MRI monitoring of nanocarrier accumulation and release using Gadolinium‐SPIO co‐labelled thermosensitive liposomes

Encapsulation of anticancer drugs in triggerable nanocarriers can beneficially modify pharmacokinetics and biodistribution of chemotherapeutic drugs, and consequently increase tumor drug concentration and efficacy, while reducing side effects. Thermosensitive liposomes release their contents triggered by hyperthermia, which can be, for example, precisely delivered using an MR Imaging‐guided focused ultrasound procedure. In such a scenario, it is attractive to demonstrate the accumulation of liposomes before applying hyperthermia, as well as to document the release of liposome content using MRI. To address this need, thermosensitive liposomes were developed and characterized, which were doubly loaded by iron oxide nanoparticles and Gd‐chelate, as opposed to loading with a single contrast agent. When intact, the transverse relaxivity of the liposomes is high allowing detection of carriers in tissue. After heating the longitudinal relaxivity steeply increases indicating release of the small molecular contents. By choosing the appropriate MR sequences, availability and release can be evaluated without interference of one contrast agent with the other. Copyright © 2016 John Wiley & Sons, Ltd.     

生物学焦域的概念及在高强度聚焦超声切除组织中的作用

本实验研究和比较了高强度聚焦超声(HIFU)所致体内深部组织凝固性坏死灶的形状和大小.结果显示参照同样的治疗参数,HIFU所致凝固性坏死灶的大小和形状在体内和体外有较大的差异.体内体积与治疗参数、靶组织的结构、功能和运动有密切关系.与物理学焦域比较,凝固性坏死灶体积亦可能命名为HIFU的生物学焦域.     

Blood flow occlusion via ultrasound image-guided high-intensity focused ultrasound and its effect on tissue perfusion

This study investigated the induction of tissue necrosis by arterial blood flow occlusion using ultrasound image-guided high-intensity focused ultrasound (HIFU). We constructed a prototype HIFU transducer in combination with an imaging probe that provided color Doppler imaging and ultrasound contrast imaging. The HIFU beam was aimed into a branch of the renal artery in vivo. The renal artery branches of eight rabbits were occluded by HIFU at an intensity of 4 kW/cm(2) (from 2 to 10 times of each sonication for 5 s). When the HIFU exposure was successful, complete cessation of blood flow was observed by color Doppler imaging with success rate of 100% (8/8). Furthermore, lack of perfusion was observed in the renal cortex with a contrast-enhanced image. Postmortem histologic evaluation showed a wedge-shaped area of infarction in six of seven cases, corresponding to the lack of the contrast medium in the ultrasound image. These results demonstrated that ultrasound image-guided HIFU can be used to induce arterial occlusion, thus producing infarction and necrosis of the perfused tissue.     

基于FPGA技术的P-HIFU系统相控信号发生器的研制

研制的相控信号发生器,基于FPGA设计,能够满足相控超声聚焦,输出路数以及对相位分辨率的要求。经过实验测定,此相控信号发生器能输出256路相位信号,每路相位信号的相位分辨率为2nS,具有实现简单,系统可靠性较高等优点。     

High-intensity focused ultrasound in ovarian cancer xenografts

INTRODUCTION: The purpose of this study was to determine whether highintensity focused ultrasound (HIFU) is an effective treatment for ovarian carcinoma in an athymic nude mouse model. METHODS: Thirty-nine female athymic nude mice were inoculated subcutaneously with 5-7xx10(6) SKOV3 human ovarian cancer cells. Thirty-two animals developed tumours and were randomly divided into three groups: HIFU (n=18), sham treatment (n=8) and control (n=6). The sonographic appearance of the tumours during therapy was recorded. After therapy, the tumours were examined transcutaneously by ultrasound every 4 days for 4 weeks. Tissue samples were taken from the treatment sites and histopathologically examined by light or electron microscopy. RESULTS: Three weeks after HIFU treatment, a 100% reduction in tumour volume was observed in all animals in the HIFU group, whereas tumours in the sham-treated and control groups continued to grow. Pathological examination of HIFU-treated tumour tissue samples showed complete coagulation necrosis of the tumour. CONCLUSION: Our results indicate that HIFU appears to be an effective therapy for ovarian carcinoma tumours in the athymic nude mouse model. We suggest that it may hold promise for the clinical treatment of late-stage and recurrent ovarian cancer.     

高强度聚焦超声作用下的组织焦域能量分析及实验验证

为研究发生空化前高强度聚焦超声(HIFU)作用的最佳治疗模式, 从声场和热场的仿真计算和新鲜离体牛肝实验验证出发,根据声能转化成热能的原理,分析了组织焦域温度上升造成组织损伤的变化过程;建立了与温度相关的组织损伤预测模型;计算了形成1 mm宽度的生物学焦域所吸收的能量;并在75、100、125、150 W这4种声功率下,按照350 J能量,共进行了24组新鲜离体牛肝组织的实验,验证该能量强度形成的生物学焦域尺寸。结果表明,经组织衰减后生物学焦域吸收的超声能量为350 J时,在新鲜离体牛肝组织中形成的生物学焦域宽度为(1.1±0.1)mm;当换能器物理学焦域的长短轴之比在4~10之间变动时,吸收350 J形成的生物学焦域宽度保持在(1.0±0.2) mm。在充分除气的均匀介质牛肝中,当换能器的物理学焦域长短轴比在4~10之间时,吸收350 J能量,声功率100 ~150 W是形成(1.0±0.2) mm宽度的生物学焦域的最佳治疗模式。     

高强度聚焦超声辐照离体及在体心肌组织的比较研究

目的　探讨并比较高强度聚焦超声(HIFU)定位损伤离体心肌及活体心肌的量效关系。方法　采用不同功率(3W ,4W ,5W)的HIFU ,在不同辐照时间(5S ,8S ,10S ,15S ,2 0S ,60S ,180S)的作用下,对5只正常猪离体心脏及8只活体兔心脏进行定位损伤,观察并测定损伤区形态及体积,并对损伤区进行病理学检查。结果　不同剂量下HIFU所致的生物学焦域范围为1～3 0 0mm3 ,不同处理因素间损伤体积具有显著性差异(P <0 .0 5 ) ,相同剂量下离体心肌受损体积大于在体心肌的受损体积。损伤形态随剂量增大由椭球形向锥体形、不规则形发展。组织学观察可见凝固性坏死及损伤区与正常心肌组织的明显分界。结论　HIFU可定点使离体心肌及活体心肌发生坏死而不伤及周围组织。     

基于GRNN的HIFU治疗中生物组织变性自动识别方法

目的 探讨一种基于广义回归神经网络 (Generalized Regression Neural Network，GRNN)的高强度聚焦超声（High intensity focused ultrasound，HIFU）治疗所致生物组织变性的自动识别方法。方法 提取超声减影图像的灰度-梯度共生矩阵及灰度差分中18个特征参数，分别利用P值假设验证法、欧几里得距离（欧氏距离）判定法对特征参数进行二次选择，最后选取欧氏距离靠前的2个最佳特征参数随机组合输入GRNN进行生物组织变性自动识别。结果 分别结合GRNN的总识别率：一次筛选掉的平均值、对比度分比二次筛选时欧氏距离靠后的小梯度优势、能量低，二次筛选得到的灰度分布不均性、梯度分布不均匀性分别约91.18%、90.20%，2个最佳特征参数组合高达98.04%。结论 经筛选后的特征参数组合输入GRNN的总识别率显著提高。     

La thérapie par ultrasons focalisés : état actuel et applications potentielles en neurochirurgie

High Intensity Focused Ultrasound (HIFU) therapy is an innovative approach for tissue ablation, based on high intensity focused ultrasound beams. At the focus, HIFU induces a temperature elevation and the tissue can be thermally destroyed. In fact, this approach has been tested in a number of clinical studies for the treatment of several tumors, primarily the prostate, uterine, breast, bone, liver, kidney and pancreas. For transcranial brain therapy, the skull bone is a major limitation, however, new adaptive techniques of phase correction for focusing ultrasound through the skull have recently been implemented by research systems, paving the way for HIFU therapy to become an interesting alternative to brain surgery and radiotherapy.