高强度聚焦超声可治疗区域的仿真研究

数值仿真不同治疗参数条件下高强度聚焦超声(high intensity focused ultrasound,HIFU)可治疗区域的变化,对HIFU治疗剂量的确定具有重要的指导意义。本文采用Westervelt方程的近似式,结合Pennes生物热传导方程,以离体猪肝组织为例,在考虑组织声学特性对HIFU焦域温度场影响的条件下,通过时域有限差分法(finite difference time domain,FDTD)对HIFU焦域温度场进行仿真研究。研究结果表明,照射时间越长,组织声学特性的影响就越明显;焦点处的最高温升相同时,可治疗区域的大小差异较小;声强越大,形成可治疗区域所需的时间也越短;当声强一定时,随着照射时间的增加,可治疗区域的长、短轴长度均呈非线性增加;在相同可治疗区域的长轴或短轴长度一定时,输入声强和照射时间呈负相关。     

高强度聚焦超声肿瘤治疗焦域的仿真研究

数值仿真是预测高强度聚焦超声(high intensity focused ultrasound,HIFU)治疗的温度分布、确定治疗剂量的有效方法之一。本研究采用Westervelt方程的近似式,并结合Pennes生物热传导方程,以猪肝肿瘤为例,在考虑肝组织声学特性对HIFU温度场影响的条件下,通过时域有限差分法仿真研究辐照时间和声强对肿瘤组织内可治疗焦域体积的影响。研究结果表明,一定声强条件下,肝组织声学特性对肿瘤内可治疗焦域的影响随着辐照时间的延长而凸显;可治疗焦域体积随时间增长或声强增大而非线性增加;相同辐照条件下,肿瘤组织内的可治疗焦域体积大于肝组织内的;当可治疗焦域体积一定时,辐照声强和辐照时间呈负相关;同时,等效热剂量判定的可治疗焦域大于温度阈值判定的可治疗焦域,且二者之差随声强而变化。     

应用微量热法构建限制性条件下微生物生长模型

用微量热计测定了金黄色和白色葡萄球菌在给定条件下生长的热谱图,按限制性条件下微生物生长的模型进行了数学处理,得出了比生长速率．还测定了在不同温度和不同酸度下的热谱曲线,确定了最适生长温度和酸度。     

高强度聚焦超声治疗中测温技术的研究

高强度聚焦超声(HIFU)是一种新兴的非侵入性局部治疗技术,它以其治疗中安全、有效、无创的优点被医学界所关注.然而,对生物组织温度的准确测量是制约该治疗技术发展的关健环节,因此,HIFU治疗中的测温技术成为人们关注的热点.本文主要介绍了近年来在HIFU治疗中,测温技术的研究现状以及两大测温方法(无损测温和有损测温),并对测温技术的发展进行展望.     

高能聚焦超声治疗晚期胰腺癌的临床研究

目的:研究高能聚焦超声(下简称HIFU)治疗晚期胰腺癌病人疼痛的疗效和外周血免疫功能的变化.方法:应用FEP-BY01肿瘤热疗机对靶组织进行超高温热疗,观察镇痛效果及外周血T细胞亚群活性变化.结果:12例具有疼痛症状的胰腺癌治疗后疼痛缓解率,总缓解率为91.6%(11/12),其中完全缓解率为3.8%(1/12),中度和明显缓解率为66.7%(8/12);治疗前与正常对照组相比,CD3无明显变化(P>0.05),CD4明显降低(P<0.05),CD8偏高,但无明显差异(P>0.05).CD4/CDB明显下降(P<0.05).与治疗后相比,CD3无明显变化,CD4、CD4/CD8呈增加趋势,CD8呈降低趋势.但均无明显差异(P>0.05).热疗未发生严重并发症.结论:HIFU治疗对胰腺癌具有较好的止痛作用,可以改善患者的细胞免疫功能.     

基于B超图像评价HIFU治疗剂量对组织损伤程度的影响

基于B超图像分析HIFU治疗中辐照剂量、组织凝固性坏死区域和图像参数之间的关系。通过对高强度聚焦超声辐照新鲜离体组织前后获得的B超图像做数字减影处理,计算图像灰度平均值,同时切片观察并记录生物组织的凝固性坏死区域大小,在此基础上得到大批量数据的统计特性。结果表明：辐照剂量、组织凝固性坏死区域与B超图像灰度平均值在一定范围内成正相关性;当凝固性坏死区域增大到一定程度时,B超图像灰度平均值不再增大,而是呈无规律分布。B超图像灰度可反映组织损伤程度,为实时监控HIFU治疗效果提供依据。     

两种不同聚焦超声源对生物媒质加热作用的比较

计算了凹球面自聚焦超声源和聚焦高斯超声源在生物媒质中产生的声场及温度场,并对其主要特征进行了分析。比较了不同条件下此两种聚焦超声源用于热疗时的有效治疗区及声焦点处的升温快慢,揭示了它们对生物组织加热作用的差异,证实最大温升主要取决于最大声吸收率。     

应用ZME-Ⅱ型大功率微波热靶点效应治疗肿瘤的临床疗效研究

目的：探讨应用办ZME-Ⅱ型大功率治疗机的微波热靶点效应治疗肿瘤的临床疗效及作用机理。方法：应用微波仪体表照射患者肿瘤部位及转移淋巴蛄厦体腔内加温治疗（用于宫颈癌等,将辐射器探入阴遗内,直接接触肿瘤）。输出功率100W,治疗温度42℃-45℃,间隔72小时热疗一次,6次为一疗程,一般热疗2—3疗程。结果：52例患者中,肿瘤消失8例,疗效显著20例,好转19例,无效5例。总有效率90．38％。结论：临床疗效证明,热疗是一种比较理想的辅助手段,为我们进一步开展热化疗的临床实验提供了理论基础和指导。同时为进一步开展热化疗多靶点效应治疗肿瘤提供了广阔的应用前景。     

在微波热疗中用附加介质层增透注入人体电磁能量的理论研究

本文以实际微波辐射器照射下平面分层均匀媒质中的电磁场理论为基础,研究了在微波热疗过程中在分层均匀生物组织模型表面附加一层无耗介质对其中的辐射场的影响。通过数值模拟对比计算了附加介质层参数取不同值时,生物组织模型中电磁场分布的变化及注入组织中能量的相应改变。结果表明,附加介质层参数的不同取值对注入组织中的能量有很大的影响;当附加介质层的参数取某些特定值时,对微波辐射有明显的增透作用。最后,分析了本论文得出的理论结果在微波热疗中的指导意义。     

应用ZME-Ⅱ型大功率微波热靶点效应治疗肿瘤的临床疗效研究

目的:探讨应用ZME-Ⅱ型大功率治疗机的微波热靶点效应治疗肿瘤的临床疗效及作用机理。方法:应用微波仪体表照射患者肿瘤部位及转移淋巴结及体腔内加温治疗(用于宫颈癌等,将辐射器探入阴道内,直接接触肿瘤)。输出功率100W,治疗温度42℃-45℃,间隔72小时热疗一次,6次为一疗程,一般热疗2-3疗程。结果:52例患者中,肿瘤消失8例,疗效显著20例,好转19例,无效5例。总有效率90.38%。结论:临床疗效证明,热疗是一种比较理想的辅助手段,为我们进一步开展热化疗的临床实验提供了理论基础和指导。同时为进一步开展热化疗多靶点效应治疗肿瘤提供了广阔的应用前景。     

Numerical study of the effect of ultrasound frequency on temperature distribution in layered tissue

The high intensity focused ultrasound (HIFU) technology can produce therapeutic benefits in deep-seated tissues of interest, selectively and noninvasively. In order to control the treatment process, it is important to recognize the heat generation in biological tissue and the parameters that have an effect on temperature rising. This study investigates the influence of frequency and source intensity on temperature distribution during high-intensity focused ultrasound (HIFU). A nonlinear full wave equation model is simulated to compute the pressure field. Additionally, the absorbed coefficient of tissue is added to the nonlinear equations to simulate accurately the wave propagation in tissue with high absorbed coefficient. In addition, temperature distribution was solved by the Pennes bio-heat equation. Conclusively, frequencies in the range of 1–1.5 MHz are prescribed to have maximum heat absorption in the focal region.     

内热源影响下的均质组织表面温度分布研究

现有的医用红外热像技术几乎都采自体表,为了提高诊断准确性,必须进一步确定体表温度分布与体内热源间的关系。基于人体内部传热机制和人体与环境的传热机制,推导出稳态下均质（各向同性）组织的表面温度分布与内部球状热源之间的关系,通过模拟计算可验证结论的准确性。     

Liquid-Solid Phase-Inversion PLGA Implant for the Treatment of Residual Tumor Tissue after HIFU Ablation

BackgroundHIFU has been shown to be a more suitable alternative for the treatment of primary solid tumors and metastatic diseases than other focal heat ablation techniques due to its noninvasive and extracorporeal nature. However, similar to other focal heat ablation techniques, HIFU is still in need of refinements due to tumor recurrence.MethodsIn this work, we investigated the effectiveness of an adjunct treatment regimen using doxorubicin (DOX)-loaded, injectable, in situ-forming, and phase-inverting PLGA as the second line of defense after HIFU ablation to destroy detrimental residual tumors and to prevent tumor recurrence. All of the statistical analyses were performed using the Statistical Package for the Social Sciences 18.0(SPSS, Inc., Chicago, IL, USA), and p< 0.05 was considered statistically significant. All of the results are presented as the means ± STDEV (standard deviation). For multiple comparisons, ANOVA (differences in tumor volumes, growth rates, apoptosis, proliferation indexes, and Bcl-2 and Bax protein levels) was used when the data were normally distributed with homogenous variance, and rank sum tests were used otherwise. Once significant differences were detected, Student-t tests were used for comparisons between two groups.ResultsOur results revealed that DOX diffused beyond the ablated tissue regions and entered tumor cells that were not affected by the HIFU ablation. Our results also show that HIFU in concert with DOX-loaded PLGA led to a significantly higher rate of tumor cell apoptosis and a lower rate of tumor cell proliferation in the areas beyond the HIFU-ablated tissues and consequently caused significant tumor volume shrinkage (tumor volumes:0.26±0.1,1.09±0.76, and 1.42±0.9cm³ for treatment, sham, and no treatment control, respectively).ConclusionsFrom these results, we concluded that the intralesional injection of DOX-loaded PLGA after HIFU ablation is significantly more effective than HIFU alone for the treatment of solid tumors.     

Inhibitory effect of 5-FU loaded ultrasound microbubbles on tumor growth and angiogenesis

The anti-neovascularization treatment is one of the effective strategies for tumor molecular target therapy. At present, the target and effect of the anti-neovascularization treatment is limited, and it is urgent to establish a new vascular targeting strategy to effectively treat tumors. In this work, we used high intensity focused ultrasound (HIFU) combined with targeted microbubbles to establish a molecular targeted ultrasound response microbubble for neovascular cells. Furthermore, the effects of drug loaded microbubbles on neovascularization and tumor cells were studied. The tumor vascular targeted and ultrasound-responsive microbubbles of 5-FU@DLL4-MBs were prepared by the thin-film dispersion method. The size and zeta potential of 5-FU@DLL4-MBs was about 1248 nm and −9.1 mV. 5-FU@DLL4-MBs released 5-FU showed an ultrasound-responsive manner, and had better vascular-targeting ability. Furthermore, the 5-FU@DLL4-MBs showed the strongest cytotoxic effect on HUVECs or HepG-2 cells and can be effectively internalized into the HUVECs cells. Thus, 5-FU@DLL4-MBs combined with HIFU can be considered as a potential method for antitumor angiogenesis in the future.     

Preliminary Investigation of a 64-element Capacitive Micromachined Ultrasound Transducer (CMUT) Annular Array Designed for High Intensity Focused Ultrasound (HIFU)

Background

Treatment of prostate cancer using endocavitary High Intensity Focused Ultrasound (HIFU) has become more commonplace since the first treatments in the 1990s. The gold standard HIFU strategy to treat prostate cancer is the complete thermal ablation of the entire prostate gland under real-time ultrasound (US) image guidance. A more desirable treatment and the current trend, however, is towards a focal treatment but more accurate and finely tunable thermal lesions are needed along with improved US imaging guidance. In this study, Capacitive Micromachined Ultrasound Transducer (CMUT) technology is being investigated, as they have shown recent promise for US imaging and potential to be used for HIFU therapy. They offer potential advantages over current piezoelectric designs in the context of ultrasound-guided HIFU (USgHIFU) focal therapies.

高能聚焦超声在治疗晚期胰腺癌中的疗效分析

目的：通过对晚期胰腺癌患者行高强度聚焦超声治疗,观察其近期疗效,为晚期胰腺癌患者的临床治疗提供一种新的选择。方法：对15例晚期胰腺癌患者行高强度聚焦超声治疗,对比治疗前后的KPS评分,疼痛感受评分,CA199,三大常规,生化检查,B超观察肿瘤回声及血供,CT观察肿瘤大小改变。结果：HIFU治疗后,患者KPS评分升高,疼痛评分下降,肿瘤标志物下降,B超观察肿瘤回声,其中10例肿瘤回声增强,11例肿瘤血供减少或消失,CT示大部分患者治疗后肿瘤体积缩小或不变,治疗后三大常规、生化和电解质无明显改变。结论：运用高强度聚焦超声治疗晚期胰腺癌患者,在改善患者临床症状方面有明显疗效,并且能缩小肿瘤体积,减少或中断肿瘤血供,是一种很有发展前景的无创治疗方法。     

Feasibility of photoacoustic evaluations on dual‐thermal treatment of ex vivo bladder tumors

A variety of thermal therapeutic methods have been investigated to treat bladder tumors but often cause bowel injury and bladder wall perforation due to high treatment dosage and limited clinical margins. The objective of the current study is to develop a dual‐thermal modality to deeply coagulate the bladder tumors at low thermal dosage and to evaluate therapeutic outcomes with high contrast photoacoustic imaging (PAI). High intensity focused ultrasound (HIFU) is combined with 532 nm laser light to enhance therapeutic depth during thermal treatments on artificial tumor‐injected bladder tissue ex vivo. PAI is employed to identify the margins of the tumors pre‐ and post‐treatments. The dual‐thermal modality achieves 3‐ and 1.8‐fold higher transient temperature changes and 2.2‐ and 1.5‐fold deeper tissue denaturation than laser and HIFU, respectively. PAI vividly identifies the position of the injected tumor and entails approximately 7.9 times higher image contrast from the coagulated tumor as that from the untreated tumor. Spectroscopic analysis exhibits that both 740 nm and 760 nm attains the maximum photoacoustic amplitudes from the treated areas. The proposed PAI‐guided dual‐thermal treatments (laser and HIFU) treatments can be a feasible therapeutic modality to treat bladder tumors in a controlled and efficient manner.

     

A multi-step directional generalized gradient vector flow snake for target tumor segmentation in US-guided high-intensity focused ultrasound ablation

Getting precise locations of target tumors can help to ensure ablation of cancerous tissues and avoid unwanted destruction of healthy tissues in high-intensity focused ultrasound (HIFU) treatment system. Because of speckle noise and spurious boundaries in ultrasound images, traditional image segmentation methods are not suitable for achieving the precise locations of target tumors in HIFU ablation. In this paper, a multi-step directional generalized gradient vector flow snake model is introduced for target tumor segmentation. In the first step, the traditional generalized gradient vector flow (GGVF) snake is used to obtain an approximate contour of the tumor. According to the approximate contour, a new distance map is generated. Subsequently, a new directional edge map is created by calculating a scalar product of the gradients of the distance map and the initial image. In this process, the gradient directional information and the magnitude information of the distance map are used to attenuate unwanted edges and highlight the real edges in the new directional edge map. Finally, a refined GGVF field is derived from a diffusion operation of the gradient vectors of the directional edge map. The GGVF field is used to refine the tumor's contour, by directing the approximate contour to edges with the desired gradient directionality. Based on the newly developed snake model, the influences of the spurious boundaries and the speckle noise are significantly reduced in the ultrasound image segmentation. Experimental results indicate that this technique is greatly useful for target tumor segmentation in HIFU treatment system     

Biochemical properties and progress in cancers of tRNA-derived fragments

tRNA-derived small RNAs (tRFs), a kind of noncoding RNAs, are generated from transfer RNAs. tRFs have some types according to their source and sizes. They play important roles in cell life and carcinogenesis. In this paper, we review the biogenesis and biological properties. We also focus on current progress of tRFs and some tsRNAs such as tRF-Leu-CAG, which have been studied or will be further investigated in tumorgenesis and diagnostic biomarkers in the clinic.     

Dimensionless solutions and general characteristics of bioheat transfer during thermal therapy

The derivation and application of the general characteristics of bioheat transfer for medical applications are shown in this paper. Two general bioheat transfer characteristics are derived from solutions of one-dimensional Pennes’ bioheat transfer equation: steady-state thermal penetration depth, which is the deepest depth where the heat effect reaches; and time to reach steady-state, which represents the amount of time necessary for temperature distribution to converge to a steady-state. All results are described by dimensionless form; therefore, these results provide information on temperature distribution in biological tissue for various thermal therapies by transforming to dimension form.