肿瘤的超声波治疗

文中就超声波热疗,高强度聚焦超声以及低频超声波在肿瘤治疗中的应用进行了描述。早期主要是利用超声波的热效应来治疗肿瘤,近年来兴起的高强度聚焦超声是热疗法的另一发展。它瞬间使肿瘤组织温度升至65℃以上,导致靶区组织凝固和坏死来达到对肿瘤的“热切除”,是一种安全、有效的肿瘤治疗手段,具有无限潜力。尽管低频超声治疗肿瘤的机制尚不明了,但因其可以诱导细胞凋亡,为肿瘤的治疗提供了新的途径,其治疗作用已受到重视。     

研究声波终止内出血有新进展

美国华盛顿大学医学院应用物理室正致力于研究利用高强度聚焦超声波终止内出血新技术,并已取得了新的进展。 在治疗过程中,医学科学家已发现,当高强度聚焦超声波被用来杀伤有害组织时,其周围组织的血液会经受一些变化,而这些变化促成血液凝固。研究者希望,利用超声波给内出血点     

HIFU治疗下生物体焦域温度分布的研究与应用

高强度聚焦超声(HIFU)为无创治疗肿瘤带来了新的途径,本文对HIFU治疗下生物体焦域热分布和热传导模型的理论进行了初步的介绍,并在理论的指导下进行不同治疗剂量的实验研究,结果表明组织内具有热波传热效应,治疗时可以根据治疗剂量的需要选取不同的参数,以达到最佳治疗效果。     

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。     

超声空化强度测量的研究进展

近几十年来,超声波已经广泛应用于生物学和医学领域,在医学领域中超声波可以作为信息载体用于探测人体的病变信息,并且可以用一定剂量的超声波作用于人体病变组织,并通过它对组织的作用达到一定的治疗目的。作为一种无创、非介入性外科技术,它的疗效和安全性越来越被人们所关注。超声波与人体组织的相互作用有三种,分别是机械机制,热学机制,和空化机制。对于机械机制和热机制人们比较熟悉,而对于空化机制则相对陌生。随着超声空化在医学中的应用越来越广泛,其安全性越来越受到人们的关心。要么是其强度迭不到治疗效果,要么是其强度过大损伤人体,因此其强度已成为人们关心的主要主题。本文主要介绍超声空化的主要探讨了几种测量方法及对超声空化有影响的几种参量,并对超声空化的发展进行了展望。     

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。     

高强度聚焦超声在药物控制释放的应用及进展

高强度聚焦超声能够以一种非侵入性的方式有效地穿透身体内部组织,聚焦在深层组织中一个很小的空间区域内,产生很强的声能,这些能量被组织吸收引起局部温度的升高。当温度到达热敏脂质体的相变温度时,磷脂烷基链构象的会发生改变,导致脂质体的通透性增强,从而能够促进药物的释放。因此,高强度聚焦超声可以被用作外源刺激控制体内特定位置热敏脂质体的药物释放。本文对高强度聚焦超声在药物控制释放领域的应用及进展进行综述。     

体外冲击波碎石焦点区域声压分布的时域有限差分法仿真研究

目的:研究体外冲击波碎石(Extracorporeal shock wave lithotropisy,ESWL)治疗中不同厚度人体组织对ESWL焦点区域大小、位置和声压分布的影响,为ESWL治疗计划的制定提供理论依据.方法:以Reichenberger的ESWL水中实验为参照例,分别建立三维单一人体组织和多层复合人体组织仿真模型,用时域有限差分(Finite Difference Time Domain,FDTD)数值仿真法,数值仿真ESWL治疗中形成的焦点区域.结果:高强度聚焦超声波在人体脂肪、肌肉层中形成的实际焦点区域大小、位置和焦点区域声压分布随着人体脂肪、肌肉层厚度的变化而变化.结论:ESWL治疗过程中由于人体组织厚度的不同,高强度聚焦超声非线性传播而形成的焦距和最大声压不同,对于不同体态的患者在ESWL治疗时,应该采用不同的焦距设定方法.     

高强度聚焦超声换能器温度场的数值仿真

相控阵高强度聚焦超声换能器可以通过换能器上不同阵元发射超声波的时间不同来实现变焦、多焦点。该论文应用Westervelt方程的近似式,结合Pennes热传导方程,以人体乳房为例,FDTD(finite difference time domain)仿真对比研究平面阵列相控聚焦换能器与曲面阵列相控聚焦换能器形成温度场的特性,同时数值仿真研究不同占空比的正弦激励函数、不同治疗频率、声强对曲面阵列相控聚焦换能器超声温度场的影响。研究结果表明曲面阵列相控聚焦换能器能有效地减少皮肤处的温升,对皮肤的伤害较小;对于曲面阵列相控聚焦换能器,不同占空比的正弦激励函数形成的可治疗区域(60℃以上)大小差别不大,但最高温度不同;随着频率升高,形成的可治疗区域体积减小;随着输入声强的增大,可治疗区域变大,但焦距不变。     

超声造影剂协同下的高强度聚焦超声对包虫原头蚴酶活性的影响

为探索高强度聚焦超声结合适宜比例的微泡造影剂对离体细粒棘球绦虫原头蚴酶活性的影响,实验分离包虫原头蚴,在原头蚴悬液中加入比例为1:80的微泡造影剂(含氟脂质体微泡),以声功率为50W的高强度聚焦超声波辐照30s,辐照后悬液涂片作酶组织化学染色,检测原头蚴三磷酸腺苷酶、葡萄糖-6-磷酸酶和琥珀酸脱氢酶的活性。结果显示,超声剂量相同时,微泡造影剂组的原头蚴三磷酸腺苷酶和琥珀酸脱氢酶活性明显低于单纯超声辐照组(P<0.05);葡萄糖-6-磷酸酶活性有一定降低;阴性对照组无酶反应物产生。高强度聚焦超声结合微泡造影剂能增强对离体原头蚴三磷酸腺苷酶和琥珀酸脱氢酶活性的抑制作用。     

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     

A review of focal therapy techniques in prostate cancer: clinical results for high-intensity focused ultrasound and focal cryoablation

The advancement of focal therapy technology for the treatment of prostate cancer (PCa) is emerging as an option for a middle ground between radical therapies and active surveillance for individuals identified with localized, low-grade PCa. Two promising techniques are high-intensity focused ultrasound (HIFU) and focal cryoablation. Both focal cryoablation and HIFU show promise, but additional prospective trials are necessary before any definitive conclusions can be made on either method's viability.     

高强度聚焦超声治疗子宫肌瘤300例的临床疗效分析

目的：探讨高强度聚焦超声（high intensity focused ultrasound,HIFU）治疗子宫肌瘤的临床疗效及其安全性。方法：回顾性分析我院2007年1月～2011年1月300例采用高强度聚焦超声治疗的子宫肌瘤患者的临床资料,比较分析治疗前后瘤体大小、病灶内部回声、临床症状改善情况、血流的变化及超声造影图像改变。结果：HIFU治疗后1、3、6及12个月,瘤体体积均较治疗前显著缩小（P〈0.05）,显效率80.33%（241例）,有效率19.33%（58例）,无效率0.33%（1例）,肌瘤所致的临床症状减轻或消失,瘤体内部回声增强,彩色血流均消失,超声造影瘤体内无灌注。治疗期间,患者出现治疗部位疼痛、骶尾部酸胀及肛门坠胀,治疗结束时症状消失;治疗过程中出现腿部疼痛、麻木症状,经过重新定位后症状消失,少数出现阴道少量流血,给予止血药;治疗后出现血尿,经大量喝水排尿后消失。结论：HIFU治疗子宫肌瘤是安全有效的,在妇科领域便于推广。     

Therapeutic strategies for localized prostate cancer

Prostate-specific antigen determinations for prostate cancer screening have led to a dramatic increase in the number of men who are diagnosed with organ-confined and therefore potentially curable prostate cancer. Advances in predicting outcomes with artificial neural networks may help to recommend one therapy over another. Less invasive forms of treatment, such as high-intensity focused ultrasound, may ultimately give patients additional options for treatment. Furthermore, attempts to better define the role of both neoadjuvant hormonal therapy and chemotherapy may give higher-risk patients better outcomes than with current treatments. These advances as well as continued research will likely lead to a day when more and more men with organ-confined disease will be cured.     

Release of endogenous danger signals from HIFU-treated tumor cells and their stimulatory effects on APCs

The effects of high-intensity focused ultrasound (HIFU) on the release of endogenous danger signals from tumor cells and subsequent activation of antigen-presenting cells (APCs) were evaluated in vitro. MC-38 mouse tumor cells were treated using a 1.1 MHz HIFU transducer under two different protocols (P-=6.7 MPa, 30% duty cycle, 5 s vs. P-=10.7 MPa, 3% duty cycle, 30 s) to produce either thermal necrosis or mechanical lysis of the tumor cells. Here, we report that HIFU treatment can cause the release of endogenous danger signals (ATP and hsp60) and exposure of dendritic cells (DCs) and macrophages to the supernatants of HIFU-treated tumor cells leads to an increased expression of co-stimulatory molecules (CD80 and CD86) with enhanced secretion of IL-12 by the DCs and elevated secretion of TNF-alpha by the macrophages. The potency in APC activation produced by mechanical lysis is much stronger than thermal necrosis of the tumor cells. These findings suggest that optimization of treatment strategy may help to enhance HIFU-elicited anti-tumor immunity.     

Synergistic effects of glycated chitosan with high-intensity focused ultrasound on suppression of metastases in a syngeneic breast tumor model

Stimulation of the host immune system is crucial in cancer treatment. In particular, nonspecific immunotherapies, when combined with other traditional therapies such as radiation and chemotherapy, may induce immunity against primary and metastatic tumors. In this study, we demonstrate that a novel, non-toxic immunoadjuvant, glycated chitosan (GC), decreases the motility and invasion of mammalian breast cancer cells in vitro and in vivo. Lung metastatic ratios were reduced in 4T1 tumor-bearing mice when intratumoral GC injection was combined with local high-intensity focused ultrasound (HIFU) treatment. We postulate that this treatment modality stimulates the host immune system to combat cancer cells, as macrophage accumulation in tumor lesions was detected after GC-HIFU treatment. In addition, plasma collected from GC-HIFU-treated tumor-bearing mice exhibited tumor-specific cytotoxicity. We also investigated the effect of GC on epithelial–mesenchymal transition-related markers. Our results showed that GC decreased the expression of Twist-1 and Slug, proto-oncogenes commonly implicated in metastasis. Epithelial-cadherin, which is regulated by these genes, was also upregulated. Taken together, our current data suggest that GC alone can reduce cancer cell motility and invasion, whereas GC-HIFU treatment can induce immune responses to suppress tumor metastasis in vivo.     

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.     

Immunocompetent orthotopic isograft mouse model of ovarian cancer for high-intensity focused ultrasound (HIFU) treatment

Ovarian epithelial carcinoma is the most common form of ovarian cancer, causing more deaths than any other cancer in women with gynecologic malignancies in the United States. The poor outcome for women with late-stage ovarian cancer underscores the need for early detection strategies and for new treatment options to be developed. High-intensity focused ultrasound (HIFU) is a therapeutic modality that is safe and effective against various types of solid tumors, and has the potential to serve as a treatment for ovarian cancer. Use of an appropriate animal model is important in obtaining relevant data for translational research. The purpose of the study reported here was to modify and create an immunocompetent orthotopic tumor isograft model for evaluation of intra-operative HIFU application. This model would resemble the clinical presentation of human patients with late-stage ovarian cancer. We were able to consistently produce a surgical model that presented with a single large, intra-abdominal tumor nodule within the left ovarian bursa, as well as multiple small nodules on the surface of other organs and tissues. This technique may also be used to refine other tumor models, using the ovarian bursa as an implant site for heterotopic tumor isografts.     

Effect of combination of high-intensity ultrasound treatment and dextran glycosylation on structural and interfacial properties of buckwheat protein isolates

This study investigated the effects of high-intensity ultrasound and glycosylation on the structural and interfacial properties of the Maillard reaction conjugates of buckwheat protein isolate (BPI). The covalent attachment of dextran to BPI was confirmed by examination of the Fourier-transform infrared spectra. Emulsifying properties of the conjugates obtained by ultrasound treatment were improved as compared to those obtained by classical heating. Structural feature analyses suggested that conjugates obtained by ultrasound treatment had less α-helix and more random coil, higher surface hydrophobicity and less compact tertiary structure as compared to those obtained by classical heating. The surface activity measurement revealed that the BPI–dextran conjugates obtained by ultrasound treatment were closely packed and that each molecule occupied a small area of the interface. Combination of ultrasonic treatment and glycosylation was proved to be an efficient way to develop new stabilizers and thickening agents for food in this study.     

Laparoscopic and percutaneous ablative techniques in the treatment of renal cell carcinoma

Widespread use of computed tomography, ultrasound, and magnetic resonance imaging has led to an increase in detection of relatively small renal masses, and approaches to managing them have evolved in the last two decades. Indications for nephron-sparing surgery have expanded, and minimally invasive procedures, which can confer advantages over open surgery, are now available. Ablative techniques offer a combination of nephron-sparing and minimally invasive approaches. Ablative techniques include cryoablation, radiofrequency ablation (RFA), and high-intensity focused ultrasound (HIFU). Cryoablation and RFA have been relatively safe. HIFU has been associated with serious side effects in animal models, and is not yet acceptable for use in humans. Ablative techniques require long-term studies to confirm lasting efficacy. The best modality for tumor targeting, monitoring of therapy, and follow-up is still under investigation. Debate exists regarding the best method for ensuring adequate intraoperative tumor cryoablation. For minimally invasive ablative measures to gain a place as nephron-sparing approaches, they should show both equivalent efficacy and reduced morbidity relative to those of open partial nephrectomy. These techniques should currently be reserved for selected patients and should be compared to the evolving modality of laparoscopic partial nephrectomy.