Image-guided acoustic hemostasis for hemorrhage in the posterior liver

We investigated the use of ultrasound image-guided high intensity focused ultrasound (HIFU) to stop bleeding from injuries in the posterior liver. A HIFU transducer with focal length of 3.5 cm and frequency of 3.2 MHz was integrated with an intraoperative high-resolution ultrasound-imaging probe. Wedge tissue extractions, 30-mm long, 5-mm wide and 8-mm deep, were made in the posterior liver surface of five pigs to induce bleeding. The device was positioned on the anterior surface of the liver and HIFU was applied using ultrasound image-guidance. Hemostasis was achieved in 66 +/- 18 s (mean +/- standard deviation) for 17 HIFU treatments. During 7 min of sham HIFU treatment, none of the control incisions (n = 7) became hemostatic. Ultrasound image-guided HIFU offers a promising method for hemostasis in surgical settings in which the hemorrhage site is hidden and/or not accessible.     

负压吸附式止血敷贴的制备及其生物相容性

背景：部分止血材料存在有毒性及价格昂贵的缺陷。目的：观察负压吸附式止血敷贴在动物体内的生物相容性。方法：健康家猪6只在肝及肾划出长约1cm,深约0.5cm的条形切口,用负压吸附式止血敷贴覆盖。移植前观察检测血常规、肝肾功能及体液免疫学指标;移植后第14天观察再次检测血常规、肝肾功能及体液免疫学指标,并观察局部组织形态学变化。结果与结论：植入前后血生化和免疫学等指标差异无显著性意义（P〉0.05）,肝肾组织切片显示无明显炎症反应,未见明显纤维细胞包膜。动物体内实验提示,负压吸附式止血敷贴无毒性、无排斥反应、无免疫反应、无过敏反应,具有良好的生物相容性。     

A feasibility study of high intensity focused ultrasound for liver biopsy hemostasis

This study was conducted to demonstrate the feasibility of high intensity focused ultrasound (HIFU) application to control post-liver-biopsy hemorrhage. Anesthetized Yorkshire pigs (n = 3; mean weight = 23.0 kg) were used and the liver organ was exposed surgically by an open laparotomy. Core biopsies were performed on the hepatic parenchyma with 14-gauge (n = 41) and 18-gauge (n = 33) core biopsy needles. The focus of HIFU (4.23 MHz) field was applied for 15 to 45 s to the needle entry site in the liver immediately after needle retraction. Blood loss from a biopsy site was determined using surgical sponges as absorbent applied at the site. Mean blood loss for control sites was 6.16 g (14-gauge, n = 20) and 1.22 g (18-gauge, n = 10). Virtually no blood loss was measured for biopsies after HIFU application (n = 44) for using needles of both sizes. Our results indicate that intraoperative HIFU application could successfully induce hemostasis after liver biopsy in a porcine model.     

生物学焦域的概念及在高强度聚焦超声切除组织中的作用

本实验研究和比较了高强度聚焦超声(HIFU)所致体内深部组织凝固性坏死灶的形状和大小.结果显示参照同样的治疗参数,HIFU所致凝固性坏死灶的大小和形状在体内和体外有较大的差异.体内体积与治疗参数、靶组织的结构、功能和运动有密切关系.与物理学焦域比较,凝固性坏死灶体积亦可能命名为HIFU的生物学焦域.     

Synergistic Ablation of Liver Tissue and Liver Cancer Cells with High-Intensity Focused Ultrasound and Ethanol

We investigated the combined effect of ethanol and high-intensity focused ultrasound (HIFU), first, on heating and cavitation bubble activity in tissue-mimicking phantoms and porcine liver tissues and, second, on the viability of HepG2 liver cancer cells. Phantoms or porcine tissues were injected with ethanol and then subjected to HIFU at acoustic power ranging from 1.2 to 20.5 W (HIFU levels 1–7). Cavitation events and the temperature around the focal zone were measured with a passive cavitation detector and embedded type K thermocouples, respectively. HepG2 cells were subjected to 4% ethanol solution in growth medium (v/v) just before the cells were exposed to HIFU at 2.7, 8.7 or 12.0 W for 30 s. Cell viability was measured 2, 24 and 72 h post-treatment. The results indicate that ethanol and HIFU have a synergistic effect on liver cancer ablation as manifested by greater temperature rise and lesion volume in liver tissues and reduced viability of liver cancer cells. This effect is likely caused by reduction of the cavitation threshold in the presence of ethanol and the increased rate of ethanol diffusion through the cell membrane caused by HIFU-induced streaming, sonoporation and heating.     

Experimental Studies and Clinical Experiences on Treatment of Secondary Hypersplenism with Extracorporeal High-Intensity Focused Ultrasound

The aim of this study is to investigate the efficacy and safety of extracorporeal high-intensity focused ultrasound (HIFU) in treatment of hypersplenism. Fifteen adult dogs, weighing 13–18 kg were divided into three groups: sham group, SVL group undergoing splenic vein ligation (SVL) after laparotomy, and SVL + HIFU group receiving SVL followed by extracorporeal HIFU. Pathologic and hematologic analyses were performed. We also reviewed the clinical data of 19 patients with secondary hypersplenism caused by liver cirrhosis or hepatocellular carcinoma who underwent extracorporeal HIFU. Extracorporeal HIFU significantly diminished the volume of the spleen of animals, coupled with occurrence of coagulation necrosis and fibrosis in the target area. Both platelet and red blood cell counts were significantly restored by HIFU intervention. Similarly, HIFU treatment improved the hematologic parameters in patients with hypersplenism, and no major complications were encountered. Extracorporeal HIFU intervention is effective and safe in managing secondary hypersplenism.     

Real-time visualization of high-intensity focused ultrasound treatment using ultrasound imaging

High-intensity focused ultrasound (HIFU) and conventional B-mode ultrasound (US) imaging were synchronized to develop a system for real-time visualization of HIFU treatment. The system was tested in vivo in pig liver. The HIFU application resulted in the appearance of a hyperechoic spot at the focus that faded gradually after cessation of HIFU exposure. The duration of HIFU exposure needed for a hyperechoic spot to appear, was inversely related to the HIFU intensity. The threshold intensity required to produce a hyperechoic spot in liver in < 1 s was 970 W/cm(2), in situ. At this HIFU dose, no immediate cellular damage was observed, providing a potential for pretreatment targeting. The real-time visualization method was used in hemostasis of actively bleeding internal pelvic vessels, allowing targeting and monitoring of successful treatment. Real-time US imaging may provide a useful tool for image-guided HIFU therapy.     

HIFU联合HL-1损伤正常兔肝脏组织的体内实验研究

目的　探讨一种脂质体 (HIFU L iposomes- 1,HL - 1)增强兔肝高强度聚焦超声 (high intensity focused ultrasound,HIFU )能量沉积和灰阶超声实时监控的效果。方法　将兔随机分为 A,B两组 ,A组右肝为实验侧 (HL - 1侧 ) ,左肝为生理盐水侧 ,B组相反。输入生理盐水后以一定参数行 A组左肝或 B组右肝 HIFU损伤 ;然后输入 HL - 1以相同参数行对侧组织 HIFU损伤 ;记录 HIFU靶区 B超灰度值。实验后 2 4h解剖 ,测量凝固性坏死组织大小、计算能效因子 (energy efficiency factor,EEF)并行组织病理检查。结果　灰度增强出现率在 A、 B两组的 HL - 1侧均有所增加 ,但差异无显著性 (P>0 .0 5 ) ;A,B两组 HL - 1侧的 EEF均明显低于对照侧 (P<0 .0 1) ;损伤组织大体观及病理检查两组两侧均为典型的凝固性坏死。结论　 HL - 1联合 HIFU能导致靶区组织发生凝固性坏死 ,并有增强正常兔肝脏组织 HIFU能量沉积的作用 ,灰阶超声对靶区组织凝固性坏死的实时监控作用有待进一步研究。     

可吸收材料生物蛋白胶及明胶海绵在肝部分切除的应用

背景：生物蛋白胶广泛应用于各种外科手术中对富含小血管创面渗血的处理。目的：通过在肝部分切除中应用组织可吸收性医用生物蛋白胶,分析其对手术时间及肝部分切除后止血效果的影响。方法：对42例肝部分切除患者随机等分为实验组和对照组。实验组在肝部分切除后,缺损处喷洒医用生物蛋白胶封闭,并以明胶海绵剪成多块小片段混合医用生物蛋白胶以覆盖断面来代替常规缝合断面。对照组仅缝合收拢肝组织缺损。结果与结论：实验组使用的生物蛋白胶可迅速附着于创面,实验组患者肝部分切除的手术时间、出血量、引流量及渗血持续时间均明显小于对照组（P〈0.05）,且2组患者的住院天数和住院费用的差异无显著性意义（P〉0.05）。提示在肝部分切除中应用医用生物蛋白胶可以在不增加患者费用及住院时间的同时,有效降低手术时间、减少肝部分切除后出血。     

碳酸氢铵溶液增效HIFU消融新鲜离体牛肝的研究

目的 研究碳酸氢铵溶液增效HIFU消融离体牛肝的作用。方法 用HIFU以不同功率消融离体牛肝,比较不同浓度的碳酸氢铵溶液的实验组与注射PBS的对照组在灰度差值、灰度区域面积及凝固性坏死体积的差别并进行统计学分析。结果 当HIFU消融功率为150w时,各浓度碳酸氢铵溶液组在灰度差值、灰度面积及凝固性坏死体积方面均显著高于PBS对照组（P＜0.05）;而以其他功率进行HIFU消融时,情况并不完全一致。结论 在功率合适时,碳酸氢铵溶液具备增效HIFU消融离体牛肝的作用。     

高强度超声聚焦刀治疗早期前列腺癌26例

【目的】探讨高强度超声聚焦刀（HIFU）治疗早期前列腺癌的临床效果. 【方法】对26个活检证实的局限性前列腺癌患者用FEB- BY02型超声聚焦刀实施了共计42次治疗。【结果】活检证明26例患者治疗完全有效，前列腺特异抗原（PSA）及前列腺体积均较术前明显降低。【结论】HIFU能对早期前列腺癌进行无创的治疗，不易诱发严重的并发症，而且，与其他治疗前列腺癌的方法不同，HIFU可重复治疗。HIFU可能成为局限性前列腺癌患者一个有效的选择，其长期效果有待进一步研究。     

温敏性壳聚糖止血膜的止血作用及体内降解吸收

背景：尽管温敏性壳聚糖是壳聚糖的一种,但其止血效果、组织相容性及体内代谢吸收情况还需要验证。目的：探讨温敏性壳聚糖止血膜的止血作用、体内降解和组织相容性。方法：取SD大鼠48只,随机均分为4组,同时进行两种实验：①制作肝脏创面出血模型,其中3组分别采用温敏性壳聚糖止血膜、纤维素止血棉和明胶海绵止血材料贴敷大鼠肝创面止血,以不做任何处理的为空白对照。记录出血时间及出血量。②在上述3组大鼠的股四头肌内分别再植入对应的止血材料,空白对照组不植入任何材料。术后1,2,3,4,6周取两处创面行大体观察,术后4周行苏木精-伊红染色和电镜观察。结果与结论：温敏性壳聚糖组、纤维素组止血时间和出血量少于空白对照组、明胶海绵组（P 〈0.05）。温敏性壳聚糖止血膜于术后6周完全降解,纤维素止血棉于术后3周完全降解,明胶海绵于术后2周完全降解。温敏性壳聚糖组肝小叶结构完整,肝细胞结构基本正常,肿胀轻,炎症细胞浸润程度轻,电镜显示整个肝细胞外形结构清楚,细胞核无破损,细胞器良好;肌肉纤维结构完整,炎症细胞浸润程度轻,电镜显示肌纤维走向整齐,肌细胞核形态正常,细胞器良好。可见温敏性壳聚糖止血膜具有较好的止血作用和组织相容性。     

HIFU体外块"切除"动物肝脏、肾脏和肌肉的剂量研究

目的　用能效因子( energy- efficiency factor,EEF)作为高强度聚焦超声( high intensity focused ultrasound,HIFU)治疗剂量学评价指标来研究HIFU切除组织块的治疗剂量。方法　按照由束损伤→片损伤→块损伤的治疗原则,使用声强为70 0 0～2 770 0 W/ cm2 ,扫描线长3 0 mm,扫描速度3 mm/ s,束损伤的空间间距5～1 0 mm,片损伤的空间间距5 mm,在山羊肝脏、肾脏和肌肉中形成一个凝固性坏死块。并把形成单位体积凝固性坏死所需的超声能量叫做HIFU治疗的EEF,用EEF作为HIFU治疗剂量学评价指标。结果　按照束损伤→片损伤→块损伤的组合方式能在山羊肝脏、肾脏、肌肉中形成一个完整的凝固性坏死块,且中间没有正常组织残留。在山羊肾脏中形成一个凝固性坏死块的EEF明显大于在山羊肝脏中形成一个凝固性坏死块的EEF,而相比于肾脏和肝脏,在山羊肌肉中形成一个凝固性坏死块的EEF最小。结论　本研究表明同一超声能量在不同的靶组织中所产生的凝固性坏死体积不同,组织的结构、功能状态对HIFU治疗肿瘤的效果具有较大的影响,HIFU治疗剂量学的研究有望为临床治疗肿瘤提供剂量学指导     

兔VX2肝癌高能聚焦超声治疗后的磁共振灌注加权成像

目的 探讨高能聚焦超声(HIFU)治疗兔VX2肝癌后的磁共振灌注加权成像(PWI)的成像技术及特征.方法 新西兰大白兔20只,平均随机分成治疗组与对照组,制作肝癌模型.瘤株接种2周后进行常规MR及PWI扫描.此后治疗组行HIFU单次治疗,14 d后对两组均行PWI检查,选取病灶与周围正常肝组织的感兴趣区(ROI),采用信号强度-时间曲线的最大信号下降斜率(SRSmax)作为定量指标,分析不同ROI的SRSmax下降程度及规律.结果 对照组肿瘤中央区与瘤旁肝实质SRSmax的差异无统计学意义,治疗组内VX2瘤中央区、周边区及瘤旁肝实质SRSmax的差异均有统计学意义.治疗组与对照组肿瘤周边区SRSmax的差异有统计学意义.结论 兔肝VX2瘤PWI表现与肿瘤坏死程度、范围基本相符, PWI可用于评价HIFU治疗后肝脏肿瘤的血管生成、破坏状况.     

超声评价高强度聚焦超声治疗肝癌疗效的应用价值

目的评价高强度聚焦超声(HIFU)治疗肝癌的疗效及超声在疗效评价中的应用价值。方法HIFU治疗肝癌患者78例,通过术中实时超声监控及治疗前后彩色多普勒超声对比评价治疗效果。结果HIFU术中靶区声像图灰阶值增高(P<0.01)。HIFU术后肿瘤回声增强,体积缩小或不增大(P<0.01),血供一定程度减少或消失(P<0.05)。患者的生存期延长(P<0.01)。结论HIFU治疗肝癌局部疗效明确,是一种很有发展前景的无创治疗肝癌的方法。超声是HIFU术中监控及术后判断疗效的一种有效方法。     

肝移植出血特点及活化重组人凝血因子Ⅶ在移植中的应用

背景:如何评估肝移植过程中的出血、止血、凝血功能以及使用怎样的止血措施解决凝血问题,目前还没有常规止血指导方案.目的:探讨肝移植过程中各时间段出血特点并观察活化重组人凝血因子Ⅶ在肝移植中的应用效果.设计、时间及地点:回顾性病例分析及对比观察实验,2001-04/2006-07中山大学附属第二医院普通外科完成.对象:2001-04/2003-03接受肝移植患者15例为回顾性研究对象;2003-03/2006-07接受肝移植的28例患者,随机均分为2组:活化重组人凝血因子Ⅶ组和对照组.方法:对前期15例肝移植患者出血规律进行回顾性分析并统计各个时间段出血特点.对后期28例患者进行对比观察,活化重组人凝血因子Ⅶ组移植前10 min静脉推注活化重组人凝血因子Ⅶ 70～80μg/kg,推注速度为3～5 min.对照组同样方式推注50mL的生理盐水.主要观察指标:15例接受肝移植患者各时期的出血量:14例患者使用活化重组人凝血因子Ⅶ前及用药后30 min的凝血酶原时间、活化的部分凝血活酶时间及血总量.结果:广泛渗血是造成肝移植过程中出血的主要原因,在病肝切除阶段的广泛渗血是主要的出血时间段,活化重组人凝血因子ⅤⅡ可以较好地改善多种凝血功能指标,使血栓弹力图指标r,k,α角度和最大振幅及常规指标凝血酶原和部分凝血活酶时间改善.活化重组人凝血因子Ⅶ组较对照组移植过程出血明显减少;活化重组人凝血因子ⅤⅡ组较对照组移植时间明显缩短;活化重组人凝血因子Ⅶ组14例在观察期间均未发生血栓并发症.结论:肝移植切肝时间相的广泛渗血为肝移植主要出血时间.活化重组人凝血因子Ⅶ可以成功的地应用于肝移植.     

Temperature Dependence of Tissue Thermal Parameters Should Be Considered in the Thermal Lesion Prediction in High-Intensity Focused Ultrasound Surgery

This study considers the temperature-dependent thermal parameters (specific heat capacity, thermal diffusivity and thermal conductivity) used when predicting the temperature rise of tissue exposed to high-intensity focused ultrasound (HIFU). Numerical analysis was performed using the Khokhlov–Zabolotskaya–Kuznetsov equation coupled with a bioheat transfer function. The thermal parameters were set as the functions of temperature using experimental data. The results revealed that, for liver tissue exposed to HIFU with a focal intensity of 3000 W/cm² for 10 s, the predicted focal temperature rise was 23% lower and the thermal lesion area 41% smaller than those predicted without considering the temperature dependence. The prediction was validated by experimental observations on thermal lesions visualized in a tissue-mimicking phantom. The present results suggest that temperature-dependent thermal parameters should be considered in the prediction of HIFU-induced temperature rise to avoid lowering ultrasonic output settings for HIFU surgery. The aim of the present study was to investigate how significantly the temperature dependence of the thermal parameters affects the thermal dose imposed on the tissue by a typical clinical HIFU device. A numerical simulation was performed using a thermo-acoustic algorithm coupling the non-linear Khokhlov–Zabolotskaya–Kuznetsov (KZK) equation (Meaney et al. 1998; Filonenko and Khokhlova 2001) and a bio-heat transfer (BHT) equation (Pennes 1948). Thermal parameters of liver tissue were modeled in the present study as functions of temperature and were incorporated into the BHT equation to compensate for the variations in thermal parameters with temperature. Experimental validation was achieved by comparing the predictions with the thermal lesions formed in the tissue-mimicking phantoms.     

Contrast-enhanced ultrasound assessment of tissue response to high-intensity focused ultrasound

We report the use of contrast-enhanced ultrasonography as an immediate means of assessing the clinical response to high-intensity focused ultrasound (US) or HIFU treatment of liver tumours. HIFU is a noninvasive transcutaneous technique for the ablation of tumours that has been shown to destroy tumour vasculature, as well as to cause coagulative necrosis of tumour cells. As a dynamic indicator of tissue perfusion, microbubble contrast agents have already been reported to increase the diagnostic sensitivity of ultrasonography in the detection of liver tumours. This report documents the ability of one i.v. microbubble contrast agent (SonoVue, Bracco, Italy) to delineate the extent of HIFU ablation by comparison of pre- and immediately posttreatment perfusion within the target tumour. Observed changes were seen to correlate well with the ablated volume on histologic evaluation of the treated volume. This is the first time that this imaging technique has been reported in this setting.     

双层止血带子宫下段捆绑下子宫重建在前置胎盘产后出血中的应用效果

目的探讨双层止血带子宫下段捆绑下子宫重建在前置胎盘产后出血中的应用效果。方法选取我院妇产科2016年6月至2019年6月收治的60例前置胎盘产后出血患者,随机将其分为对照组和研究组,每组30例。对照组接受常规止血治疗,研究组在常规治疗的基础上采用双层止血带子宫下段捆绑下子宫重建治疗。比较两组的治疗效果。结果研究组的术中出血量及术后24 h出血量均少于对照组,止血时间短于对照组(P<0.05),且研究组没有子宫切除患者,对照组有2例患者因为止血效果不佳进行了子宫切除手术。研究组的术后输血量少于对照组(P<0.05);两组的术后输血、腹部切口感染、产褥感染及贫血发生率均无显著差异(P>0.05)。两组的新生儿脐动脉血pH值、PCO2、PO2、Apgar评分和体重无显著差异(P>0.05)。结论双层止血带子宫下段捆绑下子宫重建在前置胎盘产后出血患者中的止血效果显著,能够减少术中和术后的出血量,安全性高,疗效确切,且对新生儿无不利影响,母婴安全,值得临床推广。     

Free autogenous soft tissue graft with the argon laser

A sufficient amount of dense keratinized connective tissue attached to bone and the cervical area of the tooth is required for functional masticatory mucosa. Periodontal plastic surgery has furnished numerous reconstructive and regenerative techniques to correct the mucogingival defect. Laser technology has provided the ability for tissue fusion and incisions with better visual and mechanical access, decreased intraoperative time, improved hemostasis, and less postoperative discomfort. This article describes a technique for incisions and tissue fusion for gingival grafts with an argon laser.