Passive acoustic mapping with absolute time-of-flight information and delay-multiply-sum beamforming.

BACKGROUND: Passive acoustic mapping (PAM) is showing increasing application potential in monitoring ultrasound therapy by spatially resolving cavitation activity. PAM with the relative time-of-flight information leads to poor axial resolution when implemented with ultrasound diagnostic transducers. Through utilizing the absolute time-of-flight information preserved by the transmit-receive synchronization and applying the common delay-sum (DS) beamforming algorithm, PAM axial resolution can be greatly improved in the short-pulse excitation scenario, as with active ultrasound imaging. However, PAM with the absolute time-of-flight information (referred as AtPAM) suffers from low imaging resolution and weak interference suppression when the DS algorithm is applied. PURPOSE: This study aims to propose an enhanced AtPAM algorithm based on delay-multiply-sum (DMS) beamforming, to address the shortcomings of the DS-based AtPAM algorithm. METHODS: In DMS beamforming, the element signals delayed by the absolute time delays are first processed with a signed square-root operation and then multiplied in pairs and finally summed, the resulting beamformed output is further band-pass filtered. The performances of DS- and DMS-based AtPAMs are compared by experiments, in which an ultrasound diagnostic transducer (a linear array) is employed to passively sense the wire signals generated by an unfocused ultrasound transducer and the cavitation signals generated by a focused therapeutic ultrasound transducer in a flow phantom. The AtPAM image quality is assessed by main-lobe width (MLW), intensity valley value (IVV), area of pixels (AOP), signal-to-interference ratio (SIR), and signal-to-noise ratio (SNR). RESULTS: The single-wire experimental results show that compared to the DS algorithm, the DMS algorithm leads to an enhanced AtPAM image with a decreased transverse MLW of 0.15 mm and an improved SIR and SNR of 31.50 and 18.77 dB. For the four-wire images, the transverse (axial) IVV is decreased by 18.37 dB (13.11 dB) and the SIR (the SNR) is increased by 26.13 dB (18.47 dB) when using the DMS algorithm. The cavitation activity is better highlighted by DMS-based AtPAM, which decreases the AOP by 0.81 mm2 (-10-dB level) and 4.43 mm2 (-20-dB level) and increases the SIR and SNR by 20.14 and 10.48 dB respectively. The pixel distributions of AtPAM images of both wires and cavitation activity also indicate a better suppression of the DMS algorithm in sidelobe and noise. CONCLUSIONS: The experimental results illustrate that the DMS algorithm can improve the image quality of AtPAM compared to the DS algorithm. DMS-based AtPAM is beneficial for detecting cavitation activity during short-pulse ultrasound exposure with high resolution, and further for monitoring short-pulse ultrasound therapy.

Feasibility investigation of logarithmic Nakagami parametric imaging in recovering underestimated perfusion metrics of DCEUS in the uneven acoustic field.

PURPOSE: Owing to acoustic-pressure dependence, amplitudes of backscattered-echoes of encapsulated microbubbles (MBs) are unavoidably regulated by an uneven acoustic field, resulting in the misestimation of hemodynamics in conventional amplitude-coding dynamic contrast-enhanced ultrasound (DCEUS) with focused pulse transmission. This study aimed to investigate the feasibility and performance of Nakagami statistical-feature parametric imaging to recover the above misestimation. METHODS: Logarithmic Nakagami parameter (m)-coding DCEUS scheme was investigated via simulation and in vitro MB phantoms as well as in vivo kidney-perfusion experiments of four rabbits in the uneven acoustic fields with two different focal depths. In vivo tissue artifacts for m estimation were suppressed by pulse-inversion second-harmonic imaging and its robustness was enhanced by multiscale moment-estimation strategy. Time-Nakagami-m curves and the corresponding perfusion metrics of intensity and volume were calculated from the logarithmic m-coding DCEUS images within the prefocal and focal regions. These curves and metrics were further compared with the perfusion curves and metrics estimated from the conventional amplitude-coding images within the same regions. RESULTS: Compared with amplitudes of nonlinear scattering MB echoes, their logarithmic m values were relatively independent of the changes in acoustics pressures. Compared with the fixed-scale moment-estimation, the perfusion intensity estimated from logarithmic m-coding DCEUS scheme using multiscale statistical moment-estimation had smaller differences between the prefocal and focal regions. The differences of perfusion intensity induced by an uneven acoustic field decreased to 3.47% ± 1.58 %. The differences decreased by the logarithmic m-coding DCEUS scheme were further regulated by threshold values of m estimation. CONCLUSIONS: The logarithmic m-coding DCEUS scheme could recover the underestimated MB backscattered-echoes and the misestimated perfusion intensity induced by the uneven acoustic field. The scheme had the potential to weaken the limitation of microvasculature identification and hemodynamic characterization marked by MBs within tissues or tumors in the uneven acoustic field.

Dual apodization with cross-correlation combined with robust Capon beamformer applied to ultrasound passive cavitation mapping.

PURPOSE: Passive acoustic mapping (PAM) has received increasing attention in recent years and has an extremely widespread application prospect in real-time monitoring of ultrasound treatment. When using a diagnostic ultrasound transducer, such as a linear-array transducer, the initially used time exposure acoustics (TEA) algorithm will produce high-level artifacts. To address this problem, we recently proposed an enhanced algorithm for linear-array PAM by introducing dual apodization with the cross-correlation (DAX) method into TEA. But due to that the delay and sum beamformer used to create RX1 and RX2 is non-adaptive, the remaining X-type artifacts cannot be completely suppressed, yielding unsatisfactory image quality. This study aims to propose an improved version by combining DAX and robust Capon beamformer (DAX-RCB). METHODS: Different from the delay and sum beamformer in the DAX-TEA algorithm, in the proposed version, the two sets of channel signals from a pair of complementary receive apodizations are beamformed by the RCB method, which may make passive cavitation images much less sensitive to X-type artifacts. The performance of the DAX-RCB algorithm is validated by simulations and in vitro experiments and compared with the initially used TEA algorithm and the previous DAX-TEA and RCB algorithms. Four indexes, including passive energy beam (PEB) size, image signal-to-background ratio (ISBR), energy estimation ratio (EER), and computing time, are used to evaluate the algorithm performance. RESULTS: Consider an example of the 8-8 alternating pattern (a pair of complementary apodizations are obtained by extracting eight elements every eight elements), the experimental results show that the A-6dB area (2D PEB size) of the proposed DAX-RCB is significantly reduced by 11.0 and 6.8 mm2 when compared with TEA and DAX-TEA and is not significantly reduced when compared with RCB, the ISBR is significantly improved by 19.6, 10.8, and 5.6 dB compared with TEA, DAX-TEA, and RCB, and the EER of DAX-RCB is over 90%. The simulation tests indicate that the DAX-RCB algorithm is also applicable to the image enhancement in the double-source scenario and the high-level noise scenario but at a risk of low energy estimation. The improvement of algorithm performance is accompanied by an increase in the computing time. The proposed DAX-RCB consumes 113.3%, 29.5%, and 17.8% more time than TEA, DAX-TEA, and RCB. CONCLUSIONS: The proposed DAX-RCB can be considered as an effective reconstruction algorithm for passive cavitation mapping and provide an appropriate monitoring means for ultrasound therapy, especially for cavitation-mediated applications.

Numerical and experimental investigation of impacts of nonlinear scattering encapsulated microbubbles on Nakagami distribution.

PURPOSE: The Nakagami statistical model and Nakagami shape parameter m have been widely used in linear tissue characterization and preliminarily characterized the envelope distributions of nonlinear encapsulated microbubbles (EMBs). However, the Nakagami distribution of nonlinear scattering EMBs lacked a systematical investigation. Thus, this study aimed to investigate the Nakagami distribution of EMBs and illustrate the impact of EMBs' nonlinearity on the Nakagami model. METHOD: A group of simulated EMB phantoms and in vitro EMB dilutions with an increasing concentration distribution under various EMB nonlinearities, as regulated by acoustic parameters, were characterized by using the window-modulated compounding Greenwood-Durand estimator. RESULTS: Raw envelope histograms of simulated and in vitro EMBs were well matched with the Nakagami distribution with a high correlation coefficient of 0.965 ± 0.021 (P < 0.005). The mean values and gradients of m parameters of simulated and in vitro EMBs were smaller than those of linear scatterers due to the stronger nonlinearity. These m values exhibited a quasi-linear improvement with the increase in second harmonic nonlinear-to-linear component ratio regulated by pulse lengths and excitation frequencies at low- and high-concentration conditions. CONCLUSIONS: The Nakagami distribution was suitable for the EMBs characterization but the corresponding m parameter was affected by the EMBs' nonlinearity. These validations provided support and nonlinear impact assessment for the EMBs' characterization using the Nakagami statistical model in the future.

Delay multiply and sum beamforming method applied to enhance linear-array passive acoustic mapping of ultrasound cavitation.

PURPOSE: Passive acoustic mapping (PAM) has been proposed as a means of monitoring ultrasound therapy, particularly nonthermal cavitation-mediated applications. In PAM, the most common beamforming algorithm is a delay, sum, and integrate (DSAI) approach. However, using DSAI leads to low-quality images for the case where a narrow-aperture receiving array such as a standard B-mode linear array is used. This study aims to propose an enhanced linear-array PAM algorithm based on delay, multiply, sum, and integrate (DMSAI). METHODS: In the proposed algorithm, before summation, the delayed signals are combinatorially coupled and multiplied, which means that the beamformed output of the proposed algorithm is the spatial coherence of received acoustic emissions. We tested the performance of the proposed DMSAI using both simulated and experimental data and compared it with DSAI. The reconstructed cavitation images were evaluated quantitatively by using source location errors between the two algorithms, full width at half maximum (FWHM), size of point spread function (A50 area), signal-to-noise ratio (SNR), and computational time. RESULTS: The results of simulations and experiments for single cavitation source show that, by introducing DMSAI, the FWHM and the A50 area are reduced and the SNR is improved compared with those obtained by DSAI. The simulation results for two symmetric or nonsymmetric cavitation sources and multiple cavitation sources show that DMSAI can significantly reduce the A50 area and improve the SNR, therefore improving the detectability of multiple cavitation sources. CONCLUSIONS: The results indicate that the proposed DMSAI algorithm outperforms the conventionally used DSAI algorithm. This work may have the potential of providing an appropriate method for ultrasound therapy monitoring.

Passive cavitation mapping using dual apodization with cross-correlation in ultrasound therapy monitoring.

Recently, passive acoustic mapping (PAM) has been successfully applied for dynamic monitoring of ultrasound therapy by beamforming acoustic emissions of cavitation activity during ultrasound exposure. The most widely used PAM algorithm in the literature is time exposure acoustics (TEA), which is a standard delay, sum, and integrate algorithm. However, it results in large point spread function (PSF) and serious imaging artifacts for the case where a narrow-aperture receiving array such as a standard B-mode linear array is used, therefore degrading the quality of cavitation image. To address these challenges, in this paper, we proposed a novel PAM algorithm namely dual apodization with cross-correlation (DAX)-based TEA, in which DAX was originally used as a reconstruction algorithm in medical ultrasound imaging. In the proposed algorithm, two sets of signals were beamformed by two receive apodization functions with alternating elements enabled, and the cross-correlation coefficient of the two signals served as a weighting factor that would be multiplied to the sum of the two signals. The performance of the proposed algorithm was tested on simulated channel data obtained using a multi-bubble model, and experiments were also performed in an in vitro vessel phantom with flowing microbubbles as cavitation nuclei. The reconstructed cavitation images were evaluated quantitatively using established quality metrics including full width at half maximum (FWHM), A-6dB area, and signal-to-noise ratio (SNR). The results suggested that the proposed algorithm significantly outperformed the conventionally used TEA algorithm. This work may have the potential of providing a useful tool for highly accurate localization of cavitation activity during ultrasound therapy.

Bubble-echo based deconvolution of contrast-enhanced ultrasound imaging: Simulation and experimental validations.

PURPOSE: Improvement of both the imaging resolution and the contrast-to-tissue ratio (CTR) is a current emphasis of contrast-enhanced ultrasound (CEUS) for microvascular perfusion imaging. Based on the strong nonlinear characteristics of contrast agents, the CTRs have been significantly enhanced using various advanced CEUS methods. However, the imaging resolution of these methods is limited by the finite bandwidth of the imaging process. This study aimed to propose a bubble-echo based deconvolution (BED) method for CEUS with both improved resolution and CTR. METHOD: The method is built on a modified convolution model and uses novel bubble-echo based point-spread-functions to reconstruct the images by regularized inverse Wiener filtering. Performances of the proposed BED for three CEUS modes are investigated through simulations and in vivo perfusion experiments. RESULTS: BED of fundamental imaging was found to have the highest improvement in imaging resolution with the resolution gain up to 2.0 ± 0.2 times, which was comparable to the approved cepstrum-based deconvolution (CED). BED of second-harmonic imaging had the best performance in CTR with an enhancement of 9.8 ± 2.3 dB, which was much higher than CED. Pulse inversion BED had both a better resolution and a higher CTR. CONCLUSION: All results indicate that BED could obtain CEUS image with both an improved resolution and a high CTR, which has important significance to microvascular perfusion evaluation in deep tissue.

Efficient and controllable thermal ablation induced by short-pulsed HIFU sequence assisted with perfluorohexane nanodroplets.

A HIFU sequence with extremely short pulse duration and high pulse repetition frequency can achieve thermal ablation at a low acoustic power using inertial cavitation. Because of its cavitation-dependent property, the therapeutic outcome is unreliable when the treatment zone lacks cavitation nuclei. To overcome this intrinsic limitation, we introduced perfluorocarbon nanodroplets as extra cavitation nuclei into short-pulsed HIFU-mediated thermal ablation. Two types of nanodroplets were used with perfluorohexane (PFH) as the core material coated with bovine serum albumin (BSA) or an anionic fluorosurfactant (FS) to demonstrate the feasibility of this study. The thermal ablation process was recorded by high-speed photography. The inertial cavitation activity during the ablation was revealed by sonoluminescence (SL). The high-speed photography results show that the thermal ablation volume increased by ∼643% and 596% with BSA-PFH and FS-PFH, respectively, than the short-pulsed HIFU alone at an acoustic power of 19.5 W. Using nanodroplets, much larger ablation volumes were created even at a much lower acoustic power. Meanwhile, the treatment time for ablating a desired volume significantly reduced in the presence of nanodroplets. Moreover, by adjusting the treatment time, lesion migration towards the HIFU transducer could also be avoided. The SL results show that the thermal lesion shape was significantly dependent on the inertial cavitation in this short-pulsed HIFU-mediated thermal ablation. The inertial cavitation activity became more predictable by using nanodroplets. Therefore, the introduction of PFH nanodroplets as extra cavitation nuclei made the short-pulsed HIFU thermal ablation more efficient by increasing the ablation volume and speed, and more controllable by reducing the acoustic power and preventing lesion migration.

Nakagami-m parametric imaging for characterization of thermal coagulation and cavitation erosion induced by HIFU.

Nowadays, both thermal and mechanical ablation techniques of HIFU associated with cavitation have been developed for noninvasive treatment. A specific challenge for the successful clinical implementation of HIFU is to achieve real-time imaging for the evaluation and determination of therapy outcomes such as necrosis or homogenization. Ultrasound Nakagami-m parametric imaging highlights the degrading shadowing effects of bubbles and can be used for tissue characterization. The aim of this study is to investigate the performance of Nakagami-m parametric imaging for evaluating and differentiating thermal coagulation and cavitation erosion induced by HIFU. Lesions were induced in basic bovine serum albumin (BSA) phantoms and ex vivo porcine livers using a 1.6 MHz single-element transducer. Thermal and mechanical lesions induced by two types of HIFU sequences respectively were evaluated using Nakagami-m parametric imaging and ultrasound B-mode imaging. The lesion sizes estimated using Nakagami-m parametric imaging technique were all closer to the actual sizes than those of B-mode imaging. The p-value obtained from the t-test between the mean m values of thermal coagulation and cavitation erosion was smaller than 0.05, demonstrating that the m values of thermal lesions were significantly different from that of mechanical lesions, which was confirmed by ex vivo experiments and histologic examination showed that different changes result from HIFU exposure, one of tissue dehydration resulting from the thermal effect, and the other of tissue homogenate resulting from mechanical effect. This study demonstrated that Nakagami-m parametric imaging is a potential real-time imaging technique for evaluating and differentiating thermal coagulation and cavitation erosion.

Passive acoustic mapping of cavitation using eigenspace-based robust Capon beamformer in ultrasound therapy.

Pulse-echo imaging technique can only play a role when high intensity focused ultrasound (HIFU) is turned off due to the interference between the primary HIFU signal and the transmission pulse. Passive acoustic mapping (PAM) has been proposed as a tool for true real-time monitoring of HIFU therapy. However, the most-used PAM algorithm based on time exposure acoustic (TEA) limits the quality of cavitation image. Recently, robust Capon beamformer (RCB) has been used in PAM to provide improved resolution and reduced artifacts over TEA-based PAM, but the presented results have not been satisfactory. In the present study, we applied an eigenspace-based RCB (EISRCB) method to further improve the PAM image quality. The optimal weighting vector of the proposed method was found by projecting the RCB weighting vector onto the desired vector subspace constructed from the eigenstructure of the covariance matrix. The performance of the proposed PAM was validated by both simulations and in vitro histotripsy experiments. The results suggested that the proposed PAM significantly outperformed the conventionally used TEA and RCB-based PAM. The comparison results between pulse-echo images of the residual bubbles and cavitation images showed the potential of our proposed PAM in accurate localization of cavitation activity during HIFU therapy.

Real-time monitoring of controllable cavitation erosion in a vessel phantom with passive acoustic mapping.

Cavitation erosion in blood vessel plays an important role in ultrasound thrombolysis, drug delivery, and other clinical applications. The controllable superficial vessel erosion based on ultrasonic standing wave (USW) has been used to effectively prevent vessel ruptures and haemorrhages, and optical method is used to observe the experiments. But optical method can only work in transparent media. Compared with standard B-mode imaging, passive acoustic mapping (PAM) can monitor erosion in real time and has better sensitivity of cavitation detection. However, the conventionally used PAM has limitations in imaging resolution and artifacts. In this study, a unique PAM method that combined the robust Capon beamformer (RCB) with the sign coherence factor (SCF) was proposed to monitor the superficial vessel erosion in real time. The performance of the proposed method was validated by simulations. In vitro experiments showed that the lateral (axial) resolution of the proposed PAM was 2.31±0.51 (3.19±0.38) times higher than time exposure acoustics (TEA)-based PAM and 1.73±0.38 (1.76±0.48) times higher than RCB-based PAM, and the cavitation-to-artifact ratio (CAR) of the proposed PAM could be improved by 22.5±3.2dB and 7.1±1.2dB compared with TEA and RCB-based PAM. These results showed that the proposed PAM can precisely monitor the superficial vessel erosion and the erosion shift after USW modulation. This work may have the potential of developing a useful tool for precise spatial control and real-time monitoring of the superficial vessel erosion.

High-contrast active cavitation imaging technique based on multiple bubble wavelet transform.

In this study, a unique method that combines the ultrafast active cavitation imaging technique with multiple bubble wavelet transform (MBWT) for improving cavitation detection contrast was presented. The bubble wavelet was constructed by the modified Keller-Miksis equation that considered the mutual effect among bubbles. A three-dimensional spatial model was applied to simulate the spatial distribution of multiple bubbles. The effects of four parameters on the signal-to-noise ratio (SNR) of cavitation images were evaluated, including the following: initial radii of bubbles, scale factor in the wavelet transform, number of bubbles, and the minimum inter-bubble distance. And the other two spatial models and cavitation bubble size distributions were introduced in the MBWT method. The results suggested that in the free-field experiments, the averaged SNR of images acquired by the MBWT method was improved by 7.16 ± 0.09 dB and 3.14 ± 0.14 dB compared with the values of images acquired by the B-mode and single bubble wavelet transform (SBWT) methods. In addition, in the tissue experiments, the averaged cavitation-to-tissue ratio of cavitation images acquired by the MBWT method was improved by 4.69 ± 0.25 dB and 1.74± 0.29 dB compared with that of images acquired by B-mode and SBWT methods.