超极化Xenon对慢阻肺的可视化加权成像（英文）

超极化气体3He或者129Xe扩散加权成像已经被证明了能够有效检测慢性阻塞性肺部疾病(COPD)中肺部微结构的改变.相比于3He,129Xe更便宜而且更容易获得,但是129Xe成像中较低的信噪比致使129Xe的肺部表面扩散系数(ADC)的测量面临着许多困难.在该研究中,为了得到更高的图像信噪比,作者对气球模型,健康大鼠和COPD大鼠进行了单个b值(14 cm2/s)的扩散加权超极化129Xe磁共振成像(MRI).所有的COPD模型大鼠是通过烟熏和注射内毒素(LPS)进行诱导得到的.在7 T磁共振成像仪上面获得了大鼠肺实质的超极化129Xe ADC值分布图.COPD大鼠肺实质的129Xe ADC值是0.044 22±0.002 9和0.042 34±0.002 3 cm2/s(Δ=0.8/1.2 ms),远大于健康大鼠肺实质的129Xe ADC值0.037 7±0.002 3和0.036 7±0.001 3 cm2/s.而且COPD大鼠肺实质相关的129Xe ADC直方图也表现出了一定的展宽.这些结果说明了COPD大鼠肺泡空腔的增大能够通过129Xe在肺里面的ADC增长和相关直方图的拓宽反应出来,从而证明了单个b值的扩散加权MRI方法可以有效地对COPD大鼠进行检测.     

超极化Xenon 对慢阻肺的可视化加权成像

超极化气体3He 或者¹²⁹Xe 扩散加权成像已经被证明了能够有效检测慢性阻塞性肺部疾病(COPD)中肺部微结构的改变．相比于³He,¹²⁹Xe 更便宜而且更容易获得,但是¹²⁹Xe 成像中较低的信噪比致使¹²⁹Xe 的肺部表面扩散系数(ADC)的测量面临着许多困难．在该研究中,为了得到更高的图像信噪比,作者对气球模型,健康大鼠和COPD大鼠进行了单个b 值(14 cm2/s)的扩散加权超极化¹²⁹Xe 磁共振成像(MRI)．所有的COPD模型大鼠是通过烟熏和注射内毒素(LPS)进行诱导得到的．在7 T 磁共振成像仪上面获得了大鼠肺实质的超极化¹²⁹Xe ADC 值分布图．COPD 大鼠肺实质的¹²⁹Xe ADC 值是0.044 22±0.002 9 和0.042 34±0.002 3 cm2/s (Δ = 0.8/1.2 ms),远大于健康大鼠肺实质的¹²⁹Xe ADC 值0.037 7±0.002 3 和0.036 7±0.001 3 cm2/s．而且COPD 大鼠肺实质相关的¹²⁹Xe ADC 直方图也表现出了一定的展宽．这些结果说明了COPD 大鼠肺泡空腔的增大能够通过129Xe 在肺里面的ADC 增长和相关直方图的拓宽反应出来,从而证明了单个b 值的扩散加权MRI 方法可以有效地对COPD 大鼠进行检测．     

超极化129Xe磁共振分子影像学

磁共振分子影像学发展的主要瓶颈之一在于灵敏度的限制,基于激光光泵和自旋交换技术能获得增强4~5个量级的超极化¹²⁹Xe磁共振信号,因此超极化¹²⁹Xe磁共振分子影像学相对于传统MRI在灵敏度上表现出巨大的优势. 围绕提高灵敏度这一核心MRI问题及其在科学研究中的应用,该文介绍了目前基于超极化¹²⁹Xe的生物分子探针的基本结构和原理,阐述了与之相关的分子影像学方法和技术,同时评述了当前的最新研究进展和发展方向.     

超极化129Xe自动收集-升华装置研究

因其较高的核自旋极化度所提供的探测灵敏度，超极化¹²⁹Xe气体已被成功应用于动物和人体磁共振成像（MRI）.但是，在超极化¹²⁹Xe的收集-升华过程中，多种因素会导致¹²⁹Xe核自旋弛豫，进而限制其应用范围.本文通过理论模型分析和实验测量，验证了温度、磁场、螺旋冷阱材质等对冷冻恢复过程中超极化¹²⁹Xe弛豫的影响；同时，测量了自动收集-升华装置的稳定性.研究结果表明，升华方式和冷阱材质对¹²⁹Xe极化度损耗的影响显著；自制收集-升华装置的自动化程度高、长时间稳定，¹²⁹Xe极化度的恢复率可达到85.6% ± 4.7%.本研究非常有助于提升超极化¹²⁹Xe在动物和人体MRI中的使用效率.     

胶束型磁共振成像分子探针的设计与应用

飞速发展的分子影像学在肿瘤的早期诊断及检测中发挥着越来越重要的作用.磁共振成像(MRI)是分子影像学的重要分支，具有其他成像技术不可比拟的优越性和广阔的发展前景.它不需要放射性示踪剂，没有电离辐射，具有高的空间、时间分辨率和组织对比度.近年来，新型磁共振分子探针及成像序列取得了一系列进展，包括环境响应型分子探针、¹⁹F成像、¹²⁹Xe超极化成像以及化学交换饱和转移成像等，进一步拓展了MRI的应用范围.研究和开发靶向性好、弛豫效率高且安全性好的新型多模态MRI造影剂，进一步提高灵敏度是MRI领域的一项重要课题，例如将胶束的特性与一些MRI新方法结合，寻找合适的胶束体系，以提高MRI分子探针的灵敏度；或者引入多模态分子探针，弥补磁共振方法的不足.本文综述了胶束型MRI分子探针核心技术的研究进展与应用，并指出分子影像技术在生物医学工程研究和临床诊断中的重要性.     

新型葫芦[6]脲纳米颗粒超极化129Xe"分子笼"研究

在相同浓度下,超极化¹²⁹Xe的核磁共振（NMR）灵敏度是传统质子NMR的10 000倍以上,但单原子Xe不具有靶向性,只有单一NMR信号.若超极化¹²⁹Xe与“分子笼”相结合,就能获得新的“笼”内Xe信号,为发展超极化¹²⁹Xe分子探针奠定基础.因此,构建新型的“分子笼”是发展新型超极化¹²⁹Xe分子探针的一个重要方向.葫芦[6]脲纳米颗粒的出现能改善以葫芦[6]脲为主体的¹²⁹Xe分子探针水溶性差、信号弱等缺点.本文构建了水溶性的葫芦[6]脲纳米颗粒,并发现其具有葫芦[6]脲/纳米颗粒内部两个“笼”内¹²⁹Xe信号.这一发现使这种纳米颗粒具有成为超极化¹²⁹Xe分子探针的潜力,能降低检测结果中假阳性和假阴性的发生率,值得更深入的探索和研究.     

超极化气体肺部磁共振成像

磁共振成像(MRI)技术具有非侵入、无放射性的特点,在临床疾病诊断中具有独特的优势,但是肺部空腔的特殊结构使传统质子MRI无法对其直接成像.自旋交换光抽运(SEOP)方法可以使惰性气体原子的极化度增强4个量级以上,从而使肺部的气体MRI成为可能.该文介绍了超极化惰性气体肺部MRI的最新研究进展,包括超极化气体磁共振相关参数的测量方法、肺部通气结构成像、肺部气体交换功能成像,同时比较了常用于肺部MRI气体的优点和缺点.     

低场流动系统中超极化129Xe气体辐射阻尼的研究

辐射阻尼现象通常只有在高磁场中,利用高分辨率谱仪,才能观测到液态,像水质子这样具有大自旋浓度的信号.但是我们在低场流动系统中,利用光泵自旋交换的方法,获得高度极化的129Xe气体,从而使我们能观测到,流动系统下超极化129Xe的气态辐射阻尼信号.     

低场流动系统中超极化^129Xe气体辐射阻尼的研究

辐射阻尼现象通常只有在高磁场中，利用高分辨率谱仪，才能观测到液态，像水质子这样具有大自旋浓度的信号。但是我们在低场流动系统中，利用光泵自旋交换的方法，获得高度极化的^129Xe气体，从而使我们能观测到，流动系统下超极化^129Xe的气态辐射阻尼信号。     

功能磁共振成像技术及其在脑科学研究中的应用

功能磁共振成像(functional magnetic resonance imaging,fMRI)是用磁共振成像的方法研究人脑和神经系统的功能,它是磁共振成像的一种应用和深入发展.磁共振成像(magnetic resonance imaging,MRI)是核磁共振成像的简称,它是基于核磁共振(nuclear magnetic resonance,NMR)这一物理现象发展起来的.1946年物理学家首先发现核磁共振现象,直到70年代初,它一直沿着高分辨核磁共振波谱学的方向发展.1972年达马迪安(R.Damadian)提出磁共振成像的设想,并指出可以用磁共振成像仪扫描人体检查疾病.1973年劳特伯(P.Lauterbur)在<自然>杂志上发表了用试管样品得到的磁共振截面像,显示了磁共振成像的可能性.从此开始了磁共振成像的发展时期.1980年在实验室中获得了足够清晰的有医学诊断意义的人的头部磁共振图像.磁共振成像仪逐渐形成产业,开始进入医院,主要用于观测人体内部解剖学结构,确定肿瘤和其他疾病的位置.1990年对动物的实验表明,有可能用磁共振成像研究大脑功能.1991年发表了第一幅有意义的人的大脑功能的图像,显示出视觉刺激在大脑的反应,开始了脑功能磁共振成像的研究.至今刚刚过了几年的时间,这一研究领域已经得到了迅速发展.     

Magnetic resonance imaging of dissolved hyperpolarized Xe using a membrane-based continuous flow system

A technique for continuous production of solutions containing hyperpolarized ¹²⁹Xe is explored for MRI applications. The method is based on hollow fiber membranes which inhibit the formation of foams and bubbles. A systematic analysis of various carrier agents for hyperpolarized ¹²⁹Xe has been carried out, which are applicable as contrast agents for in vivo MRI. The image quality of different hyperpolarized Xe solutions is compared and MRI results obtained in a clinical as well as in a nonclinical MRI setting are provided. Moreover, we demonstrate the application of ¹²⁹Xe contrast agents produced with our dissolution method for lung MRI by imaging hyperpolarized ¹²⁹Xe that has been both dissolved in and outgassed from a carrier liquid in a lung phantom, illustrating its potential for the measurement of lung perfusion and ventilation.     

An investigation of pipeline materials for continuous hyperpolarized 129Xe gas spectroscopy

In order to establish a continuous hyperpolarized xenon-129 (HP-129Xe) gas delivery system for MR imaging, the effect of the metallic materials in the gas pipeline on the signal intensity was investigated. In the gas pipeline, an appropriate surface is needed to minimize wall relaxation by the HP-129Xe gas caused by the interaction between the HP gas and the surface, which can lead to signal loss. Although Pyrex glass is a popular material for the HP gas chamber, it is fragile under heat or physical stress. In this study, five stainless steel tubes (STs) prepared with different surface film-forming processes were examined. The MR signal intensities of HP-129Xe gas that passed through each tube were then compared. The film passivated by iron fluoride maintained the highest level of hyperpolarization, whereas that passivated by chromium oxide maintained the lowest. A ST with an appropriate passive film may be a useful alternative to a Pyrex glass pipeline.     

Theoretical prediction and experimental measurement of the field dependence of the apparent transverse relaxation of hyperpolarized noble gases in lungs

In this work, computer modeling based on a finite element method is used to simulate the T2* relaxation of hyperpolarized noble gases (HNG) in the lungs. A physical model of lung airways consisting of a phantom constructed from micro-capillary fibers of diameters similar to the size of lung airways with semi-permeable walls is also presented. The fibers are surrounded by a liquid medium (water) of magnetic susceptibility similar to lung tissue. Theoretical predictions of the field strength dependence of T2* for 129Xe in the phantom and in vivo rat lung are presented. These predictions are in good agreement with experimental T2* values obtained from the phantoms and in vivo rat lungs (160, 19 and 8 ms) at three different field strengths (0.074, 1.89 and 3T, respectively) using hyperpolarized 129Xe. The strong dependence of T2* on field strength is consistent with the theoretical prediction that low fields may be optimal for HNG MR imaging of the lungs as the decreased T2* at high fields necessitates an increase in bandwidth for conventional MR imaging.     

A rapid and precise probe for measurement of liquid xenon polarization

The relaxation time of liquid (129)Xe is very long (>15 min) and the signal at thermal equilibrium is weak. Therefore, determination of the absolute polarization enhancement of hyperpolarized (129)Xe by direct measurement is tedious. We demonstrate a fast and precise alternative, based on the dipolar field created by liquid hyperpolarized (129)Xe contained in a cylindrical sample tube. The dipolar field is homogeneous in the bulk of the tube and adds to the external field, causing a shift in the Larmor frequencies of all nuclear spins. We show that the frequency shift of the proton in CHCl(3) (chloroform), which dissolves homogeneously in xenon over a fairly broad temperature range, is an excellent probe for (129)Xe polarization. Frequency measurements are precise and the experiment is much faster than by direct measurement. Furthermore the (129)Xe polarization is minimally disturbed since no rf pulses are applied directly to (129)Xe and since chloroform is a fairly weak source of (129)Xe relaxation. The experiments are reproducible and require only standard NMR instrumentation.     

T(1) of (129)Xe in blood and the role of oxygenation.

In previous experiments by the authors, in which hyperpolarized (129)Xe was dissolved in fresh blood samples, the T(1) was found to be strongly dependent on the oxygenation level, the values increasing with oxygenation: T(1) was about 4 s in deoxygenated samples and about 13 s in oxygenated samples. C. H. Tseng et al. (1997, J. Magn. Reson. 126, 79-86), on the other hand, recently reported extremely long T(1) values using hyperpolarized (129)Xe to create a "blood foam" and found that oxygenation decreased T(1). In their experiments, the continual and rapid exchange of hyperpolarized (129)Xe between the gas phase (within blood-foam bubbles) and the dissolved phase (in the skin of the bubbles) necessitated a complicated analysis to extract the effective blood T(1). In the present study, the complications of hyperpolarized (129)Xe exchange dynamics have been avoided by using thermally polarized (129)Xe dissolved in whole blood and in suspensions of lysed red blood cells (RBC). During T(1) measurements in whole blood, the samples were gently and continuously agitated, for the entire course of the experiment, to avert sedimentation. Oxygenation was found to markedly increase the T(1) of (129)Xe in blood, as originally measured, and it shifts the RBC resonance to a higher frequency. Carbon monoxide has a similar but somewhat stronger effect.     

Production of nitrogen-free, hyperpolarized 129Xe gas

129 Xe with a nuclear polarization far above the thermal equilibrium value (hyperpolarized) is used in NMR studies to increase sensitivity. Gaseous, adsorbed, or dissolved xenon is utilized in physical, chemical, and medical applications. With the aim in mind to study single-crystal surfaces by NMR of adsorbed hyperpolarized ¹²⁹Xe, three problems have to be solved. The reliable production of ¹²⁹Xe with highest nuclear polarization possible, the separation of the xenon gas from the necessary quench gas nitrogen without polarization loss, and the dosing/delivery of small amounts of polarized xenon gas to a sample surface. Here we describe an optical pumping setup that regularly produces xenon gas with a ¹²⁹Xe nuclear polarization of 0.7(±0.07). We show that a freeze–pump–thaw separation of xenon and nitrogen is feasible without a significant loss in xenon polarization. The nitrogen partial pressure can be suppressed by a factor of 400 in a single separation cycle. Dosing is achieved by using the low vapor pressure of a frozen hyperpolarized xenon sample. Received: 12 June 1998     

XeNA: An automated ‘open-source’ Xe hyperpolarizer for clinical use

Here we provide a full report on the construction, components, and capabilities of our consortium’s “open-source” large-scale (~ 1 L/h) ¹²⁹Xe hyperpolarizer for clinical, pre-clinical, and materials NMR/MRI (Nikolaou et al., Proc. Natl. Acad. Sci. USA, 110, 14150 (2013)). The ‘hyperpolarizer’ is automated and built mostly of off-the-shelf components; moreover, it is designed to be cost-effective and installed in both research laboratories and clinical settings with materials costing less than $125,000. The device runs in the xenon-rich regime (up to 1800 Torr Xe in 0.5 L) in either stopped-flow or single-batch mode—making cryo-collection of the hyperpolarized gas unnecessary for many applications. In-cell ¹²⁹Xe nuclear spin polarization values of ~ 30%–90% have been measured for Xe loadings of ~ 300–1600 Torr. Typical ¹²⁹Xe polarization build-up and T₁ relaxation time constants were ~ 8.5 min and ~ 1.9 h respectively under our spin-exchange optical pumping conditions; such ratios, combined with near-unity Rb electron spin polarizations enabled by the high resonant laser power (up to ~ 200 W), permit such high P_Xe values to be achieved despite the high in-cell Xe densities. Importantly, most of the polarization is maintained during efficient HP gas transfer to other containers, and ultra-long ¹²⁹Xe relaxation times (up to nearly 6 h) were observed in Tedlar bags following transport to a clinical 3 T scanner for MR spectroscopy and imaging as a prelude to in vivo experiments. The device has received FDA IND approval for a clinical study of chronic obstructive pulmonary disease subjects. The primary focus of this paper is on the technical/engineering development of the polarizer, with the explicit goals of facilitating the adaptation of design features and operative modes into other laboratories, and of spurring the further advancement of HP-gas MR applications in biomedicine.     

MR-compatible ventilator for small animals: computer-controlled ventilation for proton and noble gas imaging

We describe an MR-compatible ventilator that is computer controlled to generate a variety of breathing patterns, to minimize image degrading effects of breathing motion, and to support delivery of gas anesthesia and experimental inhalational gases. A key feature of this ventilator is the breathing valve that attaches directly to the endotracheal tube to reduce dead volume and allows independent control of inspiratory and expiratory phases of ventilation. This ventilator has been used in a wide variety of MR and x-ray microscopy studies of small animals, especially for MR imaging the lungs with hyperpolarized gases ((3)He & (129)Xe).     

Time resolved spectroscopic NMR imaging using hyperpolarized Xe

We have visualized the melting and dissolution processes of xenon (Xe) ice into different solvents using the methods of nuclear magnetic resonance (NMR) spectroscopy, imaging, and time resolved spectroscopic imaging by means of hyperpolarized ¹²⁹Xe. Starting from the initial condition of a hyperpolarized solid Xe layer frozen on top of an ethanol (ethanol/water) ice block we measured the Xe phase transitions as a function of time and temperature. In the pure ethanol sample, pieces of Xe ice first fall through the viscous ethanol to the bottom of the sample tube and then form a thin layer of liquid Xe/ethanol. The xenon atoms are trapped in this liquid layer up to room temperature and keep their magnetization over a time period of 11 min. In the ethanol/water mixture (80 vol%/20%), most of the polarized Xe liquid first stays on top of the ethanol/water ice block and then starts to penetrate into the pores and cracks of the ethanol/water ice block. In the final stage, nearly all the Xe polarization is in the gas phase above the liquid and trapped inside the pores. NMR spectra of homogeneous samples of pure ethanol containing thermally polarized Xe and the spectroscopic images of the melting process show that very high concentrations of hyperpolarized Xe (about half of the density of liquid Xe) can be stored or delivered in pure ethanol.     

Human Pulmonary Hyperpolarized ~(129)Xe MRI: a Preliminary Study

We study the feasibility and safety of human lung hyperpolarized(HP)~(129)Xe magnetic resonance imaging(MRI).There is no significant change in physiological parameters before and after the examinations of all subjects.Compared with computed tomography, HP~(129)Xe MRI is sensitive to earlier and smaller ventilation defects. The distribution of the HP~(129)Xe MRI signal reflects the pulmonary compliance with the gravity gradient. This is the first application of HP~(129)Xe MRI ventilation imaging in China, and this technology is expected to provide more useful information for clinical practice.