摘要
子宫肌瘤是女性生殖系统最常见的良性肿瘤。高强度聚焦超声通过聚焦超声束直接作用于瘤体后,造成肌瘤组织的凝固性坏死,从而阻止肌瘤的生长、使其缩小或消失,减轻或缓解肌瘤引起的症状或体征。超声消融子宫肌瘤首先要通过治疗计划系统(treatment planning system,TPS)制定治疗计划,TPS包括辅助治疗方法、超声换能器、3D适形扫描技术和治疗剂量投放等。治疗剂量学标准化是临床适宜技术推广的关键,超声消融剂量学研究就是考虑有效性、安全性和治疗效率的前提下,将超声消融生物学效应量化,确立消融体积与治疗剂量的关系即超声消融的能效关系。超声能量在生物组织中沉积形成生物学焦域(biological focal region,BFR),通过BFR的移动实现肿瘤的热消融。BFR是可以通过理论进行预测的。能效因子(energy efficiency factor,EEF)为超声与生物组织相互作用的量化指标,对同一超声换能器,影响因素包括:靶区深面到皮肤表面的距离、靶组织的结构和功能状态、组织声环境、扫描方式、辅助治疗等。本研究旨在总结超声消融子宫肌瘤的剂量学数据,建立EEF剂量模型,用以临床预测治疗一定体积的肿瘤所需的治疗剂量。为超声消融治疗子宫肌瘤的TPS的制定和优化提供剂量学基础。
目的
通过核磁共振影像学的超声消融结果,在安全性与有效性的基础上,总结超声消融子宫肌瘤的剂量学数据,建立EEF剂量模型,用以临床预测治疗一定体积的肿瘤所需的治疗剂量。为超声消融治疗子宫肌瘤的TPS的制定和优化提供剂量学基础。
资料与方法
1.研究对象2006年12月至2009年1月,对重庆医科大学附属第一医院子宫肌瘤患者142例,年龄21～51岁,平均38.8±5.6岁。
入选标准(1)临床诊断的子宫肌瘤患者经超声检查及核磁共振成像进一步确认;(2)绝经前妇女;(3)有子宫肌瘤的相关症状或心理影响渴望得到治疗,拒绝手术,要求保留子宫;(4)治疗系统机载超声可以显示的肌瘤,肌瘤最大径>1.5cm,肌壁间肌瘤,非带蒂的浆膜下和粘膜下子宫肌瘤;(5)能准确地交流治疗过程中的感受;(6)同意接受镇静镇痛下超声消融治疗。
排除标准(1)宫颈肌瘤;(2)合并妇科其他疾病者(如阴道炎、盆腔炎、肿瘤等);(3)月经期妇女、孕妇(妊娠试验阳性)及哺乳期妇女;(4)结缔组织病或接受过腹部大剂量放疗者;(5)未控制的糖尿病及肝肾功能异常者;(6)严重心、脑血管疾患:不稳定性心绞痛、半年内有心肌梗塞、心律失常需用药物控制者、严重高血压及心力衰竭者;(7)半年内有脑梗塞、脑出血者;(8)有核磁共振及钆剂过敏的患者。
2.研究设备
JC型聚焦超声肿瘤治疗系统重庆海扶?(HIFU)技术有限公司研制,治疗超声换能器中心组合有超声显像探头。治疗超声换能器频率0.8 MHz,功率0 W～400 W可调,物理学焦域为1.5 mm×1.5 mm×10 mm ,循环脱气水(< 3 ppm )耦合。机载显像超声参数:频率3.5MHz.
核磁共振成像系统Magnetom Symphony 1.5T MR Tim系统( Siemens, Germany )。序列设置: T1加权自旋回波序列(TR 502ms、TE 12ms,层厚4 mm,层距1 mm);T2加权自旋回波序列(TR 4,000ms、TE 98ms,层厚6 mm,层距0.875 mm);增强T1加权梯度回波序列(TR 5.13ms,TE 2.37ms,层厚2.5mm,层距0.5 mm),线圈:Body Matrx/large Loop coil。
实验用药品对比造影剂钆双胺注射液(欧乃影gadodiamid)0.5 mmol / ml,剂量为15～20 ml。
3.研究方法
3.1治疗前影像学评估
入选病人经过盆腔超声和核磁共振影像学评估。子宫肌瘤CDFI血供分级标准:0级:肌瘤内未见血流信号;Ⅰ级:肌瘤内少量血流,可见1～2处点状血流;Ⅱ级:肌瘤内中量血流,可见1条主要血管,其长度超过肌瘤的半径或见2～3条小血管;Ⅲ级:肌瘤内丰富血流,可见4条以上血管或血管相互连通;Ⅳ级:肌瘤周边血管呈网状包绕整个肌瘤(抱球征),并有树枝状多个分支伸入肌瘤内部,血管相互交织成网状,或血管直径达3 mm以上。
子宫肌瘤T2WI信号强度分类标准:Ⅰ类,低信号:肌瘤信号低于或等于骨骼肌;Ⅱ类,等信号:肌瘤信号低于或等于子宫肌层,高于骨骼肌;Ⅲ类,高低混杂信号:肌瘤信号显示为高于子宫肌层与等低于子宫肌层信号混杂;Ⅳ类,高信号:肌瘤信号均匀高于子宫平滑肌或以高信号为主的混杂信号。
3.2超声消融
治疗前准备:①肠道准备:治疗前日导泻,治疗当天早晨清洁灌肠;②皮肤准备:下腹部备皮,脱脂、脱气;③膀胱准备:治疗前留置导尿管。
镇静镇痛的实施:枸橼酸芬太尼和咪唑安定联合应用,控制镇静深度达到ramsy 3～4级,镇痛效果要求患者疼痛评分小于4分为佳。超声消融治疗:①消融范围:为瘤内消融,焦点范围:距子宫内膜15 mm;距肌瘤假包膜5 mm;距近骶骨肌瘤深面15 mm;距近腹壁肌瘤浅面10 mm;治疗层距:层距5 mm;点距5 mm;②消融过程:病人俯卧于治疗床上,下腹部前壁置于脱气水中的聚焦超声换能器上方,治疗前机载超声显像定位以确保有安全的声通道,避免损伤肠道等非靶区组织;根据病人对声照射引起的感觉反应和超声显像的实时灰度变化调整治疗剂量,点扫描和线段扫描结合完成治疗,靶区出现团块状高回声改变或整体灰度明显增加为治疗终点。治疗后病人在观察室休息两小时,可由家属陪同离院回家。
观察指标:①治疗剂量参数:治疗时间、照射时间、治疗功率;②可接受度:疼痛评分;③安全性指标:不良反应。3.3治疗后影像学评价
治疗后0～3月内,行增强MRI检查,MR成像参数及扫描序列同治疗前。
3.4治疗并发症评价标准依据国际介入放射治疗协会制定的SIR分类法。
3.5剂量学分析方法剂量用能效因子(energy effect factor,EEF)表示: EEF=η. Pt / V (J/mm3)η表示聚焦系数(= 0.7),P为声功率(W),t为照射时间,V为无灌注区体积(non-perfused volume,NPV)(mm3),EEF为单位体积消融所需能量(J/mm3)。
3.6统计学方法采用SPSS13.0统计软件,进行统计学分析。
结果
1.消融结果142例病人(168个肌瘤)接受一次性超声消融治疗。平均径线4.4±1.6 (1.5～12.3)cm,平均体积62.57±85.87 (1.9～747.1)cm3。治疗时间平均2.7±1.3小时(14～471分钟),照射时间33±19分钟(2～79分钟)。体积消融率84.70±22.96%(有增强MRI结果的165个肌瘤)。
2.治疗耐受性评价疼痛评分0～4分占研究对象的85 %。
3.并发症和副反应33.10%(47/142)病人发生不同程度的不良反应,94.92%属SIR A-B类并发症,无介入放射协会的SIR D-F类并发症发生。B类并发症2例,1例治疗后24小时内下腹部疼痛,要求止痛治疗;1例病人腹股沟区皮肤浅Ⅱ°烧伤,给予局部换药处理;SIR C类并发症包括3例病人,需要延长住院时间,2例病人治疗后1天出现体温升高超过38.5℃,经治疗48小时内恢复正常;1例病人尿潴留,留置尿管,48小时内恢复自行排尿。
4.剂量学研究结果腹壁组织(厚度小于50mm)与子宫肌瘤超声消融所需剂量之间缺乏相关性;子宫肌瘤的大小、位置、血供分级、T2WI信号强度以及声通道子宫肌壁厚度与单位组织超声消融所需剂量有线性相关关系。
结论
1.镇静镇痛下超声消融子宫肌瘤可以达到充分消融。
2.能效因子(EEF)直接反映子宫肌瘤超声消融能效关系的规律性,EEF可作为子宫肌瘤剂量学研究的量化指标。
3.在临床可获得数据中,子宫肌瘤的位置、大小、血供分级和T2WI信号强度可作为预测消融剂量的指标。
4.子宫肌瘤超声消融剂量模型:
(1)超声、MRI联合应用预测剂量模型: [χ1 =肌瘤位置(前壁=1,后壁=2),χ2 =肌瘤直径(cm),χ3 =肌瘤Adler血供分级+1,χ4 =肌瘤T2WI信号强度]
(2)超声影像特征预测模型: [χ1 =肌瘤位置(前壁=1,后壁=2),χ2 =肌瘤直径(cm),χ3 =肌瘤Adler血供分级+1 ]
(3) MRI影像特征预测剂量模型: [χ1 =肌瘤位置(前壁=1,后壁=2),χ2 =肌瘤直径(cm),χ3 =肌瘤T2WI信号强度] y =3.052+6.095·x1 -0.383·x2+2.827·x3+5.135?x4 y =6.202+5.557·x1 -0.180·x2+2.144·x3 y =8.759+6.816·x1 -0.332·x2+4.881·x3
Uterine fibroids are the most common tumor in the female reproductive system. High-intensity focused ultrasound (HIFU) induce the tissue coagulative necrosis by non-invasive focusing in areas of tumors. It results in tumor shrinkage and symptomatic relief and solution with uterus sparing。The Treatment Planning System (TPS) is the important unit in the HIFU ablation , which comprise with adjunctive treat methods, ultrasound transducer (frequency and focal length),3D conformal scanning regiem and dosimetry. Ultrasound ablation dosimetry for clinical treatment should base on the effectiveness, safety and efficiency. The dosimetry study is to clarify the relationship between ultrasound energy and treatment efficiency,defined ablation region and dosage of ultrasound。Ultrasound energy deposite in the tissue and induce biological focal region (BFR)。Tumor was thermal ablated by BFR moving,which is predictable theoretically. Energy efficiency factor (EEF) is a tool to quantitate the interaction of ultrasound energy and biological tissue. Apart from the acoustic characteristic of transducer, EEF be influenced with the distance from tumor depth to the skin surface,histological structure and functional condition, tissue acoustic environment, scanning mode and adjunctive therapy methods, etc.
This study construct the dosage equations by analyzing the dosimetry data from the ultrasound ablation for the treatment of uterine fibroids, aimed to predict dosage according to the treat volume and to provide a basis for TPS clinical application.
Objective
Based on the results of MR imaging, to establish multi linear regression model by analyzing the dosimetry data from the ultrasound ablation for the treatment of uterine fibroids, considering the safety and efficacy. Materials and Methods
1. Subjects
From December 2006 to January 2009, 142 patients, aged 21 to 51 years old with a mean of 38.8 years old, were recruited in this prospective study.
Inclusion criteria: (1)The diagnosis was confirmed by ultrasonography and magnetic resonance imaging (MRI); (2) Premenopausal women; (3) Patients desire to be treated for symptoms or psychological aims, refused to surgery treatment; (4)Uterine fibroids, maximum diameter exceed 1.5cm, is visible on ultrasound guided HIFU system; (5) Patients who were able to communicate with the nurse or physician for their sensations during the procedure; (6) A detailed written description of focused ultrasound ablation was provided to all patients, and written informed consent was obtained from each patient.
Exclusion criteria: (1) Cervical fibroids; (2) Patients with gynecological disorder other than uterine fibroids ( inc. vaginitis, pelvic inflammatory disease, tumors, etc); (3) Women in menstrual period, pregnancy (HCG examination shows positive) or lactation; (4) Patients received radiotherapy with high-dose on lower abdomen or with connective tissue disease; (5) Patients with diabetes not controlled or on dialysis; (6) Patients with unstable cardiac status (inc. unstable angina pectoris on medication; documented myocardial infarction within six months of protocol entry; congestive heart failure requiring medication (other than diuretic); currently taking anti-arrhythmic drugs; severe hypertension (diastolic BP > 100 mmHg on medication); presence of cardiac pacemaker); (7) Patient has severe cerebrovascular disease (multiple CVA or CVA within six months); (8) Contraindication to MRI and sensitivity to gadolinium-DTPA.
2. Equipment
JC Focused Ultrasound Tumor Therapeutic System [developed by Chongqing Haifu? (HIFU) Tech Co., Ltd., Chongqing, China], a 3.5 MHz B-mode ultrasonography (US) probe is integrated within the unit for real-time US monitoring. Therapeutic US transducer deliver the power with 0W-400W, work at a frequency of 0.8 MHz. The frequency of ultrasonography (US) is 3.5 MHz.
Magnetom Symphony 1.5T MR Tim unit ( Siemens, Germany ). Body Matrx/large Loop coil. Gd-DTPA: Gadodiamid 0.5 mmol / ml (15-20 ml).
3. Methods
3.1Pre-treatment image evaluation A clinical imaging evaluation, including pelvic US and MRI, were completed before HIFU ablation. The vascular distribution of uterine fibroids classified to grade 0, gradeⅠ, gradeⅡ, gradeⅢ, gradeⅣ, according Adler grading methods. The T2WI sign intensity of uterine fibroids classified to type 1, low intensity; type 2, intermediate intensity; type 3, heterogeneous intensity; type 4, high intensity.
3.2 Ultrasound ablation Preparation:①Bowel preparation: purgation 1 day before procedure, cleaning enema at operation day morning;②Skin preparation: shaved the hairs, degreased and degased on the skin in the acoustic pathway;③Bladder preparation: insert and place the urinary catheter. Conscious-sedation: fentanyl and Midazolam for ramsy grade 3-4 analgesic to control the pain scale less than 4 scores.
Protocal of HIFU ablation:①Treat region limited within pseudo-capsule: 15 mm distance to endometria; 5 mm distance to pseudo-capsule; 15 mm distance to depth of fibroids near to sacrum; 10 mm distance to front surface of fibroids near to abdominal wall; slice-slice distance: 5 mm; point-point distance: 5 mm;②HIFU ablation procedure: patient lies down in the prone position on the treatment system with the anterior abdominal wall placed above the transducer in a sealed tank of degassed water. Real-time guiding ultrasonography was used to determine the location of fibroid and avoid to damage the non-targeted structures, such as the intestinal tract. The therapeutic energy was regulated based on the tolerance of patients and the feedback from the gray scale in ultrasonography. Sonications were exposured by point scanning and line scanning. Hyperechoic regions appear on the ultrasound image and covered the planning treatment region. After the procedure, all of the patients were observed in a recovery room for 2 hours before they are discharged .
Document data:①Dose parameters: treatment time, sonication time and ultrasonic power;②Acceptability: pain scoring for sensation during sonications;③Safety evaluation: side effects and complications.
3.3 Post-treatment image evaluation Enhanced MR imaging was performed 0-3 months after the treatment for each patient according to imaging parameter pre-treatment used.
3.4 Complications SIR grading system was used to categorize the severity.
3.5 Dosimetry analysis
Energy effect factor(EEF) was used as quantitative unit for dose. The equation as follows: ηis focus coefficient ( = 0.7); P is ultrasonic power (W); t is sonication time; V is non-perfusion volume (NPV) (mm3); EEF is dosage for a unit tissue ablation.
3.6 Statistical Analysis SPSS 13.0 Statistical software package and Microsoft Excel statistical function was used to analyze the data. Statistical significance is defined as a P value less than 0.05.
Results
1. Ablation technical results One hundred forty-two patients with 168 fibroids underwent single HIFU ablation procedure. The mean size of uterine fibroids was 4.4±1.6 (range: 1.5 to 12.3) cm and mean volume was 62.57±85.87 (range: 1.9 to 747.1) cm3. The mean treatment time was 2.7±1.3 hours (range: 14 to 471) mins and mean sonication time was 33±19 (range: 2 to 79) mins. Overall, follow-up MR imaging was obtained in 139 patients with 165 fibroids within 3 months after treatment. The mean ratio of NPV is 84.70±22.96%.
2. Acceptability
Eight-five patients tolerate the procedure well with 0-4 pain scores.
3. Complications
Forty-seven (33.10%) patients experienced side-effects and complications. 94.92% events are SIR classification A-B. No SIR classification D-F events occurred. One woman experienced skin burnⅡgrade in the groin area, typical protection was administrated. Two women experienced axillary temperature measurement more than 38.5℃, recovery in 48 hours after treatment. One woman underwent catheterization for urinary retention, resolved within 48 hours.
4. Results of dosimetry
The ultrasonic dose are linear correlation with the size, location, and vascular distribution and T2WI sign intensity of uterine fibroids. There is no correlation relationship between ultrasonic ablation dose and abdominal wall thickness.
Conclusions
1. Sufficient treat volume for uterine fibroids ablation is feasibility using fentanyl and Midazolam for conscious-sedation.
2. Energy efficiency factor (EEF), a direct reflection of relationship between ultrasound energy and ablation efficacy for uterine fibroids. It could be used as a quantitative measurement.
3. In the clinical practice, the size, location, vascular distribution and T2WI sign intensity of uterine fibroids could be used as measures for prediction of ultrasound ablation dose.
4. Prediction equation of ultrasound ablation dose for uterine fibroids as follows:
(1) Prediction equation based on CDFI and MRI images (χ1 is the location,χ2 is the size,χ3 is 1 plus Adler classification of vascular distribution andχ4 is T2WI sign intensity of uterine fibroids.)
(2) Prediction equation based on CDFI images (χ1 is the location,χ2 is the size andχ3 is 1 plus Adler classification of vascular distribution of uterine fibroids.)
(3) Prediction equation based on MRI images ?y? =3.052+6.095?x1 ?0.383?x2+2.827?x3+5.135?x4?y? =6.202+5.557?x1 ?0.180?x2+2.144?x3?y? =8.759+6.816?x1 ?0.332?x2+4.881?x3 (χ1 is the location,χ2 is the size andχ3 is T2WI sign intensity of uterine fibroids.)
引文
[1] Ling F W, Duff P. Obstetrics and Gynecology Principles for Practice[M].New York:McGraw Hill,1996: 1158.
[2] Kennedy JE. High-intensity focused ultrasound in the treatment of solid tumours[J].Nat Rev Cancer.2005,5(4): 321-327.
[3]汪伟,刘文英,周洁敏等.高强度聚焦超声治疗症状性子宫肌瘤的初步临床研究[J].中华超声影像学杂志.2002,11(3): 161-163.
[4] Wang ZB, Bai J, Li FQ, et a1. Study of a“biological focal region of high-intensity focused ultrasound[J].Ultrasound Med Biol. 2003, 29(5): l749-1754].
[5]冯若,张樯,李发琪等.高强聚焦超声辐照剂量与组织热坏死体元之间的关系[J].自然科学进展.2004,14(7): 819-821.
[6]熊正爱,杜永洪,邹建中等.高强度聚焦超声照射猴子宫对卵巢功能的影响研究[J].中华超声影像学杂志.2003,12(11): 687-689.
[7] Rabkin BA, Zderic V, Vaezy S. Hyperechoic ultrasound images of HIFU therapy: involvement of cavitation[J].Ultrasound Med Biol.2005,31(7): 947-956.
[8]高强度聚焦超声肿瘤治疗系统临床应用指南(试行) [J].中华医学杂志.2005,85(l2): 796-797。
[9]周英,周永健,聂玉强,等.高强度聚焦超声治疗子宫肌瘤的超声图像研究[J].广州医药.2005,36(3): 48-50.
[10] Goldberg SN, Grassi CJ, Cardella JF, et al. Image-guided tumor ablation: standardization of terminology and reporting criteria[J]. Radiology. 2005, 235(3): 728-739.
[11] Wu F, Wang ZB, Chen WZ, et al. Extracorporeal focused ultrasound surgery for treatment of human solid carcinomas: Early Chinese clinical experience. Ultrasound. Med Biol, 2004, 30(2): 245-260.
[12]周永昌,郭万学主编.超声医学[M].北京:科学技术文献出版社. 2006, p1026-1027.
[13]顾美礼,伍烽,王智彪等.高强度聚焦超声治疗子宫肌瘤的剂量学研究[J].中华物理医学与康复杂志[J].2003, 25(8): 454-457.
[14] Meaney PM, Cahill MD, ter Haar GR. The intensity dependence of lesion position shift during focused ultrasound surgery[J]. Ultrasound Med Biol. 2000,26(3): 441-450.
[15] Wang ZB, Bai J, Li FQ, et a1. Study of a“biological focal region of high-intensity focused ultrasound[J]. Ultrasound Med Biol.2003,29(5): 749-754.
[16]李发琪,王智彪,杜永洪等.高强度聚焦超声“切除”组织的剂量学研究[J].生物医学工程学杂志.2006,23(4): 839-843.
[1]白晋,李发琪,杜永洪等.高强度聚焦超声形成生物学焦域的剂量学研究.第三军医大学学报[J].2004, 26(15): 1378-1380.
[2]周永昌,郭万学主编.超声医学[M].北京:科学技术文献出版社. 2006, p1026-1027.
[3] Wang ZB,Bai J,Li FQ, et a1.Study of a“biological focal region of high-intensity focused ultrasound[J]. Ultrasound Med Biol,2003,29:l749-1754.
[4]李发琪,白晋,王智彪等.HIFU在牛肝组织中的传播衰减研究[J].生物医学工程学杂志[J].2003, 20(4): 675-678.
[5]李发琪,王智彪,杜永洪等.高强度聚焦超声“切除"组织的剂量学研究[J].生物医学工程学杂志[J].2006, 23(4): 839-843.
[6]王智彪,李发琪,冯若主编.治疗超声原理与应用[M].南京:南京大学出版社.2008, p112-126.
[7] Baker KG, Robertson VJ, Duck FA. A review of therapeutic ultrasound: biophysical effects[J]. Phys Ther. 2001.81(7):1351-1358.
[8]杜功焕,朱哲民,龚秀芬等.声学基础[M].南京:南京大学出版社.2001, p472.
[9] Chen L, ter Haar G, Hill CR. Influence of ablated tissue on the formation of high-intensity focused ultrasound lesions[J]. Ultrasound Med Biol. 1997;23(6):921-931.
[10] Wu F, Chen WZ, Bai J et al. Pathological changes in human malignant carcinoma treated with high-intensity focused ultrasound[J]. Ultrasound Med Biol. 2001, 27(8): 1099-1106.
[11] 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.
[12] McDannold N, Tempany CM, Fennessy FM, et al. Uterine leiomyomas: MR imaging-based thermometry and thermal dosimetry during focused ultrasound thermal ablation[J]. Radiology. 2006. 240(1):263-72.
[1] Meaney PM, Cahill MD, ter Haar GR. The intensity dependence of lesion position shift during focused ultrasound surgery[J]. Ultrasound Med Biol. 2000,26(3):441-450.
[2] Wang ZB, Bai J, Li FQ, et a1. Study of a“biological focal region of high-intensity focused ultrasound[J]. Ultrasound Med Biol. 2003,29: l749-1754.
[3]周永昌,郭万学主编.超声医学[M].北京:科学技术文献出版社. 2006, p1026-1027.
[4]曹泽毅主编.中华妇产科学. [M].北京:人民卫生出版社. 2004,2087-2091.
[5]王智彪,李发琪,冯若主编.治疗超声原理与应用[M].南京:南京大学出版社.2008, p121.
[6] Schwartz LB, Zawin M, Carcangiu ML, et al. Does pelvic magnetic resonance imaging differentiate among the histologic subtypes of uterine leiomyomata? [J] Fertil Steril. 1998, 70(3): 580-587.
[7] Zawin M, McCarthy S, Scoutt LM, et al. High-field MRI and US evaluation of the pelvis in women with leiomyomas[J]. Magn Reson Imaging. 1990, 8(4): 371-376.
[8] Vitiello D, McCarthy S. Diagnostic imaging of myomas[J]. Obstet Gynecol Clin North Am. 2006, 33(1): 85-95.
[9] Fleischer AC. Color Doppler sonography of uterine disorders[J]. Ultrasound Q. 2003, 19(4):179-189.
[10]张彩虹.子宫肌瘤的彩超诊断与手术病理对照分析[J].中国超声诊断杂志.2003, 4(4): 309-310.
[11] Adler DD, Carson PL, Rubin JM, et al. Doppler ultrasound color flow imaging in the study of breast cancer: preliminary findings[J]. Ultrasound Med Biol. 1990, 16(6): 553-9.
[12]孙立群.超声评价HIFU治疗子宫肌瘤相关血流灌注变化研究[D].重庆医科大学. 2008.
[13] Funaki K, Fukunishi H, Funaki T, et al. Magnetic resonance-guided focused ultrasound surgery for uterine fibroids: relationship between the therapeutic effects and signal intensity of preexisting T2-weighted magnetic resonance images[J]. Am J Obstet Gynecol. 2007, 196(2): 184.e1-6.
[14]李发琪,杜永洪,王智彪等. HIFU体外块“切除”动物肝脏、肾脏和肌肉的剂量研究[J].中国超声医学杂志. 2005, 21(4): 252-255.
[15] Schwartz LB, Zawin M, Carcangiu ML, et al. Does pelvic magnetic resonance imaging differentiate among the histologic subtypes of uterine leiomyomata? [J]. Fertil Steril. 1998,70(3): 580-587.
[16] Moghadam R, Lathi RB, Shahmohamady B, et al. Predictive value of magnetic resonance imaging in differentiating between leiomyoma and adenomyosis[J]. JSLS. 2006, 10(2): 216-219.
[17] Chen L, ter Haar G, Hill CR. Influence of ablated tissue on the formation of high-intensity focused ultrasound lesions[J]. Ultrasound Med Biol. 1997, 23(6): 921-931.
[18]李发琪,王智彪,杜永洪等.高强度聚焦超声“切除"组织的剂量学研究[J].生物医学工程学杂志.2006, 23(4): 839-843.
[19] Wu F, Chen WZ, Bai J et al. Pathological changes in human malignant carcinoma treated with high-intensity focused ultrasound[J]. Ultrasound Med Biol. 2001, 27(8): 1099-1106.
[20] 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.
[21] McDannold N, Tempany CM, Fennessy FM, et al. Uterine leiomyomas: MR imaging-based thermometry and thermal dosimetry during focused ultrasound thermal ablation[J]. Radiology. 2006, 240(1): 263-272.
[22] Walocha JA, Litwin JA, Miodoński AJ. Vascular system of intramural leiomyomata revealed by corrosion casting and scanning electron microscopy[J]. Hum Reprod. 2003, 18(5): 1088-1093.
[23] Pelage JP, Cazejust J, Pluot E, et al.Uterine Fibroid Vascularization and Clinical Relevance to Uterine Fibroid Embolization[J].Radiographics. 2005, 25 Suppl 1: S99-117.
[24] Kennedy JE. High-intensity focused ultrasound in the treatment of solid tumours[J]. Nat Rev Cancer. 2005, 5(4): 321-327.
[25] Goldberg SN, Grassi CJ, Cardella JF, et al. Image-guided tumor ablation: standardization of terminology and reporting criteria[J]. Radiology. 2005, 235(3): 728-739.
[26] Goto A, Takeuchi S, Sugimura K, et al. Usefulness of Gd-DTPA contrast-enhanced dynamic MRI and serum determination of LDH and its isozymes in the differential diagnosis of leiomyosarcoma from degenerated leiomyoma of the uterus[J]. Int J Gynecol Cancer. 2002, 12(4): 354-361.
[27] Yamashita Y, Torashima M, Takahashi M, et al. Hyperintense uterine leiomyoma at T2-weighted MR imaging: differentiation with dynamic enhanced MR imaging and clinical implications[J]. Radiology.1993, 189(3): 721-725.
[1]周永昌,郭万学主编.超声医学[M].科学技术出版社. 2006, p1026-1027.
[2]张文彬,董伟主编.SPSS统计分析高级教程[M].高等教育出版社.2004, p 91-117.
[1] Ling F W, Duff P.Obstetrics and Gynecology Principles for Practice[M].New York:McGraw Hill. 1996: 1158.
[2] Kennedy JE. High-intensity focused ultrasound in the treatment of solid tumours.Nat Rev Cancer[J]. 2005, 5(4): 321-327.
[3]汪伟,刘文英,周洁敏等.高强度聚焦超声治疗症状性子宫肌瘤的初步临床研究[J].中华超声影像学杂志. 2002,11(3): 161-163.
[4] Chapman A, ter Haar G.Thermal ablation of uterine fibroids using MR-guided focused ultrasound-a truly non-invasive treatment modality. Eur Radiol[J].2007,17(10): 2505-2511.
[5]王智彪.聚焦超声治疗技术在妇科领域的研究与应用[J].中华妇产科杂志.2006,41(9): 638-640.
[6] Leslie TA, Kennedy JE. High intensity focused ultrasound in the treatment of abdominal and gynaecological diseases[J].Int J Hyperthermia. 2007,23(2): 173-182.
[7] Wang ZB, Bai J,Li FQ, ET a1.Study of a“biological focal region of high-intensity focused ultrasound[J].Ultrasound Med Biol. 2003, 29(5): 749-754.
[8]冯若,张樯,李发琪等.高强聚焦超声辐照剂量与组织热坏死体元之间的关系[J].自然科学进展. 2004,14(7): 819-821.
[9]熊正爱,杜永洪,邹建中等.高强度聚焦超声照射猴子宫对卵巢功能的影响研究[J].中华超声影像学杂志.2003,12(11): 687-689.
[10]Rabkin BA, Zderic V, Vaezy S.Hyperechoic ultrasound images of HIFU therapy: involvement of cavitation[J].Ultrasound Med Biol. 2005,31(7): 947–956.
[11]高强度聚焦超声肿瘤治疗系统临床应用指南(试行)[J].中华医学杂志. 2005, 85(l2): 796-797.
[12]周英,周永健,聂玉强等.高强度聚焦超声治疗子宫肌瘤的超声图像研究[J].广州医药. 2005,36(3): 48-50.
[13]Clement GT, Hynynen K. Ultrasound phase-contrast transmission imaging oflocalized thermal variation and the identification of fat/tissue boundaries[J]. Phys Med Biol. 2005,50 (7): 1585–1600.
[14]Curiel L, Souchon R, Rouviere O, et al. Elastography for the follow-up of high-intensity focused ultrasound prostate cancer treatment: initial comparison with MRI[J]. Ultrasound Med Biol.2005, 31(11): 1461–1468.
[15]Konofagou E, Thierman J, Hynynen K. The use of ultrasound stimulated acoustic emission in the monitoring of modulus changes with temperature[J]. Ultrasonics. 2003,41(5): 337–345.
[16]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.
[17]McDannold N, Tempany CM, Fennessy FM, et al. Uterine leiomyomas: MR imaging-based thermometry and thermal dosimetry during focused ultrasound thermal ablation[J]. Radiology. 2006,240(1): 263-272.
[18]Funaki K, Fukunishi H, Funaki T, et al. Magnetic resonance-guided focused ultrasound surgery for uterine fibroids: relationship between the therapeutic effects and signal intensity of preexisting T2-weighted magnetic resonance images[J].Am J Obstet Gynecol.2007,196(2):184.e1-6.
[19]顾美礼,伍烽,王智彪等.高强度聚焦超声治疗子宫肌瘤的剂量学研究[J].中华物理医学与康复杂志.2003,25(8): 454-457.
[20]李发琪,王智彪,杜永洪等.高强度聚焦超声“切除”组织的剂量学研究[J].生物医学工程学杂志. 2006,23(4): 839-843.
[21]Yu T, Fan X, Xiong S, et al. Microbubbles assist goat liver ablation by high intensity focused ultrasound[J]. Eur Radiol. 2006,16(7): 1557-1563.
[22]Di Lieto A, De Falco M, Staibano S, et al. Effects of gonadotropin releasing hormone agonists on uterine volume and vasculature and on the immunohistochemical expression of basic fibroblast growth factor (bFGF) in uterine leiomyomas[J]. Int J Gynecol Pathol. 2003,22: 353–358.
[23]Smart OC, Hindley JT, Regan L, et al.Magnetic resonance guided focused ultrasound surgery of uterine fibroids--the tissue effects of GnRH agonist pre-treatment[J].Eur J Radiol.2006,59(2):163-167.
[1] Ling F W, Duff P.Obstetrics and Gynecology Principles for Practice[M].New York:McGraw Hill.1996: 1158.
[2]张嵘,梁碧玲,付加平等.子宫肌瘤的MRI表现与临床病理相关性研究[J].中华放射学杂志. 2003, 37(10): 954.
[3] Schwartz LB, Zawin M, Carcangiu ML, et al. Does pelvic magnetic resonance imaging differentiate among the histologic subtypes of uterine leiomyomata? [J]. Fertil Steril. 1998, 70 (3) : 580.
[4]温海燕,陈文直,王智彪.子宫肌瘤的MRI影像特性研究[J].第三军医大学学报.2008, 30(12): 1176-1178.
[5] Goldberg SN, Ahmed M. Minimally invasive image-guided therapies for hepatocellular carcinoma[J]. J Clin Gastroenterol. 2002, 35(5-S2) : 115.
[6] Swe TT, Onitsuka H, Kawamoto K, et al. Uterine leiomyoma: correlation between signal intensity on magnetic resonance imaging and pathologic characteristics[J]. Radiat Med. 1992, 10(6):235-242.
[7]杨新月,沈钧康,陆之安等.子宫平滑肌瘤的磁共振研究[J].放射学实践.2003,18(4): 246-248.
[8] Yamashita Y, Torashima M, Takahashi M, Tanaka N et al. Hyperintense uterine leiomyoma at T2-weighted MR imaging: differentiation with dynamic enhanced MR imaging and clinical implications[J]. Radiology.1993, 189(3) : 721.
[9] Hricak H, Finck S, Honda G, et al. MR imaging in the evaluation of benignuterine masses: value of gadopentetate dimeglumine-enhanced T1-weighted images[J]. AJR Am J Roentgenol. 1992,158(5):1043-1450.
[10] Mittl RL Jr, Yeh IT, Kressel HY. High-signal-intensity rim surrounding uterine leiomyomas on MR images: pathologic correlation[J]. Radiology. 1991,180(1): 81-83.
[11] Goto A, Takeuchi S, Sugimura K, et al. Usefulness of Gd-DTPA contrast-enhanced dynamic MRI and serum determination of LDH and its isozymes in the differential diagnosis of leiomyosarcoma from degenerated leiomyoma of the uterus[J]. Int J Gynecol Cancer. 2002 ,12 (4): 354-361.
[12] Crosignani PG, Vercellini P, Meschìa M,et al. GnRH agonists before surgery for uterine leiomyomas[J]. A review. J Reprod Med. 1996, 41(6): 415-21.
[13] Takahashi K, Okada M, Imaoka I,et al. Value of magnetic resonance imaging in predicting efficacy of GnRH analogue treatment for uterine leiomyoma[J]. Hum Reprod. 2001, 16(9) : 1989.
[14] Matsuno Y, Yamashita Y, Takahashi M,et al. Predicting the effect of gonadotropin-releasing hormone (GnRH) analogue treatment on uterine leiomyomas based on MR imaging[J]. Acta Radiol. 1999;40(6): 656-62
[15] Okuda S, Oshio K, Shinmoto H,et al. Semiquantitative assessment of MR imaging in prediction of efficacy of gonadotropin-releasing hormone agonist for volume reduction of uterine leiomyoma: initial experience[J]. Radiology. 2008, 248(3): 917-924
[16] Burn PR, McCall JM, Chinn RJ,et al. Uterine fibroleiomyoma: MR imaging appearances before and after embolization of uterine arteries[J]. Radiology. 2000 , 214(3): 729-734.
[17] deSouza NM, Williams AD. Uterine arterial embolization for leiomyomas: perfusion and volume changes at MR imaging and relation to clinical outcome[J]. Radiology. 2002 , 222(2): 367-374.
[18] Jha RC, Ascher SM, Imaoka I,et al. Symptomatic fibroleiomyomata: MR imaging of the uterus before and after uterine arterial embolization[J]. Radiology. 2000, 217(1): 228-235.
[19] Cura M, Cura A, Bugnone A. Role of magnetic resonance imaging in patient selection for uterine artery embolization[J]. Acta Radiol. 2006, 7(10): 1105-1114
[20] Nikolaidis P, Siddiqi AJ, Carr JC,et al. Incidence of nonviable leiomyomas oncontrast material-enhanced pelvic MR imaging in patients referred for uterine artery embolization[J]. J Vasc Interv Radiol. 2005,16(11):1465-1471.
[21] Chrisman HB, West D, Corpuz B,et al. Primary failure of uterine artery embolization: use of magnetic resonance imaging to select patients for repeated embolization[J]. J Vasc Interv Radiol. 2005,16(8): 1143-1147.
[22] Kr?ncke TJ, Hamm B. Role of magnetic resonance imaging (MRI) in establishing the indication for, planning, and following up uterine artery embolization (UAE) for treating symptomatic leiomyomas of the uterus[J]. Radiologe. 2003, 43(8): 624-633.
[23] Kitamura Y, Ascher SM, Cooper C,et al. Imaging manifestations of complications associated with uterine artery embolization[J]. Radiographics. 2005, 25 Suppl 1: S119-132.
[24]朱丽,陈文直,陈锦云等.子宫肌瘤超声消融与MRI信号特征关系的初步研究.第三军医大学学报2009, (14)
[25] Rouvière O, Lyonnet D, Raudrant A, et al. MRI appearance of prostate following transrectal HIFU ablation of localized cancer[J].Eur Urol. 2001, 40(3): 265-274.
[26]熊正爱,杜永洪,龚晓波等. MRI在HIFU治疗后随访中的作用[J].重庆医科大学学报. 2005, 30(3): 452-455
[27] 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
[28] Yoon SW, Lee C, Cha SH, et al. Patient selection guidelines in MR-guided focused ultrasound surgery of uterine fibroids: a pictorial guide to relevant findings in screening pelvic MRI[J]. Eur Radiol. 2008, 18(12): 2997-3006.
[29] Funaki K, Fukunishi H, Funaki T, et al. Magnetic resonance-guided focused ultrasound surgery for uterine fibroids: relationship between the therapeutic effects and signal intensity of preexisting T2-weighted magnetic resonance images[J]. Am J Obstetrics & Gynecology. 2007, 196 (2) : 184.
[30] Lénárd ZM, McDannold NJ, Fennessy FM, et al. Uterine leiomyomas: MR imaging-guided focused ultrasound surgery--imaging predictors of success[J]. Radiology. 2008, 49(1): 187-194.
[31] Arleo EK, Khilnani NM, Ng A, et al. Features influencing patient selection for fibroid treatment with magnetic resonance-guided focused ultrasound[J]. J Vasc Interv Radiol. 2007, 18(5): 681-685.
[32] Hesley GK, Gorny KR, Henrichsen TL, et al. A clinical review of focused ultrasound ablation with magnetic resonance guidance: an option for treating uterine fibroids[J]. Ultrasound Q. 2008, 4(2): 131-139.
[33]邓凤莲,邹建中,孙立群等. MRI评价高强度聚焦超声治疗子宫肌瘤对骶骨的影响[J].中国医学影像学杂志. 2008, 16(6): 401-404.
[34] Sewell PE, Arriola RM, Robinette L, et al. Real-time I-MR-imaging--guided cryoablation of uterine fibroids[J]. J Vasc Interv Radiol. 2001, 12(7): 891-893.
[35] Sakuhara Y, Shimizu T, Kodama Y,et al. Magnetic resonance-guided percutaneous cryoablation of uterine fibroids: early clinical experiences[J]. Cardiovasc Intervent Radiol. 2006 , 29(4): 552-558.
[36] Law P, Gedroyc WM, Regan L. Magnetic resonance-guided percutaneous laser ablation of uterine fibroids[J]. J Magn Reson Imaging. 2000, 12(4): 565-570.