超顺磁性氧化铁纳米粒子在脑磁共振成像中的应用

超顺磁性氧化铁纳米粒子的磁性及生物相容性,使其在生物医学多个领域的应用研究都逐渐发展起来。本文介绍磁共振成像（MRI）及脑功能磁共振成像（fMRI）基本原理。列举不同性能的磁性氧化铁粒子作为磁共振成像对比剂在脑科学应用中的研究进展。表面结合单克隆抗体、蛋白质、多肽、核苷酸分子或其它特殊聚合物的磁性氧化铁粒子具有吸收特异性（靶向性）,结合MRI可实现对脑部病变前期改变、药物输运及治疗的监测,对细胞、生物分子包括mRNA的成像及探测。经葡聚糖或聚乙二醇修饰的超顺磁性氧化铁纳米粒子血液半衰期较长,可作为对比剂用于脑fMRI成像。控制氧化铁纳米粒子的粒度及表面修饰物的物理化学性质、提高饱和磁化强度、借以接枝以各种靶向性的物质、开发具有荧光-磁性等多种性能的复合纳米粒子及掌握纳米粒子与生物分子、细胞、及生物组织之间的相互作用,则需要更深入的研究。     

脑部化学交换饱和转移成像研究

化学交换饱和转移(chemical exchange saturation transfer,CEST)成像是在磁化传递及化学交换理论基础上发展起来的一种磁共振成像新方法,其扩展了磁共振分子影像新领域,但还处于研究阶段。其以细胞内物质为内源性对比剂,通过水信号间接检测代谢物信息,进行组织的酸碱度成像及其各种代谢物成像。本文主要探讨MRI领域中与水相关的化学交换饱和转移现象,阐述其原理、研究现状及其在不同场强磁共振仪上脑部疾病的应用。     

超极化13C磁共振的进展及应用

【摘要】近年来，超极化对比剂在MRI应用中得到了积极的发展。通过动态核极化(dynamic nuclear polarization，DNP)的方法使原子核自旋极化达到热平衡之上来增强分子磁共振信号，这一过程称为“超极化”(hyperpolarization，HP)。该技术克服了传统磁共振信号低、不能实时监测体内代谢过程的缺点。超极化13C磁共振成像在多种癌症及其他疾病的代谢影像学中显示出了一定的价值。本文综述了常用的超极化13C生物探针、超极化状态的获取、超极化13C 磁共振动物及临床研究的进展，并展望了其发展趋势。     

冠状动脉粥样硬化斑块磁共振成像研究进展

当前直接显示冠状动脉管壁和粥样斑块为磁共振成像(MRI)研究的热点之一,这是因为不引起冠状动脉管腔50%以上狭窄程度的粥样硬化斑块常为具有破裂倾向的易损斑块,斑块破裂随后血栓形成是导致心肌梗死的主要原因。无创性、高分辨率MRI具有显示冠状动脉粥样硬化斑块、判定斑块成分的潜力。本综述总结冠脉斑块MR成像原理,描述现有MRI技术下斑块的信号特点,并讨论MR在斑块成像的新对比剂、靶向分子成像等方面的研究进展。     

新型MRI对比剂——钆贝葡胺的临床应用

MRI对比剂的引入将进一步提高组织对比度以及病变与组织之间的对比,从而提高病变的检出率以及对病变的定性能力。Gd-BOPTA是一种由顺磁性钆离子和螯合剂BOPTA结合的新型对比剂,为钆喷替酸葡甲胺(Gd-DTPA)的衍生物,即在Gd-DTPA分子上添加苯环而成。Gd-BOPTA因其强化程度高、具肝脏组织特异性、较宽的成像时间窗以及高安全性,使之能进一步提高MRI对疾病的诊断及鉴别诊断能力,是一种具广阔应用前景的新型钆类对比剂。     

智能响应性磁共振纳米分子成像探针研究进展

智能响应性纳米分子探针可以实现肿瘤靶向定位、快速响应、灵敏诊断、精确治疗疾病,这需要精确的成像来监测探针的分布和肿瘤的位置。近年来,磁共振成像(MRI)由于其具有高灵敏度,低背景噪声等特点受到了广泛的关注。磁共振成像作为临床上最为广泛和安全诊断方法之一,为疾病诊断和肿瘤靶向治疗提供影像学指导。研究者对智能响应性MR纳米分子成像探针检测如pH变化、酶活性、还原环境和乏氧等方面进行了深入的研究。这篇文章将对智能响应性磁共振纳米分子成像探针的成像最新研究进展进行综述。     

以纳米分子探针为基础的分子影像技术在肿瘤早期检测中的应用

包含纳米材料、纳米器件以及纳米表征测量等的纳米技术,对生物、医学的进步产生了巨大影响.尤其利用纳米材料独特的颗粒及光学、电学等特性,结合现代医学影像技术,如光学成像、CT、PET/SPECT、MRI及超声成像(US)等,有可能在肿瘤发生初期进行早期特异性检测和有效的靶向治疗,使影像医学从对传统的解剖和生理功能的研究进展到分子水平成像,实现靶向分子成像,探索疾病的分子水平变化,在疾病早期做出明确诊断.     

促进医工深度融合，打造品牌学术期刊

近年来,磁共振成像(MRI)技术发展迅速,新的快速成像的序列的出现,线圈技术的新进展,以及特定靶器官的MRI对比剂的研发与应用,使得MRI从单纯的形态学研究向形态与功能相结合的方向发展,并逐渐从宏观走向微观。分子影像学可用于基因治疗与表达的监测、肿瘤血管生成和受体成像等。     

基于扩散磁共振成像的脑组织微结构成像在脑肿瘤诊疗中的应用

扩散MRI(diffusion MRI, dMRI)是一种利用水分子扩散速率和方向变化产生信号对比的成像技术,成像效果主要取决于MR信号采集及后处理中所采用的定量物理模型,对于在体无创揭示脑组织与脑部疾病的微结构信息方面具有重要的应用价值。近年来,dMRI领域中不断有新成像技术涌现,诸如基于新型扩散编码的多维度扩散成像（multidimensional diffusion,MDD）、平均表观传播MRI (mean apparent propagator MRI, MAP-MRI)以及基于多隔室模型的轴突定向扩散和密度成像（neurite orientation dispersion and density imaging, NODDI）等技术。本文从信号采集和模型拟合两个方面综述了基于dMRI的多种脑组织微结构成像技术目前的发展概况,以及其在脑胶质瘤和脑转移瘤等常见脑肿瘤中的初步应用,主要包括脑肿瘤的鉴别诊断、分级评估、分子分型、疗效评估和预后预测等临床关切的问题。未来,有待进一步优化基于dMRI的脑组织微结构成像技术的成像条件,比如设置合适的b值范围及成像时间,并进一步深入研究和比较...     

膝关节腔及周围滑膜囊积液的MRI定量测定

背景:MRI是目前膝关节疾病影像诊断的金标准,但还不能对膝关节积液准确定量.目的:对膝关节腔内注入不同量对比剂的标本进行MRI观察,为临床确诊膝关节腔及周围滑膜囊内不同量积液提供客观依据和定量标准.设计、时间及地点:金标准定量观察,于2008-10/12在成都医学院第一附属医院影像科MRI室完成.材料:选取新鲜成人尸体正常膝关节10件.方法:对10件无积液、积气、结构正常的成人尸体膝关节腔内穿刺留针,通过穿刺针向关节腔内依次注入,5,10,15,20,30,40mL对比剂,分别于每次注射后行冠状面、矢状面、横断面T2WI,度4mm,间距1mm,MRI扫描.主要观察指标:在膝关节冠状面、矢状面和横断面上,观察不同量对比剂在膝关节腔及周围囊内的分布位置.结果:①在膝关节冠状面MRI扫描:注入10 mL对比剂时,经膝关节内侧中点处,关节腔内均可见高信号;注入15 mL对比剂时,经股骨和骸骨间,关节腔内均可见高信号;20 mL对比剂时,经股骨内、外侧骸后缘处,80％股骨后上内、外侧隐窝内出现高信号.②在膝关节正中矢状层面内侧1.5cm处MRI扫描;5 mL对比剂时,高信号区呈前粗后细达裸间隆起前缘,70%胫骨内侧髁后上方可见高信号区;10 mL对比剂时,髌上囊下1/3段出现高信号;15,20 mL对比剂时,80%骸上囊中1/3段出现高信号;30,40mL对比剂时,膝关节后上内、外侧隐窝均可见高信号区.③在膝关节横断面经髌骨尖下缘处MRI扫描:对比剂5mL时,90％关节腔后1/3段可见高信号;对比剂>10 mL,70％股骨前缘平面出现高信号区.结论:通过对膝关节腔及周围滑膜囊注入不同量对比剂,可建立不同量积液的参照标准,对MRI诊断膝关节腔及周围滑膜囊积液具有重要价值.     

Design of ProCAs (Protein‐Based Gd3+ MRI Contrast Agents) with High Dose Efficiency and Capability for Molecular Imaging of Cancer Biomarkers

Magnetic resonance imaging (MRI) is the leading imaging technique for disease diagnostics, providing high resolution, three‐dimensional images noninvasively. MRI contrast agents are designed to improve the contrast and sensitivity of MRI. However, current clinically used MRI contrast agents have relaxivities far below the theoretical upper limit, which largely prevent advancing molecular imaging of biomarkers with desired sensitivity and specificity. This review describes current progress in the development of a new class of protein‐based MRI contrast agents (ProCAs) with high relaxivity using protein design to optimize the parameters that govern relaxivity. Further, engineering with targeting moiety allows these contrast agents to be applicable for molecular imaging of prostate cancer biomarkers by MRI. The developed protein‐based contrast agents also exhibit additional in vitro and in vivo advantages for molecular imaging of disease biomarkers, such as high metal‐binding stability and selectivity, reduced toxicity, proper blood circulation time, and higher permeability in tumor tissue in addition to improved relaxivities.     

Current Development of Molecular Coronary Plaque Imaging using Magnetic Resonance Imaging towards Clinical Application

Cardiovascular disease (CVD) remains the leading cause of death in Western countries despite improvements in prevention, diagnosis and treatment. Atherosclerosis is a chronic inflammatory disease that remains clinically silent for many decades. Sudden rupture of “high-risk/vulnerable” plaques has been shown to be responsible for the majority of acute cardiovascular events, including myocardial infarction and stroke. Therefore, early detection of biological processes associated with atherosclerosis progression and plaque instability may improve diagnosis and treatment and help to better monitor the effectiveness of therapeutic interventions. Molecular magnetic resonance imaging (MRI) is a promising tool to detect molecular and cellular changes in the carotid, aortic and coronary vessel wall including endothelial dysfunction, inflammation, vascular remodelling, enzymatic activity, intraplaque haemorrhage and fibrin deposition and thus may allow early detection of unstable lesions and improve the prediction of future coronary events. Evaluation of atherosclerosis at both, the preclinical and clinical level includes non-contrast-enhanced (NCE) and contrast-enhanced (CE) MRI with and without the use of MR contrast agents. To increase the biological information obtained by MRI a variety of targeted-specific molecular probes have been developed for the non-invasive visualization of particular biological processes at the molecular and cellular level. This review will discuss the recent advances in molecular MRI of atherosclerosis, covering both pulse sequence development and also the design of novel contrast agents, for imaging atherosclerotic disease in vivo.     

Iron phosphide nanoparticles as a pH-responsive T1 contrast agent for magnetic resonance tumor imaging

In this work, the potential of FeP nanoparticles as a pH-responsive T₁ contrast agent was investigated. The FeP nanoparticles have good biocompatibility and can significantly amplify T₁ magnetic resonance signals in response to the acidic microenvironment of solid tumors, holding great promise in serving as an acid-activatable T₁ contrast agent for tumor imaging.

In this work, the potential of FeP nanoparticles as a pH-responsive T₁ contrast agent was investigated.

Magnetic resonance imaging (MRI) is currently one of the most powerful medical imaging techniques due to its noninvasive character, deep tissue penetration, and ability to provide images with excellent anatomical details.^1–3 MRI contrast agents are a group of contrast media that can improve the accuracy and specificity of MRI.^4–6 In general, MRI contrast agents can be divided into T₁ positive contrast agents and T₂ negative contrast agents according to the relaxation processes. T₁ contrast agents shorten the longitudinal relaxation time of water protons, resulting in a brighter signal, while T₂ contrast agents reduce the transverse relaxation time, leading to a darker signal.^7,8 Nanomaterials containing paramagnetic metal ions (e.g., Gd³⁺, Mn²⁺, and Fe³⁺) have been widely used as T₁ MRI contrast agents.^9–14 On the other hand, magnetic nanoparticles with high saturation magnetization are the most commonly used as T₂ contrast agents because they can generate a local magnetic field in the presence of the external magnetic field to accelerate the dephasing of surrounding water protons.^15–17The exploitation of highly specific and sensitive imaging contrast agents is of great importance for precise disease diagnosis.¹⁸ Activatable imaging contrast agents that can respond to biological stimulis (e.g., pH, redox potential, and enzyme) to produce contrast signals, have emerged as the next generation of molecular imaging probes.^19–22 They can minimize the signal from nontarget background, therefore greatly improve the target-to-background ratio. Conventional T₁ contrast agents such as Gd₂O₃ nanoparticles and MnO nanoparticles have been demonstrated that can afford effective T₁ shortening effect to improve the visibility. However, these contrast agents continuously emit signals are “always on”, which fail to response to pathological parameters and hence lack in specificity and sensitivity. Activatable MRI contrast agents that only generate signals in response to a certain stimuli (e.g., physiological difference in pH in tumor microenvironment) thus are highly desirable, because they not only greatly enhance the specificity and sensitivity of disease diagnosis, but also potentially allow MRI to monitor biological processes.^23–25 Herein, we report a novel pH-activatable T₁ contrast agent based on FeP nanoparticles. We found that the as-synthesized FeP nanoparticles can respond to the acidic microenvironment of solid tumor to produce significant T₁ contrast enhancement by releasing paramagnetic Fe ions. Furthermore, both in vitro and in vivo investigations indicate that the FeP nanoparticles have good biocompatibility that show no obvious cytotoxicity and harmful effects. Therefore, the FeP nanoparticles can potentially serve as an acid-responsive T₁ MRI contrast agent for tumor imaging.     

Imaging Atherosclerotic Plaques with MRI: Role of Contrast Agents

Magnetic resonance imaging (MRI) represents one of the most promising techniques for noninvasive evaluation of atherosclerotic plaques. During the last 10 years, acquisition techniques dedicated to vascular wall imaging have been developed for MRI and offer images with high spatial resolution atherosclerotic plaques in the aorta and carotid arteries. Major components of atherosclerotic plaques can be identified based on differences in their intrinsic contrast with MRI. In addition to morphologic aspects, detection of biological activities in atherosclerotic plaques with MRI could bring new hints for the identification of high-risk plaques. A large array of MR contrast agents has become available during the last 10 years and tested for the evaluation of atherosclerotic plaques. In this review, we will discuss the advantages and drawbacks of several classes of MR contrast agents developed for atherosclerotic plaque imaging using representative examples.     

Molecular imaging in cardiovascular magnetic resonance imaging: current perspective and future potential

The development of novel imaging agents and techniques is allowing some biological events to be imaged in vivo with magnetic resonance imaging (MRI) at the cellular and subcellular level. In this paper, the use of novel gadolinium chelates and superparamagnetic iron oxide nanoparticles for molecular MRI of the cardiovascular system is extensively reviewed. The physical properties of these imaging agents and the pulse sequences best suited to their visualization are extensively discussed. The application of molecular MRI in diseases of the vasculature and myocardium is then reviewed. The clinical experience to date, as well as the promise and potential impact of molecular MRI, is extensively discussed.     

Imaging of the lymphatic system: new horizons

The lymphatic system is a complex network of lymph vessels, lymphatic organs and lymph nodes. Traditionally, imaging of the lymphatic system has been based on conventional imaging methods like computed tomography (CT) and magnetic resonance imaging (MRI), whereby enlargement of lymph nodes is considered the primary diagnostic criterion for disease. This is particularly true in oncology, where nodal enlargement can be indicative of nodal metastases or lymphoma. CT and MRI on their own are, however, anatomical imaging methods. Newer imaging methods such as positron emission tomography (PET), dynamic contrast‐enhanced MRI (DCE‐MRI) and color Doppler ultrasound (CDUS) provide a functional assessment of node status. None of these techniques is capable of detecting flow within the lymphatics and, thus, several intra‐lymphatic imaging methods have been developed. Direct lymphangiography is an all‐but‐extinct method of visualizing the lymphatic drainage from an extremity using oil‐based iodine contrast agents. More recently, interstitially injected intra‐lymphatic imaging, such as lymphoscintigraphy, has been used for lymphedema assessment and sentinel node detection. Nevertheless, radionuclide‐based imaging has the disadvantage of poor resolution. This has lead to the development of novel systemic and interstitial imaging techniques which are minimally invasive and have the potential to provide both structural and functional information; this is a particular advantage for cancer imaging, where anatomical depiction alone often provides insufficient information. At present the respective role each modality plays remains to be determined. Indeed, multi‐modal imaging may be more appropriate for certain lymphatic disorders. The field of lymphatic imaging is ever evolving, and technological advances, combined with the development of new contrast agents, continue to improve diagnostic accuracy. Published in 2006 by John Wiley & Sons, Ltd.     

Magnetic resonance imaging of liver malignancies

The histological structure of the liver is complex, consisting of hepatocytes, biliary epithelium, and mesenchymal cells. From this large variety of cells, a broad spectrum of benign and malignant liver lesions in originate. An accurate diagnosis of these lesions is mandatory for choosing an appropriate therapeutic approach. With the recent developments in hardware and software, magnetic resonance imaging (MRI) has emerged as the method of choice in the diagnostic workup of focal liver lesions, in particular in the pretherapeutic stage. The introduction of high-field MRI at 3.0 T in the routine workup and the selective use of liver-specific contrast agents, including hepatobiliary and reticuloendothelial agents, have also strengthened the role of MRI in liver imaging. In this overview article, we will review the recent developments in 3.0-T MRI and MRI contrast agents in the diagnostic workup of the most common malignant liver tumors.     

A single diamagnetic catalyCEST MRI contrast agent that detects cathepsin B enzyme activity by using a ratio of two CEST signals

CatalyCEST MRI can detect enzyme activity by monitoring the change in chemical exchange with water after a contrast agent is cleaved by an enzyme. Often these molecules use paramagnetic metals and are delivered with an additional non‐responsive reference molecule. To improve this approach for molecular imaging, a single diamagnetic agent with enzyme‐responsive and enzyme‐unresponsive CEST signals was synthesized and characterized. The CEST signal from the aryl amide disappeared after cleavage of a dipeptidyl ligand with cathepsin B, while a salicylic acid moiety was largely unresponsive to enzyme activity. The ratiometric comparison of the two CEST signals from the same agent allowed for concentration independent measurements of enzyme activity. The chemical exchange rate of the salicylic acid moiety was unchanged after enzyme catalysis, which further validated that this moiety was enzyme‐unresponsive. The temperature dependence of the chemical exchange rate of the salicylic acid moiety was non‐Arrhenius, suggesting a two‐step chemical exchange mechanism for salicylic acid. The good detection sensitivity at low saturation power facilitates clinical translation, along with the potentially low toxicity of a non‐metallic MRI contrast agent. The modular design of the agent constitutes a platform technology that expands the variety of agents that may be employed by catalyCEST MRI for molecular imaging. Copyright © 2015 John Wiley & Sons, Ltd.     

超声对比剂的材料学特点及临床应用

背景：目前临床上应用的超声对比剂均是含有不同包膜材料和气体成分的微泡对比剂,微泡对比剂的出现使超声诊断技术得到了较大的发展。目的：探讨超声对比剂的材料学研究特点,及超声对比剂在临床疾病治疗中的应用。方法：超声对比剂是由气体微泡和外部包裹的膜物质组成,包膜材料主要分为白蛋白、大分子脂质体、多聚体和各种表面活性剂等。超声造影是通过增强背向散射信号来成像。超声对比剂研究的发展大致分为3个阶段,造影相关技术包括二次谐波、组织特异性显像、反相脉冲谐波成像、相干造影成像技术、对比脉冲序列、能量多普勒谐波成像、间歇谐波成像技术、编码谐波成像和超声造影三维成像。结果与结论：超声对比剂形式的不同主要是通过改变微泡包膜和气体的性质和设计来实现的。微气泡能够实现超声对比剂的显影作用,还可在药物传输上发挥功能。新型的微泡超声对比剂不仅可以提供血流灌注学信息,还可以通过靶向作用于病变组织,分析病变的发生机制,使微泡对比剂的诊断更准确。随着微泡对比剂材料学研究以及制备工艺完善,使超声对比剂具有良好的生物相容性。不仅可以用于各种状态下的特异性超声造影,还可以利用空化效应携带药物或治疗基因向目标组织转移释放。微泡造影技术具有治疗、诊断和超声成像的功能,是一种安全、高效、无创的诊断和靶向传输治疗手段。