Blood flow occlusion via ultrasound image-guided high-intensity focused ultrasound and its effect on tissue perfusion

This study investigated the induction of tissue necrosis by arterial blood flow occlusion using ultrasound image-guided high-intensity focused ultrasound (HIFU). We constructed a prototype HIFU transducer in combination with an imaging probe that provided color Doppler imaging and ultrasound contrast imaging. The HIFU beam was aimed into a branch of the renal artery in vivo. The renal artery branches of eight rabbits were occluded by HIFU at an intensity of 4 kW/cm(2) (from 2 to 10 times of each sonication for 5 s). When the HIFU exposure was successful, complete cessation of blood flow was observed by color Doppler imaging with success rate of 100% (8/8). Furthermore, lack of perfusion was observed in the renal cortex with a contrast-enhanced image. Postmortem histologic evaluation showed a wedge-shaped area of infarction in six of seven cases, corresponding to the lack of the contrast medium in the ultrasound image. These results demonstrated that ultrasound image-guided HIFU can be used to induce arterial occlusion, thus producing infarction and necrosis of the perfused tissue.     

Image-guided acoustic hemostasis for hemorrhage in the posterior liver

We investigated the use of ultrasound image-guided high intensity focused ultrasound (HIFU) to stop bleeding from injuries in the posterior liver. A HIFU transducer with focal length of 3.5 cm and frequency of 3.2 MHz was integrated with an intraoperative high-resolution ultrasound-imaging probe. Wedge tissue extractions, 30-mm long, 5-mm wide and 8-mm deep, were made in the posterior liver surface of five pigs to induce bleeding. The device was positioned on the anterior surface of the liver and HIFU was applied using ultrasound image-guidance. Hemostasis was achieved in 66 +/- 18 s (mean +/- standard deviation) for 17 HIFU treatments. During 7 min of sham HIFU treatment, none of the control incisions (n = 7) became hemostatic. Ultrasound image-guided HIFU offers a promising method for hemostasis in surgical settings in which the hemorrhage site is hidden and/or not accessible.     

Real-time visualization of high-intensity focused ultrasound treatment using ultrasound imaging

High-intensity focused ultrasound (HIFU) and conventional B-mode ultrasound (US) imaging were synchronized to develop a system for real-time visualization of HIFU treatment. The system was tested in vivo in pig liver. The HIFU application resulted in the appearance of a hyperechoic spot at the focus that faded gradually after cessation of HIFU exposure. The duration of HIFU exposure needed for a hyperechoic spot to appear, was inversely related to the HIFU intensity. The threshold intensity required to produce a hyperechoic spot in liver in < 1 s was 970 W/cm(2), in situ. At this HIFU dose, no immediate cellular damage was observed, providing a potential for pretreatment targeting. The real-time visualization method was used in hemostasis of actively bleeding internal pelvic vessels, allowing targeting and monitoring of successful treatment. Real-time US imaging may provide a useful tool for image-guided HIFU therapy.     

一种用于HIFU聚焦性能评价的仿组织透明体模

目的建立一种用于高强度聚焦超声(HIFU)聚焦性能评价的仿组织透明体模。方法仿组织透明体模主要由聚丙烯酰胺和作为温度敏感指示剂的蛋清混合而成。在B超的监控下使用声功率160W的HIFU在不同的辐照时间下定点辐照体模和新鲜离体牛肝脏,肉眼观察HIFU在体模和新鲜离体牛肝脏中形成的生物学焦域(BFR)形态并测量BFR的长短轴。结果可用肉眼观察HIFU在仿组织透明体模中产生的BFR,其形态呈椭球体,实时超声监控为强回声,BFR的长、短轴随辐照时间的增加而增大。但在相同的辐照参数下,HIFU在仿组织透明体模中产生的BFR的长、短轴小于HIFU在新鲜离体牛肝脏中形成的BFR的长、短轴。结论该仿组织透明体模在用于HIFU聚焦性能的评价方面展示出良好的前景。     

A feasibility study of high intensity focused ultrasound for liver biopsy hemostasis

This study was conducted to demonstrate the feasibility of high intensity focused ultrasound (HIFU) application to control post-liver-biopsy hemorrhage. Anesthetized Yorkshire pigs (n = 3; mean weight = 23.0 kg) were used and the liver organ was exposed surgically by an open laparotomy. Core biopsies were performed on the hepatic parenchyma with 14-gauge (n = 41) and 18-gauge (n = 33) core biopsy needles. The focus of HIFU (4.23 MHz) field was applied for 15 to 45 s to the needle entry site in the liver immediately after needle retraction. Blood loss from a biopsy site was determined using surgical sponges as absorbent applied at the site. Mean blood loss for control sites was 6.16 g (14-gauge, n = 20) and 1.22 g (18-gauge, n = 10). Virtually no blood loss was measured for biopsies after HIFU application (n = 44) for using needles of both sizes. Our results indicate that intraoperative HIFU application could successfully induce hemostasis after liver biopsy in a porcine model.     

Assessment of arterial stenosis in a flow model with power Doppler angiography: accuracy and observations on blood echogenicity

The objective of the project was to study the influence of various hemodynamic and rheologic factors on the accuracy of 3-D power Doppler angiography (PDA) for quantifying the percentage of area reduction of a stenotic artery along its longitudinal axis. The study was performed with a 3-D power Doppler ultrasound (US) imaging system and an in vitro mock flow model containing a simulated artery with a stenosis of 80% area reduction. Measurements were performed under steady and pulsatile flow conditions by circulating, at different flow rates, four types of fluid (porcine whole blood, porcine whole blood with a US contrast agent, porcine blood cell suspension and porcine blood cell suspension with a US contrast agent). A total of 120 measurements were performed. Computational simulations of the fluid dynamics in the vicinity of the axisymmetrical stenosis were performed with finite-element modeling (FEM) to locate and identify the PDA signal loss due to the wall filter of the US instrument. The performance of three segmentation algorithms used to delineate the vessel lumen on the PDA images was assessed and compared. It is shown that the type of fluid flowing in the phantom affects the echoicity of PDA images and the accuracy of the segmentation algorithms. The type of flow (steady or pulsatile) and the flow rate can also influence the PDA image accuracy, whereas the use of US contrast agent has no significant effect. For the conditions that would correspond to a US scan of a common femoral artery (whole blood flowing at a mean pulsatile flow rate of 450 mL min⁻¹), the errors in the percentages of area reduction were 4.3 ± 1.2% before the stenosis, −2.0 ± 1.0% in the stenosis, 11.5 ± 3.1% in the recirculation zone, and 2.8 ± 1.7% after the stenosis, respectively. Based on the simulated blood flow patterns obtained with FEM, the lower accuracy in the recirculation zone can be attributed to the effect of the wall filter that removes low flow velocities. In conclusion, the small errors reported in vitro may support the clinical use of this technique.     

Application of high-intensity focused ultrasound for umbilical artery occlusion in a rabbit model.

OBJECTIVES: To investigate the application of high-intensity focused ultrasound (HIFU) for fetal umbilical artery blood flow occlusion in a rabbit model. METHODS: A prototype HIFU transducer in combination with an imaging probe with Doppler capability was constructed. Using this transducer, HIFU was applied at 1.4, 2.75 or 5.5 kW/cm(2) through the maternal abdominal skin to the fetal intra-abdominal umbilical arteries of four time-mated Japanese White rabbits (11 fetuses) on gestational day 25. Courses of 5-s HIFU exposure were performed until cessation of umbilical blood flow and cardiac arrest were confirmed by Doppler ultrasonography. Fetal necropsy was performed and exposed lesions were assessed by microscopic histological analysis. RESULTS: The mean diameter of the fetal umbilical artery was 0.6 +/- 0.2 mm and the mean peak systolic velocity of arterial blood flow was 44.7 +/- 18.5 cm/s. When HIFU was applied at 5.5 kW/cm(2), blood flow was completely occluded within 15 courses. HIFU exposure brought about vacuolar degeneration and destruction of elastic fibers in the tunica media of the artery. CONCLUSIONS: HIFU can be used to occlude umbilical artery blood flow in fetal rabbits.     

Gel phantom for use in high-intensity focused ultrasound dosimetry

An optically transparent phantom was developed for use in high-intensity focused ultrasound (US), or HIFU, dosimetry studies. The phantom is composed of polyacrylamide hydrogel, embedded with bovine serum albumin (BSA) that becomes optically opaque when denatured. Acoustic and optical properties of the phantom were characterized as a function of BSA concentration and temperature. The speed of sound (1544 m/s) and acoustic impedance (1.6 MRayls) were similar to the values in soft tissue. The attenuation coefficient was approximately 8 times lower than that of soft tissues (0.02 Np/cm/MHz for 9% BSA). The nonlinear (B/A) coefficient was similar to the value in water. HIFU lesions were readily seen during formation in the phantom. In US B-mode images, the HIFU lesions were observed as hyperechoic regions only if the cavitation activity was present. The phantom can be used for fast characterization and calibration of US-image guided HIFU devices before animal or clinical studies.     

彩色多普勒超声评价子宫肌瘤高强度聚焦超声治疗前后卵巢动脉血流动力学改变

目的探讨彩色多普勒超声在观察高强度聚焦超声（HIFU）治疗子宫肌瘤前后卵巢血供变化中的价值。方法32例子宫肌瘤患者在HIFU治疗前后行卵巢动脉彩色多普勒超声检查,测定收缩期最大血流速度（Vmax）、舒张末期血流速度（Vmin）、阻力指数（RI）和搏动指数（PI）,比较HIFU治疗前后卵巢动脉血流动力学变化。32例患者中随机抽取20例于术前及术后复查时检测卵泡刺激素（FSH）、黄体生成素（LH）、雌二醇（E2）和孕酮（P）。结果32例子宫肌瘤患者HIFU术前后卵巢动脉各血流动力学参数无明显变化,P〉0．05;20例患者HIFU治疗前后卵巢内分泌激素比较差异亦无统计学意义（P〉0．05）。结论HIFU治疗子宫肌瘤对卵巢动脉的血供及功能无明显影响。     

Multigate Doppler measurements of ultrasonic attenuation and blood hematocrit in human arteries

A clinically applicable method for noninvasive measurement of hematocrit based on 20 MHz multigate Doppler ultrasound was developed. The ultrasound attenuation coefficient in blood is obtained by measuring the power of the signal coming from gates at different depths. A robust averaging method is introduced, which provides stable and repeatable results by using the echo signals from all depths inside the vessel. In vitro measurements have been done on porcine blood with hematocrit ranging from 3.0% to 65.0%. Steady and pulsatile flow conditions have been simulated using a peristaltic pump. The attenuation coefficient indicated the linear relation to hematocrit. The resulting correlation coefficient was R = 0.999 for the continuous blood flow and R = 0.992 for pulsatile flow. In vivo measurements have been performed in the brachial artery in 43 patients with hematocrit in the range of 32.0% to 49.3%. The mean absolute error has been 3.24% with a standard deviation of 3.72%.     

Functional and histological changes in rat femoral arteries by HIFU exposure

This study was an investigation of arterial contractility in response to high-intensity focused ultrasound (HIFU) and of histologic changes to the artery with various intensities of HIFU. We constructed a prototype HIFU transducer in combination with an imaging probe that provides color Doppler imaging and Doppler velocimetry. HIFU was applied through the skin to deep femoral arteries in left thighs of Sprague-Dawley rats; color images of the blood flow were used to aim the HIFU beam. Peak intensities used were 530, 1080, 2750 and 4300 W/cm2. The duration of each HIFU exposure was 5 s. HIFU was applied to five focal spots of each leg. These focal spots were aligned with a spacing of 1.0 mm so as to form a line across the artery. Blood flow occlusion was accomplished by HIFU at an intensity of 4300 W/cm2, but the flow continued with the lower intensities. Peak systolic velocities (PSVs) of blood flow as measured by Doppler velocimetry increased in the arteries to which HIFU had been applied at 1080 and 2750 W/cm2. The increase corresponded with HIFU intensity. Exposure to HIFU at 530 W/cm2 did not change the blood flow velocity. Histologic studies have demonstrated that exposure to HIFU at 2750 and 4300 W/cm2 leads to vacuolar degeneration and destruction of elastic fibers of the tunica media of the artery. Exposure at 1080 W/cm2 led to increased PSV, but did not induce histologic changes in the vessel wall. In conclusion, the response of the artery to HIFU varied with intensity. Vascular contraction without tissue degeneration occurred at low intensity; with increasing intensity, the tissue degeneration detectable in histology reduced the vascular diameter and, finally, at high intensity, the blood flow was occluded. Although these phenomena appeared to be mainly due to thermal effects, mechanical effects might have some role, particularly on vascular contraction.     

Hemostasis using high intensity focused ultrasound.

High intensity focused ultrasound (HIFU) has been shown to be an effective method of hemostasis, in animal studies, for both solid organs and blood vessels. Two distinct effects of HIFU, thermal and mechanical, appear to contribute to hemostasis. Acoustic hemostasis may provide an effective method in surgery and prehospital settings for treating trauma and elective surgery patients. A review of the methodology is given.     

Liver hemostasis using high-intensity focused ultrasound

Liver hemorrhage, the major cause of death in hepatic trauma, is notoriously difficult to control. We report on the use of high-intensity focused ultrasound (HIFU) to arrest the bleeding from incisions made in rabbit livers. A HIFU transducer, with a spherically curved aperture of 6.34 cm² area, a focal length of 4 cm and a frequency of 3.3 MHz was used. In approximately 94% of the incisions, the hemorrhage was reduced to a slow oozing of blood in less than 2 min. The maximum temperature of liver tissue around the incision area, during HIFU application, was measured to be 86°C. The mechanism of hemostasis, confirmed by histological examination, appears to be coagulative necrosis of a volume of liver tissue around the incision. We believe that acoustic hemostasis, with the unique characteristic of “volume cauterization”, offers a novel method for the management of liver hemorrhage and, thus, has major clinical implications.     

High-intensity focused ultrasound treatment for twin reversed arterial perfusion sequence

Twin reversed arterial perfusion (TRAP) sequence is a serious complication of monochorionic twin pregnancies, in which arterioarterial anastomoses allow blood flow from a 'pump' fetus to an acardiac fetus via reversed flow in the latter's umbilical artery. Several trial treatments for TRAP sequence have been reported, but all of these have been invasive. We present a case of TRAP sequence in which high-intensity focused ultrasound (HIFU) was applied to the umbilical artery of the anomalous twin at 26 weeks as a non-invasive fetal therapy. The HIFU intensity was set at approximately 2300 W/cm(2) with exposure periods of 10 s. Color Doppler ultrasound showed a decrease in blood supply to the anomalous twin, although complete occlusion of the targeted vessel was not achieved. Delivery was by Cesarean section at 29 weeks' gestation and the pump twin survived, without severe clinical complications at 6 months. Copyright ? 2012 ISUOG. Published by John Wiley & Sons, Ltd.     

Hemostasis of punctured vessels using Doppler-guided high-intensity ultrasound.

The use of Doppler ultrasound was investigated to determine if it would aid in guiding the application of high-intensity focused ultrasound (HIFU) to stop bleeding from punctured vessels. Major vessels (abdominal aorta, illiac, carotid, common femoral and superficial femoral arteries and the jugular vein) were surgically exposed, punctured and treated in anesthetized pigs. Treatment was applied when the Doppler sounds indicated the focus coincided with the bleeding site. In 89 treatment trials, the average time to achieve major hemostasis (a point where bleeding was reduced to a level of only oozing) was 8 s, and for complete hemostasis was 13 s. These times were significantly shorter than those of an identical former study in which only visual guidance was used. In that study, the average times for major and complete hemostasis were 40 and 62 s, respectively. The advantage of Doppler guidance in applying HIFU in treating bleeding vessels was demonstrated.     

Measurement of coronary flow using high-frequency intravascular ultrasound imaging and pulsed Doppler velocimetry: in vitro feasibility studies.

The recent development of intravascular ultrasound imaging offers the potential to measure blood flow as the product of vessel cross-sectional area and mean velocity derived from pulsed Doppler velocimetry. To determine the feasibility of this approach for measuring coronary artery flow, we constructed a flow model of the coronary circulation that allowed flow to be varied by adjusting downstream resistance and aortic driving pressure. Assessment of intracoronary flow velocity was accomplished using a commercially available end-mounted pulsed Doppler catheter. Cross-sectional area of the coronary artery was measured using a 20 MHz mechanical imaging transducer mounted on a 4.8 F catheter. The product of mean velocity and cross-sectional area was compared with coronary flow measured by timed collection in a graduated cylinder by linear regression analysis. Excellent correlations were obtained between coronary flow calculated by the ultrasound method and measured coronary flow at both ostial (r = 0.99, standard error of the estimate [SEE] = 13.9 ml/min) and distal (r = 0.98, SEE = 23.0 ml/min) vessel locations under steady flow conditions. During pulsatile flow, calculated and measured coronary flow also correlated well for ostial (r = 0.98, SEE = 12.7 ml/min) and downstream (r = 0.99, SEE = 9.3 ml/min) locations. That the SEE was lower for pulsatile as compared with steady flow may be explained by the blunting of the flow profile across the vessel lumen by the acceleration phase of pulsatile flow. These data establish the feasibility of measuring coronary artery blood flow using intravascular ultrasound imaging and pulsed Doppler techniques.     

高强度聚焦超声治疗子宫肌瘤疗效研究

目的探讨高强度聚焦超声治疗子宫肌瘤的有效性,评价超声造影对HIFU治疗的疗效判断。方法选择HIFU治疗的子宫肌瘤患者88例,共检出肌瘤138枚,于治疗前和治疗后彩色多普勒血流显像及超声造影检查,观察瘤体大小、内部及周边组织回声和血流灌注对比变化。结果治疗2~5d后肌瘤内部回声不均匀性增强,血流信号减少,肌瘤内无造影剂显示,肌瘤内时间强度曲线幅度减低。治疗3个月后肌瘤缩小,平均有效率52%,肌瘤内部回声均发生变化,血流信号消失,临床症状改善。结论HIFU治疗子宫肌瘤有效。超声造影可早期客观评估子宫肌瘤血流灌注状态,有效评价HIFU治疗的效果,作为治疗后判断疗效是一项较好的检测指标。     

A Tissue Mimicking Polyacrylamide Hydrogel Phantom for Visualizing Thermal Lesions Generated by High Intensity Focused Ultrasound

An optically transparent tissue-mimicking (TM) phantom whose acoustic properties are close to those of tissue was constructed for visualizing therapeutic effects by high intensity focused ultrasound (HIFU). The TM phantom was designed to improve a widely used standard bovine serum albumin (BSA) polyacrylamide hydrogel (PAG), which attenuated ultrasound far less than tissue and, unlike tissue, did not scatter ultrasound. A modified recipe has been proposed in the study by adding scattering glass beads with diameters of 40–80 μm (0.002% w/v) and by raising the concentration of acrylamide (30% v/v). The TM BSA-PAG constructed has an acoustic impedance of 1.67 MRayls, a speed of sound of 1576 m/s, an attenuation coefficient of 0.52 dB/cm at 1 MHz, a backscattering coefficient of 0.242 × 10⁻³ 1/sr/cm at 1 MHz and a nonlinear parameter (B/A) of 5.7. These parameters are close to those of liver. The thermal and optical properties are almost the same as the standard BSA-PAG. The characteristic features of the thermal lesions by HIFU were observed to be more accurately visualized in the TM BSA-PAG than in the standard BSA-PAG. In conclusion, the proposed TM BSA-PAG acoustically mimics tissue better than the standard BSA-PAG and is expected to be preferentially used for assuring if a clinical HIFU device produces the thermal lesion as planned.     

Flow index evaluation of 3-D volume flow images: an in vivo and in vitro study

Three-dimensional (3-D) ultrasound imaging has improved evaluation of organ circulation and might contribute new information on maternal and fetal blood supply. Flow index (FI) of 3-D color images has been proposed as a measure of perfusion. The aim of this study was to evaluate whether the 3-D FI is a parameter of volume flow and flow velocity in a human vessel and in a flow phantom. A 1-cm-long strip of the uterine artery was recorded in 3-D power Doppler (3D-PD) mode in a cross-sectional study of 170 normal singleton pregnancies between 26 and 42 weeks' gestation. A fixed ultrasound system installation was used during the examination. The VOCAL software integrated in the ultrasound unit calculated vessel volume and FI. Reproducibility of the measurements was tested. The method was also tested on a commercially available flow phantom. Reproducibility measurements gave satisfactory results, both in terms of inter- and intraobserver variation. Unexpectedly, in normal pregnancy, the uterine artery FI decreased slightly with gestation. Uterine artery vessel volume increased, however, with gestational age. A poor correlation was found between the FI and both flow velocity and volume flow in the flow phantom. In conclusion, 3D-PD imaging can give impressive anatomical pictures of organ vascular tree. However, the new FI is poorly related to flow velocity or volume of flow.     

Confocal dual‐frequency enhances the damaging effect of high‐intensity focused ultrasound in tissue‐mimicking phantom

The volume of the lesions created by conventional single‐frequency high‐intensity focused ultrasound (HIFU) is small, which leads to long treatment duration in patients who are undergoing tumor ablation. In this study, the lesions induced by confocal dual‐frequency HIFU in an optically transparent tissue‐mimicking phantom were investigated and compared with the lesions created by conventional single‐frequency HIFU. The results show that using different exposure times resulted in lesions of different sizes in both dual‐frequency and single‐frequency HIFU modes at the same spatially averaged intensity level (ISAL = 4900?W?cm^?2), but the lesion dimensions made in dual‐frequency mode were significantly larger than those made in single‐frequency mode. Difference frequency acoustic fields that exist in the confocal region of dual‐frequency HIFU may be the reason for the enlargement of the lesions' dimensions. The dual‐frequency HIFU mode may represent a new technique to improve the ablation efficiency of HIFU. The total time for the ablation of a tumor can be reduced, thus requiring less therapy time and reducing possible patient complications.