Improvement in Multi-Angle Plane Wave Image Quality Using Minimum Variance Beamforming with Adaptive Signal Coherence.

For ultrasound multi-angle plane wave (PW) imaging, the coherent PW compounding (CPWC) method provides limited image quality because of its conventional delay-and-sum beamforming. The delay-multiply-and-sum (DMAS) method is a coherence-based algorithm that improves image quality by introducing signal coherence among either receiving channels or PW transmit angles into the image output. The degree of signal coherence in DMAS is conventionally a global value for the entire image and thus the image resolution and contrast in the target region improves at the cost of speckle quality in the background region. In this study, the adaptive DMAS (ADMAS) is proposed such that the degree of signal coherence relies on the local characteristics of the image region to maintain the background speckle quality and the corresponding contrast-to-noise ratio (CNR). Subsequently, the ADMAS algorithm is further combined with minimum variance (MV) beamforming to increase the image resolution. The optimal MV estimation is determined to be in the direction of the PW transmit angle (Tx) for multi-angle PW imaging. Our results show that, using the PICMUS dataset, TxMV-ADMAS beamforming significantly improves the image quality compared with CPWC. When the p value is globally fixed to 2 as in conventional DMAS, though the main-lobe width and the image contrast in the experiments improve from 0.57 mm and 27.0 dB in CPWC, respectively, to 0.24 mm and 38.0 dB, the corresponding CNR decreases from 12.8 to 11.3 due to the degraded speckle quality. With the proposed ADMAS algorithm, however, the adaptive p value in DMAS beamforming helps to restore the CNR value to the same level of CPWC while the improvement in image resolution and contrast remains evident.

Ultrasound Monitoring of Simultaneous high-intensity focused ultrasound (HIFU) therapy using minimum-peak-sidelobe coded excitation.

Bipolar sequences can be readily transmitted by ultrasound (US) pulser hardware with the full driving voltage to boost the echo magnitude in B-mode monitoring of HIFU treatment. In this study, a novel single-transmit bipolar sequence with minimum-peak-sidelobe (MPS) level is developed not only to restore the image quality of US monitoring but also remove acoustic interference from simultaneous HIFU transmission. The proposed MPS code is designed with an equal number of positive and negative bits and the bit duration should be an integer multiple of the period of the HIFU waveform. In addition, different permutations of code sequence are searched in order to obtain the optimal encoding. The received imaging echo is firstly decoded by matched filtering to cancel HIFU interference and to enhance the echo magnitude of US monitoring. Then, Wiener filtering is applied as the second-stage pulse compression to improve the final image quality. Simulations and phantom experiments are performed to compare the single-transmit MPS decoding with conventional two-transmit methods such as pulse-inversion subtraction (PIS) and Golay decoding for their performance in simultaneous US monitoring of HIFU treatment. Results show that the MPS decoding effectively removes HIFU interference even in the presence of tissue motion. The image quality of PIS and Golay decoding, on the other hand, is compromised by the uncancelled HIFU components due to tissue motion. Simultaneous US monitoring of tissue ablation using the proposed MPS decoding has also demonstrated to be feasible in ex-vivo experiments. Compared to the notch filtering that also allows single-transmit HIFU elimination, the MPS decoding is preferrable because it does not suffer from the tradeoff between residual HIFU and speckle deterioration in US monitoring images.

Improved source localization in passive acoustic mapping using delay-multiply-and-sum beamforming with virtually augmented aperture.

High-intensity focused ultrasound (HIFU) is a promising non-invasive treatment method whose applications include tissue ablation, hemostasis, thrombolysis and blood-brain barrier opening etc. Its therapeutic effects come from the thermal necrosis and the mechanical destruction associated with acoustic cavitation. Passive acoustic mapping (PAM) is capable of simultaneous monitoring of HIFU-induced cavitation events using only receive beamforming. Nonetheless, conventional time exposure acoustics (TEA) algorithm has poor spatial resolution and suffers from the X-shaped artifacts. These factors lead to difficulties in precise localization of cavitation source. In this study, we proposed a novel adaptive PAM method which combines Delay-Multiply-and-Sum (DMAS) beamforming with virtual augmented aperture (VA) to overcome the problem. In DMAS-VA beamforming, the magnitude of each channel waveform is scaled by p-th root while the phase is multiplied by L. The p and L correspond respectively to the degree of signal coherence in DMAS beamforming and the augmentation factor of aperture size. After channel sum, p-th power is applied to restore the dimensionality of source strength and then the PAM image is reconstructed by accumulating the signal power over the observation time. Based on simulation and experimental results, the proposed DMAS-VA has better image resolution and image contrast compared with the conventional TEA. Moreover, since the VA method may introduce grating lobes into PAM because of the virtually augmented pitch size, DMAS coherent factor (DCF) is further developed to alleviate these image artifacts. Results indicate that, with DCF weighting, the PAM image of DMAS-VA beamforming could be constructed without detectable image artifacts from grating lobes and false main lobes.

Ultrasound Ultrafast Power Doppler Imaging with High Signal-to-Noise Ratio by Temporal Multiply-and-Sum (TMAS) Autocorrelation.

Coherent plane wave compounding (CPWC) reconstructs transmit focusing by coherently summing several low-resolution plane-wave (PW) images from different transmit angles to improve its image resolution and quality. The high frame rate of CPWC imaging enables a much larger number of Doppler ensembles such that the Doppler estimation of blood flow becomes more reliable. Due to the unfocused PW transmission, however, one major limitation of the Doppler estimation in CPWC imaging is the relatively low signal-to-noise ratio (SNR). Conventionally, the Doppler power is estimated by a zero-lag autocorrelation which reduces the noise variance, but not the noise level. A higher-lag autocorrelation method such as the first-lag (R(1)) power Doppler image has been developed to take advantage of the signal coherence in the temporal direction for suppressing uncorrelated random noises. In this paper, we propose a novel Temporal Multiply-and-Sum (TMAS) power Doppler detection method to further improve the noise suppression of the higher-lag method by modulating the signal coherence among the temporal correlation pairs in the higher-lag autocorrelation with a tunable pt value. Unlike the adaptive beamforming methods which demand for either receive-channel-domain or transmit-domain processing to exploit the spatial coherence of the blood flow signal, the proposed TMAS power Doppler can share the routine beamforming architecture with CPWC imaging. The simulated results show that when it is compared to the original R(1) counterpart, the TMAS power Doppler image with the pt value of 2.5 significantly improves the SNR by 8 dB for the cross-view flow velocity within the Nyquist rate. The TMAS power Doppler, however, suffers from the signal decorrelation of the blood flow, and thus, it relies on not only the pt value and the flow velocity, but also the flow direction relative to the geometry of acoustic beam. The experimental results in the flow phantom and in vivo dataset also agree with the simulations.

Effect of Dialysis Modalities on All-Cause Mortality and Cardiovascular Mortality in End-Stage Kidney Disease: A Taiwan Renal Registry Data System (TWRDS) 2005-2012 Study.

Introduction: End-stage kidney disease (ESKD) patients who need renal replacement therapy need to face a dialysis modality decision: the choice between hemodialysis (HD) and peritoneal dialysis (PD). Although the global differences in HD/PD penetration are affected by health-care policies, these two modalities may exert different effects on survival in patients with ESKD. Although Taiwan did not implicate PD as first policy, we still need to compare patients' outcomes using two modalities in a nation-wise database to determine future patients' care and health policies. Methods: We used the nationwide Taiwan Renal Registry Data System (TWRDS) database from 2005 to 2012 and included 52,900 patients (48,371 on HD and 4529 on PD) to determine all-cause and cardiovascular mortality among ESKD patients. Results: Age-matched survival probability from all-cause mortality was significantly lower in patients on PD than in those on HD (p < 0.05). The adjusted hazard ratios of 3-year and 5-year all-cause and cardiovascular mortality were significantly higher in PD compared with HD. The presence of comorbid conditions including myocardial infarction, coronary artery disease (CAD), diabetes mellitus (DM), hypoalbuminemia, hyperferritinemia and hypophosphatemia was related with significantly higher all-cause and CV mortality in PD patients. No significant difference was noted among younger patients <45 years of age regardless of DM and/or comorbid conditions. Conclusion: Although PD did not have the survival advantage compared to HD in all dialysis populations, PD was related with superior survival in younger non-DM patients, regardless of the presence of comorbidities. Similarly, for younger ESKD patients without the risk of CV disease, both PD and HD would be suitable dialysis modalities.

Golay-Encoded Ultrasound Monitoring of Simultaneous High-Intensity Focused Ultrasound Treatment: A Phantom Study.

Ultrasound (US) imaging has high potential in monitoring high-intensity focused US (HIFU) treatment due to its superior temporal resolution. However, US monitoring is often hindered by strong HIFU interference, which overwhelms the echoes received by the imaging array. In this study, a method of Golay-encoded US monitoring is proposed to visualize the imaged object for simultaneous HIFU treatment. It effectively removes HIFU interference patterns in real-time B-mode imaging and improves the metrics of image quality, such as peak signal-to-noise ratio (PSNR), structural similarity (SSIM), and contrast ratio (CR). Compared to the pulse-inversion sequence, the N -bit Golay sequence can boost the echo magnitude of US monitoring by another N times and, thus, exhibits higher robustness. Simulations show that a sinusoidal HIFU waveform can be fully eliminated using Golay decoding when the bit duration of the N -bit Golay sequence ( N is the power of 4) coincides with either odd (Case I) or even (Case II) integer multiples of the HIFU quarter period. Experimental results also show that the Golay decoding with Case II can increase the PSNR of US monitoring images by more than 30 dB for both pulse- and continuous-wave HIFU transmissions. The SSIM index also effectively improves to about unity, indicating that the B-mode image with HIFU transmission is visually indistinguishable from that acquired without HIFU transmission. Though Case I is inferior to Case II in the elimination of even-order HIFU harmonic, they together enable a more flexible selection of imaging frequencies to meet the required image resolution and penetration for Golay-encoded US monitoring.

DMAS Beamforming with Complementary Subset Transmit for Ultrasound Coherence-Based Power Doppler Detection in Multi-Angle Plane-Wave Imaging.

Conventional ultrasonic coherent plane-wave (PW) compounding corresponds to Delay-and-Sum (DAS) beamforming of low-resolution images from distinct PW transmit angles. Nonetheless, the trade-off between the level of clutter artifacts and the number of PW transmit angle may compromise the image quality in ultrafast acquisition. Delay-Multiply-and-Sum (DMAS) beamforming in the dimension of PW transmit angle is capable of suppressing clutter interference and is readily compatible with the conventional method. In DMAS, a tunable p value is used to modulate the signal coherence estimated from the low-resolution images to produce the final high-resolution output and does not require huge memory allocation to record all the received channel data in multi-angle PW imaging. In this study, DMAS beamforming is used to construct a novel coherence-based power Doppler detection together with the complementary subset transmit (CST) technique to further reduce the noise level. For p = 2.0 as an example, simulation results indicate that the DMAS beamforming alone can improve the Doppler SNR by 8.2 dB compared to DAS counterpart. Another 6-dB increase in Doppler SNR can be further obtained when the CST technique is combined with DMAS beamforming with sufficient ensemble averaging. The CST technique can also be performed with DAS beamforming, though the improvement in Doppler SNR and CNR is relatively minor. Experimental results also agree with the simulations. Nonetheless, since the DMAS beamforming involves multiplicative operation, clutter filtering in the ensemble direction has to be performed on the low-resolution images before DMAS to remove the stationary tissue without coupling from the flow signal.

Computationally efficient minimum-variance baseband delay-multiply-and-sum beamforming for adjustable enhancement of ultrasound image resolution.

Baseband Delay-Multiply-and-Sum (BB-DMAS) beamforming takes advantage of the baseband spatial coherence of receiving aperture to improve image resolution and contrast. Meanwhile, the side-lobe clutter and noise level can also be effectively suppressed in BB-DMAS beamforming due to their low coherence when being detected by channels in different spatial locations. BB-DMAS scales the magnitude of channel signal by p-th root and restores the output dimensionality by p-th power after channel summation. Higher p value introduces more spatial coherence into DMAS beamforming and provides higher image resolution at the cost of background speckle quality. In this study, a computationally efficient integration of BB-DMAS with minimum-variance (MV) beamforming is developed so that the image resolution can be drastically improved with low p value (e.g. p < 2) while maintaining the speckle quality. For each image pixel, the proposed MV-DMAS only requires single MV estimation to optimize the aperture apodization for DMAS beamforming. Our simulation results show that, with p = 1.5, the -6-dB lateral width of wire reflector noticeably improves from 0.22 mm to 0.13 mm by adopting MV estimation in BB-DMAS beamforming. In MV-DMAS, the suppression of uncorrelated random noises also remains effective. Experimental results not only confirm the superior resolution in MV-DMAS beamforming but also demonstrates comparable image contrast and speckle quality to BB-DMAS counterpart. In conclusion, MV-DMAS beamforming can provide improvement in image resolution while maintaining the other image quality metrics using an efficient combination of moderate spatial coherence and MV estimation of receiving aperture apodization in ultrasonic imaging.

Estimation of Ultrasound Echogenicity Map from B-Mode Images Using Convolutional Neural Network.

In ultrasound B-mode imaging, speckle noises decrease the accuracy of estimation of tissue echogenicity of imaged targets from the amplitude of the echo signals. In addition, since the granular size of the speckle pattern is affected by the point spread function (PSF) of the imaging system, the resolution of B-mode image remains limited, and the boundaries of tissue structures often become blurred. This study proposed a convolutional neural network (CNN) to remove speckle noises together with improvement of image spatial resolution to reconstruct ultrasound tissue echogenicity map. The CNN model is trained using in silico simulation dataset and tested with experimentally acquired images. Results indicate that the proposed CNN method can effectively eliminate the speckle noises in the background of the B-mode images while retaining the contours and edges of the tissue structures. The contrast and the contrast-to-noise ratio of the reconstructed echogenicity map increased from 0.22/2.72 to 0.33/44.14, and the lateral and axial resolutions also improved from 5.9/2.4 to 2.9/2.0, respectively. Compared with other post-processing filtering methods, the proposed CNN method provides better approximation to the original tissue echogenicity by completely removing speckle noises and improving the image resolution together with the capability for real-time implementation.

Nifedipine Modulates Renal Lipogenesis via the AMPK-SREBP Transcriptional Pathway.

Lipid accumulation in renal cells has been implicated in the pathogenesis of obesity-related kidney disease, and lipotoxicity in the kidney can be a surrogate marker for renal failure or renal fibrosis. Fatty acid oxidation provides energy to renal tubular cells. Ca2+ is required for mitochondrial ATP production and to decrease reactive oxygen species (ROS). However, how nifedipine (a calcium channel blocker) affects lipogenesis is unknown. We utilized rat NRK52E cells pre-treated with varying concentrations of nifedipine to examine the activity of lipogenesis enzymes and lipotoxicity. A positive control exposed to oleic acid was used for comparison. Nifedipine was found to activate acetyl Coenzyme A (CoA) synthetase, acetyl CoA carboxylase, long chain fatty acyl CoA elongase, ATP-citrate lyase, and 3-hydroxy-3-methyl-glutaryl-coenzyme A (HMG CoA) reductase, suggesting elevated production of cholesterol and phospholipids. Nifedipine exposure induced a vast accumulation of cytosolic free fatty acids (FFA) and stimulated the production of reactive oxygen species, upregulated CD36 and KIM-1 (kidney injury molecule-1) expression, inhibited p-AMPK activity, and triggered the expression of SREBP-1/2 and lipin-1, underscoring the potential of nifedipine to induce lipotoxicity with renal damage. To our knowledge, this is the first report demonstrating nifedipine-induced lipid accumulation in the kidney.

Ultrasound Baseband Delay-Multiply-and-Sum (BB-DMAS) nonlinear beamforming.

Compared to conventional Delay-and-Sum (DAS) beamforming, Delay-Multiply-and-Sum (DMAS) imaging uses multiplicative coupling of channel pairs for spatial coherence of receiving aperture to improve image resolution and contrast. However, present DMAS imaging is based on the radio-frequency (RF) channel signals (RF-DMAS) and thus requires large oversampling to avoid aliasing and switching of band-pass filtering to isolate the corresponding spectral components for imaging. Baseband DMAS (BB-DMAS) beamforming in this study is based on the demodulated channel signals to provide similar results but with simplified signal processing. The BB-DMAS beamforming scales the magnitude of time-delayed channel signal by p-th root while maintaining the phase. After channel sum, the output dimensionality is restored by p-th power. The multiplicative coupling in BB-DMAS always renders baseband signal and thus the need for oversampling is eliminated. Besides, the BB-DMAS can use any rational p values to provide flexible image quality and an explicit relation between BB-DMAS beamforming and channel-domain phase coherence exists. Our results show that the image characteristics between BB-DMAS and RF-DMAS are similar. The suppression of lateral side lobe level, grating lobe level and uncorrelated random noises gradually increases with the rational p value in BB-DMAS beamforming. The image contrast improves from -24.8 dB in DAS to -34.3 dB, -43.0 dB and -51.4 dB in BB-DMAS, respectively with p value of 1.5, 2.0 and 2.5. In conclusion, BB-DMAS beamforming provides flexible manipulation of image quality by introducing baseband spatial coherence in the ultrasonic imaging.

Synthetic transmit aperture beamforming for sound velocity estimation using channel-domain differential phase gradient - A phantom study.

In medical ultrasound imaging system, degradation of image quality occurs due to mismatch between beamforming sound velocity and propagating sound velocity in tissue. Channel-domain differential phase gradient has been previously utilized to optimize the beamforming sound velocity but its efficacy is limited to transmit focal depth. Specifically, low spatial coherence of channel signal in the non-focal region could lead to over-estimation of beamforming sound velocity. In order to alleviate the estimation bias of beamforming sound velocity, synthetic transmit aperture beamforming is proposed in this study to maintain the spatial coherence of channel data over the entire imaging depth. By combining channel signals from adjacent scanlines to remedy the focusing quality in the non-focal region, the zero of differential phase gradient between the left and right sub-apertures can accurately determine the optimal sound velocity for beamforming. Results indicate that the synthetic transmit aperture beamforming effectively reduces the estimation bias of beamforming sound velocity from 4.3% to 0.1% in the simulations and from 8.8% to 0.1% in phantom measurement. With the optimized sound velocity, the lateral resolution improves by 14.5%. Compared to our previous work, the improved method also exhibits higher robustness of sound velocity estimation in the presence of random noises. The variation of sound velocity estimation decreases from 59.1 m/s with the previous method to 16.9 m/s with the improved method in our simulation when the channel SNR is -25 dB.

High-Order Hadamard-Encoded Transmission for Tissue Background Suppression in Ultrasound Contrast Imaging: Memory Effect and Decoding Schemes.

Hadamard-encoded multipulses (HEM) transmit has recently been utilized for tissue background suppression in ultrasound contrast imaging to enhance the contrast-to-tissue ratio (CTR). Nonetheless, the second-harmonic component in HEM transmit results in residual tissue background after decoding and, thus, compromises the detection of contrast microbubbles. Theoretically, high-order HEM transmit can produce harmonic-free background but the memory effect, which considers the nonlinear contribution of previous bit waveform into the next one in the progress of harmonic generation, may limit the achievable tissue suppression. In this paper, three possible harmonic-free pairs using time-shifted subtraction (SH1, SH2, and SH3) in the fourth-order Hadamard decoding are analyzed and experimentally compared using hydrophone measurement and B-mode imaging. Moreover, the orthogonal decoding (OD) of HEM transmit is also proposed with pulse-inversion harmonic suppression (PIHS) to remedy memory effect on the tissue background. Results show that SH3, which utilizes the third and fourth rows for decoding, provides the lowest magnitude of tissue background among all possible decoding pairs and performs comparably to the reference PI and amplitude-modulation sequence in terms of CTR. For PIHS-OD, the pulse subtraction effectively removes the harmonic interferences from memory effect and, thus, further improves the CTR by 5.4 dB compared to SH3. For high-order HEM transmit, PIHS-OD can help to eliminate the residual tissue background due to memory effect and is comparable to Hadamard decoding in temporal resolution and possible motion artifacts.

Adaptive optimization of ultrasound beamforming sound velocity using sub-aperture differential phase gradient.

Ultrasound array imaging systems rely on a presumed beamforming sound velocity to calculate the time compensation of each element for receive focusing. The mismatch between the tissue sound velocity and the beamforming sound velocity can degrade the focusing quality due to loss of phase coherence. Since the tissue sound velocity cannot be known in prior, an adaptive optimization of beamforming sound velocity is required to improve the image quality. Differential phase gradient of channel data is proposed to estimate the optimal sound velocity for beamforming. The sound velocity optimization is achieved when the differential phase gradient between the left and the right sub-apertures approaches zero. Channel-domain autocorrelation is utilized for the estimation of phase gradient due to its high rejection to noise interference and low computational complexity. Results indicate that, compared to the conventional phase variance method, the proposed differential phase gradient reduces the standard deviation of sound velocity estimation from 0.5% to 0.2% while the accuracy remains comparable. The contrast ratio of the cyst region achieves the peak when the optimized sound velocity is utilized for beamforming. The lateral resolution of point target also improves by 14.3% after sound velocity optimization. The proposed method increases the robustness of sound velocity optimization. It is suggested to be implemented at transmit focal depth and without beam steering for better performance.

Autocorrelation-based generalized coherence factor for low-complexity adaptive beamforming.

BACKGROUND: Generalized coherence factor (GCF) can be adaptively estimated from channel data to suppress sidelobe artifacts. Conventionally, Fast Fourier Transform (FFT) is utilized to calculate the full channel spectrum and suffers from high computation load. In this work, autocorrelation (AR)-based algorithm is utilized to provide the spectral parameters of channel data for GCF estimation with reduced complexity. METHODS: Autocorrelation relies on the phase difference among neighboring channel pairs to estimate the mean frequency and bandwidth of channel spectrum. Based on these two parameters, the spectral power within the defined range of main lobe direction can be analytically computed from a pseudo spectrum with the presumed shape as the GCF weighting value. A bandwidth factor Q can be further included in the formulation of pseudo channel spectrum to optimize the performance. RESULTS: While the GCF computation complexity of a N-channel system reduces from O(Nlog2N) with FFT to O(N) with AR, the lateral side-lobe level is effectively suppressed in the GCF-AR method. In B-mode speckle imaging, the GCF-AR method can provide a higher image contrast together with a relatively low speckle variation. The resultant Contrast-to-Noise Ratio (CNR) improves from 6.7 with GCF-FFT method to 9.0 with GCF-AR method. CONCLUSION: GCF-AR method reduces the computation complexity of adaptive imaging while providing superior image quality. GCF-AR method is more resistant to the speckle black-region artifacts near strong reflectors and thus improves the overall image contrast.

Supplementary Golay pair for range side lobe suppression in dual-frequency tissue harmonic imaging.

BACKGROUND: In dual-frequency (DF) harmonic imaging, the second harmonic signal at second harmonic (2f0) frequency and the inter-modulation harmonic signal at fundamental (f0) frequency are simultaneously imaged for spectral compounding. When the phase-encoded Golay pair is utilized to improve the harmonic signal-to-noise ratio (SNR), however, the DF imaging suffers from range side lobe artifacts due to spectral cross-talk with other harmonic components at DC and third harmonic (3f0) frequency. METHODS: In this study, a supplementary Golay pair is developed to suppress the range side lobes in combination with the original Golay pair. Since the phase code of the DC interference cannot be manipulated, the supplementary Golay is designed to reverse the polarity of the 3f0 interference and the f0 signal while keeping the 2f0 signal unchanged. For 2f0 imaging, the echo summation of the supplementary and the original Golay can cancel the 3f0 interference. On the contrary, the echo difference between the two Golay pairs can eliminate the DC interference for f0 imaging. RESULTS: Hydrophone measurements indicate that the range side lobe level (RSLL) increases with the signal bandwidth of DF harmonic imaging. By using the combination of the two Golay pairs, the achievable suppression of RSLL can be 3 and 14 dB, respectively for the f0 and 2f0 harmonic signal. B-mode phantom imaging also verifies the presence of range side lobe artifacts when only the original Golay pair is utilized. In combination with the supplementary Golay pair, the artifacts are effectively suppressed. The corresponding range side lobe magnitude reduces by about 8 dB in 2f0 imaging but remains unchanged in f0 imaging. Meanwhile, the harmonic SNR improves by 8-10 dB and the contrast-to-noise ratio of harmonic image increases from about 1 to 1.2 by spectral compounding. CONCLUSION: For DF tissue harmonic imaging, the spectral cross-talk in Golay excitation results in severe range side lobe artifacts. To restore the image quality, two particular phase-encoded Golay pairs are required to perform either echo summation or difference for elimination of unwanted harmonic components.

Range side lobe inversion for chirp-encoded dual-band tissue harmonic imaging.

Dual-band (DB) harmonic imaging is performed by transmitting and receiving at both fundamental band (f0) and second-harmonic band (2f0). In our previous work, particular chirp excitation has been developed to increase the signal- to-noise ratio in DB harmonic imaging. However, spectral overlap between the second-order DB harmonic signals results in range side lobes in the pulse compression. In this study, a novel range side lobe inversion (RSI) method is developed to alleviate the level of range side lobes from spectral overlap. The method is implemented by firing an auxiliary chirp to change the polarity of the range side lobes so that the range side lobes can be suppressed in the combination of the original chirp and the auxiliary chirp. Hydrophone measurements show that the RSI method reduces the range side lobe level (RSLL) and thus increases the quality of pulse compression in DB harmonic imaging. With the signal bandwidth of 60%, the RSLL decreases from -23 dB to -36 dB and the corresponding compression quality improves from 78% to 94%. B-mode images also indicate that the magnitude of range side lobe is suppressed by 7 dB when the RSI method is applied.

The lifetime and attenuation properties measurements of a US/MR multimodality molecular probe.

In our previous studies we explored the potential of using a combined US/magnetic resonance (MR) multimodality contrast agent, albumin-gadolinium-diethylenetriaminepentacetate (Gd-DTPA) MBs, to induce BBB opening and for distinguishing between FUS-induced BBB opening and intracerebral hemorrhage in MR T1-weighted contrast imaging. According to the previous study in the literature, 1-2 µm bubbles have more pronounced acoustic activity at frequencies above 10 MHz. The present study developed a new targeted US/MR multimodality MB and the acoustic properties were compared with two commercial MBs, SonoVue and Targestar SA. The acoustic activities of these 1.15-2.78 µm MBs with different shells at 10 MHz were investigated. The feasibility of designing a new targeted US/MR multimodality MB was investigated. The lifetime (survival of MBs in the liquid suspension) and attenuation properties of lipid MBs (SonoVue and Targestar SA), albumin-(Gd-DTPA) MBs, and avidin-conjugated albumin (avidin-albumin)-(Gd-DTPA) MBs at 10 MHz were investigated with the pulse-echo substitution method. It was found that incorporating avidin into the albumin MBs and avidin-albumin-(Gd-DTPA) MBs affects the size distribution but does not affect the concentration of MBs produced. The avidin-albumin-shelled MBs had more significant nonlinear activity at 4-18 MHz (p=0.025), while the nonlinear activity of the other MBs peaked at 6-24 MHz (p=0.003-0.044). Moreover, the incorporation of paramagnetic metal ions into the MB shells increased their attenuation coefficients. With regard to the lifetime of these agents, the attenuations of the SonoVue and Targestar SA lipid MBs were 87.96% and 8.74%, respectively, while those of albumin MBs, avidin-albumin MBs, albumin-(Gd-DTPA) MBs, and avidin-albumin-(Gd-DTPA) MBs were 49.52%, 41.38%, 74.69%, and 100%, respectively. Avidin conjugation decreased the lifetime of the albumin MBs, but not that of the lipid MBs. The incorporation of paramagnetic metal ions into the shells of albumin MBs did not decrease the lifetime.

Dual-frequency tissue harmonic suppression using phase-coded pulse sequence: proof of concept using a phantom.

BACKGROUND: The presence of tissue harmonic generation during acoustic propagation is one major limitation in nonlinear detection of microbubble contrast agents. However, conventional solutions for tissue harmonic suppression are not applicable in dual-frequency (DF) harmonic imaging. In DF harmonic imaging, the second harmonic signal at second harmonic (2f(0)) frequency and the inter-modulation harmonic signal at fundamental (f(0)) frequency are simultaneously generated for imaging and both need to be suppressed to improve contrast-to-tissue ratio (CTR). In this study, a novel phase-coded pulse sequence is developed to accomplish DF tissue harmonic suppression. METHODS: Phase-coded pulse sequence utilizes multiple firings with equidistant transmit phase for harmonic cancellation in the sum of respective echoes. For the f(0) transmit component, the transmit phase comes from the equidistant set of {-2π/3, 0, 2π/3} to suppress the second harmonic signal at 2f(0) frequency. Moreover, in order to provide the inter-modulation harmonic suppression at f(0) frequency, the 2f(0) transmit phase has to be particularly manipulated for the corresponding f(0) transmit phase. RESULTS: The proposed three-pulse sequence can remove not only the second-order harmonic signal but also other higher-order counterparts at both f(0) and 2f(0) frequencies. Measurements were performed at f(0) equal to 2.25 MHz and using hydrophone in water and contrast agents in tissue phantom. Experimental results indicate that the sequence reduces the tissue harmonic magnitude by about 20 dB along the entire axial depths and the corresponding CTR improves at both frequencies. CONCLUSION: In DF harmonic imaging, the proposed phase-coded sequence can effectively remove the tissue harmonic background at both f(0) and 2f(0) frequencies for improvement of contrast detection.

Chirp-encoded excitation for dual-frequency ultrasound tissue harmonic imaging.

Dual-frequency (DF) transmit waveforms comprise signals at two different frequencies. With a DF transmit waveform operating at both fundamental frequency (f(0)) and second-harmonic frequency (2f(0)), tissue harmonic imaging can be simultaneously performed using not only the conventional 2f(0) second-harmonic signal but also using the f(0 )frequency-difference harmonic signal. Nonetheless, when chirp excitation is incorporated into the DF transmit waveform for harmonic SNR improvement, a particular waveform design is required to maintain the bandwidth of the f(0) harmonic signal. In this study, two different DF chirp waveforms are proposed to produce equal harmonic bandwidth at both the f(0) and 2f(0) frequencies to achieve speckle reduction by harmonic spectral compounding and to increase harmonic SNR for enhanced penetration and sensitivity. The UU13 waveform comprises an up-sweeping f(0) chirp and an up-sweeping 2f(0) chirp with triple bandwidth, whereas the UD11 waveform includes an up-sweeping f(0) chirp and a down-sweeping 2f(0) chirp with equal bandwidth. Experimental results indicate that the UU13 tends to suffer from a high range side lobe level resulting from 3f(0) interference. Consequently, the 2f(0) harmonic envelopes of the UD11 and the UU13 waveforms have compression qualities of 87% and 77%, respectively, when the signal bandwidth is 30%. When the bandwidth increases to 50%, the compression quality of the 2f(0) harmonic envelope degrades to 78% and 54%, respectively, for the UD11 and the UU13 waveforms. The compression quality value of the f0 harmonic envelope remains similar between the two DF transmit waveforms for all signal bandwidths. B-mode harmonic images also show that the UD11 is less contaminated by range side lobe artifacts than is the UU13. Compared with a short pulse with equal bandwidth, the UD11 waveform not only preserves the same spatial resolution after compression but also improves the image SNR by about 10 dB. Moreover, the image contrast-to-noise ratio (CNR), defined as the ratio of the mean to the standard deviation of image intensity in the speckle region, can be increased from 1.0 to about 1.2 when DF spectral compounding is performed. Therefore, it is concluded that the UD11 waveform is a potential solution for chirp-encoded DF harmonic imaging.