Real-Time Monitoring of High-Intensity Focused Ultrasound Treatment Using Axial Strain and Axial-Shear Strain Elastograms

Axial strain elastograms (ASEs) have been found to help visualize sonographically invisible thermal lesions. However, in most studies involving high-intensity focused ultrasound (HIFU)-induced thermal lesions, elastography imaging was performed separately later, after the lesion was formed. In this article, the feasibility of monitoring, in real time, tissue elasticity variation during HIFU treatment and immediately thereafter is explored using quasi-static elastography. Further, in addition to ASEs, we also explore the use of simultaneously acquired axial-shear strain elastograms (ASSEs) for HIFU lesion visualization. Experiments were performed on commercial porcine liver samples in vitro. The HIFU experiments were conducted at two applied acoustic power settings, 35 and 20 W. The experimental setup allowed us to interrupt the HIFU pulse momentarily several different times during treatment to perform elastographic compression and data acquisition. At the end of the experiments, the samples were cut along the imaging plane and photographed to compare size and location of the formed lesion with those visualized on ASEs and ASSEs. Single-lesion and multiple-lesion experiments were performed to assess the contribution of ASEs and ASSEs to lesion visualization and treatment monitoring tasks. At both power settings, ASEs and ASSEs provided accurate location information during HIFU treatment. At the low-power setting case, ASEs and ASSEs provide accurate lesion size in real-time monitoring. Lesion appearance in ASEs and ASSEs was affected by the cavitation bubbles produced at the high-power setting. The results further indicate that the cavitation bubbles influence lesion appearance more in ASEs than in ASSEs. Both ASEs and ASSEs provided accurate size information after a waiting period that allowed the cavitation bubbles to disappear. The results indicate that ASSEs not only improve lesion visualization and size measurement of a single lesion, but, under certain conditions, also help to identify untreated gaps between adjacent lesions with high contrast.     

Use of overpressure to assess the role of bubbles in focused ultrasound lesion shape in vitro

Overpressure--elevated hydrostatic pressure--was used to assess the role of gas or vapor bubbles in distorting the shape and position of a high-intensity focused ultrasound (HIFU) lesion in tissue. The shift from a cigar-shaped lesion to a tadpole-shaped lesion can mean that the wrong area is treated. Overpressure minimizes bubbles and bubble activity by dissolving gas bubbles, restricting bubble oscillation and raising the boiling temperature. Therefore, comparison with and without overpressure is a tool to assess the role of bubbles. Dissolution rates, bubble dynamics and boiling temperatures were determined as functions of pressure. Experiments were made first in a low-overpressure chamber (0.7 MPa maximum) that permitted imaging by B-mode ultrasound (US). Pieces of excised beef liver (8 cm thick) were treated in the chamber with 3.5 MHz for 1 to 7 s (50% duty cycle). In situ intensities (I(SP)) were 600 to 3000 W/cm(2). B-mode US imaging detected a hyperechoic region at the HIFU treatment site. The dissipation of this hyperechoic region following HIFU cessation corresponded well with calculated bubble dissolution rates; thus, suggesting that bubbles were present. Lesion shape was then tested in a high-pressure chamber. Intensities were 1300 and 1750 W/cm(2) ( +/- 20%) at 1 MHz for 30 s. Hydrostatic pressures were 0.1 or 5.6 MPa. At 1300 W/cm(2), lesions were cigar-shaped, and no difference was observed between lesions formed with or without overpressure. At 1750 W/cm(2), lesions formed with no overpressure were tadpole-shaped, but lesions formed with high overpressure (5.6 MPa) remained cigar-shaped. Data support the hypothesis that bubbles contribute to the lesion distortion.     

Enhancement of ultrasound-accelerated thrombolysis by echo contrast agents: dependence on microbubble structure

The combination of ultrasound (US) exposure and ultrasound contrast agent (UCA) further increases the amount of drug-mediated thrombolysis. The aim of this study was to examine the efficacy of the combination of US and UCA on tissue plasminogen activator (tPA) thrombolysis, and the dependence on the microbubble structure. A catheter-type transducer capable of US emission (10 MHz, spatial peak temporal average intensity = 1.02 W/cm² and peak negative pressure = 0.33 MPa) in the continuous-wave mode was employed. In 28 artificial white thrombi, serial changes in acoustic properties monitored by echography and histopathology during the tPA-mediated thrombolysis were analyzed. The thrombi were assorted to 4 groups; UCA nontreated (Control), sonicated albumin (A)-, SH-U508A (SH)- and dodecafluoropentane emulsion (DDFP)-treated groups. Persistence of microbubble opacification and thrombus weight were also measured. After the sample was suspended in a beaker with tPA (8000U) and 100 mL of saline, the UCA was administered and the mixture exposed to US for 10 min. Weight reduction of the thrombus was greatest in the DDFP Group (−49 ± 8%), and that in the A Group (−8 ± 5%) was not significantly different from that in the Control Group (−5 ± 1%). The persistence of the microbubbles expressed as the decay of the time-intensity curve, was longest in the DDFP Group. The echo intensity of the superficial layer of the thrombus exposed to US was high and weight loss was marked. Multiple cavity formation was observed histopathologically. The stability of the microbubbles was an important factor of the US and UCA enhancement effect on tPA-mediated thrombolysis. This combination therapy has potential for clinical application in patients with thrombotic arterial and venous occlusion and left arterial thrombus.     

Temperature Dependence of Tissue Thermal Parameters Should Be Considered in the Thermal Lesion Prediction in High-Intensity Focused Ultrasound Surgery

This study considers the temperature-dependent thermal parameters (specific heat capacity, thermal diffusivity and thermal conductivity) used when predicting the temperature rise of tissue exposed to high-intensity focused ultrasound (HIFU). Numerical analysis was performed using the Khokhlov–Zabolotskaya–Kuznetsov equation coupled with a bioheat transfer function. The thermal parameters were set as the functions of temperature using experimental data. The results revealed that, for liver tissue exposed to HIFU with a focal intensity of 3000 W/cm² for 10 s, the predicted focal temperature rise was 23% lower and the thermal lesion area 41% smaller than those predicted without considering the temperature dependence. The prediction was validated by experimental observations on thermal lesions visualized in a tissue-mimicking phantom. The present results suggest that temperature-dependent thermal parameters should be considered in the prediction of HIFU-induced temperature rise to avoid lowering ultrasonic output settings for HIFU surgery. The aim of the present study was to investigate how significantly the temperature dependence of the thermal parameters affects the thermal dose imposed on the tissue by a typical clinical HIFU device. A numerical simulation was performed using a thermo-acoustic algorithm coupling the non-linear Khokhlov–Zabolotskaya–Kuznetsov (KZK) equation (Meaney et al. 1998; Filonenko and Khokhlova 2001) and a bio-heat transfer (BHT) equation (Pennes 1948). Thermal parameters of liver tissue were modeled in the present study as functions of temperature and were incorporated into the BHT equation to compensate for the variations in thermal parameters with temperature. Experimental validation was achieved by comparing the predictions with the thermal lesions formed in the tissue-mimicking phantoms.     

高强度聚焦超声联合超声造影剂增强治疗效果的研究进展

高强度聚焦超声(HIFU)以其安全性、无创性、有效性的特点正日益成为治疗和辅助治疗多种肿瘤的新方法。超声造影剂(UCA)通过改变靶组织声学特性显著地提高了HIFU的治疗效果,在HIFU临床应用过程中显示了重要的应用价值。本文就HIFU联合UCA治疗的作用机理及其增强治疗效果的实验研究进展进行综述。     

The effect of the scanning pathway in high-intensity focused ultrasound therapy on lesion production

Because tumors are much larger in size compared with the beam width of high-intensity focused ultrasound (HIFU), raster scanning throughout the entire target is conventionally performed for HIFU thermal ablation. Thermal diffusion affects the temperature elevation and the consequent lesion formation. As a result, the lesion will grow continuously over the course of HIFU therapy. The purpose of this study was to investigate the influence of scanning pathways on the overall thermal lesion. Two new scanning pathways, spiral scanning from the center to the outside and spiral scanning from the outside to the center, were proposed with the same HIFU parameters (power and exposure time) for each treatment spot. The lesions produced in the gel phantom and bovine liver were compared with those using raster scanning. Although more uniform lesions can be achieved using the new scanning pathways, the produced lesion areas (27.5 ± 12.3 mm² and 65.2 ± 9.6 mm², respectively) in the gel phantom are significantly smaller (p < 0.05) than those using raster scanning (92.9 ± 11.8 mm²). Furthermore, the lesion patterns in the gel phantom and bovine liver were similar to the simulations using temperature and thermal dose-threshold models, respectively. Thermal diffusion, the scanning pathway and the biophysical aspects of the target all play important roles in HIFU lesion production. By selecting the appropriate scanning pathway and varying the parameters as ablation progresses, HIFU therapy can achieve uniform lesions while minimizing the total delivered energy and treatment time.     

碘化油与高功率聚焦超声破坏肝组织的协同升温效应研究

本实验首次研究生物组织因素（媒质）对高轼率聚焦超声（HIFU）破坏肝组织的影响。采用国产HIFU样机（1．1MHz）．体外观察其靶区在碘化油或蓖麻油不同媒质存在的温度变化。结果显示：不论在高功率（500W/cm2）和低功率（136W/cm2）超声照射下，碘化油使靶区温度升高显著高于无碘的蓖麻油（P=0．0008和P=0．0004）．提示碘比油与HIFU治疗有协同升温作用。用HIFU（1．1MHz，500W/cm2，20s）照射离体肝组织．发现肝内注射碘化油组靶区温度显著高于注射蓖麻油组（P=0．0239），且前者破坏程度和范围均明显大于后者，提示碘化油配合HIFU治疗肝肿瘤具有潜在的增效、定位和导向作用。     

高强度聚焦超声辐照离体及在体心肌组织的比较研究

目的　探讨并比较高强度聚焦超声(HIFU)定位损伤离体心肌及活体心肌的量效关系。方法　采用不同功率(3W ,4W ,5W)的HIFU ,在不同辐照时间(5S ,8S ,10S ,15S ,2 0S ,60S ,180S)的作用下,对5只正常猪离体心脏及8只活体兔心脏进行定位损伤,观察并测定损伤区形态及体积,并对损伤区进行病理学检查。结果　不同剂量下HIFU所致的生物学焦域范围为1～3 0 0mm3 ,不同处理因素间损伤体积具有显著性差异(P <0 .0 5 ) ,相同剂量下离体心肌受损体积大于在体心肌的受损体积。损伤形态随剂量增大由椭球形向锥体形、不规则形发展。组织学观察可见凝固性坏死及损伤区与正常心肌组织的明显分界。结论　HIFU可定点使离体心肌及活体心肌发生坏死而不伤及周围组织。     

Correlation between inertial cavitation dose and endothelial cell damage in vivo

Previous in vivo studies have demonstrated that vascular endothelial damage can result when vessels containing gas-based microbubble ultrasound contrast agent (UCA) are exposed to MHz-frequency pulsed ultrasound (US) of sufficient pressure amplitudes, presumably as a result of inertial cavitation (IC). The hypothesis guiding this research was that IC is the primary mechanism by which the vascular endothelium (VE) is damaged when a vessel is exposed to pulsed 1-MHz frequency US in the presence of circulating UCA. The expectation was that a correlation should exist between the magnitude and duration of IC activity and the degree of VE damage. Rabbit auricular vessels were exposed in vivo to 1.17-MHz focused US of variable peak rarefaction pressure amplitude (1, 3, 6.5 or 9 MPa), using low duty factors (0.04% or 0.4%), pulse lengths of 500 or 5000 cycles, with varying treatment durations and with or without infusion of a shelled microbubble contrast agent. A broadband passive cavitation detection system was used to measure IC activity in vivo within the targeted segment of the blood vessel. The magnitude of the detected IC activity was quantified using a previously reported measure of IC dose. Endothelial damage was assessed via scanning electron microscopy image analysis. The results supported the hypothesis and demonstrate that the magnitude of the measured IC dose correlates with the degree of VE damage when UCA is present. These results have implications for therapeutic US-induced vascular occlusion.     

Utility of a tumor-mimic model for the evaluation of the accuracy of HIFU treatments. results of in vitro experiments in the liver

Presented in this article is a tumor-mimic model that allows the evaluation, before clinical trials, of the targeting accuracy of a high intensity focused ultrasound (HIFU) device for the treatment of the liver. The tumor-mimic models are made by injecting a warm solution that polymerizes in hepatic tissue and forms a 1 cm discrete lesion that is detectable by ultrasound imaging and gross pathology. First, the acoustical characteristics of the tumor-mimics model were measured in order to determine if this model could be used as a target for the evaluation of the accuracy of HIFU treatments without modifying HIFU lesions in terms of size, shape and homogeneity. On average (n = 10), the attenuation was 0.39 +/- 0.05 dB.cm(-1) at 1 MHz, the ultrasound propagation velocity was 1523 +/- 1 m.s(-1) and the acoustic impedance was 1.84 +/- 0.00 MRayls. Next, the tumor-mimic models were used in vitro in order to verify, at a preclinical stage, that lesions created by HIFU devices guided by ultrasound imaging are properly positioned in tissues. The HIFU device used in this study is a 256-element phased-array toroid transducer working at a frequency of 3 MHz with an integrated ultrasound imaging probe working at a frequency of 7.5 MHz. An initial series of in vitro experiments has shown that there is no significant difference in the dimensions of the HIFU lesions created in the liver with or without tumor-mimic models (p = 0.3049 and p = 0.8796 for the diameter and depth, respectively). A second in vitro study showed that HIFU treatments performed on five tumor-mimics with safety margins of at least 1 mm were properly positioned. The margins obtained were on average 9.3 +/- 2.7 mm (min. 3.0 - max. 20.0 mm). This article presents in vitro evidence that these tumor-mimics are identifiable by ultrasound imaging, they do not modify the geometry of HIFU lesions and, thus, they constitute a viable model of tumor-mimics indicated for HIFU therapy.     

Image-guided HIFU neurolysis of peripheral nerves to treat spasticity and pain

Spasticity, a major complication of central nervous system disorders, signified by uncontrollable muscle contractions, is very difficult to treat effectively. We report on the use of ultrasound (US) image-guided high-intensity focused US (HIFU) to target and suppress the function of the sciatic nerve complex of rabbits in vivo, as a possible treatment of spasticity. The image-guided HIFU device included a 3.2-MHz spherically curved transducer and an intraoperative imaging probe. A focal acoustic intensity of 1480 to 1850 W/cm(2), applied using a scanning method, was effective in achieving complete conduction block in 100% of 22 nerve complexes with HIFU treatment times of 36 +/- 14 s (mean +/- SD). Gross examination showed blanching of the nerve at the HIFU treatment site and lesion volumes of 2.8 +/- 1.4 cm(3) encompassing the nerve complex. Histologic examination indicated axonal demyelination and necrosis of Schwann cells as probable mechanisms of nerve block. With accurate localization and targeting of peripheral nerves using US imaging, HIFU could become a promising tool for the suppression of spasticity.     

Selective reduction of multifetal pregnancy using high-intensity focused ultrasound in the rabbit model.

OBJECTIVE: High-order multifetal pregnancies carry a significant risk of obstetric complications and poor pregnancy outcome. Selective reduction has traditionally been performed using transabdominal and transvaginal ultrasound-guided intracardiac injection of potassium chloride. We have previously shown that high-intensity focused ultrasound (HIFU) can create a coagulative tissue necrosis in the sheep fetus. The objective of this study was to investigate the feasibility of non-invasive selective fetal reduction using HIFU in a rabbit model. METHODS: A protocol for HIFU-induced tissue coagulation was developed in the rabbit model. The fetal heart was targeted with ultrasound-guided tissue ablation by a HIFU beam. Five time-mated does between 20-29 days' gestation underwent transabdominal fetal cardiac ablation in a total of 11 fetuses. The HIFU system consisted of a 7-MHz high-power transducer, operated at 2000 W/cm2. The fetal heart rate was observed using real-time ultrasound with Doppler flow velocimetry. All lesions were assessed macroscopically and by histological analysis. RESULTS: Severe bradycardia leading to asystole was observed in all targeted fetuses with ultrasound examination. Dissection of fetuses demonstrated a necrotic intrathoracic lesion similar in size to the HIFU focus (approximately 1 x 9 mm). None of the surrounding fetuses was found to have bradycardia during the procedure or a macroscopic lesion on dissection. CONCLUSION: In this pilot study HIFU seems promising to ablate even highly vascularized tissue in the fetus.     

Radiation-force technique to monitor lesions during ultrasonic therapy

This report describes a monitoring technique for high-intensity focused ultrasound (US), or HIFU, lesions, including protein-denaturing lesions (PDLs) and those made for noninvasive cardiac therapy and tumor treatment in the eye, liver and other organs. Designed to sense the increased stiffness of a HIFU lesion, this technique uniquely utilizes the radiation force of the therapeutic US beam as an elastographic push to detect relative stiffness changes. Feasibility was demonstrated with computer simulations (treating acoustically induced displacements, concomitant heating, and US displacement-estimation algorithms) and pilot in vitro experimental studies, which agree qualitatively in differentiating HIFU lesions from normal tissue. Detectable motion can be induced by a single 5 ms push with temperatures well below those needed to form a lesion. Conversely, because the characteristic heat diffusion time is much longer than the characteristic relaxation time following a push, properly timed multiple therapy pulses will form lesions while providing precise control during therapy.     

Development of a Numerical Model of High-Intensity Focused Ultrasound Treatment in Mobile and Elastic Organs: Application to a Beating Heart

High-intensity focused ultrasound (HIFU) is a promising method used to treat cardiac arrhythmias, as it can induce lesions at a distance throughout myocardium thickness. Numerical modeling is commonly used for ultrasound probe development and optimization of HIFU treatment strategies. This study was aimed at describing a numerical method to simulate HIFU thermal ablation in elastic and mobile heart models. The ultrasound pressure field is computed on a 3-D orthonormal grid using the Rayleigh integral method, and the attenuation is calculated step by step between cells. The temperature distribution is obtained by resolution of the bioheat transfer equation on a 3-D non-orthogonally structured curvilinear grid using the finite-volume method. The simulation method is applied on two regions of the heart (atrioventricular node and ventricular apex) to compare the thermal effects of HIFU ablation depending on deformation, motion type and amplitude. The atrioventricular node requires longer sonication than the ventricular apex to reach the same lesion volume. Motion considerably influences treatment duration, lesion shape and distribution in cardiac HIFU treatment. These results emphasize the importance of considering local motion and deformation in numerical studies to define efficient and accurate treatment strategies.     

Visualisation of HIFU lesions using elastography of the human prostate in vivo: preliminary results

An imaging system was developed for prostate elastography in vivo using a transrectal ultrasound (US) probe to guide high-intensity focused US (HIFU) therapy of prostate cancer. Uniform compression was applied using a balloon, while a sector image was acquired. Strain was calculated from the gradient of the displacements obtained from the ultrasonic signal using the cross-correlation technique. Elastograms were acquired on a total of 31 patients undergoing HIFU therapy for localised prostate cancer. For two patients, only part of the prostate was treated and posttherapy magnetic resonance imaging (MRI) confirmed the size and position of the HIFU lesions seen in the elastograms as low strain areas, with a strain contrast ratio between 1.6 and 3.2. The whole prostate was treated for the next 29 patients. After treatment, the whole prostate appeared to be stiff in the elastograms and a 40% to 60% (mean 50%) decrease in average strain was observed when compared to strains measured before HIFU application. Tumours identified by biopsies and sonograms could occasionally be seen in the preoperative elastograms. Decorrelation effects occurred mainly because of low sonographic signal-to-noise ratio (SNR) and of out-of-plane motion induced by respiration.     

Visualization of HIFU-induced lesion boundaries by axial-shear strain elastography: a feasibility study

In this paper, we report on a study that investigated the feasibility of reliably visualizing high-intensity focused ultrasound (HIFU) lesion boundaries using axial-shear strain elastograms (ASSE). The HIFU-induced lesion cases used in the present work were selected from data acquired in a previous study. The samples consisted of excised canine livers with thermal lesions produced by a magnetic resonance-compatible HIFU system (GE Medical System, Milwaukee, WI, USA) and were cast in a gelatin block for the elastographic experiment. Both single and multiple HIFU-lesion samples were investigated. For each of the single-lesion samples, the lesion boundaries were determined independently from the axial strain elastogram (ASE) and ASSE at various iso-intensity contour thresholds (from -2 dB to -6 dB), and the area of the enclosed lesion was computed. For samples with multiple lesions, the corresponding ASSE was analyzed for identifying any unique axial-shear strain zones of interest. We further performed finite element modeling (FEM) of simple two-inclusion cases to verify whether the in vitro ASSE obtained were reasonable. The results show that the estimation of the lesion area using ASSE is less sensitive to iso-intensity threshold selection, making this method more robust compared with the ASE-based method. For multiple lesion cases, it was shown that ASSE enables high-contrast visualization of a “thin” untreated region in between multiple fully-treated HIFU-lesions. This contrast visualization was also noticed in the FEM predictions. In summary, the results demonstrate that it is feasible to reliably visualize HIFU lesion boundaries using ASSE. (E-mail: Arun.K.Thittai@uth.tmc.edu)     

Real-Time Monitoring of High-Intensity Focused Ultrasound Thermal Therapy Using the Manifold Learning Method

High-intensity focused ultrasound (HIFU) induces thermal lesions by increasing the tissue temperature in a tight focal region. The main ultrasound imaging techniques currently used to monitor HIFU treatment are standard pulse-echo B-mode ultrasound imaging, ultrasound temperature estimation and elastography-based methods. The present study was carried out on ex vivo animal tissue samples, in which backscattered radiofrequency (RF) signals were acquired in real time at time instances before, during and after HIFU treatment. The manifold learning algorithm, a non-linear dimensionality reduction method, was applied to RF signals which construct B-mode images to detect the HIFU-induced changes among the image frames obtained during HIFU treatment. In this approach, the embedded non-linear information in the region of interest of sequential images is represented in a 2-D manifold with the Isomap algorithm, and each image is depicted as a point on the reconstructed manifold. Four distinct regions are chosen in the manifold corresponding to the four phases of HIFU treatment (before HIFU treatment, during HIFU treatment, immediately after HIFU treatment and 10-min after HIFU treatment). It was found that disorganization of the points is achieved by increasing the acoustic power, and if the thermal lesion has been formed, the regions of points related to pre- and post-HIFU significantly differ. Moreover, the manifold embedding was repeated on 2-D moving windows in RF data envelopes related to pre- and post-HIFU exposure data frames. It was concluded that if mean values of the points related to pre- and post-exposure frames in the reconstructed manifold are estimated, and if the Euclidean distance between these two mean values is calculated and the sliding window is moved and this procedure is repeated for the whole image, a new image based on the Euclidean distance can be formed in which the HIFU thermal lesion is detectable.     

In vitro ablation of cardiac valves using high-intensity focused ultrasound

The purpose of this study was to evaluate the possibility of using high-intensity focused ultrasound (US), or HIFU, to create lesions in cardiac valves in vitro. Calf mitral valves and aortic valves were examined. Focused US energy was applied with an operating frequency of 4.67 MHz at a nominal acoustic power of 58 W for 0.2, 0.3 and 0.4 s at 4-s intervals. Mitral valve perforation was achieved with 20.8 +/- 3.7 exposures of 0.2 s, 15.4 +/- 2.1 exposures of 0.3 s or 11.2 +/- 2.3 exposures of 0.4 s. Aortic valve perforation was achieved with 13.3 +/- 2.4 exposures of 0.2 s, 10.3 +/- 2.2 exposures of 0.3 s or 8.4 +/- 1.8 exposures of 0.4 s. The mean diameter of the perforated area was 1.09 +/- 0.11 mm. The lesions were slightly discolored and coagulation of tissue around the perforation was observed. HIFU was successful in perforating cardiac valves. With further refinement, HIFU may prove useful for valvulotomy or valvuloplasty.     

Combination of thermal and cavitation effects to generate deep lesions with an endocavitary applicator using a plane transducer: ex vivo studies

In the high-intensity focused ultrasound (US), or HIFU, field, it is well-known that the cavitation effect can be used to induce lesions of larger volume. The principle is based on the increase in the equivalent attenuation coefficient of the tissue in the presence of the bubbles created by cavitation. The elementary lesions produced by combination of cavitation and thermal effects, using focused transducers, were spherical and developed upstream of the focal point. This paper presents a method that combines cavitation with a thermal effect to obtain deeper lesions using a plane transducer, rather than a focused one. The cavitation effect was produced by delivering intensities of 60 W/cm2 at the face of the transducer for 0.5 s. The applicator was then rotated through 90 degrees at a constant speed of between 0.5 and 1.5 degrees /s. During this rotation, ex vivo tissues were exposed continuously to an acoustic intensity of 14 W/cm2 to combine the cavitation effect with a thermal effect. The necroses were, on average, twice as deep when the cavitation effect was used as those obtained with a thermal effect alone. Observed macroscopically, the lesions have a very well-delimited geometry. Temperature measurements made at different angles of treatment have shown that they were coagulation necroses.     

Impact of Preconditioning Pulse on Lesion Formation During High-Intensity Focused Ultrasound Histotripsy

Therapeutic applications with high-intensity focused ultrasound (HIFU) fall into two classifications—one using thermal effect for coagulation or ablation while generally avoiding cavitation and the other using cavitation-mediated mechanical effects while suppressing heating. Representative of the latter, histotripsy uses HIFU at low duty factor to create energetic bubble clouds inside tissue to liquefy a region and has the advantages in real-time monitoring and lesion fidelity to treatment planning. We explored the impact of a preconditioning/heating pulse on histotripsy lesion formation in porcine muscle samples. During sonication, a targeted square region 9 mm wide (lateral to the focal plane) was scanned in a raster pattern with a step size of 0.75 mm. The 20-s exposure at each treatment location consisted of a 5-s duration preconditioning burst at spatial-peak intensities from 0–1386 W/cm² followed by 5000 tone bursts at high intensity (with spatial-peak pulse-average intensity of 47.34 kW/cm², spatial-peak temporal-average intensity of 284 W/cm², peak compressional pressure of 102 MPa and peak rarefactional pressure of 17 MPa). The temperature increase for all exposures was measured using a thermal imager immediately after each exposure. Lesion volume increased with increasing amplitude of the preconditioning pulse until coagulation was observed, but lesion width/area did not change significantly with the amplitude. In addition, the lesion dimensions became smaller when the global tissue temperature was raised before applying the histotripsy pulsing sequence. Therefore, the benefit of the preconditioning pulse was not caused by global heating.