HIFU联合微泡造影剂辐照离体再灌注人子宫肌瘤标本的声像图特点
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摘要
研究背景
子宫肌瘤是女性生殖系统最常见的一种良性肿瘤,多见于30～50岁妇女。多无症状,少数表现为阴道出血、腹部触及肿物、压迫症状等。是月经过多和异常子宫出血的主要原因。目前对于症状性子宫肌瘤的主要治疗方法包括手术治疗,药物治疗,微创治疗,高强度聚焦超声(High intensity focused ultrasound,HIFU)治疗等。HIFU技术因无电离辐射、非侵入性、可重复治疗等在子宫肌瘤治疗领域极具潜力。在HIFU辐照靶区过程中,组织声环境(Acoustic environment in tissue,AET)是影响HIFU能量沉积的重要因素。近年来,研究表明微泡造影剂是一种提高HIFU疗效的增效剂,且HIFU治疗效率与微泡造影剂的剂量相关。
子宫肌瘤没有成型的动物模型,故本研究构造人子宫肌瘤标本的离体再灌注模型,观察单纯HIFU辐照以及HIFU联合不同浓度微泡造影剂辐照标本后靶区灰度随时间动态变化规律以及辐照后不同时间点靶区回声增强区域面积与凝固性坏死面积的相关性,为HIFU联合微泡造影剂治疗子宫肌瘤的超声实时监控提供依据。
目的
通过HIFU联合不同浓度微泡造影剂辐照离体再灌注人子宫肌瘤标本,探讨HIFU辐照标本后不同时间点靶区灰度随时间动态变化特点以及辐照后不同时间点靶区回声增强区域面积与凝固性坏死面积的相关系数,为掌握辐照剂量、终止辐照时间及声像图判断靶区凝固性坏死范围提供依据。
材料和方法
1研究对象
因子宫肌瘤而做子宫全切术的新鲜完整离体子宫标本18个,征询患者意愿获得同意并经学校伦理委员会同意后取得。
2设备及药品
BT-50E型蠕动泵(重庆杰恒蠕动泵有限公司生产),转速0.1～50rpm,出水量0.001～18ml/min。
Philips IU22彩色多普勒超声诊断仪,探头频率3.5MHz。JC200型聚焦超声肿瘤治疗系统及灰度处理软件(重庆海扶(HIFU)技术有限公司生产)。
SonoVue超声微泡造影剂(意大利博莱科公司(Bracco)生产)肝素,乳酸林格液,氯化三苯基四氮唑(Triphenyl tetrazolium chloride,TTC)染色液。
3方法
3.1标本的准备:获取离体子宫标本后即刻行肝素化处理,双侧子宫动脉插管,接通蠕动泵泵入肝素化的乳酸林格液。应用彩色多普勒血流成像(Color Doppler flowing image,CDFI)及脉冲多普勒(Pulse wave,PW)成像技术观察标本再灌注情况,采集彩色多普勒及脉冲多普勒频谱信号。
3.2实验分组:单纯HIFU辐照组,HIFU联合造影剂辐照组
3.3 HIFU辐照:单纯HIFU辐照组将连接体外灌流装置的离体子宫标本放入盛脱气水的容器内。开启蠕动泵,持续泵入乳酸林格液。选择无囊性变的子宫肌瘤平面进行HIFU定点辐照。辐照参数:辐照声功率:200w;辐照深度20mm;辐照方式:定点辐照;辐照时间:5s、10s。每次采集HIFU辐照前及辐照后即刻、1、2、5min的靶区声像图,测量靶区灰度值并测量辐照后各个时间点声像图上靶区回声增强区域面积。辐照后剖开标本,寻找损伤点,进行TTC染色,测量凝固性坏死面积后石蜡切片行HE染色光镜观察。采用SAS8.1统计软件包分析不同辐照参数对靶区灰度、凝固性坏死面积的影响及辐照后不同时间点靶区灰度值差异是否具有统计学意义,并计算辐照后不同时间点声像图上靶区回声增强区域面积与凝固性坏死面积的相关系数。HIFU联合微泡造影剂辐照组在接通蠕动泵后,通过灌流装置的三通开关向标本内注入不同浓度SonoVue超声微泡造影剂。通过机载超声选取有造影剂充填的子宫肌瘤平面进行HIFU辐照。辐照参数、观察指标、统计方法、辐照后处理同HIFU组。
结果
1.对经过肝素抗凝的离体人子宫肌瘤标本进行再灌注后, CDFI检查见肌瘤周边彩色信号填充,肌瘤内部偶见点状彩色信号,并见类似门静脉的带状等速PW频谱信号。表明肌瘤标本再灌注成功,已经将乳酸林格液泵入离体子宫肌瘤标本的肌瘤内部。
2. HIFU定点辐照标本,辐照后不同时间点靶区灰度值不同,辐照后即刻靶区灰度值最高,辐照后1min后靶区灰度值趋于稳定。辐照参数200w,辐照时间10s,辐照深度20mm,辐照结束1min时靶区灰度值为29.40±3.44。辐照后不同时间点,靶区回声增强区域面积呈下降趋势,不同时间点声像图上靶区回声增强区域面积与凝固性坏死面积具有很高的相关系数,辐照结束2min靶区回声增强区域面积与凝固性坏死面积相关系数最高,达0.99957。
3. HIFU联合微泡造影剂定点辐照标本时,辐照结束2min后靶区灰度值趋于稳定。辐照结束5min声像图上靶区回声增强区域面积与凝固性坏死面积面积相关系数最高,达0.92。
结论
1.建立离体子宫肌瘤标本再灌注模型,可以模拟在体子宫的血液循环状态,为子宫肿瘤的基础与临床研究提供接近在体环境的平台。
2.单纯HIFU辐照后,靶区灰度值在辐照结束1min趋于稳定,辐照结束2min靶区回声增强区域面积与凝固性坏死面积相关系数最高。
3. HIFU联合微泡造影剂辐照后,靶区灰度值需要比单纯HIFU辐照组更长的时间才能趋于稳定,靶区回声增强区域面积与凝固性坏死面积的相关系数较单纯HIFU辐照组降低。
4.辐照参数相同,微泡造影剂浓度越高,辐照后靶区灰度越高。
5.微泡造影剂需要达到一定浓度,才能达到增加靶区凝固性坏死面积的目的。
Backgrounds
Hysteromyoma is the most common benign tumor of female reproductive system, predilection in women of 30-50 years old, which is the main cause of menometrorrhagia and abnormal uterine bleeding(AUB), although most of patients suffered of it are absence of symptoms while a few appear vaginal bleeding, lump touched from abdomen, bladder oppression, torsion of pedicle et al. At present, the main therapies of hysteromyoma with symptoms include operation, drug treatment, small trauma treatment, High intensity focused ultrasound (HIFU) treatment, et al. HIFU has great potential for treatment of hysteromyoma for its advantages of no ionization radiation, noninvasive and retreatmentable.
In the process of HIFU radiance target area, Acoustic environment in tissue (AET) is an important factor that influence the accumulation of HIFU energy. In recent years, many researches suggested that ultrasonic contrast agent was an potentiator of improving HIFU therapeutic effect in a dose-dependent manner.
There is no good animal model of hysteromyoma, therefore, ex vivo circulation model of human hysteromyoma were constructed to investigate dynamic variances of gray scales in target area after perfused with SonVue in different dose and radiance by HIFU and observe the correlation between hyperechogenicity area and actual necrosis area at different time points after radiance and provide evidences for ultrasound real time monitoring the process of treating hysteromyoma by HIFU with SonVue.
Objective
Dynamic variances of gray scales in target area after human ex vivo hysteromyoma reperfused with SonVue in different dose and radiance by HIFU and the correlation between hyperechogenicity area and necrosis area at different time points after radiance were investigated to obtain the accurate radiance dose, exposure time and how to judge necrosis area by ultrasound.
Materials and methods
Subjects
18 complete fresh ex vivo uterus from patients suffered from hystero- myoma by total hysterectomy was obtained with the permission of patients and school Ethics Committee.
Equipments and drugs
BT-50E peristaltic pump (Chongqing Jieheng peristaltic pump limited company), rotation speed:0.1-50rpm, stream speed:0.001-18ml/min.
Philips IU22 color doppler ultrasonograph, frequency of probe: 3.5MHz.
JC200 HIFU device and gray measure software (Chongqing HAIFU (HIFU) Technology Co, Ltd).
SonoVue (Bracoo, Milan, Iatly ) was used as contrast agent in the study.
Heparin, Ringer lactate solution, Triphenyl tetrazolium chloride (TTC) staining solution
Methods
Ex vivo uteruses were pumped into heparinizated Ringer-Locke liquor from both uterine arteries by peristaltic pump immediately after obtained. Then the reperfusion information of uterus was detected by Color doppler flowing image (CDFI) and Pulse wave(PW) imaging. Grouping:Single HIFU radiance group, HIFU with SonoVue group
In single HIFU radiance group, ex vivo uterus connected with vitro perfusion device was put into container with de-aerated water. Then the peristaltic pump was opened and Ringer-Locke liquor was pumped into uterus from the peristaltic pump. Hysteromyoma planes without cystis degeneration were selected to radiate by HIFU in fixed points. Parameter: acoustic power:200w;depth:20mm;radiance mode:fixed-point radiance; exposure time:5s, 10s. Sonograms of target area were captured every time before HIFU radiance and after radiance for 0, 1, 2, 5min and gray scale and hyperechogenicity areas of target area sonograms were measured. Hysteromyoma was split and stained by TTC after HIFU radiance to search lesion area and measure necrosis area before paraffin section and HE staining were progressed. Influences of different dosage of HIFU on gray scale of target area and differences between gray scales of different time were analyzed by SAS8.1 statistical package and coefficient correlation between hyperechogenicity areas of target sonograms and necrosis areas was calculated.
In HIFU with SonoVue group, SonoVue of different concentrations was pumped into hysteromyoma from the 3-way stop cock of peristaltic pump after the pump was turned on. Hysteromyoma planes filled with SonoVue were selected by ultrasound and radiated by HIFU. Radiance parameters, observing indexes, statistical method, postdose treatment were similar to single HIFU group.
Results 1.After heparin anticoagulant ex vivo human hysteromyoma
specimens were reperfused, CDFI showed chroma signal filled the periphery of hysteromyoma and occasionally punctiform chroma signals were seen in the hysteromyoma and barred constant speed PW frequency spectrum signals like portal veins were seen. It indicated that reperfusion of hysteromyoma specimens was successful and Ringer lactate solution has been pumped into the inner of hysteromyoma.
2.Target gray scales were different at different time points after single radiance by HIFU in fixed. The gray scale values were highest 0min after radiance and trended to stable 1min after radiance. The target gray scale values was 29.40±3.44 1min after radiance by HIFU with an acoustic power of 200w, radiance depth of 20 mm and exposure time of 10s. Hyperechogenicity areas of target depressed in a time-dependent manner. The coefficient correlation between hyperechogenicity areas of target sonograms and necrosis areas was high and got highest 2min after radiance, the highest correlation coefficient was 0.99957.
3.In HIFU associated with SonoVue group, the gray scale values trended stable 2min after radiance. The coefficient correlation between hyperechogenicity areas of target sonograms and necrosis areas got highest at the time point 5min after radiance.
Conclusion
1.Reperfusion model of ex vivo hysteromyoma specimens was constructed to imitate the blood circulation of in vivo uterus and provide in vivo environments of basic and clinic research on hysteromyoma.
2.1min after single radiance by HIFU, the target gray scale values trended stable. The coefficient correlation between hyperechogenicity areas of target sonograms and necrosis areas was highest 2min after radiance.
3.After radiance by HIFU associated with SonoVue, the target gray scale values needs more time to trended stable and the coefficient correlation between hyperechogenicity areas of target sonograms and necrosis areas was lower.
4.The target gray scale values increases with the concentration of microbubble.
5.It needs enough concentration of microbubble to increase the curativeeffect of HIFU.
子宫肌瘤是女性生殖系统最常见的一种良性肿瘤,多见于30～50岁妇女。多无症状,少数表现为阴道出血、腹部触及肿物、压迫症状等。是月经过多和异常子宫出血的主要原因。目前对于症状性子宫肌瘤的主要治疗方法包括手术治疗,药物治疗,微创治疗,高强度聚焦超声(High intensity focused ultrasound,HIFU)治疗等。HIFU技术因无电离辐射、非侵入性、可重复治疗等在子宫肌瘤治疗领域极具潜力。在HIFU辐照靶区过程中,组织声环境(Acoustic environment in tissue,AET)是影响HIFU能量沉积的重要因素。近年来,研究表明微泡造影剂是一种提高HIFU疗效的增效剂,且HIFU治疗效率与微泡造影剂的剂量相关。
子宫肌瘤没有成型的动物模型,故本研究构造人子宫肌瘤标本的离体再灌注模型,观察单纯HIFU辐照以及HIFU联合不同浓度微泡造影剂辐照标本后靶区灰度随时间动态变化规律以及辐照后不同时间点靶区回声增强区域面积与凝固性坏死面积的相关性,为HIFU联合微泡造影剂治疗子宫肌瘤的超声实时监控提供依据。
目的
通过HIFU联合不同浓度微泡造影剂辐照离体再灌注人子宫肌瘤标本,探讨HIFU辐照标本后不同时间点靶区灰度随时间动态变化特点以及辐照后不同时间点靶区回声增强区域面积与凝固性坏死面积的相关系数,为掌握辐照剂量、终止辐照时间及声像图判断靶区凝固性坏死范围提供依据。
材料和方法
1研究对象
因子宫肌瘤而做子宫全切术的新鲜完整离体子宫标本18个,征询患者意愿获得同意并经学校伦理委员会同意后取得。
2设备及药品
BT-50E型蠕动泵(重庆杰恒蠕动泵有限公司生产),转速0.1～50rpm,出水量0.001～18ml/min。
Philips IU22彩色多普勒超声诊断仪,探头频率3.5MHz。JC200型聚焦超声肿瘤治疗系统及灰度处理软件(重庆海扶(HIFU)技术有限公司生产)。
SonoVue超声微泡造影剂(意大利博莱科公司(Bracco)生产)肝素,乳酸林格液,氯化三苯基四氮唑(Triphenyl tetrazolium chloride,TTC)染色液。
3方法
3.1标本的准备:获取离体子宫标本后即刻行肝素化处理,双侧子宫动脉插管,接通蠕动泵泵入肝素化的乳酸林格液。应用彩色多普勒血流成像(Color Doppler flowing image,CDFI)及脉冲多普勒(Pulse wave,PW)成像技术观察标本再灌注情况,采集彩色多普勒及脉冲多普勒频谱信号。
3.2实验分组:单纯HIFU辐照组,HIFU联合造影剂辐照组
3.3 HIFU辐照:单纯HIFU辐照组将连接体外灌流装置的离体子宫标本放入盛脱气水的容器内。开启蠕动泵,持续泵入乳酸林格液。选择无囊性变的子宫肌瘤平面进行HIFU定点辐照。辐照参数:辐照声功率:200w;辐照深度20mm;辐照方式:定点辐照;辐照时间:5s、10s。每次采集HIFU辐照前及辐照后即刻、1、2、5min的靶区声像图,测量靶区灰度值并测量辐照后各个时间点声像图上靶区回声增强区域面积。辐照后剖开标本,寻找损伤点,进行TTC染色,测量凝固性坏死面积后石蜡切片行HE染色光镜观察。采用SAS8.1统计软件包分析不同辐照参数对靶区灰度、凝固性坏死面积的影响及辐照后不同时间点靶区灰度值差异是否具有统计学意义,并计算辐照后不同时间点声像图上靶区回声增强区域面积与凝固性坏死面积的相关系数。HIFU联合微泡造影剂辐照组在接通蠕动泵后,通过灌流装置的三通开关向标本内注入不同浓度SonoVue超声微泡造影剂。通过机载超声选取有造影剂充填的子宫肌瘤平面进行HIFU辐照。辐照参数、观察指标、统计方法、辐照后处理同HIFU组。
结果
1.对经过肝素抗凝的离体人子宫肌瘤标本进行再灌注后, CDFI检查见肌瘤周边彩色信号填充,肌瘤内部偶见点状彩色信号,并见类似门静脉的带状等速PW频谱信号。表明肌瘤标本再灌注成功,已经将乳酸林格液泵入离体子宫肌瘤标本的肌瘤内部。
2. HIFU定点辐照标本,辐照后不同时间点靶区灰度值不同,辐照后即刻靶区灰度值最高,辐照后1min后靶区灰度值趋于稳定。辐照参数200w,辐照时间10s,辐照深度20mm,辐照结束1min时靶区灰度值为29.40±3.44。辐照后不同时间点,靶区回声增强区域面积呈下降趋势,不同时间点声像图上靶区回声增强区域面积与凝固性坏死面积具有很高的相关系数,辐照结束2min靶区回声增强区域面积与凝固性坏死面积相关系数最高,达0.99957。
3. HIFU联合微泡造影剂定点辐照标本时,辐照结束2min后靶区灰度值趋于稳定。辐照结束5min声像图上靶区回声增强区域面积与凝固性坏死面积面积相关系数最高,达0.92。
结论
1.建立离体子宫肌瘤标本再灌注模型,可以模拟在体子宫的血液循环状态,为子宫肿瘤的基础与临床研究提供接近在体环境的平台。
2.单纯HIFU辐照后,靶区灰度值在辐照结束1min趋于稳定,辐照结束2min靶区回声增强区域面积与凝固性坏死面积相关系数最高。
3. HIFU联合微泡造影剂辐照后,靶区灰度值需要比单纯HIFU辐照组更长的时间才能趋于稳定,靶区回声增强区域面积与凝固性坏死面积的相关系数较单纯HIFU辐照组降低。
4.辐照参数相同,微泡造影剂浓度越高,辐照后靶区灰度越高。
5.微泡造影剂需要达到一定浓度,才能达到增加靶区凝固性坏死面积的目的。
Backgrounds
Hysteromyoma is the most common benign tumor of female reproductive system, predilection in women of 30-50 years old, which is the main cause of menometrorrhagia and abnormal uterine bleeding(AUB), although most of patients suffered of it are absence of symptoms while a few appear vaginal bleeding, lump touched from abdomen, bladder oppression, torsion of pedicle et al. At present, the main therapies of hysteromyoma with symptoms include operation, drug treatment, small trauma treatment, High intensity focused ultrasound (HIFU) treatment, et al. HIFU has great potential for treatment of hysteromyoma for its advantages of no ionization radiation, noninvasive and retreatmentable.
In the process of HIFU radiance target area, Acoustic environment in tissue (AET) is an important factor that influence the accumulation of HIFU energy. In recent years, many researches suggested that ultrasonic contrast agent was an potentiator of improving HIFU therapeutic effect in a dose-dependent manner.
There is no good animal model of hysteromyoma, therefore, ex vivo circulation model of human hysteromyoma were constructed to investigate dynamic variances of gray scales in target area after perfused with SonVue in different dose and radiance by HIFU and observe the correlation between hyperechogenicity area and actual necrosis area at different time points after radiance and provide evidences for ultrasound real time monitoring the process of treating hysteromyoma by HIFU with SonVue.
Objective
Dynamic variances of gray scales in target area after human ex vivo hysteromyoma reperfused with SonVue in different dose and radiance by HIFU and the correlation between hyperechogenicity area and necrosis area at different time points after radiance were investigated to obtain the accurate radiance dose, exposure time and how to judge necrosis area by ultrasound.
Materials and methods
Subjects
18 complete fresh ex vivo uterus from patients suffered from hystero- myoma by total hysterectomy was obtained with the permission of patients and school Ethics Committee.
Equipments and drugs
BT-50E peristaltic pump (Chongqing Jieheng peristaltic pump limited company), rotation speed:0.1-50rpm, stream speed:0.001-18ml/min.
Philips IU22 color doppler ultrasonograph, frequency of probe: 3.5MHz.
JC200 HIFU device and gray measure software (Chongqing HAIFU (HIFU) Technology Co, Ltd).
SonoVue (Bracoo, Milan, Iatly ) was used as contrast agent in the study.
Heparin, Ringer lactate solution, Triphenyl tetrazolium chloride (TTC) staining solution
Methods
Ex vivo uteruses were pumped into heparinizated Ringer-Locke liquor from both uterine arteries by peristaltic pump immediately after obtained. Then the reperfusion information of uterus was detected by Color doppler flowing image (CDFI) and Pulse wave(PW) imaging. Grouping:Single HIFU radiance group, HIFU with SonoVue group
In single HIFU radiance group, ex vivo uterus connected with vitro perfusion device was put into container with de-aerated water. Then the peristaltic pump was opened and Ringer-Locke liquor was pumped into uterus from the peristaltic pump. Hysteromyoma planes without cystis degeneration were selected to radiate by HIFU in fixed points. Parameter: acoustic power:200w;depth:20mm;radiance mode:fixed-point radiance; exposure time:5s, 10s. Sonograms of target area were captured every time before HIFU radiance and after radiance for 0, 1, 2, 5min and gray scale and hyperechogenicity areas of target area sonograms were measured. Hysteromyoma was split and stained by TTC after HIFU radiance to search lesion area and measure necrosis area before paraffin section and HE staining were progressed. Influences of different dosage of HIFU on gray scale of target area and differences between gray scales of different time were analyzed by SAS8.1 statistical package and coefficient correlation between hyperechogenicity areas of target sonograms and necrosis areas was calculated.
In HIFU with SonoVue group, SonoVue of different concentrations was pumped into hysteromyoma from the 3-way stop cock of peristaltic pump after the pump was turned on. Hysteromyoma planes filled with SonoVue were selected by ultrasound and radiated by HIFU. Radiance parameters, observing indexes, statistical method, postdose treatment were similar to single HIFU group.
Results 1.After heparin anticoagulant ex vivo human hysteromyoma
specimens were reperfused, CDFI showed chroma signal filled the periphery of hysteromyoma and occasionally punctiform chroma signals were seen in the hysteromyoma and barred constant speed PW frequency spectrum signals like portal veins were seen. It indicated that reperfusion of hysteromyoma specimens was successful and Ringer lactate solution has been pumped into the inner of hysteromyoma.
2.Target gray scales were different at different time points after single radiance by HIFU in fixed. The gray scale values were highest 0min after radiance and trended to stable 1min after radiance. The target gray scale values was 29.40±3.44 1min after radiance by HIFU with an acoustic power of 200w, radiance depth of 20 mm and exposure time of 10s. Hyperechogenicity areas of target depressed in a time-dependent manner. The coefficient correlation between hyperechogenicity areas of target sonograms and necrosis areas was high and got highest 2min after radiance, the highest correlation coefficient was 0.99957.
3.In HIFU associated with SonoVue group, the gray scale values trended stable 2min after radiance. The coefficient correlation between hyperechogenicity areas of target sonograms and necrosis areas got highest at the time point 5min after radiance.
Conclusion
1.Reperfusion model of ex vivo hysteromyoma specimens was constructed to imitate the blood circulation of in vivo uterus and provide in vivo environments of basic and clinic research on hysteromyoma.
2.1min after single radiance by HIFU, the target gray scale values trended stable. The coefficient correlation between hyperechogenicity areas of target sonograms and necrosis areas was highest 2min after radiance.
3.After radiance by HIFU associated with SonoVue, the target gray scale values needs more time to trended stable and the coefficient correlation between hyperechogenicity areas of target sonograms and necrosis areas was lower.
4.The target gray scale values increases with the concentration of microbubble.
5.It needs enough concentration of microbubble to increase the curativeeffect of HIFU.
引文
[1] Evans P, Brunsell S. Uterine fibroid tumors:diagnosis and treatment [J]. Am Fam Physician. 2007, 75(10):1452-1453.
[2]张风仪,蒋泽清.子宫良性病变行子宫切除术卵巢的去留问题[J].中国实用妇科与产科杂志, 1999.15(12):712.
[3]刘朝晖,廖秦平,何键,等.81例妇科恶性肿瘤妇女术后性生活分析[J].实用妇产科杂志, 2000, 16(3):155.
[4] Dixon D, Parrott EC, Segars JH, et al. NIH congress: uterine leiomyoma research [J]. Fertil Steril.2006, 86(4):800-806.
[5] Spies JB, Spector A, Roth AR, et a1.Complication after uterine artery embolization for leiomyomas [J]. Obstet Gynecol, 2002, 100(5):873-880.
[6]常淑芳,伍烽,白晋,等.高强度聚焦超声定位损伤离体人子宫肌瘤的研究[J].中国超声医学杂志. 200l,17(2): 97～100.
[7]常淑芳,顾美礼,王智彪,等.高强度聚焦超声扫描损伤离体人子宫肌瘤的能效关系研究[J].重庆医科大学学报.2003, 28(5):562～570.
[8] Tempany CM, Stewart EA, McDannold N, et al.MR imaging-guided focused ultrasound surgery of uterine leiomyomas:a feasibility study [J].Radiology, 2003, 226(3):897-905.
[9] Stewart EA, Gedroyc WM, Tempany CM, et al.Focused ultrasound treatment of uterine fibroid tumors:safety and feasibility of a noninvasive thermoablative technique [J].Am J Obstet Gynecol, 2003, 189(1): 48-54.
[10] Hindley J, Gedroyc WM, Regan L, et al. MRI guidance of focused ultrasound therapy of uterine fibroids: early results [J].Am J Roentgenol, 2004, 183(6): 1713-1719.
[11] Stewart EA, Rabinovici J, Tempany CM, et al. Clinical outcomes of focused ultrasound surgery for the treatment of uterine fibroids [J].Fertil Steril, 2006, 85(1): 22-29.
[12]汪伟,刘文英,周清敏,等.高强度聚焦超声治疗症状性子宫肌瘤的初步临床研究[J].中华超声影像杂志.2002, 11(3):161～163.
[13]肖雁冰,王智彪,李发琪,等.高强度聚焦超声(HIFU)增效剂及研究现状[J].临床超声医学杂志2005, 7(1):39-41.
[14]熊树华,王智彪,陈文直,等.高强度聚焦超声增效作用的实验研究[J].中国超声医学杂志, 2003, 19(12):881-884.
[15] Miller D L, Thomas RM.Contrast-agent gas bodies enhance hemolysis induced by ithotripter shock waves and high-intensity focused ultrasound in whole blood [J].Ultrasound Med Biol, 1996, 22(8):1089-1095.
[16] Dalecki D, Raeman CH, Child SZ, et a1.Hemolysis in vivo from exposure to pulsed ultrasound [J].Ultrasound Med Biol, 1997, 23:307-313.
[17] Tran BC, Seo J, Hall TL, etal.Microbubble enhanced cavitation for noninvasive ultmsound surgery [J].IEEE Trans Ultmson Fen'oelectr Freq Control, 2003, 50 (10):1296-1304.
[18] Yu T, Wang G, Hu K, eta1.A microbubble agent improves the therapeutic efficiency of high intensity focused ultrasound:a rabbit kidney study [J]. UrolRes, 2004, 32 (1):14-19.
[19] Tachibana K, Tachibana S.Albumin micmbubble echo-contrast material as an eahancer for ultrasound accelerated thrombolysis [J] . Cireulation, 1995, 92 (5) 1148-1150.
[20] Fry, NT Sanghvi, RS Foster, et al.Ultrasound and microbubbles: their generation, detection and potential utilization in tissue and organ therapy-experimental [J] Ultrasound Med Biol. 1995 ;21 (9): 1227-1237.
[21] Chen W S, Lafon C, Vaezy S, etal.Mechanisms of lesion formation in high intensity focused ultrasound therapy. Ultrasonics Symposium, 2002. Proceedings. 2002. IEEE:398-407.
[22] Tojo S, Sakai T, Kanazawa S, et al. Perfusion of the isolated human uterus [J]. Acta Obstet Gynec Scand, 1972, 51(3): 265-273.
[23] Braun M, Zerbe H, Kietzmann M.Tissue concentration of intrauterine andintravenously administered amoxicillin in the isolated hemoperfused bovine uterus model and in healthy cows [J]. Berl Munch Tierarztl Wochenschr. 2009; 122(1-2):51-57.
[24] Br?nnstr?m M. Uterine transplantation: a future possibility to treat women with uterus factor infertility [J]. Minerva Med. 2007, 98(3):211-216.
[25] Bulletti C, Prefetto RA, Bazzocchi G, et al. Electromechanical activities of human uteri during extra-corporeal perfusion with ovarian steroids [J]. Hum Reprod, 1993, 8:1558-1563.
[26] Gail R, ter Haar.High-intensity focused ultrasound for the treatment of tumors [J]. Echocardiography.2001, 4(18):317-322.
[27] Yang R, Kopecky KK, Rescorla FJ, et al.Sonographic and focused ultrasound [J]. Invest Radiol.1993, 9(28):796-801.
[28]邹建中,陈文直,摩翠蓉,等.高强度聚焦超声治疗骨肉瘤的声像图表现[J].中华超声影像学杂志.2000, 9(2):695-696.
[29]邹建中,廖翠蓉,王志刚,等.正常肝脏声像图定量分析研究[J].中国医学影像技术[J]1995, 11(2);105-107.
[30]邹建中,龚晓波,贺雪梅,等.HIFU辐照离体组织靶区无灰度变化有坏死现象研究.临床超声医学杂志.2008, 10(9);581-583.
[31]刘丽萍,肖子文,肖雁冰,等.超声对高强度聚焦超声治疗的实时监控研究[J].中华超声影像学杂志. 2005, 14(3):222-224
[32] Hanajiri K, Maruyama T, Kaneko Y, et al.Microbubble-induced increase in ablation of liver tumors by high-intensity focused ultrasound.Hepatol Res [J].2006, 36 (4):308-314.
[33] Kaneko Y, Maruyama T, Takesgami K, etal.Use of a microbubble agent to increase the effects of high intensity focused ultrasound on liver tissue [J].Eur J Radiol. 2005, 15:1415-1420.
[34] Unger EC, Matsum TO, Matsumaga TO, et al.Therapeutic applications of micro- bubble [J].Eur J Radiol.2002, 42:160-168.
[1]刘付强,刘萍,邵丽琴,等.B超引导下自凝刀射频治疗子宫肌瘤204例分[J].中国实用妇科与产科杂志,2004,10(13):987-989.
[2]朱卫珍.自凝刀射频治疗子宫肌瘤160例临床分析[J].基层医学论坛, 2008, 12(20):583-584.
[3]陈湘云,罗启东.微波治疗脱入阴道的子宫粘膜下肌瘤[J].中华妇产科杂志1997,32(1):30.
[4] Cowan BD,Sewell PE, Howard JC, et al.Interventional magnetic resonance imaging cryotherapy of uterine fibroid tumors:preliminary observation[J]. Am J Obstet Gynecol, 2002,186(6):1183-1187.
[5]夏恩兰主编.妇科内镜学.第1版,北京:人民卫生出版社,2001:142.
[6]李励军,林力华,池慧娟等.腹腔镜下子宫肌瘤剥除术78例临床分析[J].安徽医药,2009,13(1):64.
[7] Saville LE.Laparoscopy and major retroperitoneal vascular injuries [J].Surgical Endoscopy1995.9(1O):1096-1100.
[8] Bishoff JL,Allaf ME,Kirkels W.et al.Laparoscopic bowel injury;incidence and clinical presentation[J].Journal of Urology. 1999, 16l(3):887-890.
[9] Heaston DK,Mineau DE,Brown BJ,et al.Transcatheter arterial embolization for control of persistent massive puerperal hemorrhage after bilateral surgical hypogastric artery ligation[J]. Am J Roentgenol, 1979, 133 (1):152-154.
[10] Ravina JH, Herbreteau D, Ciraru-Vigneron N, etal.Arterial embolization to treat uterine myomata.Lancet,1995,346(9):671-672.
[11] Ravina JH. Embolization of uterine myomata:methods, limits and future. XIIFIGO World Congress of Gynecologist and Obstetrics 2003.
[12]朱文群,谭可,李尚富等.高强度聚焦超声治疗子宫肌瘤疗效观察[J]中国现代医学杂志,2008,18(6):755-756.
[13] TEMPANY CM,STEWART EA,MCDANNOLD N,et al. MR imaging-guided focused ultrasound surgery of uterine leiomyomas:a feasibility study[J]. Radiology, 2003, 226:897-905.
[14]汪伟,文英周,清敏,等.高强度聚焦超声治疗症状性子宫肌瘤的初步临床研究[J].中华超声影像杂志,2002,11:161-163.
[15]柯庆华,周世琼,陈朝晖等高强度聚焦超声治疗72例子宫肌瘤临床分析[J]中华临床医师杂志(电子版),2007, 1(3):61-63.
[16]谢红宁,车艳玲,刘杰,等.超声引导下瘤内无水乙醇注射治疗子宫肌瘤的初步研究[J].中国实用妇科与产科杂志,2000,16(4):225-226.
[2]张风仪,蒋泽清.子宫良性病变行子宫切除术卵巢的去留问题[J].中国实用妇科与产科杂志, 1999.15(12):712.
[3]刘朝晖,廖秦平,何键,等.81例妇科恶性肿瘤妇女术后性生活分析[J].实用妇产科杂志, 2000, 16(3):155.
[4] Dixon D, Parrott EC, Segars JH, et al. NIH congress: uterine leiomyoma research [J]. Fertil Steril.2006, 86(4):800-806.
[5] Spies JB, Spector A, Roth AR, et a1.Complication after uterine artery embolization for leiomyomas [J]. Obstet Gynecol, 2002, 100(5):873-880.
[6]常淑芳,伍烽,白晋,等.高强度聚焦超声定位损伤离体人子宫肌瘤的研究[J].中国超声医学杂志. 200l,17(2): 97～100.
[7]常淑芳,顾美礼,王智彪,等.高强度聚焦超声扫描损伤离体人子宫肌瘤的能效关系研究[J].重庆医科大学学报.2003, 28(5):562～570.
[8] Tempany CM, Stewart EA, McDannold N, et al.MR imaging-guided focused ultrasound surgery of uterine leiomyomas:a feasibility study [J].Radiology, 2003, 226(3):897-905.
[9] Stewart EA, Gedroyc WM, Tempany CM, et al.Focused ultrasound treatment of uterine fibroid tumors:safety and feasibility of a noninvasive thermoablative technique [J].Am J Obstet Gynecol, 2003, 189(1): 48-54.
[10] Hindley J, Gedroyc WM, Regan L, et al. MRI guidance of focused ultrasound therapy of uterine fibroids: early results [J].Am J Roentgenol, 2004, 183(6): 1713-1719.
[11] Stewart EA, Rabinovici J, Tempany CM, et al. Clinical outcomes of focused ultrasound surgery for the treatment of uterine fibroids [J].Fertil Steril, 2006, 85(1): 22-29.
[12]汪伟,刘文英,周清敏,等.高强度聚焦超声治疗症状性子宫肌瘤的初步临床研究[J].中华超声影像杂志.2002, 11(3):161～163.
[13]肖雁冰,王智彪,李发琪,等.高强度聚焦超声(HIFU)增效剂及研究现状[J].临床超声医学杂志2005, 7(1):39-41.
[14]熊树华,王智彪,陈文直,等.高强度聚焦超声增效作用的实验研究[J].中国超声医学杂志, 2003, 19(12):881-884.
[15] Miller D L, Thomas RM.Contrast-agent gas bodies enhance hemolysis induced by ithotripter shock waves and high-intensity focused ultrasound in whole blood [J].Ultrasound Med Biol, 1996, 22(8):1089-1095.
[16] Dalecki D, Raeman CH, Child SZ, et a1.Hemolysis in vivo from exposure to pulsed ultrasound [J].Ultrasound Med Biol, 1997, 23:307-313.
[17] Tran BC, Seo J, Hall TL, etal.Microbubble enhanced cavitation for noninvasive ultmsound surgery [J].IEEE Trans Ultmson Fen'oelectr Freq Control, 2003, 50 (10):1296-1304.
[18] Yu T, Wang G, Hu K, eta1.A microbubble agent improves the therapeutic efficiency of high intensity focused ultrasound:a rabbit kidney study [J]. UrolRes, 2004, 32 (1):14-19.
[19] Tachibana K, Tachibana S.Albumin micmbubble echo-contrast material as an eahancer for ultrasound accelerated thrombolysis [J] . Cireulation, 1995, 92 (5) 1148-1150.
[20] Fry, NT Sanghvi, RS Foster, et al.Ultrasound and microbubbles: their generation, detection and potential utilization in tissue and organ therapy-experimental [J] Ultrasound Med Biol. 1995 ;21 (9): 1227-1237.
[21] Chen W S, Lafon C, Vaezy S, etal.Mechanisms of lesion formation in high intensity focused ultrasound therapy. Ultrasonics Symposium, 2002. Proceedings. 2002. IEEE:398-407.
[22] Tojo S, Sakai T, Kanazawa S, et al. Perfusion of the isolated human uterus [J]. Acta Obstet Gynec Scand, 1972, 51(3): 265-273.
[23] Braun M, Zerbe H, Kietzmann M.Tissue concentration of intrauterine andintravenously administered amoxicillin in the isolated hemoperfused bovine uterus model and in healthy cows [J]. Berl Munch Tierarztl Wochenschr. 2009; 122(1-2):51-57.
[24] Br?nnstr?m M. Uterine transplantation: a future possibility to treat women with uterus factor infertility [J]. Minerva Med. 2007, 98(3):211-216.
[25] Bulletti C, Prefetto RA, Bazzocchi G, et al. Electromechanical activities of human uteri during extra-corporeal perfusion with ovarian steroids [J]. Hum Reprod, 1993, 8:1558-1563.
[26] Gail R, ter Haar.High-intensity focused ultrasound for the treatment of tumors [J]. Echocardiography.2001, 4(18):317-322.
[27] Yang R, Kopecky KK, Rescorla FJ, et al.Sonographic and focused ultrasound [J]. Invest Radiol.1993, 9(28):796-801.
[28]邹建中,陈文直,摩翠蓉,等.高强度聚焦超声治疗骨肉瘤的声像图表现[J].中华超声影像学杂志.2000, 9(2):695-696.
[29]邹建中,廖翠蓉,王志刚,等.正常肝脏声像图定量分析研究[J].中国医学影像技术[J]1995, 11(2);105-107.
[30]邹建中,龚晓波,贺雪梅,等.HIFU辐照离体组织靶区无灰度变化有坏死现象研究.临床超声医学杂志.2008, 10(9);581-583.
[31]刘丽萍,肖子文,肖雁冰,等.超声对高强度聚焦超声治疗的实时监控研究[J].中华超声影像学杂志. 2005, 14(3):222-224
[32] Hanajiri K, Maruyama T, Kaneko Y, et al.Microbubble-induced increase in ablation of liver tumors by high-intensity focused ultrasound.Hepatol Res [J].2006, 36 (4):308-314.
[33] Kaneko Y, Maruyama T, Takesgami K, etal.Use of a microbubble agent to increase the effects of high intensity focused ultrasound on liver tissue [J].Eur J Radiol. 2005, 15:1415-1420.
[34] Unger EC, Matsum TO, Matsumaga TO, et al.Therapeutic applications of micro- bubble [J].Eur J Radiol.2002, 42:160-168.
[1]刘付强,刘萍,邵丽琴,等.B超引导下自凝刀射频治疗子宫肌瘤204例分[J].中国实用妇科与产科杂志,2004,10(13):987-989.
[2]朱卫珍.自凝刀射频治疗子宫肌瘤160例临床分析[J].基层医学论坛, 2008, 12(20):583-584.
[3]陈湘云,罗启东.微波治疗脱入阴道的子宫粘膜下肌瘤[J].中华妇产科杂志1997,32(1):30.
[4] Cowan BD,Sewell PE, Howard JC, et al.Interventional magnetic resonance imaging cryotherapy of uterine fibroid tumors:preliminary observation[J]. Am J Obstet Gynecol, 2002,186(6):1183-1187.
[5]夏恩兰主编.妇科内镜学.第1版,北京:人民卫生出版社,2001:142.
[6]李励军,林力华,池慧娟等.腹腔镜下子宫肌瘤剥除术78例临床分析[J].安徽医药,2009,13(1):64.
[7] Saville LE.Laparoscopy and major retroperitoneal vascular injuries [J].Surgical Endoscopy1995.9(1O):1096-1100.
[8] Bishoff JL,Allaf ME,Kirkels W.et al.Laparoscopic bowel injury;incidence and clinical presentation[J].Journal of Urology. 1999, 16l(3):887-890.
[9] Heaston DK,Mineau DE,Brown BJ,et al.Transcatheter arterial embolization for control of persistent massive puerperal hemorrhage after bilateral surgical hypogastric artery ligation[J]. Am J Roentgenol, 1979, 133 (1):152-154.
[10] Ravina JH, Herbreteau D, Ciraru-Vigneron N, etal.Arterial embolization to treat uterine myomata.Lancet,1995,346(9):671-672.
[11] Ravina JH. Embolization of uterine myomata:methods, limits and future. XIIFIGO World Congress of Gynecologist and Obstetrics 2003.
[12]朱文群,谭可,李尚富等.高强度聚焦超声治疗子宫肌瘤疗效观察[J]中国现代医学杂志,2008,18(6):755-756.
[13] TEMPANY CM,STEWART EA,MCDANNOLD N,et al. MR imaging-guided focused ultrasound surgery of uterine leiomyomas:a feasibility study[J]. Radiology, 2003, 226:897-905.
[14]汪伟,文英周,清敏,等.高强度聚焦超声治疗症状性子宫肌瘤的初步临床研究[J].中华超声影像杂志,2002,11:161-163.
[15]柯庆华,周世琼,陈朝晖等高强度聚焦超声治疗72例子宫肌瘤临床分析[J]中华临床医师杂志(电子版),2007, 1(3):61-63.
[16]谢红宁,车艳玲,刘杰,等.超声引导下瘤内无水乙醇注射治疗子宫肌瘤的初步研究[J].中国实用妇科与产科杂志,2000,16(4):225-226.
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