高强度聚焦超声联合全氟戊烷液滴在乳腺癌治疗增效中的实验研究

目的:探讨高强度聚焦超声(High-Intensity Focused Ultrasound,HIFU)联合全氟戊烷液滴(Perfluoropentane droplets,PFP),对小鼠乳腺癌4T1细胞治疗的增效作用。方法:制备PFP,检测其平均粒径及形态结构。试验设立三组:HIFU假照组,单纯HIFU治疗组,HIFU联合PFP治疗组。流式细胞仪检测HIFU分组治疗乳腺癌细胞后细胞存活率及死亡率;体内动物试验分组处理后,二维超声观察HIFU辐照前后肿瘤回声灰度变化情况,超声造影剂灌注缺损面积占总面积百分比评价不同治疗方式对裸鼠皮下移植瘤的消融能力。结果:所制备的PFP平均粒径为1.2μm,形态呈规则球形。细胞试验显示,HIFU联合PFP治疗组乳腺癌细胞死亡率(23.50±1.34)%显著高于单纯HIFU治疗组(14.34±0.55)%和HIFU假照组(11.76±0.62)%(P<0.05);动物试验显示HIFU联合PFP治疗组肿瘤消融面积占总面积百分比(84.03±4.47)%显著高于单纯HIFU治疗组(41.23±4.24)%(P<0.05),HIFU假照组无明显灌注缺损区域。结论:HIFU联合PFP可显著增强对乳腺癌细胞及组织的消融能力。     

HIFU治疗裸鼠皮下移植瘤超声和磁共振变化的初步观察

目的初步探讨高强度聚焦超声对裸鼠卵巢癌皮下移植瘤治疗前后的超声和磁共振变化.方法HIFU治疗裸鼠卵巢癌模型12例,高强度聚焦超声治疗肿瘤外侧1/2,治疗前后进行超声和磁共振检查.结果(1)治疗前肿瘤组织超声表现为低回声,彩色和能量多普勒检测肿瘤内部及周边均有少许血流信号;治疗后肿瘤组织回声增强,彩色和能量多普勒检测肿瘤治疗区域内部及周边均无血流信号.(2)磁共振检查治疗区域肿瘤组织增强后未见明显强化.结论HIFU能准确破坏卵巢肿瘤,治疗过程中超声定位准确、方便,治疗后磁共振有助于评价其疗效,为临床应用提供实验依据.     

兔VX2移植性骨肿瘤模型超声影像学表现

建立兔VX2移植性骨肿瘤模型,为高强度聚焦超声（HIFU）治疗骨肿瘤提供理想的实验动物模型。将VX2瘤块植入到20只兔的右侧胫骨髓腔内建立骨肿瘤模型,连续进行超声和磁共振影像学检查并观察其生长特性,确定HIFU治疗骨肿瘤的最佳时间。结果表明成瘤率达100%,1～2周肿瘤在髓内生长,超声可观察肿瘤引起的骨膜反应,2～3周肿瘤开始破坏骨皮质,超声可观察到髓内肿瘤及向髓外软组织侵犯情况,3～4周肿瘤中心有坏死及液化,并开始出现远处转移。可见超声可监测VX2骨肿瘤生长情况,HIFU治疗VX2骨肿瘤模型最佳时间为植瘤后3周左右。     

超声造影早期评价HIFU治疗兔移植性骨肿瘤的初步研究

目的:观察兔VX2移植性骨肿瘤经高强度聚焦超声(High Intensity Focused Ultrasound,HIFU)治疗前后超声造影的图像变化,以评价高强度聚焦超声治疗骨肿瘤的疗效。方法:将VX2瘤块植入20只兔的右侧胫骨髓腔内,三周后进行HIFU治疗。治疗前后均推注超声微泡造影剂,对肿瘤治疗前后的超声造影图像进行比较。结果:治疗前超声造影显示,右侧胫骨髓内肿瘤快速、明显强化,与周边组织分界清楚,测得病灶平均大小为,上下径(17.614±0.955)mm,前后径(10.414±1.142)mm。治疗后造影,治疗区域显示为造影剂灌注缺损区,平均范围为上下径(8.010±0.584)mm,前后径(7.540±0.499)mm,未经治疗的肿瘤组织仍有超声造影剂灌注。结论:超声造影成像清楚地显示肿瘤范围以及治疗后灌注缺损区的大小,通过反映治疗后肿瘤的血供改变来评价HIFU治疗肿瘤的疗效。     

双频高强度聚焦超声换能器应用研究进展

高强度聚焦超声(High Intensity Focused Ultrasound,HIFU)消融实体肿瘤已在临床治疗中展示出良好的应用前景。HIFU消融肿瘤技术由于其使靶区肿瘤组织瞬时升温至60℃以上,产生不可逆性凝固性坏死,同时不影响靶区外正常组织而被广泛应用。目前治疗用超声主要使用单频率高强度聚焦超声,但其临床应用的主要限制是靶区组织消融时间较长,靶区外正常组织损伤风险较大。缩短靶区组织消融时间,对于提高HIFU治疗效率,更好地应用于临床较为关键。在总结HIFU换能器的特性和影响HIFU治疗因素的基础上,综述了应用不同类型的双频HIFU换能器强空化和缩短靶区组织消融时间等方面的研究进展。     

高强度聚焦超声消融滋养动脉治疗子宫肌瘤的临床价值

目的：探讨高强度聚焦超声消融滋养动脉治疗子宫肌瘤的可行性及有效性。方法：47例直径4~10cm肌壁间肌瘤,高强度聚焦超声治疗前通过彩色多普勒及超声造影确定肌瘤滋养动脉的蒂,对该区域进行消融,观察治疗前后肌瘤内部彩色多普勒及超声造影等影像学变化、随访临床症状及并发症。结果：治疗后肌瘤体积有不同程度的缩小,瘤体假包膜环状血流信号消失,肌瘤内部处于持续无灌注状态,部分患者临床症状消失或明显改善。结论：HIFU消融滋养动脉治疗子宫肌瘤能够缩短治疗时间,减少并发症,是一种微创和有效的方法。     

高强度聚焦超声损伤兔肌肉组织的超声影像学变化的初步研究

探讨高强度聚焦超声损伤兔肌肉组织的超声图像变化。采用高强度聚焦超声经皮照射20只新西兰大白兔双侧后肢肌肉,其中18只于照射前1d、照射后10min、照射后1d,3d,7d,14d,21d,28d进行二维超声、彩色多普勒和能量多普勒超声检查,并于照射后28天处死后测量凝固灶大小。另2只分别于照射后1d及照射后50d解剖,行病理学检查。(1)HIFU照射后凝固灶外周可见强回声带至低回声带的演变过程。(2)HIFU照射后第1d,测量的凝固灶体积最大(1476.59±308.64mm3),第3d～第21d,凝固灶体积逐渐缩小(612.47±127.98mm3)。第28d凝固灶体积最小(343.29±54.79mm3)。超声检查在兔肌肉组织HIFU照射后的随访中发挥了重要的作用,为监测HIFU治疗人体软组织肿瘤超声图像的变化提供了实验依据。     

空化现象在新型超声波治癌中的作用

西方国家的临床试验表明:高强度聚焦超声(HIFU)能够杀死癌细胞,但很少有HIFU被应用于临床。在澳大利亚、日本和法国,临床应用也只局限于前列腺癌。然而,从1998～2002年,中国应用HIFU技术已经成功地治疗了10000多个癌症患者。这些患者有骨癌、肝癌、胰腺癌、皮肤癌等。目前,至少有三家厂商生产HIFU设备(有些已出口)。2002年8月,西雅图时报以“中国在HIFU方面的医疗优势”为题,介绍了第二届国际医疗超声研讨会(ISTU2),从中得出的结论是:“不要害怕气泡”。     

用于肿瘤治疗的高强度聚焦超声换能器及其温度场测量

高强度聚焦超声（HIFU）作为一种具有巨大潜力的、无损的、有效的肿瘤治疗手段,已得到普遍认同。本文介绍了所研制的HIFU治疗系统,对其关键部分高强度聚焦超声换能器的温度场特性,从理论上和实验上进行了深入的研究,并提出了超声声场的理论算法.     

高强度聚焦超声热疗中组织损伤的一种监测方法

用特定频率和功率的高强度聚焦超声（HIFU）照射离体猪肉组织,研究了焦点区域的B超图像变化与HIFU导致的组织损伤之间的关系,并研究了M超信号变化和温度的相关性。结果表明：逐渐增加HIFU照射次数,焦点区域组织变性,B超图像发生明显改变。靶区内灰度超过设定的阈值的区域面积增大,区域内灰度升高,两者均与照射次数成近似线性关系;模拟加热实验中M超信号也随温度升高而变化,其变化较B超更显著。与以往的方法相比,实验系统可以实时地检测到组织损伤的程度和范围,提供了一种新的可视化的HIFU治疗实时监测方法。     

180例卵巢肿瘤患者经阴道彩色多普勒超声诊断结果分析

目的:探讨超声诊断卵巢肿瘤的诊断经验,进一步提高诊断水平。方法:收集我院2012年9月-2013年8月经手术或病理检查确诊的180例卵巢肿瘤患者对其超声检查情况进行回顾性分析。结果:本组180例患者,良性肿瘤162例,占90.0%,恶性肿瘤18例,占10.0%,良性肿瘤图像表现肿块包膜完整,边界清楚,形态规则,肿块内回声规则,阻力指数(RI)为(0.67±0.13)大于0.4,搏动指数(PI)均大于1.0,最大血流速度(PSV)均小于15cm/s。恶性肿瘤的超声图像表现为肿瘤边缘不整,欠清晰,结构紊乱,隔增厚不整齐,多呈乳头状突起,边界形态不规则,内部回声不均。阻力指数(RI)为(0.38±0.02),均小于0.4,搏动指数(PI)小于1.0,最大血流速度(PSV)均大于15cm/s。结论:超声是诊断卵巢肿瘤具有无痛、可重复性强等优点,值得临床推广。     

Pulsed high-intensity focused ultrasound enhances the relative permeability of the blood-tumor barrier in a glioma-bearing rat model

The use of pulsed high-intensity focused ultrasound (HIFU) with an ultrasound contrast agent (UCA) has been shown to disrupt the blood-brain barrier (BBB) noninvasively and reversibly in the targeted regions. This study evaluated the relative permeability of the blood-tumor barrier (BTB) after sonication by pulsed HIFU. Entry into the brain of chemotherapeutic agents is impeded by the BBB even though the permeability of this barrier may be partially reduced in the presence of a brain tumor. F98 glioma-bearing rats were injected intravenously with Evans blue (EB) with or without BTB disruption induced by pulsed HIFU. Sonication was applied at an ultrasound frequency of 1 MHz with a 5% duty cycle, and a repetition frequency of 1 Hz. The accumulation of EB in brain tumor and the tumor-to-contralateral brain ratio of EB were highest after pulsed HIFU exposure. Sonication followed by EB injection showed a tumor-to-contralateral brain ratio in the target tumors which was about 2 times that of the control tumors. This research demonstrates that pulsed HIFU enhances the relative permeability of the BTB in glioma- bearing rats. The results of this pilot study support the idea that further evaluation of other treatment strategies, such as HIFU exposure in addition to combined chemotherapy or repeated pulsed HIFU exposure to increase delivery of drugs into brain tumors, might be useful.     

Characterization of digital waveforms using thermodynamic analogs: detection of contrast-targeted tissue in vivo

We describe characterization of backscatter from tumor tissue targeted with a nanoparticle-based ultrasound contrast agent in vivo using analogs of thermodynamic quantities. We apply these waveform characteristics to detection of tumor neovasculature in tumors implanted in athymic nude mice, which were imaged using a research ultrasound scanner over a 2-hour period after injection of alpha upsilon beta3-targeted perfluorocarbon nanoparticles. Images were constructed from backscattered ultrasound using two different approaches: fundamental B-mode imaging and a signal receiver based on a thermodynamic analog (H(C)). The study shows that the thermodynamic analog is capable of detecting differences in backscattered signals that are not apparent with the B-mode approach.     

Dynamic schema for near infrared detection of pressure-induced changes in solid tumors

Differentiation among malignant tumors, benign tumors, and normal tissue is highly important in the diagnosis and treatment of many malignancies. We have proposed a dynamic schema for noninvasive characterization of pressure-induced changes in solid tumors. Our hypothesis has been that the altered neovascularization processes within cancer-bearing tissues may significantly increase vascular resistance and cause a much slower response of hemoglobin concentration during a dynamic compression stimulus. This hypothesis was tested by the evaluation of data generated from human tumor clinical testing and from animal tumor model testing. In the human tumor clinical testing, a unified diagnostic criterion was derived that integrated the relative characteristics of tumor oxygen, hemoglobin, and hemoglobin dynamics. By applying such a unified criterion, we were able to differentiate benign breast lesions and malignant breast tumors with high sensitivity and specificity within a subset of 14 suspicious breast lesions with similar size and depth characteristics. In the animal testing, a stepped compression load was applied to the subcutaneous tumor deposit on an athymic NU/NU nude mouse model with subcutaneous xenograft BxPC-3 cancer. Characteristic differences were observed between the premortem tumor and the postmortem tumor in terms of pressure-induced tumor structural and functional changes.     

甲状腺肿块的超声、CT与病理对照观察

目的:研究超声与CT对甲状腺肿块的诊断的准确率。方法:我院2012年8月-2013年9月经手术病理证实为甲状腺肿块患者的病例为53例,其中恶性病例11例。对所有病例的术前超声与CT表现进行分析。结果:在显示甲状腺肿块的边缘方面,超声更为清晰(P0.05),在显示囊变坏死与钙化等状况时,两者相似,没有统计学意义(P0.05)。结论:在显示甲状腺肿块方面,超声与CT均能良好的表现出来,将二者结合使用可以有效的提升诊断的准确率。     

An Intelligent Nanotheranostic Agent for Targeting,Redox‐Responsive Ultrasound Imaging,and Imaging‐Guided High‐Intensity Focused Ultrasound Synergistic Therapy

A novel multifunctional nanotheranostic agent with targeting, redox‐responsive ultrasound imaging and ultrasound imaging‐guided high‐intensity focused ultrasound (HIFU) therapy (MSNC‐PEG‐HA_SS‐PFH, abbreviated as MPH_SS‐PFH) capabilities is developed. The redox‐responsive guest molecule release and ultrasound imaging functions can be both integrated in such a “smart” theranostic agent, which is accomplished by the redox‐triggered transition from the crosslinking state to retrocrosslinking state of the grafted polyethylene glycol‐disulfide hyaluronic acid molecules on the particle surface when reaching a reducing environment in vitro. More importantly, under the tailored ultrasound imaging guiding, in vivo Hela tumor‐bearing nude mice can be thoroughly and spatial‐accurately ablated during HIFU therapy, due to the targeted accumulation, responsive ultrasound imaging guidance and the synergistic ablation functions of nanotheranostic agent MPH_SS‐PFH in the tumors. This novel multifunctional nano‐platform can serve as a promising candidate for further studies on oncology therapy, due to its high stability, responsive and indicative ultrasound imaging of tumors, and enhanced HIFU therapeutic efficiency and spatial accuracy under ultrasound‐guidance.     

成像及波谱成像联合运用对乳腺癌早期诊断的价值

目的:探讨成像及波谱成像联合运用对乳腺癌早期诊断的临床价值。方法:收集我院2012年1月-2013年11月诊治的60例乳腺癌患者,均经siemens(西门子)Avanto1.5T超导磁共振检查。结果:60例经过手术病理或穿刺病理检查确诊良性肿瘤31例,肿瘤直径1.8cm-5.1cm,平均2.9cm,其中纤维腺瘤28例,慢性乳腺炎2例,导管内乳头状瘤1例。乳腺癌29例,肿瘤直径1.1cm-4.6cm,平均2.6cm,其中浸润性导管癌26例,导管原位癌1例,髓样癌1例,浸润性小叶癌1例。31例良性患者中流入型17例,平台型10例,流出型4例,29例恶性患者中流入型4例,平台型9例,流出型16例,两组比较有显著性差异(P0.05)。结论:成像及波谱成像联合运用对乳腺癌早期诊断有着重要的临床意义,值得临床推广。