fifth-order harmonics. A superharmonic signal is produced using an 8-mm-diam, 2.5-MHz planar piston source that is excited by eight-cycle, 2.5-MHz tone bursts. Axial and lateral field distributions of the superharmonic component and the second harmonic are first calculated based on the nonlinear KZK model and then compared with those experimentally determined at two different source pressures of 0.5 and 1 MPa. Results indicate that the amplitude of the superharmonic component can exceed that of the second harmonic, depending on the axial distance and the fundamental pressure amplitude. Also, the 3-dB beamwidth of the superharmonic component is about 23% narrower than that of the second harmonic. Additional experiments are performed in vitro using liver and fatty tissues in transmission mode and produced two-dimensional images using the fundamental, the second harmonic, and the superharmonic signals. Although the clinical applicability of this work still needs to be assessed, these results indicate that the superharmonic image quality is better than that of the other two images.     

Space-time encoding for high frame rate ultrasound imaging

Frame rate in ultrasound imaging can be dramatically increased by using sparse synthetic transmit aperture (STA) beamforming techniques. The two main drawbacks of the method are the low signal-to-noise ratio (SNR) and the motion artifacts, that degrade the image quality. In this paper we propose a spatio-temporal encoding for STA imaging based on simultaneous transmission of two quasi-orthogonal tapered linear FM signals. The excitation signals are an up- and a down-chirp with frequency division and a cross-talk of -55 dB. The received signals are first cross-correlated with the appropriate code, then spatially decoded and finally beamformed for each code, yielding two images per emission. The spatial encoding is a Hadamard encoding previously suggested by Chiao et al. [in: Proceedings of the IEEE Ultrasonics Symposium, 1997, p. 1679]. The Hadamard matrix has half the size of the transmit element groups, due to the orthogonality of the temporal encoded wavefronts. Thus, with this method, the frame rate is doubled compared to previous systems. Another advantage is the utilization of temporal codes which are more robust to attenuation. With the proposed technique it is possible to obtain images dynamically focused in both transmit and receive with only two firings. This reduces the problem of motion artifacts. The method has been tested with extensive simulations using Field II. Resolution and SNR are compared with uncoded STA imaging and conventional phased-array imaging. The range resolution remains the same for coded STA imaging with four emissions and is slightly degraded for STA imaging with two emissions due to the -55 dB cross-talk between the signals. The additional proposed temporal encoding adds more than 15 dB on the SNR gain, yielding a SNR at the same order as in phased-array imaging.     

Reflective terahertz imaging of porcine skin burns

A reflective pulsed terahertz imaging system based on direct detection was developed and used to obtain high-resolution images of a porcine skin specimen with superficial partial-thickness (second-degree) burns. Images were also obtained of the sample through ten layers of dry medical (cotton) gauze with minimal image degradation. The burned and unburned regions of skin had large differences in terahertz reflectivity, displaying clear delineation [20 dB signal-to-noise ratio (SNR) difference signal] between both regions in the images. The terahertz images also exhibited a "halo" surrounding the burn areas that may correlate to the extent of burn injury. The system operated at a center frequency of 500 GHz with 125 GHz of 3 dB bandwidth and used whiskbroom scanning to generate images with a spatial resolution of 1.5 mm. Each pixel was acquired with a 16 ms integration time, resulting in a 40 dB postdetection SNR. The simplicity and high SNR of the reflective terahertz system are promising steps toward real-time terahertz medical imaging.     

Ba1-xB2-y-zO4SixAlyGaz晶体和频可调谐深紫外飞秒激光器

介绍了一种基于新型非线性晶体Ba_1-xB_2-y-zO₄Si_xAl_yGa_z 的可调谐深紫外飞秒激光光源. 从理论上分析了基频光和倍频光在通过非线性晶体时所造成的空间走离和群速度失配, 为了补偿空间走离以及波长调谐过程中晶体折射造成的光束偏离现象, 将两块相同的倍频晶体成镜像放置来产生二次谐波. 并调节延迟线的长度来补偿基频光和倍频光之间的群速度失配, 从而提高和频转换效率. 然后通过和频方式进行三倍频和四倍频来突破晶体相位匹配条件的限制, 产生了波长低于200 nm的深紫外飞秒激光. 利用钛宝石激光器提供基频光光源, 最终在250–300 nm, 192.5–210 nm 范围内获得了高重频、可调谐超短脉冲紫外和深紫外激光. 并在基频光波长为800 nm时, 得到的二倍频、三倍频和四倍频的功率分别为1.28 W, 194 mW和5.8 mW, 相对于前一级的转换效率依次为46.14%, 15.16%和3%. 采用互相关法测量得到266.7 nm紫外激光的脉冲宽度约为640.4 fs.