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。     

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。     

扁桃花药开裂前后壁层细胞形态变化及分析

为探明扁桃花药开裂前后壁层细胞形态变化,以鹰咀扁桃鳞片开裂期、小蕾期、大蕾期和盛花期的花蕾为研究材料,运用石蜡切片法结合铁苏木精染色法、考马斯亮蓝染色法、PAS染色法对花药壁层细胞进行染色;同时用Nikon SMZ-250体视显微镜拍摄花药开裂过程,观测花粉粒长、短轴长度。结果表明:(1)从鳞片开裂期到小蕾期,花粉粒的长、短轴长度都增大,多糖颗粒数量增多,绒毡层细胞完全消失,中层细胞和药隔处细胞逐渐溶解;药室内壁细胞切向长度增加幅度大于径向长度,内、外壁长度都增大,螺旋状纤维进一步形成;表皮细胞切向长度增加幅度大于径向长度。(2)从小蕾期到大蕾期花粉粒长、短轴长度明显增大,多糖颗粒持续增多;中层细胞和药隔处细胞大部分溶解;药室内壁细胞径向、切向长度持续增大,内壁长度增大、外壁长度趋于稳定,多糖颗粒数量减少,螺旋状纤维基本形成;表皮细胞切向减小幅度大于径向。(3)从大蕾期到花药半开裂,花粉粒长、短轴长度稍微增大;中层细胞和药隔处细胞完全溶解;药室内壁细胞切向长度持续增大,径向长度趋于稳定,内壁长度持续增大,外壁长度逐渐减小,多糖颗粒数量较少;表皮细胞切向、径向长度持续减小。(4)花药半开裂后,花粉粒长、短轴长度都减小;药室内壁细胞和表皮细胞切向、径向长度都减小;药室内壁细胞内、外壁长度减小并趋于接近,内壁长度减小趋势出现晚于外壁。研究认为,扁桃花药壁层细胞形态变化是花药开裂的基础,并与花药开裂密切相关。     

基于功率谱分析的外显子三周期特性的影响因素研究

针对不同长度外显子的三周期特性强弱不同,尤其是短外显子的三周期较弱的情况,利用Matlab软件建立了DNA序列外显子仿真模型。研究了外显子长度、碱基ATCG在密码子3个位置上出现的概率及不同映射方法对外显子三周期特性的影响。研究结果表明:当碱基ATCG在密码子的3个位置的概率一定时,随着外显子长度的增加,三周期特性会越来越明显,并具有一定的函数关系;当长度一定时,碱基ATCG在密码子的3个位置上出现的概率矩阵总分布方差越大,三周期特性越来越明显;不同数值映射方法对短外显子的三周期特性也有一定影响。研究结果可为外显子尤其是短外显子的有效检测提供参考。     

短波紫外线对日本三角涡虫的损伤及六种酶活力的影响

用短波紫外线(UV-C)照射处理日本三角涡虫,观察了涡虫的损伤状况,探讨了紫外线辐射对涡虫乳酸脱氢酶(LDH)、Na -K -ATP酶、Ca2 -Mg2 -ATP酶、超氧化物歧化酶(SOD)、过氧化氢酶(CAT)和谷胱甘肽过氧比物酶(GSH-PX)活力的影响。结果表明,短波紫外线辐射对涡虫的损伤明显,照射的时间越长,涡虫在照射后出现死亡解体现象的时间就越短。随着紫外线照射时间的延长,LDH活力呈下降趋势;Na -K -ATP酶活力呈上升趋势而Ca2 -Mg2 -ATP酶活力呈下降趋势;SOD活力有明显的增加;CAT活力有增加趋势;GSH-PX活力波动较大,但总体仍呈增加趋势。不论是从紫外线对日本三角涡虫的损伤情况、还是对其六种酶活力的影响来看,日本三角涡虫是一种对紫外线辐射非常敏感的动物,在检测紫外线辐射及筛选抗紫外线辐射防护剂等方面具有潜在价值和应用前景。     

古纹状体粗核损毁对燕雀鸣声的影响

古纹状体粗核(RA)损毁对燕雀常用短叫声的声学特性基本无影响, 但对习得性长叫声的时域和声学特性产生显著的失控性影响. RA损毁可导致单音调长叫声的基本音主频率约提升500音分, 并失去2个陪音. RA损毁不仅导致变音调长叫声的高潮声和尾声的声长分别平均增长13.4%～22.1%和缩短21.2%～24.2%, 而且高潮声的偶次谐分音的频率提升系数平均下降18.5%～25.8%, 递升速率随频率增高平均下降22.7%～24.0%. 进而表明, RA对习得性发声时域和频率特性的调控是相互匹配的. 同时, 双侧RA损毁可引起发声模式混乱, 所产生的长叫声具有单音调和变音调长叫声的双重特性, 前奏呈频率提升, 高潮声为单音调声.     

肿瘤微波热消融有效毁损区域温度场分布的仿真研究

本研究针对微波热消融肿瘤治疗过程中温度分布实时监测的核心问题,利用计算机模拟生物组织温度场分布,提出了基于有限元的微波消融温度场仿真方法。分别仿真了微波发射功率、作用时间及生物组织热物性参数对温度场分布的影响。研究结果表明:功率增大25%,毁损区温度平均升高20%;功率增大50%,温度升高40%;功率增大75%,温度升高60%。作用时间延长,温度场分布基本不变,但有效毁损体积增大,时间延长2倍可使毁损体积增大150%。导热系数对热疗远场区热能的扩散产生作用。经验证发现仿真结果与实验结果误差较小,证明了仿真方法的准确性。研究结果对于通过微波消融术前模拟来确定合适的发射功率和作用时间,以及制订合理的手术计划有重要的参考价值。     

浙东南杨梅叶片气孔观察与相似性研究

对浙江省东南部台州、温州、宁波及绍兴4个地区25份杨梅地方品种材料叶片的气孔特性进行研究,测定了气孔密度、气孔面积、气孔长、短轴和气孔器长、短轴。结果表明:所有材料气孔均属于平行型;气孔密度在500～1200个/mm2之间,主栽品种东魁、荸荠和丁岙梅气孔密度偏小;气孔面积从40～80μm2不等,以50μm2较为集中;气孔器长、短轴以变异1号最大,温州土梅最小;气孔长、短轴的变化规律为长轴>短轴。利用重心距离法对气孔密度、气孔面积、气孔大小和气孔器大小进行聚类分析,从距离0.5处进行分类,可分为5类。聚类分析表明:气孔的相似度在某种程度上可以作为区别品种的依据,但要精确地研究它们之间的遗传关系,还需与分子生物学、形态学等综合手段相结合予以鉴定。     

紫外灯对麦蛾卵的杀胚效果

【目的】为明确紫外照射麦蛾卵时最佳杀胚时间。【方法】在紫外杀胚装置中,设置5-25 min（间隔5 min）的时间,对比不同使用时长的灯管的杀胚效果;设置5-40 min（间隔5 min）的时间,并在距离紫外灯管距离不同的4个位置取样,对比杀胚效果。【结果】使用时间短的紫外灯管杀胚效果显著好于使用时间长的灯管;紫外照射时间和相对位置对麦蛾卵孵化率有一定的影响,总体上照射时间短,距离远,杀胚效果较差。紫外照射25min、40min的孵化率最低,分别为0.63%和0.77%。紫外照射15min之后各取样位置的卵孵化率差异不显著,最高为6.22%。经紫外线照射的麦蛾卵颜色与正常发育卵相似,会逐渐变为红棕色,但大部分卵不会孵化。【结论】紫外照射不会立即杀死卵内胚胎;紫外灯管使用一定时间后杀胚效果显著下降;应用本研究中的杀胚装置,处理时间以20-30 min为宜。     

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.     

Inducing occlusion effect in Y-shaped vessels using high-intensity focused ultrasound: finite element analysis and phantom validation

High-intensity focused ultrasound (HIFU) surgery offers a truly non-invasive treatment method with no skin incision, but precise targeting of tumour tissues for thermotherapy. Clinical experience reveals that the efficacy of tumour destruction not only involves in coagulating necrosis, but also involves in damaging the tumour vessels, which play an important role in tumour progression. These vessels take the elevated temperature away by perfusion, resulting in uncertainty of the occlusion effect during HIFU treatment. In this study, a Y-shaped vessel model comprising common and tumour vessels and an indirect fabrication method are proposed. The physical properties of the fabricated vessel phantom are measured and compared with human tissue. Simulation is performed using finite element modelling according to the tissue parameter, perfusion rate of the tumour vessel and treatment parameters including power intensity and exposure duration. The phantom experiments are carried out with perfusion of egg white to validate the threshold time prediction obtained from the simulation results. Our findings reveal that the threshold time obtained from experiments is consistent with the simulated one.     

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。     

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.

Magnetic Resonance Imaging Assessment of Effective Ablated Volume following High Intensity Focused Ultrasound

Under magnetic resonance (MR) guidance, high intensity focused ultrasound (HIFU) is capable of precise and accurate delivery of thermal dose to tissues. Given the excellent soft tissue imaging capabilities of MRI, but the lack of data on the correlation of MRI findings to histology following HIFU, we sought to examine tumor response to HIFU ablation to determine whether there was a correlation between histological findings and common MR imaging protocols in the assessment of the extent of thermal damage. Female FVB mice (n = 34), bearing bilateral neu deletion tumors, were unilaterally insonated under MR guidance, with the contralateral tumor as a control. Between one and five spots (focal size 0.5 × 0.5 × 2.5 mm³) were insonated per tumor with each spot receiving approximately 74.2 J of acoustic energy over a period of 7 seconds. Animals were then imaged on a 7T MR scanner with several protocols. T1 weighted images (with and without gadolinium contrast) were collected in addition to a series of T2 weighted and diffusion weighted images (for later reconstruction into T2 and apparent diffusion coefficient maps), immediately following ablation and at 6, 24, and 48 hours post treatment. Animals were sacrificed at each time point and both insonated/treated and contralateral tumors removed and stained for NADH-diaphorase, caspase 3, or with hematoxylin and eosin (H&E). We found the area of non-enhancement on contrast enhanced T1 weighted imaging immediately post ablation correlated with the region of tissue receiving a thermal dose CEM43 ≥ 240 min. Moreover, while both tumor T2 and apparent diffusion coefficient values changed from pre-ablation values, contrast enhanced T1 weighted images appeared to be more senstive to changes in tissue viability following HIFU ablation.     

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.     

Echinococcus granulosus: Protoscolicidal effect of high intensity focused ultrasound

High intensity focused ultrasound (HIFU) is a new non-invasive technique which can cause cell death and tissue necrosis by focusing high-energy ultrasonic waves on a single location. The aim of our work is to investigate the damaging effect of HIFU on Echinococcus granulosus protoscolices, as well as its inhibitory effect on growth of hydatid cysts derived from protoscolices. The damaging effect of HIFU on protoscolices was investigated by following parasite mortality after irradiation, while the inhibitory effect was investigated by infection experiments in vivo. The results demonstrated that HIFU was able to damage protoscolices and the protoscolicidal effect was dose-dependent and showed late-onset. The growth of protoscolices that survived the exposure to HIFU was obviously suppressed in vitro, and the mean weight of hydatid cysts resulting from such protoscolices in the experimental group was less than that in controls. Evidences including the protoscolicidal effect, fragmentized protoscolices and low post exposure temperatures, suggest that cavitation may contribute to the protoscolicidal effect of HIFU. In addition, the structure of the germinal membrane in cysts developing from the irradiated protoscolices was not as normal or intact as that from non-irradiated ones, and morphological changes related to degeneration were observed, suggesting that HIFU could prevent protoscolices from developing normal germinal membrane and consequently stop the proliferation of secondary hydatid cysts. HIFU demonstrated damaging effect on protoscolices, inhibited the growth of protoscolices in vitro and in vivo, and could be a possible therapeutic option for cystic echinococcosis.     

Arrhythmogenic effect of acoustic cavitation in isolated rat heart perfused with physiological solution

In experiments on isolated rat hearts the effects of focused continuous and impulse ultrasound (543 Hz, with intensity up to 7.8 W/cm2 at a focal region) on a pressure developed by left ventricle and electrograms were studied. In all experiments ultrasound induced extra-excitations of the heart, which appeared when intensity was 1.35 +/- 0.21 W/cm2 (n = 9). Simultaneously with the extra-excitations the cavitation bursts were recorded at intensity of 1.52 +/- 0.18 W/cm2 (n = 6). Acoustic cavitation (after 30 sec of exposure) resulted in a significant decrease of the developed pressure (from 100.8 +/- 3.8 mm Hg to 95.1 +/- 4.3 mm Hg, p 0.001), measured in 2 min after the end of the exposure. In the absence of cavitation the ultrasound was found to have no effects on cardiac performance. Electrograms recorded during acoustic pacing show that a pattern of the heart excitation changed from stimulus to stimulus.     

Concurrent Visualization of Acoustic Radiation Force Displacement and Shear Wave Propagation with 7T MRI

Manual palpation is a common and very informative diagnostic tool based on estimation of changes in the stiffness of tissues that result from pathology. In the case of a small lesion or a lesion that is located deep within the body, it is difficult for changes in mechanical properties of tissue to be detected or evaluated via palpation. Furthermore, palpation is non-quantitative and cannot be used to localize the lesion. Magnetic Resonance-guided Focused Ultrasound (MRgFUS) can also be used to evaluate the properties of biological tissues non-invasively. In this study, an MRgFUS system combines high field (7T) MR and 3 MHz focused ultrasound to provide high resolution MR imaging and a small ultrasonic interrogation region (~0.5 x 0.5 x 2 mm), as compared with current clinical systems. MR-Acoustic Radiation Force Imaging (MR-ARFI) provides a reliable and efficient method for beam localization by detecting micron-scale displacements induced by ultrasound mechanical forces. The first aim of this study is to develop a sequence that can concurrently quantify acoustic radiation force displacements and image the resulting transient shear wave. Our motivation in combining these two measurements is to develop a technique that can rapidly provide both ARFI and shear wave velocity estimation data, making it suitable for use in interventional radiology. Secondly, we validate this sequence in vivo by estimating the displacement before and after high intensity focused ultrasound (HIFU) ablation, and we validate the shear wave velocity in vitro using tissue-mimicking gelatin and tofu phantoms. Such rapid acquisitions are especially useful in interventional radiology applications where minimizing scan time is highly desirable.