Runna Liu

Dependence of pulsed focused ultrasound induced thrombolysis on duty cycle and cavitation bubble size distribution

In this study, we investigated the relationship between the efficiency of pulsed, focused ultrasound (FUS)-induced thrombolysis, the duty cycle (2.3%, 9%, and 18%) and the size distribution of cavitation bubbles. The efficiency of thrombolysis was evaluated through the degree of mechanical fragmentation, namely the number, mass, and size of clot debris particles. First, we found that the total number and mass of clot debris particles were highest when a duty cycle of 9% was used and that the mean diameter of clot debris particles was smallest. Second, we found that the size distribution of cavitation bubbles was mainly centered around the linear resonance radius (2.5μm) of the emission frequency (1.2MHz) of the FUS transducer when a 9% duty cycle was used, while the majority of cavitation bubbles became smaller or larger than the linear resonance radius when a 2.3% or 18% duty cycle was used. In addition, the inertial cavitation dose from the treatment performed at 9% duty cycle was much higher than the dose obtained with the other two duty cycles. The data presented here suggest that there is an optimal duty cycle at which the thrombolysis efficiency and cavitation activity are strongest. They further indicate that using a pulsed FUS may help control the size distribution of cavitation nuclei within an active size range, which we found to be near the linear resonance radius of the emission frequency of the FUS transducer.

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.

Wavelet-transform-based active imaging of cavitation bubbles in tissues induced by high intensity focused ultrasound

Cavitation detection and imaging are essential for monitoring high-intensity focused ultrasound (HIFU) therapies. In this paper, an active cavitation imaging method based on wavelet transform is proposed to enhance the contrast between the cavitation bubbles and surrounding tissues. The Yang-Church model, which is a combination of the Keller-Miksis equation with the Kelvin-Voigt equation for the pulsations of gas bubbles in simple linear viscoelastic solids, is utilized to construct the bubble wavelet. Experiments with porcine muscles demonstrate that image quality is associated with the initial radius of the bubble wavelet and the scale. Moreover, the Yang-Church model achieves a somewhat better performance compared with the Rayleigh-Plesset-Noltingk-Neppiras-Poritsky model. Furthermore, the pulse inversion (PI) technique is combined with bubble wavelet transform to achieve further improvement. The cavitation-to-tissue ratio (CTR) of the best tissue bubble wavelet transform (TBWT) mode image is improved by 5.1 dB compared with that of the B-mode image, while the CTR of the best PI-based TBWT mode image is improved by 7.9 dB compared with that of the PI-based B-mode image. This work will be useful for better monitoring of cavitation in HIFU-induced therapies.

Contrast-enhanced ultrasound imaging with high CTR and improved resolution by bubble-echo based deconvolution

In microvascular perfusion imaging by contrastenhanced ultrasound (CEUS), inhibiting the strong tissue backscattering to enhance contrast-to-tissue ratio (CTR) and improving the imaging resolution to distinguish small vessels are two critical aspects. CTR has been greatly enhanced based on the strong nonlinear responses of contrast microbubbles under ultrasound insonation. However, the resolution of CEUS image is still limited by the finite bandwidth of the imaging system. In this paper, a peculiar bubble-echo based deconvolution (BED) was proposed based on a modified convolution model for CEUS to improve both CTR and resolution. A novel bubble-echo based PSF was constructed using the modified Herring equation, where bubble-echo referred to the theoretical backscattered echo from a single bubble under the insonification. Deconvolution was implemented axially using regularized inverse Wiener filtering. The efficiency of the proposed BED was verified by combining with fundamental imaging, second harmonic imaging and pulse inversion technique. Meanwhile, as comparisons, the approved cepstrum based deconvolution (CEPD) and pulse inversion bubble-wavelet imaging (PIWI) were also performed. In vivo rabbit kidney perfusion experiments were carried out to evaluate the above methods from CTR, time-intensity-curve and resolution. BED performed better than CEPD and PIWI in enhancing CTR, and had a higher resolution than PIWI. All results indicate that BED provides new CEUS methods with higher CTR and good resolution, which has important significance to microvascular perfusion evaluation in deep tissue.

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.

Strategy of high efficiency and refined high-intensity focused ultrasound and ultrasound monitoring imaging of thermal lesion and cavitation

We proposed that high efficiency high-intensity focused ultrasound (HIFU) could be achieved by using a splitting transducer with various frequencies and focusing patterns, and explored the feasibility of using ultrafast active cavitation imaging (UACI), pulse inversion (PI) sub-harmonic cavitation imaging and bubble wavelet transform imaging for monitoring of cavitation during HIFU, as well as the ultrasonic B-mode images, differential integrated backscatter (IBS) images, Nakagami images and elastography for monitoring HIFU-induced lesion. The use of HIFU splitting transducer had the potential to increase the size of the thermal lesion in a shorter duration and may improve the ablation efficiency of HIFU and would shorten the exposure duration significantly. The spatial-temporal evolution of residual cavitation bubbles at the tissue-water interface was obtained by UACI and the results showed that the UACI had a frame rate high enough to capture the transient behavior of the cavitation bubbles. The experim...

Influences of frequency-dispersive guided waves on contrast-enhanced ultrasound imaging

When emission waves (EWs) of imaging scanner hit bone, especially at an oblique incidence, guided waves (GWs) are generated from the bone cortex. GWs are multimodal and frequency-dispersive due to their non-linear propagation. Meanwhile, GWs leak to surrounding tissues and disturb SNR of acoustic signals. When microbubbles (MBs) flow through microvessels near a bone cortex, GWs can interact with MBs. The vibration and nonlinear scattering of MBs are unavoidably affected by GWs, which may disturb the image quality of ultrasound contrast imaging (UCI) near the bone surface. However, such disturbances on UCI with sub-harmonic (SH), fundamental (F), and ultra-harmonic (UH) have not been adequately addressed. This study aimed to elucidate the influences of frequency-dispersive GWs on UCI, especially with pulse inversion (PI) mode. The effects of GWs on UCI with B and PI modes were first elucidated through simulated comparison based on the modified Herring equation derived by GWs coupled EWs together and EWs alone, respectively. The GWs were reconstructed by the single-mode GWs, which were detected by using a transmitted-air gap-received (TAR) method and identified by using a smoothed pseudo-Wigner-Ville (SPWV) energy distribution superimposed with theoretical dispersion curves. Such effects were further verified by UCI in a vessel-plate flow phantom at incidence angles 0° and 22°. The influences of GWs on contrast and resolution of UCI were finally quantified by the differences in peak value (DPV) and half peak width (DHPW) of MB echoes, respectively. Based on TAR combined with SPWV methods, the coupling disturbances of EWs were removed; and the GWs with four single-modes (A0, A1, S0, and S2) and double-frequencies (3.35 and 1.62 MHz) were detected and identified. Due to the changes in MB echoes caused by GWs, the echo aliasing and gray changing occurred in all UCI methods. And DPV of MB echoes of PI SH was 4.0 times greater than that of SH, and DHPW of SH was 3.9 and 11.4 times higher than these of F and UH. Contrast of UCI was enhanced by GWs, but corresponding resolution was decreased, especially for SH and PI mode. So as a double-edged sword, the effects of GWs should be further explored to benefit UCI near the cortex.

Ultrasonic concentration imaging of cavitation bubbles using Nakagami statistical model

Cavitation is regarded as the primary mechanism in pulsed high-intensity focused ultrasound (pHIFU) therapy. Residual cavitation bubbles can be served as nuclei for the subsequent pHIFU cavitation. Therefore, information on spatial distribution especially concentration distribution of residual cavitation bubbles is important to better control pHIFU therapy. Acoustic spatial imaging of cavitation bubbles has been widely studied, while no research on quantitative bubble concentration imaging has been found. In this work, ultrasonic concentration imaging of cavitation bubbles was proposed based on Nakagami statistical model. The feasibility of Nakagami parameter m on concentration imaging of microbubbles was investigated firstly by simulation. Afterward, concentration imaging of cavitation bubbles by parameter m was performed in pHIFU experiments. Parameter m of cavitation bubbles increased with increasing concentrations and got saturated when concentrations above 16 bubbles/mm2, which indicated that parameter m could reflect bubble concentration at certain levels. Meanwhile, for the same concentration, parameter m kept almost constant under different imaging parameters, while the corresponding B-mode echoes varied greatly. Parameter m of cavitation bubbles in pHIFU decreased as bubbles dissipated gradually. All results showed that Nakagami parameter m can reflect the concentration distribution of cavitation bubbles, which provides a new method for better monitoring and optimization of pHIFU therapy.

Feasibility of micro-elastography for tissue surrounding phase-change microbubbles using bubble wavelet transform

Pathological states of soft tissue are usually correlated with changes in its mechanical properties. Currently, several sonoelastographic methods have been developed to evaluate the elastic properties. However, applicability of sonoelastography for small targets such as tissues surrounding tumor angiogenesis, is limited because of poor resolution and difficulty in producing detectable strain by external induction or internal physiological fluctuations. We propose to explore the possibility of quantifying the viscoelastic properties of soft tissues through phase-change microbubble (PCMB) dynamic in tissue and bubble wavelet transform detection method. A mother wavelet named “PCMB wavelet” was constructed according to the modified Yang-Church equation, and also expected to obtain a high correlation with echoes backscattered from the PCMBs. A transparent homogeneous tissue-mimicking polyacrylamide phantom containing nanoparticles of perfluoropentane was built. The comparison of contrast-to-tissue ratio among the images processed by continuous wavelet transform with “PCMB wavelet” of different shear elasticity and viscosity revealed the viscoelastic properties of the phantoms. The values of shear elasticity and viscosity of different kinds of phantoms were compared. This technique demonstrated the possibility to quantify the viscoelastic properties.

Cavitation Imaging in Tissues

The two predominant mechanisms by which therapeutic ultrasound works are through heating and mechanical damage, especially for high-intensity focused ultrasound (HIFU) therapies such as HIFU ablation and pulsed HIFU (pHIFU) (Kennedy in Nat Rev Cancer 5:321–327, 2005; ter Haar and Coussios in Int J Hyperth 23:89–104, 2007).