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。     

组织工程肝脏研究的相关问题

1组织工程肝脏和生物人工肝的关系? 目前的组织工程肝脏和生物人工肝都是基于肝细胞的治疗方式,利用肝细胞的功能部分代偿肝脏功能,因此两者在技术上有很多共通之处.     

让昨天告诉今天:组织工程肝脏研究的学术与技术进展

组织工程肝脏研究成果按时间年限的导读: 1888年,英国学者Carl Langenbuch首先成功施行了肘左叶切除治疗. 1963年,美国医生Tohmas E Starzl为先天性胆道闭锁的3岁男孩施行了首例肝移植手术.     

牛磺酸对兔肝脏缺血-再灌注损伤保护作用的研究

本实验拟观察牛磺酸对免肝脏缺血-再灌注损伤的保护作用，旨在寻求一种可靠的肝细胞保护剂．以减轻肝脏外科实践中缺血-再灌注所造成的肝细胞损伤．报告如下。     

自制脂质体造影剂对正常兔肝脏增强显影的早期实验研究

目的：探讨自制的脂质体造影剂对肝实的增强显像作用。方法：10只健康家兔经耳缘静脉团注0．01ml/kg的自制脂质体造影剂，测量造影前后肝实质及下腔静脉二维超声图像的灰阶值，并描记出肝实质显像的时间一强度曲线。结果：自制的脂质体造影剂能使肝实质显像明显增强，且增强时间长，高峰持续时间长达50分钟。结论：自制的脂质体造影剂能长时间显著增强肝脏的实质显像，其机理值得进一步研究。     

不同温度甘露醇对兔耳缘静脉及其周围组织损害的实验研究

目的 观察静滴不同温度甘露醇对兔耳缘静脉及其周围组织的损害。方法 将成年新西兰大白兔64只随机分为A,B,C,D 4组,依次经耳缘静脉滴入不同温度20％甘露醇,以穿刺点及穿刺点距近心端1cm处为中心,活体时各切下耳廓组织1cm^2,放入10％福尔马林溶液内固定24h作病理检查。结果 静滴不同温度20％甘露醇对兔耳缘静脉及周围组织的损害程度各异,35℃时损害最轻。结论 甘露醇温度越低,对血管及其周围组织的损伤越重。     

高强度聚焦超声定位损伤大型动物肝脏组织生物学焦域温场分布的实验研究

目的：探讨高强度聚焦超声（ＨＩＦＵ）定位损伤大型动物肝脏组织生物学焦域的温场分布以观察ＨＩＦＵ治疗对焦域周围组织的影响情况。方法：采用重庆医科大学医学超声工程研究所自行研制的ＨＩＦＵ治疗样机（１３１５３Ｗ／ｃｍ２,３ｓ,５ｓ,１０ｓ）对离体牛肝和在体猪肝脏组织进行定位损伤,用微型热偶感温头和热敏探针测定焦域中心及其外围温度。结果：辐照时间越长、焦域越大、焦域中心温度越高,但焦域外缘温升区相同,均为４．５ｍｍ。离体牛肝焦域周围组织温度升高的范围较活体猪肝脏组织焦域周围组织温度升高的范围大,活体猪肝脏组织焦域中心的温度可升达９１℃,焦域外２．５ｍｍ处组织温度正常。提示活体血流的散热,可迅速降低焦域外围组织的温度。结论：ＨＩＦＵ治疗不仅能对深部组织产生定位损伤,而且靶组织相邻的组织相当安全。     

使用组织扩张法缓慢延长和修复兔坐骨神经缺损的实验研究

目的探索使用扩张法将周围神经缓慢延长至足够长度以修复神经缺损的可行性。方法用新西兰白兔制作周围神经缺损模型，比较分析用组织扩张法将神经延长后对接与进行神经移植的治疗效果并在完成实验全过程后切取吻合后的神经进行组织学对照检查。结果原位切断对接和神经延长后对接的效果稍优于神经移植组，但统计学上无显著差异。结论使用组织扩张法缓慢延长周围神经地修复效果比自体神经移植好。     

组织多普勒超声评价阿霉素诱导兔心肌病早期收缩功能改变的实验研究

目的利用组织多普勒超声心动图评价阿霉素所致兔心肌病心肌功能的连续变化情况.方法 28只日本白兔分为两组,阿霉素组20只,每周静脉注射阿霉素2 mg/kg,8周共计16 mg/kg以期形成心肌病模型.对照组8只,每周注射相同剂量的生理盐水.分别在第0,4,6,8,10,12周进行常规和组织多普勒超声心动图检查.第12周阿霉素组和对照组各取2只处死进行组织学检查.结果阿霉素组,在10、12周左室内径显著扩大,左室射血分数和短轴缩短率显著下降(P<0.05).显著变化最早发现在第10周.二尖瓣环处心肌组织收缩峰值速度在8、10、12周显著降低(P<0.05).显著变化最早发现在第8周.病理结果显示了与人类阿霉素心肌毒性相似的改变,心肌细胞变性、线粒体和肌浆网水肿、细胞内空泡增多.对照组组织学无改变,常规和组织多普勒超声指标均未发现显著变化(P>0.05).结论在阿霉素所致兔心肌病模型中心肌收缩功能降低.组织多普勒指标能早期发现这一变化,早于常规超声心动图指标,为评价左室功能提供了一个敏感的新手段.     

脓毒症对肝脏线粒体膜损伤机制的实验研究

目的 探讨脓毒症对实验动物肝脏线粒体功能及结构的损伤机制.方法 36只新西兰兔随机分成对照组、脓毒症组和脓毒症休克组,分别予生理盐水、脂多糖(LPS)1 mg/kg、LPS 2mg/kg静脉注射,制备脓毒症和脓毒症休克实验动物模型后提取肝脏线粒体,检测丙二醛(MDA)含量、ATP酶活性、线粒体肿胀程度和线粒体膜电位变化,同时观察肝脏线粒体超微结构变化.结果 脓毒症组较对照组肝脏组织水肿加重,电镜见线粒体肿胀和膜增厚、MDA含量增高、ATP酶活性降低、线粒体膜流动性减低、膜电位差减小,且脓毒症休克组这些变化更加明显.结论 脓毒症实验动物肝细胞线粒体膜脂质过氧化、抑制线粒体膜ATP酶活性、降低跨膜电位,使线粒体结构和功能受损,导致肝功能障碍.     

高强度聚焦超声治疗及控制兔肝VX2肿瘤发展的实验研究

目的 探讨高强度聚焦超声(HIFU)治疗及控制肝肿瘤发展转移的效果.方法 采用兔肝VX2肿瘤模型进行HIFU辐照.辐照后不同时期处死动物以观察其病理变化.另以辐照组及对照组动物各8只,于2周后处死,比较肿瘤生长及肺转移的情况.结果 HIFU辐照后肿瘤细胞立即发生凝固性坏死,电镜下亦见到不可逆的破坏.2周后有6只动物的肿瘤原发灶已被完全破坏;另2只靶区外有少量肿瘤残存,其体积为59.8 mm3和10.4mm3,而对照组的肿瘤平均体积为(1571.1±349.7)mm3.辐照组有2只(25%)发生肺转移,转移结节数为10和3;对照组全部发生肺转移,转移结节数为54±30.两组差异有显著性.结论 HIFU对兔肝VX2肿瘤有很强的杀伤作用,对控制肿瘤的发展及转移有一定的疗效.     

Quantification of Liver Viscoelasticity with Acoustic Radiation Force: A Study of Hepatic Fibrosis in a Rat Model

Ultrasound elastography, based on shear wave propagation, enables the quantitative and non-invasive assessment of liver mechanical properties such as stiffness and has been found to be feasible for and useful in the diagnosis of hepatic fibrosis. Most ultrasound elastographic methods use a purely elastic model to describe liver mechanical properties. However, to describe tissue that is dispersive and to obtain an accurate measure of tissue elasticity, the viscoelasticity of the tissue should be examined. The objective of this study was to investigate the shear viscoelastic characteristics, as measured by ultrasound elastography, of liver fibrosis in a rat model and to evaluate the diagnostic accuracy of viscoelasticity for staging liver fibrosis. Liver fibrosis was induced in 37 rats using carbon tetrachloride (CCl₄); 6 rats served as controls. Liver viscoelasticity was measured in vitro using shear waves induced by acoustic radiation force. The measured mean values of liver elasticity and viscosity ranged from 0.84 to 3.45 kPa and from 1.12 to 2.06 Pa·s for fibrosis stages F0–F4, respectively. Spearman correlation coefficients indicated that stage of fibrosis was well correlated with elasticity (0.88) and moderately correlated with viscosity (0.66). The areas under receiver operating characteristic curves were 0.97 (≥F2), 0.91 (≥F3) and 1.00 (F4) for elasticity and 0.91 (≥F2), 0.79 (≥F3) and 0.74 (F4) for viscosity, respectively. The results confirmed that shear wave velocity was dispersive in frequency, suggesting a viscoelastic model to describe liver fibrosis. The study finds that although viscosity is not as good as elasticity for staging fibrosis, it is important to consider viscosity to make an accurate estimation of elasticity; it may also provide other mechanical insights into liver tissues.     

声脉冲辐射力成像评价肝纤维化与临床病理的对照研究

目的 探讨声脉冲辐射力成像评价临床肝病患者肝纤维化的价值.方法 对99例欲行肝外科手术的患者术前进行声脉冲辐射力成像检查,得出反映肝组织硬度的剪切波速度(shear wave velocity,Vs).对患者肝组织病理进行肝纤维化分期、炎症活动程度分级以及脂肪变程度分级.将Vs与病理结果做比较.结果 肝纤维化S0～S4期的Vs值分别为(1.14±0.22) m/s、(1.30±0.22)m/s、(1.36±0.38)m/s、(1.47±0.37)m/s以及(1.87±0.08) m/s,各组间差异具有统计学意义(P＜0.001);Vs与肝纤维化分期之间具有一定的相关性(r=0.541,P＜0.001),Vs预测3期及以上肝纤维化的ROC曲线下面积为0.812(P＜0.001),以1.40 m/s为最佳临界值,敏感性、特异性分别为73.2％和81.4％.炎症活动程度分级G0～G3的Vs值分别为(1.17±0.16)m/s、(1.43±0.36)m/s、(1.59±0.53) m/s以及(1.89±0.59)m/s,各组间差异有统计学意义(P＜0.001);Vs与炎症活动程度分级之间具有一定的相关性(r =0.383,P＜0.001).脂肪变程度分级F0～F4的Vs值分别为(1.61±0.42)m/s、(1.47±0.58)m/s、(1.56±0.71)m/s、1.13 m/s以及(0.94±0.95) m/s,各组间差异不具有明显统计学意义(P=0.286);Vs与脂肪变程度分级之间亦不存在明显相关性(r=-0.177,P=0.080).结论 声脉冲辐射力成像评价肝纤维化具有一定的价值,但炎症活动程度对结果具有显著的影响.     

超声组织定征的仿体研究:不同浓度淀粉悬液的声学密度定量分析

目的： 比较视频信号和超声背向散射信号测定对散射体浓度变化的敏感性, 探讨散射体浓度与其声学特性间的关系。方法： 测定 ０．１％ 到２．０％ 不同浓度淀粉悬液的视频强度和背向散射积分。结果： 淀粉悬液的浓度－视频强度和浓度－背向散射积分曲线形态相近, 均由上升支、平台、下降支组成, 背向散射积分上升幅度 （约３０ｄＢ） 大于视频信号的上升幅度 （约 ２０ｄＢ）。结论： 背向散射积分测定对散射体浓度的敏感性优于视频强度测定, 散射体浓度增大可使后方的信号衰减逐渐增大。     

肝脏肿瘤谐波造影三维超声与造影二维超声的比较

目的通过与谐波造影二维超声的比较．探讨谐波造影三维超声在评价肝脏肿瘤血供中的作用。方法采用编码谐波造影功能对21例肝脏肿瘤患者行造影二维超声检查，并在此基础上进行三维重建，比较两者在显示肿瘤血管像、灌注像、血管及灌注综合像方面的不同。结果谐波造影三维超声较造影二维超声能更清楚地显示肿瘤的血管像，显示血管及灌注综合像的能力亦优于造影二维超声，但在显示肿瘤灌注像方面，二者作用相似。结论谐波造影三维超声能更好地反映肝脏肿瘤的血供特点，可为肝脏肿瘤的影像研究提供一种新方法。     

Inactivation of Planktonic Escherichia coli by Focused 1-MHz Ultrasound Pulses with Shocks: Efficacy and Kinetics Upon Volume Scale-Up

This study addresses inactivation of E. coli in either 5- or 10-mL volumes, which were 50- to 100-fold greater than used in an earlier study (Brayman et al. 2017). Cells were treated with 1-MHz pulsed high-intensity focused ultrasound (10 cycles, 2-kHz repetition frequency, +65/–12.8 MPa focal pressures). The surviving fraction was assessed by coliform assay, and inactivation demonstrated curvilinear kinetics. The reduction of surviving fraction to 50% required 2.5 or 6 min in 5- or 10-mL samples, respectively. Exposure of 5 mL for 20 min reduced the surviving fraction to ～1%; a similar exposure of 10-mL samples reduced the surviving fraction to ～10%. Surviving cells from 5-min exposures appeared normal under light microscopy, with minimal debris; after 20 min, debris dominated. Transmission electron microscopy images of insonated samples showed some undamaged cells, a few damaged but largely intact cells and comminuted debris. Cellular damage associated with substantive but incomplete levels of inactivation can be variable, ranging from membrane holes tens of nanometers in diameter to nearly complete comminution.     

In Vivo Molecular Imaging Using Low-Boiling-Point Phase-Change Contrast Agents: A Proof of Concept Study

Sub-micron phase-change contrast agents (PCCAs) have been proposed as a tool for ultrasound molecular imaging based on their potential to extravasate and target extravascular markers and also because of the potential to image these contrast agents with a high contrast-to-tissue ratio. We compare in vivo ultrasound molecular imaging with targeted low-boiling-point PCCAs and targeted microbubble contrast agents. Both agents were targeted to the intravascular (endothelial) integrin α_vß₃via a cyclic RGD peptide (cyclo-Arg–Gly–Asp–D-Tyr–Cys) mechanism and imaged in vivo in a rodent fibrosarcoma model, which exhibits angiogenic microvasculature. Signal intensity was measured using two different techniques, conventional contrast-specific imaging (amplitude/phase modulation) and a droplet vaporization imaging sequence, which detects the unique signature of vaporizing PCCAs. Data indicate that PCCA-specific imaging is more sensitive to small numbers of bound agents than conventional contrast imaging. However, data also revealed that contrast from targeted microbubbles was greater than that provided by PCCAs. Both control and targeted PCCAs were observed to be retained in tissue post-vaporization, which was expected for targeted agents but not expected for control agents. The exact mechanism underlying this observation remains unknown.     

Ultrasonographic changes of early liver cirrhosis in chronic hepatitis B: A longitudinal study

Ultrasonography of prospectively followed chronic hepatitis B patients who developed liver cirrhosis were reevaluated in order to identify the ultrasonographic changes of early cirrhosis. Ultrasonographic features of 29 patients before and after cirrhosis were as follows: portal vein diameter—1.20 cm/1.29 cm (NS); cirrhosis score—5.69/7.52 (p < 0.01); spleen size index—21.99 cm²/25.84 cm² (NS). The result suggests that ultrasonographic diagnosis of early cirrhosis is not easy on a single occasion; however, the score system method is helpful in longitudinal follow-up chronic hepatitis patients. A careful comparison of hepatic parenchymal and surface changes are mandatory. © 1993 John Wiley & Sons, Inc.