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     

高强度聚焦超声对香猪正常肝组织辐照时间与损伤范围关系的探讨

目的探讨高强度聚焦超声（ＨＩＦＵ）非侵入性切除肝脏组织的剂量－效应关系及机体反应,旨在为体内深部组织肿瘤的无创性治疗提供实验基础。方法采用重庆医科大学医学超声工程研究所自行设计制造的ＧＬ－１型治疗样机（１．６ＭＨｚ,１３１５３Ｗ／ｃｍ２,３ｓ）,对２８只小型香猪肝脏组织进行定位损伤。于处理前１天、处理后１天、７天、１４天、２１天、２８天测定体温、体重,抽血查肝肾功能。ＨＩＦＵ后３天解剖,对肝损伤区进行体积测定和病理学检查。结果在４０ｍｍ深度范围内,ＨＩＦＵ可体外有效地定位损伤肝脏组织。辐照时间与肝组织凝固坏死体积的关系为（１２．５±５．９）ｓ／ｃｍ３。机体反应：体温在处理后１天体温升高２．２９℃,２周内体温升高１℃,２周后恢复正常。体重治疗前后无明显变化。处理前后肝肾功能无明显异常（Ｐ＞０．０５）。副作用：皮肤损伤４例（１４．２８％）,３～７天愈合;胃损伤２例（７．１４％）,禁食２天,自然进食,生存良好。结论应用高强度聚焦超声非侵入性破坏香猪肝脏组织是有效的,此技术对非侵入性局部破坏人体实体瘤将有重要的临床应用前景。     

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。     

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。     

高强度聚焦超声定位损伤离体人子宫肌瘤的研究

目的探讨高强度聚焦超声(HIFU)体外治疗子宫肌瘤的安全性、有效性及临床可行性。方法用频率0.8MHz,焦距117mm,声强5762.7W/cm2的HIFU对17例离体人子宫肌瘤进行扫描切除,并将治疗过程中声像图表现与TTC染色及组织学切片进行对比观察。结果17例子宫肌瘤在治疗后B超下均出现了强回声团,TTC染色不着色,光镜下细胞核固缩,声像图与TTC染色及组织学结果吻合,强回声区面积与凝固性坏死区面积呈显著正相关(γ＝0.878,P＜0.01)。结论HIFU能够准确安全切除子宫肌瘤,治疗前后超声图像变化是无创监测HIFU切除肌瘤的有用手段。     

脉冲高强度聚焦超声辐照离体组织所致组织摧毁术的实验研究

目的 研究高声功率,低占空比的脉冲高强度聚焦超声(pulsed high intensity focused ultrasound,pHIFU)辐照离体牛肝组织所致组织摧毁术的可行性及机制.方法 使用500 W声功率、4 Hz脉冲重复频率、1％～4％占空比的pHIFU以20 mm深度辐照离体牛肝组织60、30、20 s和15 s.辐照中,使用热电偶和被动空化检测(passive cavitation detection,PCD)系统分别对焦域处的温度和空化信号进行检测.辐照结束后,切开牛肝,观察损伤形态,进行HE染色.结果 pHIFU辐照离体牛肝组织后均有损伤形成,占空比为1％～3％的pHIFU辐照后损伤为洞状;占空比为4％的pHIFU辐照后损伤为凝固性坏死.镜下观察,洞状损伤边缘处呈絮状结构,细胞结构完全破坏,胞浆均质状,细胞核消失.占空比为1％～4％的pHIFU辐照中焦域处的最高温度分别为(41.19±1.42)℃、(45.73±1.92)℃、(53.07±2.09)℃和(64.13±2.56)℃.PCD系统所测信号的频谱中均可见明显的宽带噪声.结论 高声功率,低占空比的pHIFU辐照离体牛肝组织可致组织摧毁术,且空化参与了组织摧毁术的实施.     

占空比对脉冲高强度聚焦超声辐照离体牛肝所致损伤的影响

目的 探讨脉冲高强度聚焦超声(pulsed high intensity focused ultrasound,pHIFU)的占空比对其辐照离体牛肝所致损伤的影响.方法 将pHIFU的声功率设为300 W(声强为26 500 W/cm2),脉冲重复频率为100 Hz,辐照深度为20 mm.以3％、6％、9％、12％和15％的占与空比分别辐照离体牛肝组织10s.辐照中测量靶区温度,辐照结束后,切开牛肝组织,观察各个参数的pHIFU辐照后产生损伤的性状,取损伤组织HE染色后,行光镜观察.结果 占空比为3％、6％时平均最高温度为(35.78±3.35)℃和(36.76±3.88)℃,且肉眼观察到焦点处损伤呈空洞状,内见清亮液体;9％时平均最高温度为(50.45±3.23)℃且在焦点处可见空洞中有匀浆物质;12％、1 5％时平均最高温度为(60.00±5.65)℃和(63.14±4.11)℃,且肉眼看见明显的凝固性坏死.HE染色后,空洞损伤区镜下可见组织缺失,凝固性坏死区主要表现为胞浆淡染,细胞核固缩、染色质边集.随着占空比的增加,组织非热损伤大小形态改变不明显,热损伤大小则呈增大趋势(P＜0.05).结论 通过调整pHIFU的占空比,能使组织损伤性状发生改变.     

高强度聚焦超声体外治疗肝肿瘤的剂量学研究

目的 探讨高强度聚焦超声（ＨＦＵ）破坏肝肿瘤剂量与效应的关系。为ＨＩＦＵ体外治疗肝肿瘤的临床剂量学提供参考数据,方法 在换能器聚焦参数和工作为的前提下,观察并测定不同的输出功率、单次脉冲时间和治疗总时间致离体牛肝组织和活体猪肝脏靶区内组织凝固性坏死灶的大小。结果 肝组织内凝固性坏死灶的大小是可变的,且可能与ＨＩＦＵ治疗剂量和活体组织的生物学特性有关系。结论 肝脏靶区出现凝固性坏死是聚焦超声束作用于     

高强度聚焦超声辐照猪胰腺实验研究

目的探讨改善胰腺HIFU辐照超声通道的方法,并了解不同能量HIFU辐照对猪胰腺组织的损伤及对胃肠道的影响。方法以2头新鲜离体猪胰腺和16头在体猪胰腺体部为靶目标,活体实验中,HIFU辐照前在12头猪胃内放置球囊并注入800~1200ml脱气水,分别以高、中、低能量HIFU进行辐照,4头猪未放置球囊并以中等能量辐照,通过光镜和电镜检查观察胰腺病理损伤程度,并观察副损伤发生情况。结果胃内放置水囊后高能量组4头猪胰腺凝固性坏死程度最重,1头发生皮肤烧伤,2头结肠坏死或穿孔,4头胃黏膜损伤;中等能量组4头猪胰腺凝固性坏死程度较轻,1头发生结肠坏死;低能量组胰腺组织凝固性坏死不明显,但电镜下可见细胞器损伤,1周后出现胰腺坏死现象,未发生皮肤、胃及结肠损伤;未放置水囊组4头猪中只有1头光镜下见胰腺点状坏死,皮肤、胃及结肠的损伤较放置水囊组明显加重。结论通过胃内放置水囊的方法可有效改善猪胰腺HIFU超声通道,高能量HIFU辐照猪胰腺更易发生凝固性坏死,但对胃、结肠的损伤较重;中低能量HIFU可引起猪胰腺发生多种形式损伤或坏死,损伤程度相对较轻,但相对安全。     

高强度聚焦超声体外辐照兔股动脉后的病理学观察

目的 探讨高强度聚焦超声(HIFU)体外辐照兔股动脉后血管的破坏情况。方法HIFU的工作频率为0．8MHz，焦距135mm，焦点平均强度为8000w／cm^2。30只兔随机分为三组，采用弹力纤维维多利亚蓝和丽春红S组织化学染色方法，观察HIFU辐照兔股动脉后即日、3d和7d的病理学变化。结果HIFU辐照后，各实验组均可见兔股动脉血管内皮细胞脱落、消失，管腔有微小血栓形成；平滑肌细胞出现核固缩，细胞排列紊乱；血管弹力纤维出现崩溃和断裂等现象。结论HIFU体外辐照可以造成兔股动脉血管损伤，并导致血流动力学改变。     

Using the acoustic interference pattern to locate the focus of a high-intensity focused ultrasound (HIFU) transducer

One of the main problems encountered when using conventional B-mode ultrasound (US) for targeting and monitoring purposes during ablation therapies employing high-intensity focused US (HIFU) is the appearance of strong interference in the obtained diagnostic US images. In this study, instead of avoiding the interference noise, we demonstrate how we used it to locate the focus of the HIFU transducer in both in vitro tissue-mimicking phantoms and an ex vivo tissue block. We found that when the B-mode image plane coincided with the HIFU focal plane, the interference noise was maximally converged and enhanced compared with the off-focus situations. Stronger interference noise was recorded when the angle (alpha) between the US image plane and the HIFU axis was less than or equal to 90 degrees. By intentionally creating a target (group of bubbles) at the 3.5-MHz HIFU focus (7.1 mm in length and 0.7 mm in diameter), the position of the maximal noise convergence coincided well with the target. The difference between the predicted focus and the actual one (bubbles) on x and z axes (axes perpendicular to the HIFU central axis, Fig. 1) were both about 0.9 mm. For y axis (HIFU central axis), the precision was within 1.0 mm. For tissue block ablation, the interference noise concentrated at the position of maximal heating of the HIFU-induced lesions. The proposed method can also be used to predict the position of the HIFU focus by using a low intensity output scheme before permanent changes in the target tissue were made.     

高强度聚焦超声治疗子宫肌瘤的临床研究

目的探讨高强度聚焦超声(HIFU)治疗子宫肌瘤的安全性和有效性。方法选择180例,年龄在30-50岁之间已生育的、具有手术适应症的子宫肌瘤患者作为治疗对象。应用HIFUNIT9000型超声聚焦肿瘤消融肌瘤实施脉冲式释放高强度超声治疗。比较治疗前后患者的临床症状、Hb含量和肌瘤体积的变化。结果180例患者局部皮肤Ⅰ度烧伤者6例,未见其他严重并发症。术后3个月92.9%的月经量增多患者和96.4%的伴有尿频症状的患者恢复正常。贫血患者治疗后3月,总体血红蛋白含量明显增加。173例患者肌瘤缩小明显而不需要其他治疗手段,仅有7例因未见瘤体明显缩小或增大而进行手术治疗。结论HIFU是治疗子宫肌瘤安全、有效的方法。     

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.     

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.