基于Eclipse图形建模框架的图形化脉冲序列设计软件的实现

采用Eclipse图形建模框架（Graphical Modeling Framework,GMF）技术构建了一个图形化磁共振脉冲序列设计软件．软件具备所见即所得的特点,用户使用拖放方式所画出的脉冲序列与教科书和参考文献上的脉冲序列几乎一样．软件支持核磁共振（Nuclear Magnetic Resonance,NMR）波谱和磁共振成像（Magnetic Resonance Imaging,MRI）的脉冲序列设计,同时提供实验参数管理模块,实现脉冲序列基础上的NMR实验设计和执行预览．得益于GMF完善的模型-视图-控制器模式和强大的代码生成能力,软件开发周期大幅度缩短、扩展能力大幅度提高．     

基于CEST机制的pH成像方法、原理和应用

化学交换饱和转移（Chemical Exchange Saturation Transfer,CEST）技术作为一种新型的磁共振成像（Magnetic Resonance Imaging,MRI）技术.它的原理为溶质池中被激发饱和的质子与游离水中未被饱和的质子间的化学交换,能够引起水质子磁共振信号的下降,从而获得组织内生物分子的相关信息.由于质子间的交换速率k_ex与组织微环境的pH值之间存在直接联系,因而可以通过溶质质子的CEST信号对活体组织进行pH成像.目前用于pH成像的溶质分子既包括内源性游离的蛋白质、多肽分子,还包括一系列的外源性小分子和金属螯合物.通过不同类型的比率法、内源性胺和酰胺浓度-独立检测（Amine and Amide Concentration-independent Detection,AACID）等成像方法,能够获得肾脏、中风脑组织以及肿瘤组织的pH图谱.本文详细总结了2000年以来利用CEST技术进行pH成像方面的研究进展,包括对比剂、成像方法和相关应用,展望了活体组织pH成像的发展趋势和应用前景.     

1.5 T磁共振化学交换饱和转移成像的影响因素分析

本文探讨1.5 T磁共振化学交换饱和转移（Chemical Exchange Saturation Transfer,CEST）成像的影响因素.通过试管模型和临床病例,采用GE Signa HDe 1.5 T磁共振成像（Magnetic Resonance Imaging,MRI）扫描仪分别进行不同矩阵、激励次数、翻转角、磁化传递翻转角的CEST成像对比分析,以及不同激励次数、磁化传递翻转角的Z谱分析,并从成像组织、成像设备、成像技术等方面对原始图信号、酰胺质子转移（Amide Proton Transfer,APT）信号及Z谱进行分析研究.实验结果表明1.5 T MRI扫描仪的CEST图像信噪比相对较低,且磁场稳定性及均匀度影响了CEST成像的效果.在其他参数不变的情况下,降低采集矩阵和增加激励次数与翻转角可以增加原始图像信噪比.磁化传递翻转角为105°时,CEST成像效果最好.激励次数为2、磁化传递翻转角为105°时,所得数据符合组织Z谱情况.模型Z谱在磁化传递频率为-294~-194 Hz范围可显示30%谷氨酸（Glu）、碘剂（I₃₂₀）、纯水（H₂O）、肌酸（Cr）的信号差异,与H₂O差异最大处在-244~-214 Hz.原始图像信号30% I₃₂₀明显高于Glu、H₂O、Cr,Cr略低于Glu,APT图Cr略低于Glu.25例脑肿瘤的APT图呈高信号、12例脑梗塞的APT图呈低信号,CEST原始图像均可区分病变区域.有12例因采集时间、患者配合情况、环境及室温等影响导致CEST成像的失败.由此得出1.5 T场强下,CEST技术受到成像组织、设备、技术等因素的影响,需要进行多方面优化.在保证磁场稳定性及均匀度的情况下,优化参数的CEST成像和Z谱成像可以区分代谢物及其浓度.     

温敏性磁共振成像造影剂的研究进展

磁共振成像（MRI）技术可实现对温度的非侵入式检测．温敏性MRI造影剂能够对温度变化做出响应,进而导致与其结合的水质子的弛豫速率、信号强度或化学位移等磁共振参数发生显著改变,已作为将温度信号转化为磁共振信号的传感器广泛应用于MRI测温技术中．本文介绍了温敏性MRI造影剂的种类、原理、研究现状及其应用前景．     

基于回波平移序列的快速三维磁共振温度成像方法

高强度聚焦超声（HIFU）是一种无创的热消融疗法，为保证其安全性和有效性，需要一种精度高、速度快的测温方法在其治疗过程中对温度进行监控.基于质子共振频率位移（PRFS）的磁共振温度成像（MRT）对温度具有较高的灵敏度，且与温度具有良好的线性关系，因此常被用于引导HIFU治疗.然而在实际应用中，HIFU治疗的最大隐患在于可能造成表皮灼伤，并且灼伤区域可能与焦点区域相隔较远.因此MRT的监控范围十分重要.本文基于三维回波平移成像序列，结合可控混叠的空间并行成像技术，实现了时间分辨率为3 s的快速三维温度成像.为了验证该方法的精度，本文首先设计了仿体降温实验，利用光纤温度计验证回波平移序列测温的准确度和精确度.然后在室温条件下扫描离体猪肉组织，对比加速前后的MRT的测温精确度.在HIFU加热条件下扫描离体猪肉组织，对比加速前后的MRT的测温准确度.结果显示，本文提出的方法可以在3 s内完成三维温度精准测量，对于HIFU治疗的安全监控具有重要意义.     

微波诱导光学核极化进展

微波诱导光学核极化（Microwave-Induced Optical Nuclear Polarization,MIONP）技术利用光激发三重态样品来极化电子,再用微波将处于非热平衡态的电子极化转移到待检测原子核,将原子核的检测灵敏度提高几个量级甚至更多．这种灵敏度极化增强方法可以用来进行蛋白质结构和动力学检测、光化学和光物理进程的基础研究、量子计算和低场核磁共振（Low-field Nuclear Magnetic Resonance,Low-field NMR）与磁共振成像（Magnetic Resonance Imaging,MRI）应用研究．该文简要分析了MIONP的物理原理及其在核极化增强中的优势,结合实验条件综述了一些重要的成果．最后,对微波诱导光学核极化的前景作了展望．     

具有独立延时功能的脉冲序列发生器

在磁共振成像（Magnetic Resonance Imaging,MRI）系统中,谱仪是中心控制单元,其脉冲序列发生器输出的多通道指令分别控制各硬件部件协调工作,从而采集数据并重建图像,各硬件部件之间的相对延时会影响磁共振图像的质量或导致系统无法采集到图像.为了解决这一问题,本文设计了每个输出通道均具有可调延时功能的脉冲序列发生器,每一路通道的最大延时值为819 μs,延时步进值为50 ns,可实现对相对延时的精确补偿.由于延时功能是通过在脉冲序列发生器每个输出通道上添加独立延时电路实现的,因此具有结构简单,灵活性高的优点.     

增强低场下脑功能磁共振成像显著性的研究

实现了基于低场0.35 T磁共振成像系统的大脑功能磁共振成像（functional Magnetic Resonance Imaging,fMRI）的研究. 基于质子密度加权的快速自旋回波(Turbo Spin Echo,TSE)图像,重点研究增强低场fMRI显著性的方法,目的在于提高低场fMRI的可用性. 结果表明：健康受试者在执行手动任务期间,大脑运动区的信号强度变化可以由基于血管外质子信号增强 (Signal Enhancement by Extravascular water Protons,EEP)的对比机制探测. 优化TSE序列参数能提高图像SNR和扫描速度,并在统计分析中增加外在屏蔽图像,可以有效地提高低场下fMRI研究结果的显著性.     

基于数据采集卡和GPU的MRI信号接收设计

针对磁共振成像(Magnetic Resonance Imaging,MRI)的信号接收,提出一种基于高速数据采集卡和图形处理器(Graphic Processing Unit,GPU)的接收方法.采样每一行数据时,在谱仪输出触发脉冲的控制下,数据采集卡对前置放大器输出的信号进行直接采样.然后,使用GPU并行实现数字混频、多级滤波抽取和图像重建.GPU具有很高的运算速度,信号处理过程中可以根据需要灵活地实现滤波器的组合.同时,数据全部采用双精度浮点类型,保证了很高的运算精度,提高了重建图像的信噪比.MRI实验证明了该信号接收方法的可行性.     

磁共振技术在食品质量与安全研究中的应用

食品质量与安全的检测分析关乎人们生命健康,高效可靠的检测手段是该领域研究的必需条件.磁共振技术,包括核磁共振（NMR）和磁共振成像（MRI）,是20世纪的新兴的食品检测技术．由于该技术对样品几乎无破坏性,且具有可实时快速测量、可同时检测多成分、可获得样品内部图像等优点,因此在食品检测领域的应用越来越多．为了促进该技术在食品科学领域更为深入的应用,该文对磁共振技术在国内外食品质量和安全研究领域的应用现状进行了总结．     

Influence of dynamic tissue properties on temperature elevation and lesions during HIFU scanning therapy:Numerical simulation

When large tumors are treated,ablation of the entire volume of tumors requires multiple treatment spots formed by high intensity-focused ultrasound(HIFU)scanning therapy.The heating effect of HIFU on biological tissue is mainly reflected in temperature elevation and tissue lesions.Tissue property parameters vary with temperature and,in turn,the distribution of temperature as well as the heating effects change accordingly.In this study,an HIFU scanning therapy model considering dynamic tissue properties is provided.The acoustic fields and temperature fields are solved combining the Helmholtz wave equation with Pennes bio-heat transfer equation based on the finite element method(FEM)to investigate the effects of various tissue properties(i.e.,the attenuation coefficient,acoustic velocity,thermal conductivity,specific heat capacity,density,and blood perfusion rate)on heating performance.Comparisons of the temperature distribution and thermal lesions under static and dynamic properties are made based on the data of tissue property parameters varying with temperature.The results show that the dynamic changes of thermal conductivity,specific heat capacity,and acoustic velocity may account for the decrease of temperature elevation in HIFU treatment,while the dynamic changes of attenuation coefficient,density,and blood perfusion rate aggravate the increase of temperature on treatment spots.Compared with other properties,the dynamic change of attenuation coefficient has a greater impact on tissue temperature elevation.During HIFU scanning therapy,the temperature elevation and tissue lesions of the first treatment spot are smaller than those of the subsequent treatment spots,but the temperature on the last treatment spot drops faster during the cooling period.The ellipsoidal tissue lesion is not symmetrical;specifically,the part facing toward the previous treatment spot tends to be larger.Under the condition of the same doses,the temperature elevation and the size of tissue lesions under dynamic properties present significant growth in comparison to static properties.Besides,the tissue lesion begins to form earlier with a more unsymmetrical shape and is connected to the tissue lesion around the previous treatment spot.As a result,lesions around all the treatment spots are connected with each other to form a closed lesion region.The findings in this study reveal the influence of dynamic tissue properties on temperature elevation and lesions during HIFU scanning therapy,providing useful support for the optimization of treatment programs to guarantee higher efficacy and safety.     

高强度聚焦超声用于肿瘤治疗的研究

高强度聚焦超声（ＨＩＦＵ）能在短时间内使病变组织的温度升至７０℃以上,导致病变组织凝固坏死,是一种具有巨大潜力的、非侵入的、有效的肿瘤治疗手段。本文对ＨＩＦＵ的动物试验、临床应用及治疗装置的研究情况进行了总结,分析了该技术尚存在的问题,最后展望了其应用前景。     

Nakagami-m parametric imaging for characterization of thermal coagulation and cavitation erosion induced by HIFU

Nowadays, both thermal and mechanical ablation techniques of HIFU associated with cavitation have been developed for noninvasive treatment. A specific challenge for the successful clinical implementation of HIFU is to achieve real-time imaging for the evaluation and determination of therapy outcomes such as necrosis or homogenization. Ultrasound Nakagami-m parametric imaging highlights the degrading shadowing effects of bubbles and can be used for tissue characterization. The aim of this study is to investigate the performance of Nakagami-m parametric imaging for evaluating and differentiating thermal coagulation and cavitation erosion induced by HIFU. Lesions were induced in basic bovine serum albumin (BSA) phantoms and ex vivo porcine livers using a 1.6 MHz single-element transducer. Thermal and mechanical lesions induced by two types of HIFU sequences respectively were evaluated using Nakagami-m parametric imaging and ultrasound B-mode imaging. The lesion sizes estimated using Nakagami-m parametric imaging technique were all closer to the actual sizes than those of B-mode imaging. The p-value obtained from the t-test between the mean m values of thermal coagulation and cavitation erosion was smaller than 0.05, demonstrating that the m values of thermal lesions were significantly different from that of mechanical lesions, which was confirmed by ex vivo experiments and histologic examination showed that different changes result from HIFU exposure, one of tissue dehydration resulting from the thermal effect, and the other of tissue homogenate resulting from mechanical effect. This study demonstrated that Nakagami-m parametric imaging is a potential real-time imaging technique for evaluating and differentiating thermal coagulation and cavitation erosion.     

HIFU治疗中换能器驱动电功率变化机制及规律*

高强度聚焦超声(HIFU)治疗中的驱动电功率对治疗效率起着非常关键的作用,驱动电功率控制的精准性势必会影响治疗的效率和安全性。前期研究表明：HIFU治疗过程中焦域瞬态物理特性的变化会导致换能器的负载阻抗发生变化,进而影响HIFU驱动电功率,但驱动电功率与焦域瞬态物理特性之间的影响关系及规律尚不明确。该文基于电压、电流传感器、空化检测探头和温度传感器等器件,构建了一种HIFU治疗中驱动电功率实时监测及焦域声空化、温度检测系统。基于该实验研究系统,以离体牛心组织作为HIFU辐照对象,分别研究了HIFU焦域温度变化、声空化及组织损伤与驱动电功率之间的变化关系及规律。研究结果表明：当焦域温度升高时,驱动电功率缓慢上升,驱动电功率与温度变化有良好的相关性;当空化产生时,驱动电功率出现明显的波动;当组织出现损伤时,驱动电功率呈陡然下降的变化。三种情景下,驱动电功率变化有明显区别,这有望为区分HIFU治疗过程中焦域处发生损伤和空化以及实时监测靶组织损伤程度提供一种新的解决方案。     

Chalcone JAI‐51 improves efficacy of synchrotron microbeam radiation therapy of brain tumors

Microbeam radiation therapy (MRT), a preclinical form of radiosurgery, uses spatially fractionated micrometre‐wide synchrotron‐generated X‐ray beams. As MRT alone is predominantly palliative for animal tumors, the effects of the combination of MRT and a newly synthesized chemotherapeutic agent JAI‐51 on 9L gliosarcomas have been evaluated. Fourteen days (D14) after implantation (D0), intracerebral 9LGS‐bearing rats received either MRT, JAI‐51 or both treatments. JAI‐51, alone or immediately after MRT, was administered three times per week. Animals were kept up to ～20 weeks after irradiation or sacrificed at D16 or D28 after treatment for cell cycle analysis. MRT plus JAI‐51 increased significantly the lifespan compared with MRT alone (p = 0.0367). JAI‐51 treatment alone had no effect on rat survival. MRT alone or associated with JAI‐51 induced a cell cycle blockade in G2/M (p < 0.01) while the combined treatment also reduced the proportion of G0/G1 cells. At D28 after irradiation, MRT and MRT/JAI‐51 had a smaller cell blockade effect in the G2/M phase owing to a significant increase in tumor cell death rate (<2c) and a proportional increase of endoreplicative cells (>8c). The combination of MRT and JAI‐51 increases the survival of 9LGS‐bearing rats by inducing endoreduplication of DNA and tumor cell death; further, it slowed the onset of tumor growth resumption two weeks after treatment.     

High intensity focused ultrasound-induced gene activation in solid tumors

In this work, the activation of heat-sensitive trans-gene by high-intensity focused ultrasound (HIFU) in a tumor model was investigated. 4T1 cancer cells (2 x 10(6)) were inoculated subcutaneously in the hind limbs of Balb/C mice. The tumors were subsequently transducted on day 10 by intratumoral injection of a heat-sensitive adenovirus vector (Adeno-hsp70B-Luc at 2 x 10(8) pfu/tumor). On day 11, the tumors were heated to a peak temperature of 55, 65, 75, or 85 degrees C within 10-30 s at multiple sites around the center of the tumor by a 1.1- or 3.3-MHz HIFU transducer. Inducible luciferase gene expression was increased from 15-fold to 120-fold of the control group following 1.1-MHz HIFU exposure. Maximum gene activation (120-fold) was produced at a peak temperature of 65-75 degrees C one day following HIFU exposure and decayed to baseline within 7 days. HIFU-induced gene activation (75 degrees C-10 s) could be further improved by using a 3.3-MHz transducer and a dense scan strategy to 170-fold. Thermal stress, rather than nonthermal mechanical stress, was identified as the primary physical mechanism for HIFU-induced gene activation in vivo. Overall, these observations open up the possibility for combining HIFU thermal ablation with heat-regulated gene therapy for cancer treatment.     

Model-based PRFS thermometry using fat as the internal reference and the extended Prony algorithm for model fitting

A model-based proton resonance frequency shift (PRFS) thermometry method was developed to significantly reduce the temperature quantification errors encountered in the conventional phase mapping method and the spatiotemporal limitations of the spectroscopic thermometry method. Spectral data acquired using multi-echo gradient echo (GRE) is fit into a two-component signal model containing temperature information and fat is used as the internal reference. The noniterative extended Prony algorithm is used for the signal fitting and frequency estimate. Monte Carlo simulations demonstrate the advantages of the method for optimal water-fat separation and temperature estimation accuracy. Phantom experiments demonstrate that the model-based method effectively reduces the interscan motion effects and frequency disturbances due to the main field drift. The thermometry result of ex vivo goose liver experiment with high intensity focused ultrasound (HIFU) heating was also presented in the paper to indicate the feasibility of the model-based method in real tissue.     

Hemorrhage control in arteries using high-intensity focused ultrasound: a survival study

High-intensity focused ultrasound (HIFU) has been shown to provide an effective method for hemorrhage control of blood vessels in acute animal studies. The objective of the current study was to investigate the long-term effects of HIFU-induced hemostasis in punctured arteries. The femoral arteries ( approximately 2mm in diameter) of 25 adult anesthetized rabbits were surgically exposed, and either punctured and treated with HIFU (n=15), served as control (no puncture and no HIFU application: n=7), or were punctured and left untreated (n=3). Treated animals were allowed to recover, and examined and/or sacrificed on days 0, 1, 3, 7, 14, 28, and 60 after treatment to obtain ultrasound images and samples of blood and tissue. Hemostasis (arrest of bleeding) was achieved in all 15 of the HIFU-treated arteries. Eleven of the arteries were patent after HIFU treatment, and four arteries were occluded, as determined by Doppler ultrasound. The median HIFU application time to achieve hemostasis was 20s (range 7-55 s) for the patent arteries and 110 s (range 50-134 s) for the occluded arteries. In untreated animals, bleeding had not stopped after 120 s. One of the occluded arteries had reopened by day 14. No immediate or delayed re-bleeding was observed after HIFU treatment. Maximal blood flow velocities were similar in HIFU-treated patent vessels and control vessels. No significant difference in hematocrits was found between HIFU-treated and control groups at different time points after the procedure. Light microscopy observations of the HIFU-treated arteries showed disorganization of adventitia, and coagulation and thinning of the tunica media. The general organization of the adventitia and tunica media recovered to normal appearance within 28 days, with some thinning of the tunica media observed up to day 60. Neointimal hyperplasia was observed on days 14 and 28. The results show that HIFU can produce effective and long-term (up to 60 days) hemostasis of punctured femoral arteries while preserving normal blood flow and vessel wall structure in the majority of vessels.     

Extracorporeal high intensity focused ultrasound ablation in the treatment of 1038 patients with solid carcinomas in China: an overview

The ideal treatment of localized cancer should directly cause an irreversible and complete death of tumor cells without damage to surrounding normal tissue. High intensity focused ultrasound (HIFU) is such a potential treatment, which induces a complete coagulative necrosis of a tumor at depth through the intact skin. The idea that using an extracorporeal source of therapeutic ultrasound was introduced more than 50 years ago [J. Gen. Physiol. 26 (1942) 179]. However, up to now, most of the studies on HIFU have been dealing with animal experiments because this extracorporeal technique is very complicated in clinical applications. The purpose of this study is to introduce Chinese clinical experience of using extracorporeal HIFU for the treatment of patients with various kinds of solid tumor. From December 1997 to October 2001, a total of 1038 patients with solid tumors underwent HIFU ablation in China. Among them, 313 patients were treated at the Chongqing University of Medical Sciences, China. Pathological examination showed that the target region presented clear evidence of cellular destruction. Small blood vessels less than 2 mm in diameter were severely damaged. Follow-up diagnostic imaging revealed that there was no, or reduced, blood supply, and no uptake of radioisotope in the treated tumor after HIFU, both indicating a positive therapeutic response and an absence of viable tumor. Imaging at 6-12 months showed obvious regression of the lesion. Four-year follow-up data were significantly observed in patients with hepatocellular carcinoma, osteosarcoma, and breast cancer. An extremely low major complication rate was noted. It is concluded that HIFU ablation is a safe, effective, and feasible modality for the ablation of carcinomas.