相变高分子微球增效高强度聚焦超声消融裸鼠骨肉瘤

目的制备相变高分子微球,观察其增效高强度聚焦超声(HIFU)消融裸鼠骨肉瘤模型的效果。方法制备包裹液态氟碳的高分子微球,检测其形态、结构、粒径电位及相变条件;建立裸鼠骨肉瘤模型,随机分为空白组(不予处理)、对照组(注射生理盐水)和实验组1、2、3(注射稀释倍数分别为5、10、20倍的Pct-MP溶液),处理后立即用海级星对肿瘤进行辐照。于辐照后即刻和72h提取标本并观察坏死面积、行HE染色,并对72h提取的标本的坏死周边组织进行细胞增殖和凋亡测定。结果成功制备相变高分子微球;HIFU辐照后即刻提取的标本,实验组1、2的坏死面积与对照组差异均有统计学意义(P均0.05),但与实验组3的差异无统计学意义(P0.05);72h后提取的标本,实验组1、2的坏死面积进一步扩大、与辐照后即刻提取的标本的差异有统计学意义(P均0.05)。HIFU辐照72h后,实验组1、2、3与对照组间坏死周边组织的凋亡和增殖指数差异均有统计学意义(P均0.05)。结论在骨肉瘤裸鼠模型中,自制相变高分子微球能够增强HIFU对于骨肉瘤的消融效果,增强作用与微球浓度有关。     

高强度聚焦超声联合超声造影剂消融肝脏VX2移植瘤的实验研究

目的 探讨高强度聚焦超声(high intensity focused ultrasound,HIFU)联合超声造影剂(ultrasound contrast agents,UCA)治疗肝癌时的最适消融范围. 方法构建新西兰兔肝VX2移植肿瘤模型.51只模型兔分为3组:HIFU联合UCA沿肿瘤边缘消融肿瘤(A组)、消融肿瘤及肿瘤周围2 mm内的组织(B组)、消融肿瘤及周围4mm内的组织(C组).比较治疗后靶组织的病理情况、血清丙氨酸氨基转移酶(ALT)水平、肝内、肺及腹腔的转移情况以及生存期的差异.结果 HIFU联合UCA治疗后,各组靶区肿瘤组织均发生凝固性坏死;治疗后3 d、5 d,C组患者ALT显著升高,组间比较差异有统计学意义(F=12.933、18.37,均P＜0.01),C组最高;治疗后14 d,B组、C组ALT降至正常,组间比较差异无统计学意义(F=0.043,P＞0.05),A组ALT水平高于B组和C组(F=17.2,P＜0.05).治疗后两周肝内、肺及腹腔转移率A组均明显高于B组和c组(分别x2=9.918、6.300、7.6701,均P＜0.05),B组和C组差异无统计学意义(均P＞0.05),平均生存期A组(29 4±5.4)与B组(48±13.6)、C组(51±12.1)差异均有统计学意义(P＜0.05),B组和C组差异无统计学意义(P>0.643).结论 HIFU联合UCA在消融移植瘤周围组织2mm以上时可明显降低治疗后转移率,延长荷瘤兔的生存时间.     

靶区血管与声轴成角对脉冲高强度聚焦超声表面消融的影响:实验研究

目的探讨靶区血管与声轴成角对脉冲高强度聚焦超声(PHIFU)表面消融的影响。方法选取30只新西兰大白兔,获取胸主动脉。采用仿组织蛋清体模,在预定消融靶区埋入兔胸主动脉,根据其与声轴成角分为0°、45°和90°组,并设空白对照组,每组10个。在B超监控下采用PHIFU行表面消融,每组治疗参数设置相同。消融过程中对血管面靶区测温,消融后逐层切开体模行肉眼和超声观察,计算每组总体积(V)并进行比较,对辐照区血管行病理检查。结果空白对照组体模边缘为完整强回声带,而0°、45°、90°组血管周围部分呈低回声。空白对照组血管后面最高温度为(98.60±5.76)℃,0°组为(98.90±7.09)℃,45°组为(71.10±13.85)℃,90°组为(70.20±9.14)℃;空白对照组与45°组、90°组比较差异均有统计学意义(P均0.05)。空白对照组总坏死体积为(40 709.70±3 193.31)mm~3,0°组为(40 029.02±3 580.17)mm~3,45°组为(34 562.59±3 883.26)mm~3,90°组为(36 737.01±3 278.68)mm~3;空白对照组与0°组比较差异无统计学意义(P0.05)。血管病理检查示部分弹性纤维断裂,45°和90°组可见碎裂的细胞核。结论当靶区血管与声轴夹角为0°时,对靶区能量沉积影响最小,夹角为45°、90°时对血管壁破坏作用更强。     

包覆全氟戊烷的介孔氧化硅微球增效高强度聚焦超声表面消融离体牛肝

目的探讨包覆全氟戊烷的介孔氧化硅微球(MSNC-PFP)对HIFU表面消融离体牛肝的影响。方法根据MSNC-PFP的浓度将50块离体牛肝平均分为5组:对照组(MSNC-PFP浓度为0)、0.25 mg/ml组、0.50 mg/ml组、1.00mg/ml组、2.00mg/ml组。超声引导沿消融线路径多点注射增效剂(即MSNC-PFP)。通过HIFU线性扫描,以凝固性坏死束组合成面,6个面组合成体,对体腔内区域不直接消融。观察消融中声像图的改变。以TTC染色肉眼观察坏死范围,HE染色光镜下观察坏死程度。测量各组消融体积并评价消融效果,评价指标包括靶区覆盖指数(CI)、靶外体积指数(EI)、能效因子(EEF)。结果当MSNC-PFP浓度在1.00 mg/ml以上时,声像上为团状强回声,3~5 min后消退;MSNC-PFP浓度越高,HIFU辐照区域的灰度值改变越大。0.50、1.00、2.00mg/ml组总消融体积高于对照组,EEF值低于对照组(P均0.01)。1.00、2.00mg/ml组的CI及EI值均高于其余各组(P均0.05)。肉眼观察凝固性坏死区表现为灰白色,未坏死区则表现为红色。光镜下见当MSNC-PFP浓度≥0.50mg/ml时,形成的凝固性坏死带完整。结论采用MSNC-PFP可增大HIFU表面消融离体牛肝的消融体积,减低EEF,从而提高辐照效率。     

血管内皮抑素微泡联合聚焦超声抗结肠癌肿瘤血管生成的实验研究

目的评估靶向载血管内皮抑素微泡联合改良聚焦超声定向辐照抑制结肠皮下易位原位结肠癌肿瘤血管生成的治疗效果。方法将65只结肠皮下易位原位结肠癌肿瘤的Balb／c裸鼠模型随机分为5组,每组13只：A组为空白对照组,裸鼠肿瘤未行任何治疗组;B组为单纯超声辐照组,仅行超声辐照,未使用任何造影剂;C组为超声辐照联合SonoVue裸微泡治疗组;D组为超声辐照联合Targestar．SA裸微泡治疗组;E组为超声辐照联合包载血管内皮抑素的微泡治疗组。分别于辐照前、辐照后1、14和28d测量肿瘤体积,绘制肿瘤体积生长曲线。实时超声造影检查,脱机分析峰值强度（PI）、局部血容量（RBV）和局部血流量（RBF）等造影参数。实验结束后切除肿瘤组织行光镜及电镜病理学检查,并通过CD34免疫组织化学检测评估肿瘤坏死面积（NA）和微血管密度（MVD）。结果辐照前各组肿瘤体积的差异无统计学意义（P〉O．05）;辐照后28d,C组、D组和E组肿瘤体积明显小于A组和B组,且E组明显小于c组和D组（均P〈0．01）。辐照前各组PI、RBV和RBF的差异均无统计学意义（均P〉0．05）;辐照后28d,C组、D组和E组PI、RBF和RBV较辐照前明显降低且明显低于A组和B组（均P〈0．05）,E组明显低于C组和D组（均P〈0．05）。电镜观察显示,C、D、E组肿瘤细胞核膜消失,核染色质溶聚,呈簇状不规则排列,线粒体空泡化和微血管内皮损伤出血,以E组最为明显,而A和B组鲜见。免疫组织化学染色显示,治疗后28d,E组肿瘤组织NA明显高于其他各组,而MVD则明显低于其他各组（均P〈0．01）。结论靶向载血管内皮抑素微泡联合改良聚焦超声定向辐照可以破坏结肠皮下易位原位结肠癌肿瘤微血管,并抑制肿瘤新生血管生成,增强结肠癌的治疗效果．将来可能是具有临床应用前景的结肠癌治疗新方法。     

对比观察SonoVue与包裹全氟戊烷的介孔二氧化硅纳米微球在蛋清体模中的高强度聚焦超声增效作用

目的在蛋清体模中比较SonoVue和介孔二氧化硅纳米微球包裹的氟碳化合物增强高强度聚焦超声(HIFU)治疗效果差异,筛选适合HIFU治疗的增效剂。方法将SonoVue和包裹液态全氟戊烷的介孔二氧化硅纳米微球(MSNC-PFP)各0.3ml分别均匀混合到100ml的蛋清体模中,制成SonoVue组和MSNC-PFP组2个实验组,空白组不含增效剂。在B超引导下采用声功率160W的HIFU定点辐照10s,记录辐照区域即刻灰度变化,对比分析辐照后灰度变化区域、损伤体积、损伤形态以及能效因子(EEF)。结果辐照区回声增强范围与损伤大小一致,回声增强范围SMSNC-PFP组SSonoVue组≥S空白组;损伤体积VMSNC-PFP组VSonoVue组≥V空白组;EEFMSNC-PFP组EEFSonoVue组≤EEF空白组。MSNC-PFP组损伤形态皆为圆锥体,偏向换能器方向的损伤边缘类似棉花状,边缘局部有空隙;而SonoVue组和空白组的损伤形状皆为水滴状,边界清晰且无空隙。结论 MSNC-PFP能较SonoVue更有效地提高HIFU治疗效率。     

一种新型复合人工骨材料的制备及性能研究

目的 探讨透明质酸（hyaluronic acid,HA）/α-半水硫酸钙（α-calcium sulfate hemihydrate,α-CSH）/β-磷酸三钙（β-tricalcium phosphate,β-TCP）复合人工骨材料（以下简称复合材料）的制备及其性能。方法 采用水热法将二水硫酸钙脱水制备α-CSH,可溶性钙盐和磷酸盐反应法制备β-TCP。将α-CSH、β-TCP粉末按照不同比例（10∶0、9∶1、8∶2、7∶3、5∶5、3∶7）混合,分别与浓度为0.1%、0.25%、0.5%、1.0%、2.0%的HA溶液以及去离子水,以液固比0.30、0.35混合,制备HA/α-CSH/β-TCP、α-CSH/β-TCP复合材料。将制备样品进行扫描电镜观察、X射线衍射分析、初凝/终凝时间测定、降解测定、抗压强度测定、溃散情况观察、可注射性实验以及细胞毒性实验。结果 成功制备HA/α-CSH/β-TCP复合材料。该复合材料表面粗糙,不规则片块状颗粒、条状颗粒密集堆积,表面呈微孔结构,孔径主要在5～15μm之间。随β-TCP含量增加,复合材料初凝、终凝时间均增加,降解率降低,抗压强度呈...     

高强度聚焦超声肿瘤治疗技术原理

高强度聚焦超声波(high-intensity focused ultrasound,HIFU)是利用超声波良好的方向性、可穿透性、生物组织吸声特性等,将体外超声换能器发射的低声强超声波准确聚焦于体内的肿瘤靶组织处.聚焦后局部组织所吸声能转化为热能可使组织瞬间升温至蛋白变性阈值温度(60℃以上).该技术可使肿瘤细胞发生不可逆凝固性坏死,但不伤及焦点周围正常组织.

Abstract：

High intensity focused ultrasound (HIFU) is a novel physical tumor therapeutic technology which applies the ultrasound well targeting, focusing, tissue absorbing property, and so on. It focused outer transducer low intensity ultrasound wave and targeted in the tumor, whichcan raise the temperature above 60℃ rapidly and induce tissue irreversible coagulation necrosis, with no damage to the surrounding normal tissue. It is a new physical tumor treatment technology.     

Hollow iron-silica nanoshells for enhanced high intensity focused ultrasound

Background

High intensity-focused ultrasound (HIFU) is an alterative ablative technique currently being investigated for local treatment of breast cancer and fibroadenomas. Current HIFU therapies require concurrent magnetic resonance imaging monitoring. Biodegradable 500 nm perfluoropentane-filled iron-silica nanoshells have been synthesized as a sensitizing agent for HIFU therapies, which aid both mechanical and thermal ablation of tissues. In low duty cycle high-intensity applications, rapid tissue damage occurs from mechanical rather than thermal effects, which can be monitored closely by ultrasound obviating the need for concurrent magnetic resonance imaging.

Materials and methods

Iron-silica nanoshells were synthesized by a sol-gel method on polystyrene templates and calcined to yield hollow nanoshells. The nanoshells were filled with perfluoropentane and injected directly into excised human breast tumor, and intravenously (IV) into healthy rabbits and Py8119 tumor-bearing athymic nude mice. HIFU was applied at 1.1 MHz and 3.5 MPa at a 2% duty cycle to achieve mechanical ablation.

Results

Ex vivo in excised rabbit livers, the time to visually observable damage with HIFU was 20 s without nanoshells and only 2 s with nanoshells administered IV before sacrifice. Nanoshells administered IV into nude mice with xenograft tumors were activated in vivo by HIFU 24 h after administration. In this xenograft model, applied HIFU resulted in a 13.6 ± 6.1 mm³ bubble cloud with the IV injected particles and no bubble cloud without particles.

Conclusions

Iron-silica nanoshells can reduce the power and time to perform HIFU ablative therapy and can be monitored by ultrasound during low duty cycle operation.     

A microbubble agent improves the therapeutic efficiency of high intensity focused ultrasound: a rabbit kidney study

Eighty kidneys (40 left and 40 right kidneys) of New Zealand rabbits were ablated using high intensity focused ultrasound (HIFU), (14,300 W/cm², 1.0 MHz). Kidneys were randomly divided into two groups. HIFU was performed in the manner of linear scan in both groups. Prior to HIFU, normal saline solution and isovolumetric microbubble agent were administrated intravenously in groups I and II, respectively. HIFU was finished in all left kidneys and in 26/40 right ones. The therapeutic efficiency was reflected using necrosis rate (cubic centimeters per second), which was the tissue volume of coagulative necrosis per 1 s HIFU exposure. In both groups, predetermined volumes were damaged without harming overlying tissues. Necrosis rates were increased in group II both in left (0.0089±0.0107 vs. 0.0493±0.0777, P=0.0323) and in right (0.0039±0.0055 vs. 0.0162±0.0168, P=0.0248) kidneys. Pathological examinations confirmed that there were no intact tissue focuses within exposed regions in either group. These findings suggested that the microbubble agent improved the therapeutic efficiency of HIFU. Hemorrhage and hyperemia were also detected on the margin of the ablated tissues (both in cortex and medulla) in both groups.     

MRI监控高强度聚焦超声联合SonoVue损伤山羊肝脏组织的增效研究

目的采用MRI测温探讨高强度聚焦超声(HIFU)联合SonoVue损伤山羊肝脏组织的增效作用。方法选取南江黄羊6只,于MRI监控下对山羊肝脏进行HIFU定点辐照,辐照频率为1.0MHz、辐照深度30mm、声功率250 W、辐照时间15s。采用自身对照,于同一层面肝脏组织上选择两个辐照点,分别为HIFU联合生理盐水(0.03ml/kg)组(对照组)和HIFU联合SonoVue(0.03ml/kg)组(实验组)。在HIFU辐照过程中观测焦点处的温升情况,比较实验组和对照组的初始辐照阶段温升率、辐照过程中达到的最高温度、辐照结束后温度56℃的区域;比较实验组与对照组凝固性坏死情况,并对实验组靶区做组织病理学检查。结果实验组初始辐照阶段温升率、辐照过程中达到的最高温度、辐照结束后温度56℃区域的面积均大于对照组(P均0.05);实验组靶区为完整的凝固性坏死,且凝固性坏死体积大于对照组(P0.05)。结论超声造影剂SonoVue能够用于增强HIFU对山羊肝脏组织的损伤作用,这与微泡增强HIFU热效应有关。     

高强度聚焦超声肿瘤消融术麻醉管理的研究进展

高强度聚焦超声（HIFU）是一种无创的局部热消融技术,是治疗实体肿瘤的一种新方法,其安全性和可靠性已得到证实,目前已广泛应用于肝脏、胰腺、子宫以及前列腺等器官肿瘤的治疗。由于采用HIFU进行肿瘤治疗的患者通常处于肿瘤的终末期,全身情况较差,麻醉方式的选择须十分谨慎,不同部位的肿瘤其麻醉关注点也有所不同。本文就各种HIFU肿瘤消融术麻醉方式的选择、相关并发症和麻醉管理要点进行综述。     

高强度聚焦超声消融局限型子宫腺肌症

目的探讨高强度聚焦超声(HIFU)消融治疗局限型子宫腺肌症的应用价值。方法回顾性分析经HIFU消融治疗的60例局限型子宫腺肌症患者,观察其治疗前及治疗后1、3、6个月的影像学表现、子宫肌瘤症状严重程度及健康相关生活质量调查问卷评分情况。结果 HIFU治疗后3天内复查MRI提示平均消融率为(70.30±12.27)%。不同部位治疗前及治疗后1、3、6个月的症状严重程度评分和健康相关生活质量评分总体差异均有统计学意义(P均0.05)。局限性子宫腺肌症病灶不同时间点的体积差异均有统计学意义(P均0.05)。未见严重并发症发生。结论 HIFU治疗局限型子宫腺肌症无创、安全、有效。     

Outcomes of partial gland ablation using high intensity focused ultrasound for prostate cancer

BackgroundTo evaluate the clinical and oncological outcomes of partial gland ablation (PGA) using high intensity focused ultrasound (HIFU) technique for the clinically unilateral prostate cancer.MethodsWe performed a retrospective analysis for the 163 patients who treated by PGA for clinically unilateral prostate cancer. The PGA was performed using Focal one system with concurrent trans-urethral prostatectomy. The oncological and functional outcomes were evaluated as well as risk factors for remnant disease after PGA. Clinically significant cancer was defined as grade group ≥2.ResultsAmong the entire subjects, grade group 2 or greater was present at pre-treatment biopsy in 76.7%. Median follow-up time was 17 months and 60.1% of total subjects had follow-up biopsy at postoperative 1 year. There were 25 subjects (24.2%) with any cancer and 13 subjects (12.6%) with CS cancer at the follow-up biopsy. The preoperative age and number of positive cores at preoperative biopsy were significantly associated with positive results at follow-up biopsy. Incontinence which requires 2 or more pads per day was observed at 4 subjects (2.5%) postoperatively. There were no subjects who needed intensive care or experienced rectal complications.ConclusionThe PGA with HIFU was safe and showed good preservation of functional outcomes as well as satisfactory oncological control. The remnant disease was observed in the 24.5% of patients who underwent follow-up biopsy in the present study. Thus, further prospective study is needed to evaluate oncological and functional outcomes of PGA with HIFU more accurately.