High-intensity focused ultrasound for ex vivo kidney tissue ablation: influence of generator power and pulse duration

BACKGROUND AND PURPOSE: The therapeutic application of noninvasive tissue ablation by high-intensity focused ultrasound (HIFU) requires precise physical definition of the focal size and determination of control parameters. The objective of this study was to measure the extent of ex-vivo porcine kidney tissue ablation at variable generator parameters and to identify parameters to control lesion size. MATERIALS AND METHODS: The ultrasound waves generated by a cylindrical piezoceramic element (1.04 MHz) were focused at a depth of 100 mm using a parabolic reflector (diameter 100 mm). A needle hydrophone was used to measure the field distribution of the sound pressure. The morphology and extent of tissue necrosis were examined at generator powers of up to 400 W (P(el)) and single pulse durations of as long as 8 seconds. RESULTS: The two-dimensional field distribution resulted in an approximately ellipsoidal focus of 32 x 4 mm (-6 dB). A sharp demarcation between coagulation necrosis and intact tissue was observed. Lesion size was controlled by both the variation of generator power and the pulse duration. At a constant pulse duration of 2 seconds, a generator power of 100 W remained below the threshold doses for inducing a reproducible lesion. An increase in power to as high as 400 W induced lesions with average dimensions of as much as 11.2 x 3 mm. At constant total energy (generator power x pulse duration), lesion size increased at higher generator power. CONCLUSIONS: This ultrasound generator can induce defined and reproducible necrosis in ex-vivo kidney tissue. Lesion size can be controlled by adjusting the generator power and pulse duration. Generator power, in particular, turned out to be a suitable control parameter for obtaining a lesion of a defined size.     

Extracorporeally induced ablation of renal tissue by high-intensity focused ultrasound

OBJECTIVE: To investigate the safety and the effects on healthy renal tissue of high-intensity focused ultrasound (HIFU) applied extracorporeally. PATIENTS, MATERIALS AND METHODS: Ultrasound waves (1.04 MHz) created by a cylindrical piezo-ceramic element were focused by a parabolic reflector to a physical focus size of 32 x 4 mm (-6 dB). For an in vivo study, HIFU was applied to the healthy tissue of 24 kidneys, monitored by ultrasonography, with a maximum power of 400 W and a spatially averaged intensity (ISAL) in the focus of 1192 W/cm(2). Fourteen kidneys were removed immediately after ablation to evaluate the side-effects and the effects in the focal zone, and 10 kidneys were removed delayed after 1, 7 and 10 days. The clinical study consisted of 19 patients requiring radical nephrectomy for a renal tumour. HIFU was applied to the healthy tissue of 19 kidneys (up to 1600 W, I(SAL) = 4768 W/cm(2)) before proceeding with the radical nephrectomy. RESULTS: There were no major complications after applying HIFU to the 43 kidneys. Side-effects included skin burns (grade 3) in two patients. During the follow-up there were no further HIFU-specific side-effects. In one case (in vivo study) there was a thermal lesion of the small intestine, which was due to mis-focusing. HIFU effects in the focal zone immediately after application were: interstitial haemorrhages, fibre rupture, shrinking of the collagen fibres, and coagulation necrosis. These effects occurred sporadically, and their number and size did not correspond to the number of HIFU pulses applied. After 7 and 10 days, there was a well-demarcated coagulation necrosis in vivo. CONCLUSION: Using this device, extracorporeally applied HIFU can ablate healthy kidney tissue in vivo in combination with diagnostic online ultrasonography. The technique is safe and resulted only in minor complications (skin burns). Refinements in the technology are essential to establish HIFU as a noninvasive treatment option that allows complete and reliable tissue ablation.     

Ablation of clinically relevant kidney tissue volumes by high-intensity focused ultrasound: Preliminary results of standardized ex-vivo investigations

PURPOSE: To investigate strategies to achieve confluent kidney-tissue ablation by high-intensity focused ultrasound (HIFU). MATERIALS AND METHODS: Our model of the perfused ex-vivo porcine kidney was used. Tissue ablation was performed with an experimental HIFU device (Storz Medical, Kreuzlingen, Switzerland). Lesion-to-lesion interaction was investigated by varying the lesion distance (5 to 2.5 mm), generator power (300, 280, and 260 W), cooling time (10, 20, and 30 seconds), and exposure time (4, 3, and 2 seconds). The lesion rows were analyzed grossly and by histologic examination (hematoxylin-eosin and nicotinamide adenine dinucleotide staining). RESULTS: It was possible to achieve complete homogeneous ablation of a clinically relevant tissue volume but only by meticulous adjustment of the exposure parameters. Minimal changes in these parameters caused changes in lesion formation with holes within the lesions and lesion-to-lesion interaction. CONCLUSIONS: Our preliminary results show that when using this new device, HIFU can ablate a large tissue volume homogeneously in perfused ex-vivo porcine tissue under standardized conditions with meticulous adjustment of exposure parameters. Further investigations in vivo are necessary to test whether large tissue volumes can be ablated completely and reliably despite the influence of physiologic tissue and organ movement.     

Extracorporeal application of high-intensity focused ultrasound for prostatic tissue ablation

OBJECTIVE: To investigate the efficacy and safety of extracorporeal prostatic tissue ablation using high-intensity focused ultrasound (HIFU) in vivo in animals, and in a clinical feasibility study in men, as this is an investigational minimally invasive treatment alternative for locally confined prostatic carcinoma, but may have significant side-effects. PATIENTS, MATERIALS AND METHODS: Ultrasound (1.04 MHz excitation frequency) was generated by an extracorporeal cylindrical piezo-ceramic element and focused by a paraboloidal reflector to a focal size of 32 x 4 mm. The focal distance and aperture diameter were both 100 mm. HIFU was applied extracorporeally at different intensities and pulse duration (up to 6 s) to 11 dog prostates in vivo (median intensity 1192 W/cm2) and eight patients (median intensity 3278 W/cm2, range 2384-3576) under general anaesthesia. The lesions were assessed macroscopically and histologically after HIFU and any side-effects evaluated. RESULTS: Thermoablation was feasible in vivo and in all patients. Macroscopic analysis and histology showed sharply demarcated coagulative necrosis. Side-effects, including skin and rectal burns, occurred only after transvesical application in the in vivo study. There were no side-effects in patients after perineal application. CONCLUSION: Extracorporeal HIFU is technically feasible and induces sharply demarcated tissue damage in the prostate. From the early results of this phase 1 study, the perineal approach seems to be safe.     

Multiple high-intensity focused ultrasound probes for kidney-tissue ablation

BACKGROUND AND PURPOSE: To investigate kidney-tissue ablation by high-intensity focused ultrasound (HIFU) using multiple and single probes. MATERIALS AND METHODS: Ultrasound beams (1.75 MHz) produced by a piezoceramic element (focal distance 80 mm) were focused at the center of renal parenchyma. One of the three probes (mounted on a jig) could also be used for comparison with a single probe at comparable power ratings. Lesion dimensions were examined in perfused and unperfused ex vivo porcine kidneys at different power levels (40, 60, and 80 W) and treatment times (4, 6, and 8 seconds). RESULTS: At identical power levels, the lesions induced by multiple probes were larger than those induced by a single probe. Lesion size increased with increasing pulse duration and generator power. The sizes and shapes of the lesions were predictably repeatable in all samples. Lesions in perfused kidneys were smaller than those in unperfused kidneys. CONCLUSIONS: Ex vivo, kidney-tissue ablation by means of multiple HIFU probes offers significant advantages over single HIFU probes in respect of lesion size and formation. These advantages need to be confirmed by tests in vivo at higher energy levels.     

The application of three-dimensional contrast-enhanced ultrasound to measure volume of affected tissue after HIFU treatment for localized prostate cancer

INTRODUCTION: Adequate monitoring of volume and location of affected tissue might provide helpful information when performing localized ablative therapy for prostate cancer. We hypothesize that the change in blood flow patterns after therapy in comparison to the blood flow pattern prior to therapy can be used to locate and quantify the amount of affected tissue due to the therapy. We describe the use of three-dimensional contrast-enhanced power Doppler ultrasound (3D-CE-PDU) to determine its additive value to visualize the extent of tissue defects created by high-intensity focused ultrasound (HIFU) in correlation with the histopathology of the prostatectomy specimen. MATERIALS AND METHODS: Nine patients with biopsy-proven localized prostate cancer, who gave informed consent, were included in the protocol. HIFU treatment was performed 1 week in advance of radical retropubic prostatectomy (RRP) as part of a protocol to study the value of HIFU treatment as local ablative therapy for clinical T(1-2)N(0)M(0) prostate carcinoma. 3D-CE-PDU was performed 1 day prior to unilateral HIFU treatment of the affected lobe on biopsy indication and 1 day before RRP using 2.5 g Levovist((R)) (Schering AG, Germany) microbubble ultrasound contrast agent and a Kretz((R)) Voluson 530D ultrasound scanner (Kretztechnik AG, Austria). Ultrasound data and pathology whole-mount sections were stored digitally to allow off-line processing. Human interpretations of HIFU measurements in three-dimensional ultrasound data were based on gray-scale information (local increase in gray level) in combination with power Doppler mode (absence of blood flow). Histopathological analysis of the whole-mount section revealed a broad band of hemorrhagic necrosis in the HIFU-treated area. Using both the ultrasound data and the pathology sections, the total volume of the prostate and of the HIFU-treated area was measured, and relative volumes were obtained. RESULTS: Visual inspection of the three-dimensional reconstruction of contrast-enhanced Doppler measurements revealed the HIFU-affected prostate tissue by the absence of a blood flow pattern. Paired t tests of the relative HIFU volume indicated that Doppler results (mean 21.7%, SD +/-10.8%) differed from the pathology results (mean 32.6%, SD +/-16.0%), but a good correlation was found between the relative pathology HIFU volume (Pearson correlation r = 0.94, p<0.0015) and mean 3D-CE-PDU HIFU. Closer inspection of the pathology specimen revealed that the outer ring of the macroscopic hemorrhagic necrosis overestimated the actually dead tissue. On microscopy, the border of dead tissue appeared to be 1-2 mm inside the macroscopically identified red hemorrhagic band. 3D-CE-PDU HIFU volumes indicated by the single observers were not statistically different and correlated very well (Pearson correlation r = 0.98, p<0.001). CONCLUSION: The results illustrate that 3D-CE-PDU is a promising method to determine the size of the defect of HIFU ablative therapy for prostate carcinoma. The absence of blood flow indicated by three-dimensional power Doppler ultrasound images reflects affected tissue after HIFU treatment, and volume measurements of these areas can quantify the amount of affected tissue.     

Control of splenic bleeding by using high intensity ultrasound.

BACKGROUND: High-intensity focused ultrasound (HIFU) has been shown to control bleeding from liver incisions, and blood vessel punctures and incisions. The objective of the current study was to investigate the capability of HIFU to stop bleeding from splenic injuries in a pig model. METHODS: Surgical incisions, 25 to 50 mm in length and 2 to 8 mm in depth, were made in the spleens of five anesthetized pigs. HIFU with a frequency of 5 MHz was applied within 5 seconds of making the incision. A total of 39 incisions and HIFU treatments were performed. RESULTS: Bleeding from all incisions was stopped completely after HIFU treatment. The average times to control and completely arrest the hemorrhage were 28 and 55 seconds, respectively. The mechanisms of hemostasis appeared to be thermally induced coagulation necrosis of splenic tissue and occlusion of blood vessels by a mechanically induced homogenized splenic tissue. CONCLUSION: HIFU may provide a useful method of hemostasis for actively bleeding spleen. Because of its ability to induce hemostasis at adjustable depth, HIFU may prove to be a useful cauterization method both in the operating room and for patients who are managed nonoperatively.     

高强度聚焦超声联合纳米微泡造影剂对兔VX2乳腺移植瘤辐照效果的影响

目的观察高强度聚焦超声（HIFU）联合纳米微泡对兔VX2乳腺移植瘤辐照效果的影响。方法制备纳米微泡,于光镜、电镜下观测微泡的大小、形态、分布及稳定性。采用Zeta SIZIER 3000电位仪测定微泡的粒径、电位。60只健康纯种雌性新西兰白兔,麻醉后种植VX2肿瘤于双侧乳腺组织内。2周后,选取乳腺区肿瘤组织直径大小为10mm的兔进行实验,随机分为实验组（HIFU＋纳米微泡）和对照组（HIFU＋磷酸盐缓冲液）,辐照剂量150 W,辐照时间5s,记录HIFU辐照前后灰阶变化,辐照后行HE染色观察坏死区域大小,并进行统计学分析。结果成功制备纳米微泡,其理化性质稳定,粒径大小合理,电位均衡。实验组靶区平均灰度差明显高于对照组（P〈0.05）。HE染色示实验组发生凝固性坏死范围明显大于对照组（P〈0.001）。结论纳米微泡能明显增强的损伤效果。     

High-intensity focused ultrasound (HIFU) followed after one to two weeks by radical retropubic prostatectomy: results of a prospective study

BACKGROUND: High-intensity focused ultrasound (HIFU) consists of focused ultrasound waves emitted from a transducer that are capable of inducing tissue damage. Experimental studies have shown clear damage of malignant tissue exposed to HIFU, but knowledge of in vivo effects is limited. We studied the safety and efficacy of HIFU in patients with a T1-2 N0) M0 prostate carcinoma. METHODS: HIFU treatment was performed under general anesthesia with the Ablatherm device (Technomed Medical Systems, Lyon, France), 7-12 days prior to radical prostatectomy. Only the lobe in which carcinoma was confirmed was treated. The radical prostatectomy specimen was examined histopathologically, and the changes were compared with treatment goals. RESULTS: So far, 9 patients have been treated. On histology, a sharp delineation was noted between areas treated with HIFU and untreated areas. On the dorsal border, however, incomplete destruction of tissue was noted, and in 2 cases a small residual tumor was seen in this region. In all cases complete necrosis was seen in the treated region. CONCLUSIONS: Histology reports of radical prostatectomy specimens of patients operated 7-12 days after HIFU treatment showed marked and complete necrosis in the treated area. Due to incomplete tissue destruction at the dorsal side, however, a small focus of residual vital tumor was found in 2 of 9 patients.     

High-intensity focused ultrasound ablation of the epididymis in a canine model: a potential alternative to vasectomy

BACKGROUND AND PURPOSE: High-intensity focused ultrasound (HIFU) is a noninvasive technology capable of inducing thermal coagulative necrosis of subsurface structures without injuring intervening tissues. We have previously reported on the feasibility of HIFU vasectomy in a canine model. In this study, we evaluated the feasibility of HIFU ablation of the canine epididymis as an alternative to vasectomy. The epididymis may be a better target than the vas deferens because it is larger, more easily positioned in the HIFU focal zone, and more susceptible to occlusive injury at lower energy levels, thus reducing collateral damage. MATERIALS AND METHODS: A hand-held HIFU clamp was used to grasp the epididymides of anesthetized dogs (eight surgically exposed and six grasped transcutaneously). An ultrasound transducer in the clamp focused energy on a 1 x 3 x 8-mm target zone centered between the clamp jaws. Ultrasonic energy (6-19 W) was delivered to this target zone for various times (16-150 seconds). The vas, epididymis, and testis were harvested for histologic examination 2 weeks after ablation. RESULTS: Seven of the eight epididymides ablated after surgical exposure demonstrated histologic findings associated with occlusion (fibrosis, hemorrhage, and proximal duct dilatation). Five of the six epididymides ablated transcutaneously also demonstrated histologic evidence of occlusion. Skin burns were evident overlying three epididymides, and one testicular injury was noted adjacent to an ablated region of the epididymis. CONCLUSION: High-intensity focused ultrasound ablation of the epididymis causes injury and histologic changes associated with epididymal occlusion. Further investigations are under way to optimize ablation parameters and to confirm azoospermia with ejaculate studies. Refinement of this technology may provide a rapid noninvasive alternative to conventional vasectomy.     

应用高强度聚焦超声表面层三维消融模式消融离体牛肝组织

目的探讨高强度聚焦超声（HIFU）靶组织表面层三维消融模式的应用价值。方法取37块新鲜牛肝组织,采用HIFU连续点打法扫描,靶组织体积为40minX30mmX24mm。对实验组（表面层消融组）从深度40~16mm由深至浅依次沿靶组织周边以不同声功率、间隔时间、点间距的参数组合进行扫描,对照组（完全消融组）在同一深度依次逐层完全消融各层面。以TTC染色判定坏死范围,组织切片HE染色判定坏死程度。对两组的辐照时间及能量消耗进行统计学分析。结果实验组靶组织周边形成边界清晰、较均匀的凝固性坏死带,与对照组靶组织周边坏死体积的差异无统计学意义（卢2．64,P〉O．05）。实验组的能量消耗在深度32mm、24mm层面低于对照组,而在深度40mm、16mm层面高于对照组（P均〈O．05）;辐照时间在各个深度与对照组的差异无统计学意义（P均〉O．05）;其总辐照时间和能量消耗均低于对照组（P均〈O．05）。结论消融离体牛肝组织时,应用HIFU新型表面层三维消融模式可降低总能量消耗、缩短消融时间,提高消融效率。     

Use of high-intensity focused ultrasound to control bleeding

OBJECTIVE: High-intensity focused ultrasound (HIFU) has been shown to be effective in controlling hemorrhage from punctures in blood vessels. The objective of the current study was to investigate the capability of HIFU to stop bleeding after a more severe type of vascular injury, namely longitudinal incisions of arteries and veins. METHODS: The superficial femoral arteries, common femoral arteries, carotid arteries, and jugular veins of four anesthetized pigs were exposed surgically. A longitudinal incision, 2 to 8 mm in length, was produced in the vessel. HIFU treatment was applied within 5 seconds of the onset of the bleeding. The HIFU probe consisted of a high-power, 3.5-MHz, piezoelectric transducer with an ellipsoidal focal spot that was 1 mm in cross section and 9 mm in axial dimension. The entire incision area was scanned with the HIFU beam at a rate of 15 to 25 times/second and a linear displacement of 5 to 10 mm. A total of 76 incisions and HIFU treatments were performed. RESULTS: Control of bleeding (major hemosatsis) was achieved in all 76 treatments, with complete hemostasis achieved in 69 treatments (91%). The average treatment times of major and complete hemostasis were 17 and 25 seconds, respectively. After the treatment, 74% of the vessels in which complete hemostasis was achieved were patent with distal blood flow and 26% were occluded. The HIFU-treated vessels showed a consistent coagulation of the adventitia surrounding the vessels, with a remarkably localized injury to the vessel wall. Extensive fibrin deposition at the treatment site was observed. CONCLUSION: HIFU may provide a useful method of achieving hemostasis for arteries and veins in a variety of clinical applications.     

一种新型相变纳米微球增强高强度聚焦超声消融的实验研究

目的探讨脂质包裹1,1,2-三氯三氟乙烷相变纳米微球对高强度聚焦超声(HIFU)消融效果的影响。方法采用薄膜水化法制备脂质包裹1,1,2-三氯三氟乙烷相变纳米微球并检测其理化性质。通过离体及在体实验验证其对HIFU的增效作用。离体实验采用250 W、10s的连续波辐照离体牛肝组织。在体实验采用200 W、5s的连续波辐照活体新西兰大白兔的肝脏组织。测量、计算HIFU辐照后靶区的凝固性坏死体积、能效因子(EEF)及强回声区体积,并进行统计分析。结果相变纳米微球在溶液中呈球状、均匀分布,粒径均一。离体实验显示,注射有纳米微球的牛肝组织HIFU辐照后凝固性坏死体积、EEF及强回声区体积均大于未经处理的牛肝组织(t=28.80、19.55、14.30,P=0.01、0.02、0.02)。在体实验显示,注射有纳米微球的新西兰大白兔肝组织HIFU辐照后凝固性坏死体积、EEF及强回声区体积均大于对照组(t=9.41、13.52、15.67,P=0.02、0.01、0.01)。结论脂质包裹1,1,2-三氯三氟乙烷相变纳米微球可明显提高HIFU消融效率。     

高强度聚焦超声治疗兔肾VX2肿瘤的实验研究

目的探讨高强度聚焦超声（ＨＩＦＵ）治疗肾肿瘤的效果。方法采用兔肾ＶＸ２肿瘤模型进行ＨＩＦＵ辐照。辐照后不同时期处死动物以观察其病理变化。另以辐照组及对照组动物各６只,于２周后处死,比较肿瘤生长及肺转移的情况。结果ＨＩＦＵ辐照后肿瘤细胞立即发生凝固性坏死,电镜下亦见到不可逆的破坏。２周后有４只动物的肿瘤原发灶已被完全破坏;另２只靶区外有少量肿瘤残存,其体积为６２．８ｍｍ３和９．４ｍｍ３,而对照组的肿瘤平均体积为（１７５１．１±３５３．７）ｍｍ３。辐照组有２只（３３％）发生肺转移,转移结节数为９和３;对照组全部发生肺转移,转移结节数为５２±３４。两组差异有显著性。结论ＨＩＦＵ对兔肾ＶＸ２肿瘤有很强的杀伤作用。     

对比观察脂质纳泡与微泡在高强度聚焦超声消融兔肝中的增效作用

目的观察正常兔肝中脂质纳泡与微泡对高强度聚焦超声(HIFU)消融效果的影响,探讨纳泡的应用价值。方法采用机械振荡法联合低速离心制备纳泡,观察和分析纳泡及微泡的形态、大小及分布。18只健康新西兰兔随机分为3组:HIFU+生理盐水组、HIFU+微泡组及HIFU+纳泡组,耳缘静脉注入各溶液15s后开始HIFU辐照,辐照功率为180 W,辐照时间5s,观察HIFU辐照前后回声变化,检测靶区组织的凝固性坏死体积以及微细结构变化,并作统计学分析。结果制备的脂质纳泡粒径均一,纳泡、微泡的平均粒径分别为(588.00±53.02)nm、(3058.00±545.20)nm;HIFU+微泡组与HIFU+纳泡组,靶区凝固性坏死体积[(124.26±16.72)mm3,(121.35±11.25)mm3]差异无统计学意义(P0.05),但均显著大于HIFU+生理盐水组(62.49±4.54)mm3(P均0.05);各组坏死组织微细结构均严重破坏。结论脂质纳泡具有与微泡相同的HIFU增效作用,为纳泡在HIFU技术中的深入研究提供实验依据。     

High intensity ultrasound

High-intensity focused ultrasound (HIFU) is a technique that was first investigated in the 1940s as a method of destroying selective regions within the brain in neuro-surgical An ultrasound beam can be brought to a tight focus at a distance from its source, and if sufficient energy is concentrated within the focus, the cells lying within this focal volume are killed, whereas those lying elsewhere are spared. This is a noninvasive method of producing selective and trackless tissue destruction in deep seated targets in the body, without damage to overlying tissues. This field, known both as HIFU and focused ultrasound surgery (FUS), is reviewed in this article.     

A novel approach to energy ablative therapy of small renal tumours: laparoscopic high-intensity focused ultrasound

OBJECTIVE: High-intensity focused ultrasound (HIFU) permits targeted homogeneous ablation of tissue. The objective of this phase 1 study was to evaluate the feasibility of HIFU ablation of small renal tumours under laparoscopic control. PATIENTS AND METHODS: Ten kidneys with solitary renal tumours were treated with a newly developed 4.0 MHz laparoscopic HIFU probe. In the first two patients with 9-cm tumours, a defined marker lesion was placed prior to laparoscopic radical nephrectomy. In eight patients with a mean tumour size of 22 mm (range, 11-40), the tumour was completely ablated as in curative intent, followed by laparoscopic partial nephrectomy in seven tumours. One patient had post-HIFU biopsies and was followed radiologically. Specimens were studied by detailed and whole-mount histology, including NADH stains. RESULTS: Mean HIFU insonication time was 19 min (range, 8-42), with a mean targeted volume of 10.2 cm3 (range, 9-23). At histological evaluation both marker lesions showed irreversible and homogeneous thermal damage within the targeted site. Of the seven tumours treated and removed after HIFU, four showed complete ablation of the entire tumour. Two had a 1- to 3-mm rim of viable tissue immediately adjacent to where the HIFU probe was approximated, and one tumour showed a central area with about 20% vital tissue. There were no intra- or postoperative complications related to HIFU. CONCLUSION: The morbidity of laparoscopic partial nephrectomy mainly comes from the need to incise highly vascularized parenchyma. Targeted laparoscopic HIFU ablation may render this unnecessary, but further studies to refine the technique are needed.     

Spleen hemostasis using high-intensity ultrasound: survival and healing

BACKGROUND: Previous studies have shown that high-intensity focused ultrasound (HIFU) can effectively control bleeding of incised livers and spleens and punctured vessels. This current study investigated the long-term safety of HIFU in splenic hemostasis. METHODS: A total of 21 rabbits were randomly assigned to two groups: HIFU treatment (n = 14), and sham treatment (n = 7). All animals underwent sterile laparotomy and splenic exposure. The HIFU-treated animals received splenic incisions, 8 to 10 mm long and 4 to 5 mm deep, and immediate 9.6-MHz HIFU until hemostasis was achieved. After recovery, ultrasound images, blood samples, and histologic samples were collected on days 0, 1, 3, 7, 14, 28, and 60. RESULTS: All 14 splenic injuries were hemostatic after an average of 96 seconds of HIFU application. There was evidence of rebleeding in one animal between days 3 and 7 posttreatment. Subsequent blood analysis showed no significant difference in serial hematologic or coagulation measures between HIFU and sham groups. Histologic examination up to 60 days posttreatment revealed scarring and spleen tissue regeneration at the treatment site. CONCLUSION: HIFU provides an effective and safe method of achieving hemostasis after acute splenic injury.     

不同剂量高强度聚焦超声辐照兔肝VX2移植瘤的病理学观察

目的观察不同剂量高强度聚焦超声（HIFU）对兔肝VX2移植瘤形态和超微结构的影响。方法通过光镜、电镜观察VX2兔肝移植瘤受不同剂量高强度聚焦超声辐照后即刻、72 h时靶区的病理学特点。结果不同剂量HIFU辐照后即刻,瘤细胞大致有6种表现形式：细胞生长旺盛、可逆性损伤、不可逆性损伤改变、变性坏死、凝固性坏死和裂解坏死;72 h后主要有2类转归形式：细胞趋于正常或进一步溶解、吸收。结论 180 W为一次性HIFU辐照的最佳剂量;剂量组合或为一种更理想的肿瘤治疗方法。     

Microbubbles improve the ablation efficiency of extracorporeal high intensity focused ultrasound against kidney tissues

Objective  The necrosis rate is low when ablating kidney tissues with extracorporeal high intensity focused ultrasound (HIFU), and this drawback has been limiting the application of ultrasonic therapy. The aim of the present study was to determine whether microbubbles increased the ablation efficiency in vivo. Methods  Goat kidneys were exposed to HIFU (control group) or microbubble-assisted HIFU (experimental group). Microbubbles were intravenously injected before focused ultrasound exposure. The linear scan was employed and tissue ablation was performed in manner of a clinical regime. The necrosis rate was determined 24 h after HIFU. Pathological examinations were performed to confirm tissue necrosis and to determine whether there were unaffected tissues within the exposed volume. Results  The necrosis rate was increased in experimental group (4.17 ± 1.33 vs. 9.32 ± 2.27 mm³/s, P = 0.0007). Ablated tissues formed a hemorrhagic volume on gross examinations, and the boundary between treated and untreated areas was sharp. There was no intact tissue within the exposed volume. Hemorrhage frequently occurred in insonated parenchymas. Destructed ghost cells just inside the demarcation were full of vacuoles, when introducing microbubbles. In control group, the volumes of ablated tissues varied drastically between animals despite a same treatment template. Conclusion  Microbubbles increased the ablation efficiency of HIFU against kidney tissues. A preoperative regime might poorly predict the therapeutic outcome. T. Yu and D. Hu contributed equally to this paper.