高强度聚焦超声照射正常离体心肌组织的实验研究——局部心肌的凝固损伤范围与声辐照剂量的关系

目的　探讨高强度聚焦超声 (HIFU)非侵入性凝固局部心肌组织的能量 -效应关系。方法　采用不同强度 (110 0 0W /cm2 、15 80 0W /cm2 和 2 2 2 0 0W /cm2 )的HIFU ,在不同辐照时间 (1s、3s、5s和 8s)的作用下 ,对 2 0只正常猪离体心脏进行定位损伤 ,观察并测定损伤区的形态及体积 ,损伤区及其与周围正常组织交界处的组织同时送病理学检查。结果　不同剂量下HIFU所致的损伤体积范围分布在 (11.2± 1.9)mm3 ～(2 83 .2± 4.5 )mm3 之间 ,不同处理因素间的损伤体积差异具有显著性意义 (P <0 .0 5 )。损伤形态随剂量增大趋向不规则。组织学观察可见损伤区与周围正常组织分界明显。结论　HIFU可有效地使心肌组织发生凝固性坏死 ,但不侵及周围组织     

高强度聚焦超声辐照离体心肌组织的实验研究——局部心肌凝固剂量与温度的关系

目的　探讨在不同剂量的高强度聚焦超声 (high intensityfocusedultrasound ,HIFU )辐照下 ,正常猪离体心肌组织焦点局部的温度变化及规律。方法　应用不同声强度 (110 0 0W /cm2 、15 80 0W /cm2和 2 2 2 0 0W /cm2 )、不同辐照时间 (1s、3s、5s、7s、10s、13s和 15s)的HIFU连续定点辐照猪离体心肌组织的不同部位 ,同时通过置于焦点中心的热电耦温度计连续测温 ,观察焦域的温度变化。结果　不同剂量下焦点中心所达到的最高温度分布范围为 (66.4± 11.2 )℃～ (85 .8± 7.4)℃。不同处理因素间的最高温度差异具有显著性意义 (P <0 .0 5 ) ,停止辐照后焦点的降温曲线下降趋势由快到慢。结论　不同剂量的HIFU均可使焦点中心达到组织发生不可逆变化所需的温度 ,HIFU剂量与焦域中心温度有关 ,但不呈正比     

高强度聚焦超声定位损伤离体牛肝的量效学研究

目的 探讨不同频率、不同治疗剂量的高强度聚焦超声(HIFU)定位损伤新鲜离体牛肝的量效关系。方法 采用治疗头频率分别为5．4MHz和7．4MHz的高强度聚焦超声治疗系统在不同的治疗功率40W和50W时，分5s、8s、10s、15s、20s的治疗时间定位损伤新鲜离体牛肝，记录并测量靶区的温度和生物学焦域体积。结果 HIFU辐照5～8s可迅速提高靶区温度至64～75℃，随着治疗时间增加，温度最高可达85℃；在治疗头频率和输出功率相同时，随着辐照时间的延长，HIFU辐照部位的生物学焦域体积增大，同一部位辐照时间越长(15～20s)，生物学焦域中心越易产生炭化和空洞现象；在治疗头频率和辐照时间相同时，输出功率增大，生物学焦域体积增大；在输出功率和辐照时间相同时，频率为7．4MHz的治疗头较频率为5．4MHz的治疗头所产生的生物学焦域体积大。结论 HIFU生物学焦域的形成与治疗头的工作频率、输出功率和治疗时间密切相关，在一定的参数条件下，生物学焦域可控制，这将有助于HIFU在肿瘤治疗领域的临床应用。     

高强度聚焦超声消融活体心肌的实验研究

目的探讨高强度聚焦超声(HIFU)技术消融活体心肌的可行性。方法以4种HIFU能量在超声实时监测下消融开胸犬室壁心肌,比较消融前后靶区组织多普勒频谱、二尖瓣口血流频谱(E、A峰峰值速度)、射血分数(EF)、心肌酶(AST、LDH、CK)及肌钙蛋白T(CTnT)含量。消融结束后取心脏逐层解剖,染色确定消融范围并测量体积。光镜及电镜观察组织显微结构和细胞超微结构变化。结果①消融后靶区组织多普勒频谱即刻降低(P<0.05);EF值及E/A差异无统计学意义(P>0.05)。②心肌酶及CTnT含量有不同程度上升(P<0.05)。③所设声能量条件下消融体积在(22.1±3.4)mm3~(1239.2±22.9)mm3之间。光镜观察所有剂量组消融区均发生不可逆损伤。电镜下见消融区心肌结构出现不可逆损伤表现,周边仅表现为轻度变性,变性肌丝与消融区坏死肌丝交界清楚可辨。结论HIFU技术可以实现活体动物心肌消融,消融范围可控,在心脏消融方面可能有潜在应用价值。     

对比观察纳米微泡与微米微泡在高强度聚焦超声消融新鲜离体牛肝中的增效作用

目的探讨纳米微泡与微米微泡在增效高强度聚焦超声(HIFU)作用中的差异。方法机械振荡低速离心法制备纳米微泡。分别采用0.2、0.5和0.8 ml的纳米微泡、Sono Vue微泡及PBS溶液联合HIFU消融离体牛肝。HIFU功率为180 W,辐照时间5 s,记录各次消融靶区凝固性坏死体积大小,并行统计学分析。结果各剂量下纳米微泡组与Sono Vue组消融的组织体积均大于PBS溶液组(P﹤0.05);随着纳米微泡组与Sono Vue组剂量的增加,其消融体积均明显增加,而各PBS组差异无统计学意义(P﹥0.05)。在相同的剂量下,纳米微泡组消融体积大于Sono Vue组(P﹤0.05)。结论纳米微泡及微米微泡均能显著增强HIFU的消融效果,在相同剂量条件下,纳米微泡较微米微泡能更好地提高HIFU的治疗效果。     

肝脏HIFU治疗剂量学初步研究

目的探讨在直线扫描方式时,高强度聚焦超声(HIFU)损伤不同深度的正常羊肝组织的治疗剂量,即产生单位体积凝固性坏死所需要的超声输出能量.方法应用频率1.0MHz,焦域平均声强为5500W/cm2,对15头南疆黄羊距皮肤30mm、40mm、50mm的肝组织内行HIFU损伤,损伤范围30mm×10mm×10mm,扫描线间距和面间距均为5mm.术后3～7天内处死动物,测量凝固性坏死体积,观察治疗剂量与治疗深度的关系.结果距皮30mm深度肝脏HIFU治疗剂量为(16.6±2.72)J/mm3,40mm为(28.3±6.37)J/mm3,50mm为(44.7±3.71)J/mm3.结论HIFU致肝组织的凝固性坏死有明显的量效关系,其值随辐照深度的增加而增加.     

碳酸氢铵溶液增效高强度聚焦超声消融新鲜离体牛肝的实验研究

目的研究碳酸氢铵溶液增效高强度聚焦超声(HIFU)消融离体牛肝的作用。方法以不同功率(120 W、150 W、180 W、210 W)HIFU消融离体牛肝,比较注射碳酸氢铵溶液的实验组与注射PBS溶液的对照组的凝固性坏死体积、灰度差及灰度区域面积。结果 HIFU消融功率为120 W时,实验组出现凝固性坏死,体积约(11.53±4.93)mm~3,而对照组无明显凝固性坏死;功率为150 W时,实验组凝固性坏死体积为(50.41±33.7)mm~3,显著大于对照组[(8.60±4.14)mm~3],差异有统计学意义(P0.05);消融功率为180 W时,实验组凝固性坏死体积与对照组比较差异无统计学意义;消融功率为210 W时,实验组凝固性坏死体积为(39.84±13.62)mm~3,显著小于对照组[(62.79±11.32)mm~3],差异有统计学意义(P0.05)。当HIFU消融功率为120 W、150 W时,实验组灰度差和灰度区域面积均显著高于对照组,差异均有统计学意义(均P0.05)。结论在功率120 W、150 W时,碳酸氢铵溶液具备增效HIFU消融离体牛肝的作用。     

辐照深度对高强度聚焦超声生物学焦域的影响

目的：探讨HIFU生物学焦域在不同深度的牛肝组织中与治疗剂量的定量关系。方法：探头频率为1.0MHz在相同治疗剂量时，定位损伤不同深度的新鲜离体牛肝，测量并比较损伤灶的体积。结果：生物学焦域的体积随治疗深度的增加而减小，结论：HIFU生物学焦域体积随治疗深度的增加呈指数规律递减，VBFR=1738.2e^-0.3948D。     

植入式微波消融猪离体乳腺

目的观察植入式微波在离体猪乳腺实质的消融形态和范围,为临床应用提供参考。方法采用KY-2000型微波消融治疗仪,通过不同时间及功率组合对离体猪乳腺组织进行消融,观察其消融范围及形态。结果在功率20～60W,时间3～10min时微波消融离体猪乳腺组织的形态均为水滴形,可获得(1.65±0.06)cm～(3.78±0.10)cm的长径范围、(1.08±0.05)cm～(2.70±0.00)cm的横径范围和(1.27±0.70)cm3～(15.07±0.21)cm3的体积范围,形态规则。结论应用KY-2000型微波消融治疗仪对猪离体乳腺组织进行消融,可以达到较理想的消融体积及消融形态。     

高强度聚焦超声治疗子宫肌瘤的剂量学研究

目的 探讨高强度聚焦超声(high intensity focused ultrasound,HIFU)在不同投射方式下治疗子宫肌瘤的剂量与效应关系。方法 在声换能器聚焦参数和工作声强、频率不变的前提下,观察在不同投射时间HIFU定点损伤和扫描损伤致离体人子宫肌瘤组织凝固性坏死灶的大小,并对两种投射方式下的能效因子、形态学改变等进行比较。结果 HIFU所致的凝固性坏死灶的大小、形态与投射方式及投射时间密切相关,在同样的声强下,两组最佳能效因子差异有显著性意义(P<0.05)。结论 HIFU 治疗子宫肌瘤时采用扫描损伤优于定点损伤。     

Effects of ultrasonic exposure parameters on myocardial lesions induced by high-intensity focused ultrasound.

OBJECTIVE: This study evaluated variables relevant to creating myocardial lesions using high-intensity focused ultrasound (HIFU). Without an effective means of tracking heart motion, lesion formation in the moving ventricle can be accomplished by intermittent delivery of HIFU energy synchronized by electrocardiographic triggering. In anticipation of future clinical applications, multiple lesions were created by brief HIFU pulses in calf myocardial tissue ex vivo. METHODS: Experiments used f-number 1.1 spherical cap HIFU transducers operating near 5 MHz with in situ spatial average intensities of 13 and 7.4 kW/cm2 at corresponding depths of 10 and 25 mm in the tissue. The distance from the HIFU transducer to the tissue surface was measured with a 7.5-MHz A-mode transducer coaxial and confocal with the HIFU transducer. After exposures, fresh, unstained tissue was dissected to measure visible lesion length and width. Lesion dimensions were plotted as functions of pulse parameters, cardiac structure, tissue temperature, and focal depth. RESULTS: Lesion size in ex vivo tissue depended strongly on the total exposure time but did not depend strongly on pulse duration. Lesion width depended strongly on the pulse-to-pulse interval, and lesion width and length depended strongly on the initial tissue temperature. CONCLUSIONS: High-intensity focused ultrasound creates well-demarcated lesions in ex vivo cardiac muscle without damaging intervening or distal tissue. These initial studies suggest that HIFU offers an effective, noninvasive method for ablating myocardial tissues to treat several important cardiac diseases.     

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.     

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。     

Contrast-agent-enhanced ultrasound thermal ablation

The small thermal lesions induced when using high-intensity focused ultrasound (HIFU) to ablate tumors results in long treatment duration. In this study, the effect of using ultrasound contrast agent (UCA, Definity) to enhance the ultrasound (US) thermal effects and, thus to enlarge the lesion size, was studied in transparent tissue phantoms insonified by 1.85-MHz US with acoustical powers of 28.9 and 40.4 W. The experimental results show that the lesion size depended strongly on the electrical power and the concentration of UCA. UCA also reduced the power required to form a lesion of a certain size by about 30%. However, UCA moved the greatest heating position from the transducer focus, by 2.16 cm for 0.015% UCA at 40.4 W, and with lesions forming at the surface for UCA concentrations higher than 0.1%. An optimal result was obtained when using 0.001% UCA and 28.9-W US, which produced a lesion 12 times larger and an acceptable shift (less than half of the lesion length). UCA can effectively increase the size of the HIFU lesions, but lesion shift should be carefully considered while performing HIFU ablations.     

In vitro and in vivo ablation of porcine renal tissues using high-intensity focused ultrasound

The aim of this paper is to present issues regarding the thermal ablation of porcine renal tissues in vitro and in vivo using high-intensity focused ultrasound (HIFU). Production of lesions in the cortex in vitro is consistent, whereas lesions in the medulla are created whenever there are no air spaces in the medulla. Typically, the lesion length at 2000 W/cm2 and 5-s pulse duration is around 20 mm and the corresponding width around 3 mm. Lesioning of a large volume was achieved by moving the transducer in a grid formation. Lesioning through a fat layer is possible provided that there are no air spaces between the fat and kidney interface. It was found that, above 3200 W/cm2 with 5-s pulse duration at 4 MHz, cavitation activity occurred in most of the lesions created.     

高强度聚焦超声治疗H_(22)肝肿瘤的效果:不同治疗方案的评价

实验研究已证明高强度聚焦超声(HIFU)提供了一种局部切除肿瘤的体外治疗手段.本文选择不同方案的HIFU治疗H_(22)肝肿瘤.73只ICR H_(22)肿瘤荷鼠分对照组和HIFU治疗组.后者根据辐照时间和次数变化分不同治疗亚组.结果显示HIFU对各治疗组小鼠H_(22)肿瘤生长均有抑制作用.同一声强下,切除肿瘤的局部效果取决于辐照时间和次数.     

Characterization of extracorporeal ablation of normal and tumor-bearing liver tissue by high intensity focused ultrasound

Treatment parameters of extracorporeal high intensity focused ultrasound (HIFU) were analysed in normal and tumor-bearing rabbit liver. HIFU was generated with a 1 MHz transducer and energy was provided by a 7.5 kW power amplifier. In vivo experiments were conducted on 74 New Zealand rabbits. Normal rabbits and rabbits bearing an intrahepatic VX2 tumor were used. In group 1, spatial peak temporal peak (SPTP) intensities ranging from 1470 to 5500 W cm⁻² and exposure times from 0.5 to 5 s were tested at a constant depth in the liver; in group 2, the output power was adjusted as a function of the target depth in order to keep constant the focal in situ intensity in the liver; in group 3 (liver tumors), the focal in situ intensity was 1365 W cm⁻² in eight rabbits and 500 W cm⁻² in nine. In groups 1, 2 and 3, rabbits were sacrificed 48 h after the treatment. Groups 4 and 5 were designated for analysis of the lesion in the normal liver 4 weeks after treatment at 1000 W cm⁻² and 3000 W cm⁻² SPTP intensities, respectively. In normal rabbits, the lesion volume increased with exposure time at constant intensity; there was a negative correlation between intensity and exposure time (group 1). When the output power was adjusted as a function of the path length, the lesion size was nearly constant (group 2). In VX2 rabbits, tumor destruction rates were significantly higher in rabbits treated at 500 W cm⁻² than in rabbits treated at 1365 W cm⁻² (p < 0.05; group 3). As in the normal liver, the lesion volume increased with the exposure time at constant intensity. HIFU lesions treated at 1000 W cm⁻² (SPTP) healed as thin fibrous scars, and no severe complication occurred (group 4); at 3000 W cm⁻² (SPTP), scars were larger and perforation of a neighboring organ was seen in 7 of 11 rabbits (group 5).     

Performance assessment of HIFU lesion detection by harmonic motion imaging for focused ultrasound (HMIFU): a 3-D finite-element-based framework with experimental validation

Harmonic motion imaging for focused ultrasound (HMIFU) is a novel high-intensity focused ultrasound (HIFU) therapy monitoring method with feasibilities demonstrated in vitro, ex vivo and in vivo. Its principle is based on amplitude-modulated (AM) - harmonic motion imaging (HMI), an oscillatory radiation force used for imaging the tissue mechanical response during thermal ablation. In this study, a theoretical framework of HMIFU is presented, comprising a customized nonlinear wave propagation model, a finite-element (FE) analysis module and an image-formation model. The objective of this study is to develop such a framework to (1) assess the fundamental performance of HMIFU in detecting HIFU lesions based on the change in tissue apparent elasticity, i.e., the increasing Young’s modulus, and the HIFU lesion size with respect to the HIFU exposure time and (2) validate the simulation findings ex vivo. The same HMI and HMIFU parameters as in the experimental studies were used, i.e., 4.5-MHz HIFU frequency and 25 Hz AM frequency. For a lesion-to-background Young’s modulus ratio of 3, 6 and 9, the FE and estimated HMI displacement ratios were equal to 1.83, 3.69 and 5.39 and 1.65, 3.19 and 4.59, respectively. In experiments, the HMI displacement followed a similar increasing trend of 1.19, 1.28 and 1.78 at 10-s, 20-s and 30-s HIFU exposure, respectively. In addition, moderate agreement in lesion size growth was found in both simulations (16.2, 73.1 and 334.7 mm²) and experiments (26.2, 94.2 and 206.2 mm²). Therefore, the feasibility of HMIFU for HIFU lesion detection based on the underlying tissue elasticity changes was verified through the developed theoretical framework, i.e., validation of the fundamental performance of the HMIFU system for lesion detection, localization and quantification, was demonstrated both theoretically and ex vivo.     

HIFU体外块"切除"动物肝脏、肾脏和肌肉的剂量研究

目的　用能效因子( energy- efficiency factor,EEF)作为高强度聚焦超声( high intensity focused ultrasound,HIFU)治疗剂量学评价指标来研究HIFU切除组织块的治疗剂量。方法　按照由束损伤→片损伤→块损伤的治疗原则,使用声强为70 0 0～2 770 0 W/ cm2 ,扫描线长3 0 mm,扫描速度3 mm/ s,束损伤的空间间距5～1 0 mm,片损伤的空间间距5 mm,在山羊肝脏、肾脏和肌肉中形成一个凝固性坏死块。并把形成单位体积凝固性坏死所需的超声能量叫做HIFU治疗的EEF,用EEF作为HIFU治疗剂量学评价指标。结果　按照束损伤→片损伤→块损伤的组合方式能在山羊肝脏、肾脏、肌肉中形成一个完整的凝固性坏死块,且中间没有正常组织残留。在山羊肾脏中形成一个凝固性坏死块的EEF明显大于在山羊肝脏中形成一个凝固性坏死块的EEF,而相比于肾脏和肝脏,在山羊肌肉中形成一个凝固性坏死块的EEF最小。结论　本研究表明同一超声能量在不同的靶组织中所产生的凝固性坏死体积不同,组织的结构、功能状态对HIFU治疗肿瘤的效果具有较大的影响,HIFU治疗剂量学的研究有望为临床治疗肿瘤提供剂量学指导     

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.