磁共振技术在轻度认知障碍与阿尔茨海默病中的研究进展

阿尔茨海默病(Alzheimer’s disease,AD)是当今老年人最常见的一种原发性神经退行性疾病。其主要病理学特征表现为神经元的脱失、神经纤维缠结及老年斑形成。轻度认知障碍(mild cognitive impairment,MCI)被认为是AD及其他老年痴呆症的前驱阶段,可进一步转化成AD,且MCI与AD有着相似的病理变化。随着MCI和AD患病数的逐年增加,其给患者家属及社会增添了巨大负担,因此,对MCI和AD作出早期诊断变得尤为重要。然而,MCI和AD早期的临床表现并不突出,且实验室检查也缺乏足够的特异性,当临床医生做出明确诊断时,多数患者已处于AD的中晚期。近年来,随着磁共振技术的不断发展,多种磁共振技术已广泛地应用于MCI和AD的研究中,并为MCI及AD的早期诊断提供了重要的影像学依据。本文分别从结构性磁共振(s MRI)、静息态f MRI、磁共振弥散张量成像(DTI)、磁共振波谱成像(MRS)、磁敏感加权成像(SWI)及MRI分子影像几个方面,阐述多种磁共振技术在MCI和AD研究中的进展。     

Pulsed magneto-motive ultrasound imaging using ultrasmall magnetic nanoprobes

Nano-sized particles are widely regarded as a tool to study biologic events at the cellular and molecular levels. However, only some imaging modalities can visualize interaction between nanoparticles and living cells. We present a new technique, pulsed magneto-motive ultrasound imaging, which is capable of in vivo imaging of magnetic nanoparticles in real time and at sufficient depth. In pulsed magneto-motive ultrasound imaging, an external high-strength pulsed magnetic field is applied to induce the motion within the magnetically labeled tissue and ultrasound is used to detect the induced internal tissue motion. Our experiments demonstrated a sufficient contrast between normal and iron-laden cells labeled with ultrasmall magnetic nanoparticles. Therefore, pulsed magneto-motive ultrasound imaging could become an imaging tool capable of detecting magnetic nanoparticles and characterizing the cellular and molecular composition of deep-lying structures.     

Magnetic quantum dots in biotechnology – synthesis and applications

Quantum dots (QDs) have great promise in biological imaging, and as this promise is realized, there has been increasing interest in combining the benefits of QDs with those of other materials to yield composites with multifunctional properties. One of the most common materials combined with QDs is magnetic materials, either as ions (e.g. gadolinium) or as nanoparticles (e.g. superparamagnetic iron oxide nanoparticles, SPIONs). The fluorescent property of the QDs permits visualization, whereas the magnetic property of the composite enables imaging, magnetic separation, and may even have therapeutic benefit. In this review, the synthesis of fluorescent–magnetic nanoparticles, including magnetic QDs is explored; and the applications of these materials in imaging, separations, and theranostics are discussed. As the properties of these materials continue to improve, QDs have the potential to greatly impact biological imaging, diagnostics, and treatment.     

超顺磁氧化铁纳米探针用于磁共振分子成像的研究进展

分子影像学是近年来分子生物学和影像学相结合而形成的新型交叉学科,磁共振分子成像技术是分子影像学的重要手段之一,为临床医学诊断提供重要依据。但是由于不同组织之间的弛豫时间相互重叠等问题,导致较小的病变难以显示,磁共振造影剂能提高对软组织的分辨率,其中超顺磁性氧化铁纳米探针作为近年来发展起来的一种新型磁共振分子造影剂。由于具有敏感性、安全性、大的比表面积、高稳定性、靶向性等优点,近年来已成为国内外研究的热点之一。本文就超顺磁性氧化铁纳米探针的增强原理、制备工艺及靶向作用做一综述,以期为该技术的应用与研究提供借鉴和启示。     

Use of diffusion and perfusion magnetic resonance imaging as a tool in acute stroke clinical trials

In light of the slow progress in developing effective therapies for ischemic stroke, magnetic resonance imaging techniques have emerged as new tools in stroke clinical trials. Rapid imaging with magnetic resonance imaging, diffusion weighted imaging, perfusion imaging and angiography are being incorporated into phase II and phase III stroke trials to optimize patient selection based on positive imaging diagnosis of the ischemic pathophysiology specifically related to a drug's mechanism of action and as a direct biomarker of the effect of a treatment's effect on the brain.     

Magnetic Resonance Imaging Part II—Clinical Applications

Magnetic resonance (MR) imaging is the most promising new technology to appear in the clinical imaging arena since the advent of x-ray transmission computed tomography in the early 1970s. Five independent tissue characteristics (spin density, spin-lattice and spin-spin relaxation times, flow and spectral shift information) are accessible to MR imaging, and their relative influence in the magnetic resonance image can be varied by appropriate selection of pulse sequences and pulse times. All major organ systems appear to be amenable to MR imaging, and some are revealed with superior definition compared with their appearance in images obtained by alternate imaging technologies. Of particular interest is the superior contrast resolution in MR images of the brain and spinal cord, and the absence of bone- and motion-induced artifacts in images of the abdomen and pelvis. Applications of MR imaging to the heart and great vessels are just developing, as are new types of contrast agents for use in MR imaging. In vivo chemical spectroscopic measurements by magnetic resonance are heralded by some investigators as the most significant contribution that magnetic resonance will make ultimately to clinical diagnosis.At present, the number of MR imaging units is extremely low, and clinical studies are proceeding at a slow rate. Nevertheless, it is possible to provide a preliminary evaluation of the usefulness of MR imaging in a variety of clinical applications. This article is such an evaluation, tempered by the acknowledgement that much additional work remains to be done.     

The role of cardiac magnetic resonance imaging in differentiating the underlying causes of left ventricular hypertrophy

The onset of sudden cardiac death and large inter- and intra-familial clinical variability of hypertrophic cardiomyopathy pose an important clinical challenge. Cardiac magnetic resonance imaging is a high-resolution imaging modality that has become increasingly available in the past decade and has the unique possibility to demonstrate the presence of fibrosis or scar using late gadolinium enhancement imaging. As a result, the diagnostic and prognostic potential of cardiac magnetic resonance imaging has been extensively explored in acute and chronic ischaemic cardiomyopathy, as well as in several nonischaemic cardiomyopathies. This review aims to provide a critical overview of recently published studies on hypertrophic cardiomyopathy and discusses the role of cardiac magnetic resonance imaging in differentiating underlying causes of hypertrophic cardiomyopathy, such as familial hypertrophic cardiomyopathy, cardiac involvement in systemic disease and left ventricular hypertrophy due to endurance sports. Also, it demonstrates the use of cardiac magnetic resonance in risk stratification for the onset of sudden cardiac death, and early identification of asymptomatic family members of hypertrophic cardiomyopathy patients who are at risk for the development of hypertrophic cardiomyopathy. (Neth Heart J 2010;18:135-43.)     

Progress in n.m.r. zeugmatography imaging

Applications of nuclear magnetic resonance (n.m.r.) zeugmatographic imaging to medical diagnosis and to medical, physiological, and biological research require the development of appropriate imaging instrumentation and ancillary techniques, as well as an understanding of the biological significance of the imaging results. A whole body imaging system, relying primarily upon reconstruction from projections, is under development in the expectation that the reconstruction approach will be the most practical one for many purposes. In addition, injectable magnetic reagents that can selectively change tissue water relaxation times and image contrast are under development so as to increase the specificity and versatility of the measurements. If very high magnetic fields are employed, 31P n.m.r. zeugmatography may be practical at very low resolution for human diagnostic studies and for experiments on perfused organs and small animals. Preliminary images, showing the spatial distributions of different phosphorus metabolites in the compartments of test objects, have been obtained at 146 MHz by reconstruction techniques.     

磁性氧化铁纳米颗粒及其磁共振成像应用

磁性氧化铁纳米颗粒在磁共振成像方面的应用,已经在全世界范围内得到了广泛的关注,相关研究也被各国科学家高度重视.目前,磁性氧化铁纳米颗粒正在从早期的基于被动识别的肝部磁共振造影,快速转向基于主动识别的磁共振分子影像应用.本文将围绕磁性氧化铁纳米颗粒的生物体内应用,着重介绍磁性纳米颗粒的制备及其在疾病诊断,尤其是在肿瘤早期...     

Magnetic relaxation switches capable of sensing molecular interactions

Highly sensitive, efficient, and high-throughput biosensors are required for genomic and proteomic data acquisition in complex biological samples and potentially for in vivo applications. To facilitate these studies, we have developed biocompatible magnetic nanosensors that act as magnetic relaxation switches (MRS) to detect molecular interactions in the reversible self-assembly of disperse magnetic particles into stable nanoassemblies. Using four different types of molecular interactions (DNA-DNA, protein-protein, protein-small molecule, and enzyme reactions) as model systems, we show that the MRS technology can be used to detect these interactions with high efficiency and sensitivity using magnetic relaxation measurements including magnetic resonance imaging (MRI). Furthermore, the magnetic changes are detectable in turbid media and in whole-cell lysates without protein purification. The developed magnetic nanosensors can be used in a variety of biological applications such as in homogeneous assays, as reagents in miniaturized microfluidic systems, as affinity ligands for rapid and high-throughput magnetic readouts of arrays, as probes for magnetic force microscopy, and potentially for in vivo imaging.     

乳腺癌功能磁共振成像与生物学预后因子的研究进展

乳腺癌已成为女性最为常见的恶性肿瘤,如何对乳腺癌进行早期诊断、合理化治疗及判断预后意义重大。雌激素受体(ER)、孕激素受体(PR)、Ki-67、人表皮生长因子受体2(HER-2)等免疫组化指标在判断乳腺癌临床类型、转移情况及预后等方面具有重要作用。随着功能磁共振的发展,氢质子磁共振波谱(1H-MRS)、动态增强磁共振成像(DCE-MRI)、扩散加权成像(DWI)等被越来越广泛的用于乳腺组织的检查。研究功能磁共振与乳腺癌预后因子的相关性,对乳腺癌的临床分型、治疗及预后等方面有一定的指导作用。本文就相关进展进行综述。     

综述——新型纳米生物材料的研发：磁性纳米材料：化学合成、功能化与生物医学应用

磁性纳米材料,由于其独特的磁学性能、小尺寸效应,被广泛应用于生物医学领域．本文总结了磁性纳米材料的化学设计与合成、表面功能化方法,及其在核磁共振成像、磁控治疗、磁热疗和生物分离等生物医学领域的应用进展．     

多核磁共振19F-MRI在分子影像学中的应用

随着杂核氟、钠、磷等探针和成像技术的发展以及磁共振成像设备和序列的优化,多核磁共振迅速崛起,尤其是其在分子影像方面的研究与应用使包括心血管、肿瘤等众多疾病从传统的形态学影像诊断模式转向早期分子影像精准诊治模式。其中,19F-MRI多核磁共振分子成像近年来备受瞩目。虽然19F-MRI的成像敏感度是1H-MRI的82%,但人体只有牙齿中含有少量的氟,因此无背底噪声的干扰。19F-MRI应用氟类探针,19F自然丰度100%,且无放射性。本文简述了多核磁共振在分子影像学中的应用,并重点介绍19F-MRI分子影像及其应用探针在精准诊治方面的应用。     

Nonequilibrium Magnetic Response of Anisotropic Superparamagnetic Nanoparticles and Possible Artifacts in Magnetic Particle Imaging

Magnetic responses of superparamagnetic nanoparticles to high-frequency AC magnetic fields with sufficiently large amplitudes are numerically simulated to exactly clarify the phenomena occurring in magnetic particle imaging. When the magnetic anisotropy energy inevitable in actual nanoparticles is taken into account in considering the magnetic potential, larger nanoparticles exhibit a delayed response to alternations of the magnetic fields. This kind of delay is rather remarkable in the lower-amplitude range of the field, where the assistance by the Zeeman energy to thermally activated magnetization reversal is insufficient. In some cases, a sign inversion of the third-order harmonic response was found to occur at some specific amplitude, despite the lack in DC bias magnetic field strength. Considering the attenuation of the AC magnetic field generated in the human body, it is possible that the phases of the signals from nanoparticles deep inside the body and those near the body surface are completely different. This may lead to artifacts in the reconstructed image. Furthermore, when the magnetic/thermal torque-driven rotation of the anisotropic nanoparticles as well as the magnetic anisotropy energy are taken into account, the simulated results show that, once the easy axes are aligned toward the direction of the DC bias magnetic field, it takes time to randomize them at the field-free point. During this relaxation, the third-order harmonic response depends highly upon the history of the magnetic field. This is because non-linearity of the anhysteretic magnetization curve for the superparamagnetic nanoparticles varies with the orientations of the easy axes. This history dependence may also lead to another artifact in magnetic particle imaging, when the scanning of the field-free point is faster than the Brownian relaxations.     

Current imaging paradigms in radiation oncology

The technological revolution in imaging during recent decades has transformed the way image-guided radiation therapy is performed. Anatomical imaging (plain radiography, computed tomography, magnetic resonance imaging) greatly improved the accuracy of delineating target structures and has formed the foundation of 3D-based radiation treatment. However, the treatment planning paradigm in radiation oncology is beginning to shift toward a more biological and molecular approach as advances in biochemistry, molecular biology, and technology have made functional imaging (positron emission tomography, nuclear magnetic resonance spectroscopy, optical imaging) of physiological processes in tumors more feasible and practical. This review provides an overview of the role of current imaging strategies in radiation oncology, with a focus on functional imaging modalities, as it relates to staging and molecular profiling (cellular proliferation, apoptosis, angiogenesis, hypoxia, receptor status) of tumors, defining radiation target volumes, and assessing therapeutic response. In addition, obstacles such as imaging-pathological validation, optimal timing of post-therapy scans, spatial and temporal evolution of tumors, and lack of clinical outcome studies are discussed that must be overcome before a new era of functional imaging-guided therapy becomes a clinical reality.     

Magnetic nanoparticles for multi-imaging and drug delivery

Various bio-medical applications of magnetic nanoparticles have been explored during the past few decades. As tools that hold great potential for advancing biological sciences, magnetic nanoparticles have been used as platform materials for enhanced magnetic resonance imaging (MRI) agents, biological separation and magnetic drug delivery systems, and magnetic hyperthermia treatment. Furthermore, approaches that integrate various imaging and bioactive moieties have been used in the design of multi-modality systems, which possess synergistically enhanced properties such as better imaging resolution and sensitivity, molecular recognition capabilities, stimulus responsive drug delivery with on-demand control, and spatio-temporally controlled cell signal activation. Below, recent studies that focus on the design and synthesis of multi-mode magnetic nanoparticles will be briefly reviewed and their potential applications in the imaging and therapy areas will be also discussed.     

High-field magnetic resonance techniques for brain research

High-field magnetic resonance imaging scanners with a static magnetic field of 3 Tesla or higher are becoming ubiquitous in clinical and basic neurosciences. Given the high cost and complexity of operation, it is important to ask whether or not and how the use of high-field magnets can be beneficial for the neurosciences. What new questions can be addressed? Which new insights can we expect from these new tools? In addition, what are the limitations of these new techniques? This review discusses the three most important applications of the high-field magnetic resonance techniques for the neuroscience community: first, functional magnetic resonance imaging, second, in vivo spectroscopy, and third, in vivo fiber tracking on the basis of diffusion tensor imaging.     

医学领域的磁共振成像革命——2003年诺贝尔生理及医学奖主要工作介绍

在磁场中 ,自旋的原子核会吸收频率与其自旋频率相同的电磁波 ,使自身能量增加 ,发生能级跃迁 ,当原子核迁移回原能级时 ,就会把多余的能量以电磁波的形式释放出来 ,称为核磁共振 (NMR) .磁共振成像(MRI)利用这一原理 ,依据所释放的能量在物质内部不同结构环境中不同的衰减 ,通过外加梯度磁场检测所发射出的电磁波 ,即可得知构成这一物体原子核的位置和种类 ,据此可以绘制成物体内部的结构图像 .将这种技术用于人体内部结构的成像 ,就产生出一种革命性的医学诊断工具 .快速变化的梯度磁场的应用 ,大大加快了磁共振成像的速度 ,使该技术在临床诊断、科学研究的应用成为现实 ,极大地推动了医学、神经生理学和认知神经科学的迅速发展     

In vivo imaging of apoptosis in oncology: an update

In this review, data on noninvasive imaging of apoptosis in oncology are reviewed. Imaging data available are presented in order of occurrence in time of enzymatic and morphologic events occurring during apoptosis. Available studies suggest that various radiopharmaceutical probes bear great potential for apoptosis imaging by means of positron emission tomography and single-photon emission computed tomography (SPECT). However, for several of these probes, thorough toxicologic studies are required before they can be applied in clinical studies. Both preclinical and clinical studies support the notion that 99mTc-hydrazinonicotinamide-annexin A5 and SPECT allow for noninvasive, repetitive, quantitative apoptosis imaging and for assessing tumor response as early as 24 hours following treatment instigation. Bioluminescence imaging and near-infrared fluorescence imaging have shown great potential in small-animal imaging, but their usefulness for in vivo imaging in humans is limited to structures superficially located in the human body. Although preclinical tumor-based data using high-frequency-ultrasonography (US) are promising, whether or not US will become a routinely clinically useful tool in the assessment of therapy response in oncology remains to be proven. The potential of magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS) for imaging late apoptotic processes is currently unclear. Neither 31P MRS nor 1H MRS signals seems to be a unique identifier for apoptosis. Although MRI-measured apparent diffusion coefficients are altered in response to therapies that induce apoptosis, they are also altered by nonapoptotic cell death, including necrosis and mitotic catastrophe. In the future, rapid progress in the field of apoptosis imaging in oncology is expected.     

Magnetite nanoparticles can be coupled to microbubbles to support multimodal imaging

Microbubbles (MBs) are commonly used as injectable ultrasound contrast agent (UCA) in modern ultrasonography. Polymer-shelled UCAs present additional potentialities with respect to marketed lipid-shelled UCAs. They are more robust; that is, they have longer shelf and circulation life, and surface modifications are quite easily accomplished to obtain enhanced targeting and local drug delivery. The next generation of UCAs will be required to support not only ultrasound-based imaging methods but also other complementary diagnostic approaches such as magnetic resonance imaging or computer tomography. This work addresses the features of MBs that could function as contrast agents for both ultrasound and magnetic resonance imaging. The results indicate that the introduction of iron oxide nanoparticles (SPIONs) in the poly(vinyl alcohol) shell or on the external surface of the MBs does not greatly decrease the echogenicity of the host MBs compared with the unmodified one. The presence of SPIONs provides enough magnetic susceptibility to the MBs to accomplish good detectability both in vitro and in vivo. The distribution of SPIONs on the shell and their aggregation state seem to be key factors for the optimization of the transverse relaxation rate.