超声弹性成像在肿瘤热疗无创监测中的应用

微波或射频热消融已成为肿瘤治疗的一种重要手段。实时准确地监测肿瘤热消融温度和热凝固区变化是保证治疗安全、取得良好疗效的关键。肿瘤热疗超声无创监测技术一直是国内外研究的热点。超声弹性成像作为一种新的超声组织定征技术,在肿瘤热疗无创监测方面正受到越来越多的关注。本文介绍了基于静态弹性成像、声辐射力弹性成像以及运动电极弹性成像进行肿瘤热疗无创监测的原理及方法,概述了国内外研究现状,并从以下方面总结了发展方向：如何实现活体内监测、如何结合现有的商业超声诊断系统、如何实现测温和凝固区监测的有效结合、如何提高抗运动伪影能力,以及如何提高监测的实时性和精确性。     

癌热疗中超声无创测温方法的研究

癌热疗中组织温度的测控直接影响到热疗的效果，利用超声可以实现热疗中组织温度的无创检测。本介绍了癌热疗中目前所采用的几种超声测温方法，对各种方法的原理及存在的问题进行了分析，概述了超声无创测温当前国内外的研究现状。     

利用超声射频实现肿瘤热疗实时无创测温方法

无创测温是肿瘤热疗的技术难题,超声射频测温技术是一种临床应用前景较好的无创测温方法。本文根据4种超声射频参数对超声射频测温方法进行了综述。诸多特征参数均与温度存在一定的相关性,测量方法中超声回波时移测温技术最为成熟,测温精度达到0．24℃。频移、能量、声衰减测温方法分别受不同因素的影响,定量测温尚存在一定困难。超声特征参数提取精度的提高将有效改善测温效果,多参数融合分析和凝固区定征识别也是超声无创测温技术的发展方向。     

癌热疗中超声无创测温方法的研究

癌热疗中组织温度的测控直接影响到热疗的效果 ,利用超声可以实现热疗中组织温度的无创检测。本文介绍了癌热疗中目前所采用的几种超声测温方法 ,对各种方法的原理及存在的问题进行了分析 ,概述了超声无创测温当前国内外的研究现状     

肿瘤热疗无损测温方法的研究进展

肿瘤热疗(hyperthermia)是利用肿瘤组织对温度敏感性高于正常组织的性质,即人体正常细胞在42. 5～43℃下不会受到损伤,但大部分肿瘤细胞在该温度下会被诱导进入凋亡过程。临床上应用超声、微波或红外等作为加热源,加热并杀死肿瘤组织而使得正常组织基本不受损伤。但是对于如何精确测量肿瘤热疗的温度从而控制热疗剂量仍然是一个难题。本文综述了目前肿瘤热疗过程中电阻抗断层成像(ectrical impedance tomograph,EIT)测温、红外热图引导技术、微波辐射测温法、超声无损测温、磁共振成像测温(magnetic resonance imaging,MRI)等无损测温方法及其研究现状,展望了如何有效精确测量肿瘤热疗时的温度,为控制肿瘤热疗的热剂量提供参考,以期在不伤害正常组织的前提下,使肿瘤组织产生不可逆的损伤。     

肿瘤热疗无损测温技术研究进展及存在问题

肿瘤热疗是指用加热来治疗肿瘤的一类治疗方法。基本原理是利用物理能量加热人体全身或局部,使肿瘤组织温度上升到有效治疗温度,并维持一定时间。利用正常组织和肿瘤细胞对温度耐受能力的差异,达到既能使肿瘤细胞凋亡、又不损伤正常组织的治疗目的。肿瘤热疗已成为继手术、放疗、化疗和免疫疗法之后的第五大疗法,是治疗肿瘤的一种新的有效手段。本文分析了现阶段肿瘤热疗无损测温方法的基本原理和存在问题,对当今无损测温在肿瘤热疗方面的理论研究和技术进展进行了总结。     

磁流体肿瘤热疗中超声无损测温技术的研究进展

磁流体肿瘤热疗技术(magnetic fluid hyperthermia,MFH)作为一种安全、高效的新型肿瘤治疗方法,近年来得到快速发展。MFH中最为关键的技术之一是肿瘤的温度检测。超声无损测温法由于能够实现准确实时的温度变化检测,近年在MFH技术中受到广泛关注,现已成为MFH技术中最为重要的测温方法之一。本文综述了近年国内外在MFH超声无损测温领域中的研究现状和发展状况。首先介绍了几种常见温度无损测温技术的发展现状,然后着重介绍了超声无损测温的研究状况,最后对超声无损测温的未来发展趋势进行了展望。     

腔道肿瘤热疗辐射器在组织体模中三维热场分布的空间点阵测量法研究

热场分布是检验热疗辐射器优劣的主要判据，而目前商品机多不给定量热场图，使用时有较大盲目性。因此，研究热场分布测量方法具有重要的实际意义。本文分析了热疗辐射器对活体组织和等效体模加热的温升规律。指出要获得较佳的治疗效果，辐射器必须有较好的ＳＡＲ热场分布特性。本文提出用空间点阵法快速获得组织体模内ＳＡＲ三维热场分布，介绍了其测量原理和数据处理方法及用于该方法的单针多点测温探针原理和多点测温探针组排及装置；最后以腔道（宫颈）微波热疗辐射器为例给出了用空间点阵法测量其在等效肌肉体模中三维热场分布的实验结果。本文所用测量方法较之目前国外使用的“分开体模兼热象二维测定法”和“体模内埋设空心塑料管法”有无需打开体模、测量迅速及有较好测温精度（±０．２℃）与空间分辨率（２ｍｍ），尤其是可得到三维热场分布图像等优点。该方法和装置已用于研制具有优质热场的腔道辐射器，并在肿瘤热疗中优选辐射器和治疗方案实践获得较好效果。     

纳米微粒磁性靶向热疗作用的应用研究(文献综述)

1 热疗及磁性靶向热疗的概念 将肿瘤部位加热到41℃以上治疗恶性肿瘤的方法称热疗（Hyperthermia）。高温治疗肿瘤由来已久,很早就被认为是有效的疗法。近30年来,随着高温设备的不断更新,加热技术、测温技术的不断发展,高温疗法已成为肿瘤治疗的重要手段之一。目前常用的热疗方法如射频、微波、激光、聚焦超声、全身热疗、隔离灌注等,因对肿瘤的靶向能力差,易导致周围组织的温度升高,具有一定的创伤性,其临床应用范围有限。近年来,随着纳米技术的研究进展,在纳米水平上研制纳米磁性微粒作为药物载体又引起了人们的广泛兴趣,磁性微粒不仅可以用作药物载体,而且在交变磁场下还可发热升温,引起了人们对其在肿瘤热疗方面的潜在价值的重视。     

肿瘤局部热疗与抗肿瘤免疫

近年来,随着热生物学和热物理学的不断发展以及加温、测温、控温等方法的不断改进,热疗有了较快的发展,有望成为继手术、放疗、化疗和生物治疗后又一重要的肿瘤治疗手段.研究表明,局部的热疗不仅通过加温杀死肿瘤细胞,而且还能诱导机体产生抗肿瘤免疫,本文就局部热疗与抗肿瘤免疫的机理及其应用加以综述.     

Real-time volumetric MRI thermometry of focused ultrasound ablation in vivo: a feasibility study in pig liver and kidney

MR thermometry offers the possibility to precisely guide high-intensity focused ultrasound (HIFU) for the noninvasive treatment of kidney and liver tumours. The objectives of this study were to demonstrate therapy guidance by motion-compensated, rapid and volumetric MR temperature monitoring and to evaluate the feasibility of MR-guided HIFU ablation in these organs. Fourteen HIFU sonications were performed in the kidney and liver of five pigs under general anaesthesia using an MR-compatible Philips HIFU platform prototype. HIFU sonication power and duration were varied. Volumetric MR thermometry was performed continuously at 1.5 T using the proton resonance frequency shift method employing a multi-slice, single-shot, echo-planar imaging sequence with an update frequency of 2.5 Hz. Motion-related suceptibility artefacts were compensated for using multi-baseline reference images acquired prior to sonication. At the end of the experiment, the animals were sacrificed for macroscopic and microscopic examinations of the kidney, liver and skin. The standard deviation of the temperature measured prior to heating in the sonicated area was approximately 1 °C in kidney and liver, and 2.5 °C near the skin. The maximum temperature rise was 30 °C for a sonication of 1.2 MHz in the liver over 15 s at 300 W. The thermal dose reached the lethal threshold (240 CEM(43) ) in two of six cases in the kidney and four of eight cases in the liver, but remained below this value in skin regions in the beam path. These findings were in agreement with histological analysis. Volumetric thermometry allows real-time monitoring of the temperature at the target location in liver and kidney, as well as in surrounding tissues. Thermal ablation was more difficult to achieve in renal than in hepatic tissue even using higher acoustic energy, probably because of a more efficient heat evacuation in the kidney by perfusion.     

肿瘤射频热疗比吸收率与温度场仿真及影响参数的研究

针对非侵入性射频热疗的SAR及瞬态温度分布进行了物理、数学建模和数值模拟计算。该模型能正确反映电磁波在生物组织内的衰减,在温度场模拟中考虑了血液灌流量随组织温度变化和肿瘤区低血液灌流的特点,使模拟结果更加符合临床实际。我们还对射频热疗电磁能量分布和温度分布的特点、特别是电磁波频率、血液灌流等因素对有效治疗深度的影响作了细致的分析和讨论。对指导射频热疗临床实践具有重要的指导意义。     

多模态图像配准技术在HIFU手术中的应用

在交互式的图像导航热疗手术中 ,需要对病灶目标进行非常精确的实时成像和定位。而现有的超声成像技术很难单独完成这个任务。本研究提出了一种用手术前MRI图像重建的三维图像与手术中的超声图像进行配准的方法 ,对肝部肿瘤热疗手术中的目标进行定位。其配准方法采用的是基于肝部血管和表皮等特征的遗传配准算法。     

Fluorescence Imaging for Real-Time Monitoring of High-Intensity Focused Ultrasound Cardiac Ablation

Side effects and limitations of radio-frequency ablation of cardiac arrhythmias prompted search for alternative energy sources and means of their application. High-intensity focused ultrasound (HIFU) is becoming an increasingly attractive modality for ablation because of its unique ability for non-invasive or minimally invasive, non-contact focal ablation in 3D volume without affecting intervening and surrounding cells. The purpose of this study is to develop a real-time monitoring technique to elucidate HIFU-induced modifications of electrical conduction in cardiac tissues and to investigate the HIFU cardiac ablation process to help to achieve optimal HIFU ablation outcome. We conducted experimental studies applying HIFU at 4.23 MHz to ablate the atrio-ventricular (AV) node and ventricular tissue of Langendorff-perfused rabbit hearts. We employed fluorescent voltage-sensitive dye imaging and surface electrodes to monitor the electrical conduction activity induced by HIFU application in real time. In ventricular epicardium HIFU ablation, fluorescent imaging revealed gradual reduction of the plateau phase and amplitude of the action potential. Subsequently, conduction block and cell death were observed at the site of ablation. When HIFU was applied to the AV node, fluorescent imaging and electrograms revealed the development of the AV block. The study establishes that real-time fluorescent imaging provides novel monitoring and assessment to study HIFU cardiac ablation, which may be able to provide improved understanding of HIFU cardiac ablation process and mechanism useful for development of successful clinical applications.     

Multiparametric MRI analysis for the evaluation of MR‐guided high intensity focused ultrasound tumor treatment

For the clinical application of high intensity focused ultrasound (HIFU) for thermal ablation of malignant tumors, accurate treatment evaluation is of key importance. In this study, we have employed a multiparametric MRI protocol, consisting of quantitative T₁, T₂, ADC, amide proton transfer (APT), T_1ρ and DCE‐MRI measurements, to evaluate MR‐guided HIFU treatment of subcutaneous tumors in rats. K‐means clustering using all different combinations of the endogenous contrast MRI parameters (feature vectors) was performed to segment the multiparametric data into tissue populations with similar MR parameter values. The optimal feature vector for identification of the extent of non‐viable tumor tissue after HIFU treatment was determined by quantitative comparison between clustering‐derived and histology‐derived non‐viable tumor fractions. The highest one‐to‐one correspondence between these clustering‐based and histology‐based non‐viable tumor fractions was observed for the feature vector {ADC, APT‐weighted signal} (R² to line of identity (R²_y=x) = 0.92) and the strongest agreement was seen 3 days after HIFU (R²_y=x = 0.97). To compare the multiparametric MRI analysis results with conventional HIFU monitoring and evaluation methods, the histology‐derived non‐viable tumor fractions were also quantitatively compared with non‐perfused tumor fractions (derived from the level of contrast enhancement in the DCE‐MRI measurements) and 240 CEM tumor fractions (i.e. thermal dose > 240 cumulative equivalent minutes at 43 °C). The correlation between histology‐derived non‐viable tumor fractions directly after HIFU and the 240 CEM fractions was high, but not significant. The non‐perfused fractions overestimated the extent of non‐viable tumor tissue directly after HIFU, whereas an underestimation was observed 3 days after HIFU. In conclusion, we have shown that a multiparametric MR analysis, especially based on the ADC and the APT‐weighted signal, can potentially be used to determine the extent of non‐viable tumor tissue 3 days after HIFU treatment. We expect that this method can be incorporated in the current clinical workflow of MR–HIFU ablation therapies. Copyright © 2015 John Wiley & Sons, Ltd.     

Rapid motion correction in MR‐guided high‐intensity focused ultrasound heating using real‐time ultrasound echo information

The objective of this study was to evaluate the feasibility of integrating real‐time ultrasound echo guidance in MR‐guided high‐intensity focused ultrasound (HIFU) heating of mobile targets in order to reduce latency between displacement analysis and HIFU treatment. Experiments on a moving phantom were carried out with MRI‐guided HIFU during continuous one‐dimensional ultrasound echo detection using separate HIFU and ultrasound imaging transducers. Excellent correspondence was found between MR‐ and ultrasound‐detected displacements. Real‐time ultrasound echo‐based target tracking during MR‐guided HIFU heating is shown with the dimensions of the heated area similar to those obtained for a static target. This work demonstrates that the combination of the two modalities opens up perspectives for motion correction in MRI‐guided HIFU with negligible latency. Copyright © 2010 John Wiley & Sons, Ltd.     

基于虚拟仪器技术概念的V-HIFU无创外科系统模型

高强度聚焦超声(high intensity focused ultrasound,HIFU)作为一种新兴的无创外科肿瘤治疗技术,正日益引起人们的高度重视.本文将虚拟仪器(virtual instrument,Ⅵ)技术概念引入到HIFU研究领域,提出了一套全新的V-HIFU系统模型,并从理论上论证了其必要性与可行性,给出了详细的模块构造及具体的设计思路.V-HIFU系统实现了HIFU研究重点由治疗硬件向临床治疗计划软件的转化,它所具备的可模拟性、开放性和模块化特点有望对HIFU技术的发展产生积极的影响.     

In vivo MR guided boiling histotripsy in a mouse tumor model evaluated by MRI and histopathology

Boiling histotripsy (BH) is a new high intensity focused ultrasound (HIFU) ablation technique to mechanically fragmentize soft tissue into submicrometer fragments. So far, ultrasound has been used for BH treatment guidance and evaluation. The in vivo histopathological effects of this treatment are largely unknown. Here, we report on an MR guided BH method to treat subcutaneous tumors in a mouse model. The treatment effects of BH were evaluated one hour and four days later with MRI and histopathology, and compared with the effects of thermal HIFU (T‐HIFU). The lesions caused by BH were easily detected with T₂w imaging as a hyper‐intense signal area with a hypo‐intense rim. Histopathological evaluation showed that the targeted tissue was completely disintegrated and that a narrow transition zone (<200 µm) containing many apoptotic cells was present between disintegrated and vital tumor tissue. A high level of agreement was found between T₂w imaging and H&E stained sections, making T₂w imaging a suitable method for treatment evaluation during or directly after BH. After T‐HIFU, contrast enhanced imaging was required for adequate detection of the ablation zone. On histopathology, an ablation zone with concentric layers was seen after T‐HIFU. In line with histopathology, contrast enhanced MRI revealed that after BH or T‐HIFU perfusion within the lesion was absent, while after BH in the transition zone some micro‐hemorrhaging appeared. Four days after BH, the transition zone with apoptotic cells was histologically no longer detectable, corresponding to the absence of a hypo‐intense rim around the lesion in T₂w images. This study demonstrates the first results of in vivo BH on mouse tumor using MRI for treatment guidance and evaluation and opens the way for more detailed investigation of the in vivo effects of BH. Copyright © 2016 John Wiley & Sons, Ltd.     

HIFU在牛肝组织中形成线形凝固性坏死的剂量投放研究

探讨高强度聚集超声(High ntensity focused ultrasound,HIFU)在牛肝组织中形成线形凝固性坏死的剂量投放策略。首先在辐照深度2cm处用声强(ISAL)6500W/cm2的HIFU定点辐照牛肝1s得到一横径W为3mm的点状凝固性坏死。采用单个点状凝固性坏死相互叠加形成线形凝固性坏死时,相邻的两个单次辐照的空间间距D分别为1、2、2.5、3、4.5、5mm。当采用直线扫描形成线形凝固性坏死时,扫描速度V分别为1、3、6、7mm/s,往返次数为1。辐照结束后沿长度方向剖开,直视下观察最大剖面的损伤形态、范围、程度和损伤的完整性。结果表明,当D≤W时,采用单个点状凝固性坏死相互叠加能在牛肝中形成一个完整的线形凝固性坏死,当D>W时不能在牛肝中形成一个完整的线形凝固性坏死,且中间有正常组织的残留。当运动速度V为3mm/s,往返次数为1,采用直线扫描方式能在牛肝中形成了一个边界清楚、能量分布均匀、中间没有正常组织残留的完整的线形凝固性坏死。实验结果证实:依据单个点状凝固性坏死的声辐照和其大小确定形成线形凝固性坏死的辐照参数并进行剂量投放能够在组织中形成线形凝固性坏死。     

新型HIFU治疗头的研究

目的:肿瘤治疗中,焦区温度的实时监控和焦区体积的预测非常重要。本文旨在解决在超声治疗过程中对焦区的精确定位和对系统的声输出实现精确的实时控制的问题。方法:设计一种新型治疗头,通过在聚焦透镜上固定检测探头并整合计算机控制系统及超声图文信息管理系统。结果:不仅能实现对病灶的精确定位,并能对病灶进行实时的判断和治疗,从而实现治疗可控化。结论:新型治疗头设计的提出,可以实现对肿瘤的精确治疗的和在治疗过程中的实时检控。对HIFU治疗头的设计和研制有借鉴意义。