Intra-operative acoustic hemostasis of liver: production of a homogenate for effective treatment

Objective: We have shown that High-Intensity Focused Ultrasound (HIFU) can effectively control bleeding from injuries to solid organs such as liver, spleen, and lung. Achievement of hemostasis was augmented when a homogenate of tissue and blood was formed. The objective of this study was to investigate quantitatively the effect of homogenate production on HIFU application time for hemostasis. Possible mechanisms involved in homogenate production were also studied.Methods: Ten anesthetized rabbits had laparotomy and liver exposure. Liver incisions, 15-25 mm long and 3-4 mm deep, were made followed immediately by HIFU application. Two electrical powers of 80 and 100 W corresponding to focal acoustic intensities of 2264 and 2829 W/cm², respectively were used. Tissue and homogenate temperatures were measured. Smear and histological tissue sample analysis using light microscopy were performed.Results: In treatments with homogenate formation, hemostasis was achieved in 76 ± 1.3 s (Mean ± Standard Error Mean: SEM) at 80 W. In treatments without homogenate formation (at 80 W), hemostasis was achieved in 106 ± 0.87 s. At 100 W, hemostasis was achieved in 46 ± 0.3 s. The time required for homogenate formation, at 80 and 100 W were 60 ± 2.5 and 23 ± 0.3 s, respectively. The homogenate temperature was 83 °C (SEM 0.6 °C), and the non-homogenate tissue temperature at the treatment site was 60 °C (SEM 0.4 °C). The smear and histological analysis showed significant blood components and cellular debris in the homogenate, with some intact cells.Conclusion: The HIFU-induced homogenate of blood and tissue resulted in a statistically significant shorter HIFU application time for hemostasis. The incisions with homogenate had higher temperatures as compared to incisions without homogenate. Further studies of the correlation between homogenate formation and temperature must be done, as well as studies on the long-term effects of homogenate in achieving hemostasis.     

Weakly nonlinear focused ultrasound in viscoelastic media containing multiple bubbles

To facilitate practical medical applications such as cancer treatment utilizing focused ultrasound and bubbles, a mathematical model that can describe the soft viscoelasticity of human body, the nonlinear propagation of focused ultrasound, and the nonlinear oscillations of multiple bubbles is theoretically derived and numerically solved. The Zener viscoelastic model and Keller–Miksis bubble equation, which have been used for analyses of single or few bubbles in viscoelastic liquid, are used to model the liquid containing multiple bubbles. From the theoretical analysis based on the perturbation expansion with the multiple-scales method, the Khokhlov–Zabolotskaya–Kuznetsov (KZK) equation, which has been used as a mathematical model of weakly nonlinear propagation in single phase liquid, is extended to viscoelastic liquid containing multiple bubbles. The results show that liquid elasticity decreases the magnitudes of the nonlinearity, dissipation, and dispersion of ultrasound and increases the phase velocity of the ultrasound and linear natural frequency of the bubble oscillation. From the numerical calculation of resultant KZK equation, the spatial distribution of the liquid pressure fluctuation for the focused ultrasound is obtained for cases in which the liquid is water or liver tissue. In addition, frequency analysis is carried out using the fast Fourier transform, and the generation of higher harmonic components is compared for water and liver tissue. The elasticity suppresses the generation of higher harmonic components and promotes the remnant of the fundamental frequency components. This indicates that the elasticity of liquid suppresses shock wave formation in practical applications.     

基于分数导数研究高强度聚焦超声的非线性声场

在高强度聚焦超声(high intensity focused ultrasound, HIFU) 的研究中, 生物组织的衰减和色散性质会对声能量的空间分布产生影响. 本文提出应用分数导数修正非线性Khokhlov-Zabolotskaya-Kuznetsov (KZK)方程, 研究生物组织中非线性HIFU声场. 对三种生物仿体的衰减和声速色散的理论实验研究表明分数导数应用的可行性, 在此基础上通过数值仿真分析研究了衰减及声速随频率的变化对HIFU焦域分布的影响. 研究结果表明, 在计算强非线性聚焦超声时, 由于高次谐波的强色散作用, 引入分数导数来解决生物组织特殊的衰减以及色散问题可进一步提高HIFU治疗的安全性. 关键词： 分数导数 声衰减 色散 高强度聚焦超声     

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.     

Feasibility study of high intensity focused ultrasound (HIFU) for the treatment of hydatid cysts of the liver

This study evaluates the feasibility of using high intensity focused ultrasound (HIFU) for the treatment of hydatid cysts of the liver. HIFU ablation was carried out in 62 patients with echinococcosis of the liver. The mean age of patients was 40.76 ± 14.84 (range: 17–72 years). The effectiveness of the treatment was monitored in real-time by changes in the gray-scale, and by morphological studies, computed tomography, magnetic resonance imaging, and ultrasound.Criteria for evaluating the effectiveness of treatment in real time were outlines. Cytomorphological picture of destructive changes of parasitic elements was presented as well. Loss of embryonic elements of the parasite was observed at the subcellular level after HIFU-ablation and underlines the effectiveness of HIFU.     

Characterization of HIFU transducers designed for sonochemistry application: Cavitation distribution and quantification

Acoustic field distribution was determined in HIFU sonoreactors as well as localization of cavitation activity by crossing different techniques: modeling, hydrophone measurements, laser tomography and SCL measurements. Particular care was taken with quantification of this last technique by pixels or photon counting. Cavitation bubbles generated by HIFU are mainly located on the outer layer of the propagation cone in the post-focal zone. Greatest acoustic activity is not located at the geometrical focal, but corresponds to a high concentration of bubbles zone. On the contrary, the main sonochemical activity shifts slightly toward the transducer, whereas quenching of inertial cavitation is observed directly at the focal. Finally, SCL thresholds have been determined.     

An in vitro feasibility study of controlled drug release from encapsulated nanometer liposomes using high intensity focused ultrasound

A liposome with a diameter ranging from 150 to 200 nm has been considered to be one of the optimal vehicles for targeted drug delivery in vivo since it is able to encapsulate drug and also circulate in the blood stream stably. Its small size, however, makes controlled release of its encapsulated content difficult. A feasibility study for applications of high intensity focused ultrasound (HIFU) of the mega-hertz frequency to induce controlled release of its content was carried out. This study, using the dynamic light scattering and transmission electron microscopic observation, demonstrated 21.2% of encapsulated fluorescent materials (FITC) could be released from liposomes with an average diameter of 210 nm when exposed to continuous (cw) ultrasound at 1.1 MHz (I_SPTA = 900 W/cm²) for 10 s and the percentage release efficiency can reach to 70% after 60 s irradiation. This result also reveals that rupture of relatively large liposomes (>100 nm) and generation of pore-like defects in the membrane of small liposomes (<100 nm) due to HIFU excitation might be the main causes of the release; the inertial cavitation took place during the irradiation. The controlled drug release from liposomes by HIFU may be proven to be a potential useful modality for clinical applications.     

液体中高强度聚焦超声场及其测量

基于已知文献,文章介绍了液体中高强度聚焦超声场的基本性质,包括传播、频谱、吸收、聚焦、辐射力等特性,描述了它的物理图景和测量方法。     

Applications of high-intensity focused ultrasound in medicine: Spotlight on neurological applications

High-intensity focused ultrasound (HIFU) has the potential to become a modality of treatment for a wide range of clinical conditions. HIFU enables non-invasive, selective ablation of tissues including tumors and punctured vessels. Another promising area of research within the field of therapeutic ultrasound is the application of HIFU to treat neurological disorders by selectively targeting the brain, spinal cord, or nerves. This paper provides an overview of the current applications of focused ultrasound in medicine with an emphasis on its use in the fields of neurology and neurosurgery.     

A comparison of HIFU-induced lesion size measurement based on gross histological examination and image of bovine thigh in vitro

The aim of this study was to investigate the agreement in HIFU-induced lesion sizes between measurements based on gross histological examination and those from images. Experiments were conducted in an experimental arrangement with a three-way multiscan ultrasonic inspection system and imaging was done by B-mode ultrasound (US). Bovine thigh muscle with and without fascia lata was treated with an in situ spatially averaged focal intensity ranging between 750 W cm(-2) and 1565 W cm(-2) and sonication-time was variable from 8 to 20s. Assessment of the two measurement methods showed a rather weak correlation in the samples without fascia lata. For clarity and convenience in the discussion, sample muscles with and without fascia lata were labeled F and M, respectively. It was difficult to measure the lesion size from ultrasonographic images of F samples, so there was disagreement in the samples with fascia lata. This investigation showed that the presence of fascia lata in bovine thigh muscle has the likely effect of affecting the ultrasound image and makes it difficult to distinguish coagulated tissue from surrounding healthy tissue. There was no significant correlation between ultrasonography and the gross histological findings in M samples. Data supported that at for an in situ spatially averaged focal intensity ranging between 750 W cm(-2) and 1565 W cm(-2) and relatively shorter exposures (sonication-time variable from 1 to 8s) higher correlation between image and gross histology measurement was found in excised bovine muscle specimens.