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.     

Recent advances on optic nerve magnetic resonance imaging and post-processing

The optic nerve is known to be one of the largest nerve bundles in the human central nervous system. There have been many studies of optic nerve imaging and post-processing that have provided insights into pathophysiology of optic neuritis related to multiple sclerosis and neuromyelitis optica spectrum disorder, glaucoma, and Leber's hereditary optic neuropathy. There are many challenges in optic nerve imaging, due to the morphology of the nerve through its course to the optic chiasm, its mobility due to eye movements and the high signal from cerebrospinal fluid and orbital fat surrounding the optic nerve. Recently, many advanced and fast imaging sequences have been used with post-processing techniques in attempts to produce higher resolution images of the optic nerve for evaluating various diseases. Magnetic resonance imaging (MRI) is one of the most common imaging methodologies for the optic nerve. This review paper will focus on recent MRI advances in optic nerve imaging and explain several post-processing techniques being used for analysis of optic nerve images. Finally, some challenges and potential for future optic nerve studies will be discussed.     

Magnetic resonance imaging screening in women at genetic risk of breast cancer: imaging and analysis protocol for the UK multicentre study. UK MRI Breast Screening Study Advisory Group

The imaging and analysis protocol of the UK multicentre study of magnetic resonance imaging (MRI) as a method of screening for breast cancer in women at genetic risk is described. The study will compare the sensitivity and specificity of contrast-enhanced MRI with two-view x-ray mammography. Approximately 500 women below the age of 50 at high genetic risk of breast cancer will be recruited per year for three years, with annual MRI and x-ray mammography continuing for up to 5 years. A symptomatic cohort will be measured in the first year to ensure consistent reporting between centres. The MRI examination comprises a high-sensitivity three-dimensional contrast-enhanced assessment, followed by a high-specificity contrast-enhanced study in equivocal cases. Multiparametric analysis will encompass morphological assessment, the kinetics of contrast agent uptake and determination of quantitative pharmacokinetic parameters. Retrospective analysis will identify the most specific indicators of malignancy. Sensitivity and specificity, together with diagnostic performance, diagnostic impact and therapeutic impact will be assessed with reference to pathology, follow-up and changes in diagnostic certainty and therapeutic decisions. Mammography, lesion localisation, pathology and cytology will be performed in accordance with the UK NHS Breast Screening Programme quality assurance standards. Similar standards of quality assurance will be applied for MR measurements and evaluation.     

Magnetic nanoparticle-based cancer therapy

Nanoparticles(NPs) with easily modified surfaces have been playing an important role in biomedicine.As cancer is one of the major causes of death,tremendous efforts have been devoted to advance the methods of cancer diagnosis and therapy.Recently,magnetic nanoparticles(MNPs) that are responsive to a magnetic field have shown great promise in cancer therapy.Compared with traditional cancer therapy,magnetic field triggered therapeutic approaches can treat cancer in an unconventional but more effective and safer way.In this review,we will discuss the recent progress in cancer therapies based on MNPs,mainly including magnetic hyperthermia,magnetic specific targeting,magnetically controlled drug delivery,magnetofection,and magnetic switches for controlling cell fate.Some recently developed strategies such as magnetic resonance imaging(MRI) monitoring cancer therapy and magnetic tissue engineering are also addressed.     

MRI-guided focused ultrasound treatments

Focused ultrasound (FUS) allows noninvasive focal delivery of energy deep into soft tissues. The focused energy can be used to modify and eliminate tissue for therapeutic purposes while the energy delivery is targeted and monitored using magnetic resonance imaging (MRI). MRI compatible methods to deliver these exposures have undergone rapid development over the past 10 years such that clinical treatments are now routinely performed. This paper will review the current technical and clinical status of MRI-guided focused ultrasound therapy and discuss future research and development opportunities.     

物理学中的演生现象

在物理学过去的发展历史中,还原论的观点一直是物理学工作者进行研究的最基本的指导原则.它对整个学科的发展起到了巨大的推动作用,并取得了辉煌的成就.但是,以还原论为基础来研究和讨论复杂系统的合作现象时,却遇到了前所未有的挑战,从而使演生论的思想孕育而生,并成为当今物理学研究的重要指导原则.文章详细介绍了凝聚物理学中典型的演生现象的形成和发展的历史过程,主要的研究内容和研究方法,以及所取得的重要进展.     

“Molecular” MR imaging at high fields

Magnetic resonance imaging (MRI) and spectroscopy (MRS) have contributed considerably to clinical radiology, and a variety of MR techniques have been developed to evaluate pathological processes as well as normal tissue biology at the cellular and molecular level. However, in comparison to nuclear imaging, MRI has relatively poor sensitivity for detecting true molecular changes or for detecting the presence of targeted contrast agents, though these remain under active development. In recent years very high field (7 T and above) MRI systems have been developed for human studies and these provide new opportunities and technical challenges for molecular imaging. We identify 5 types of intrinsic contrast mechanisms that do not require the use of exogenous agents but which can provide molecular and cellular information. We can derive information on tissue composition by (i) imaging different nuclei, especially sodium (ii) exploiting chemical shift differences as in MRS (iii) exploiting specific relaxation mechanisms (iv) exploiting tissue differences in the exchange rates of molecular species such as amides or hydroxyls and (v) differences in susceptibility. The increased signal strength at higher fields enables higher resolution images to be acquired, along with increased sensitivity to detecting subtle effects caused by molecular changes in tissues.     

Comparison of fast field-cycling magnetic resonance imaging methods and future perspectives

ABSTRACT

Fast field-cycling (FFC) nuclear magnetic resonance relaxometry is a well-established method to determine the relaxation rates as a function of magnetic field strength. This so-called nuclear magnetic relaxation dispersion gives insight into the underlying molecular dynamics of a wide range of complex systems and has gained interest especially in the characterisation of biological tissues and diseases. The combination of FFC techniques with magnetic resonance imaging (MRI) offers a high potential for new types of image contrast more specific to pathological molecular dynamics. This article reviews the progress in FFC-MRI over the last decade and gives an overview of the hardware systems currently in operation. We discuss limitations and error correction strategies specific to FFC-MRI such as field stability and homogeneity, signal-to-noise ratio, eddy currents and acquisition time. We also report potential applications with impact in biology and medicine. Finally, we discuss the challenges and future applications in transferring the underlying molecular dynamics into novel types of image contrast by exploiting the dispersive properties of biological tissue or MRI contrast agents.     

Earlier detection of tumor treatment response using magnetic resonance diffusion imaging with oscillating gradients

An improved method for detecting early changes in tumors in response to treatment, based on a modification of diffusion-weighted magnetic resonance imaging, has been demonstrated in an animal model. Early detection of therapeutic response in tumors is important both clinically and in pre-clinical assessments of novel treatments. Noninvasive imaging methods that can detect and assess tumor response early in the course of treatment, and before frank changes in tumor morphology are evident, are of considerable interest as potential biomarkers of treatment efficacy. Diffusion-weighted magnetic resonance imaging is sensitive to changes in water diffusion rates in tissues that result from structural variations in the local cellular environment, but conventional methods mainly reflect changes in tissue cellularity and do not convey information specific to microstructural variations at sub-cellular scales. We implemented a modified imaging technique using oscillating gradients of the magnetic field for evaluating water diffusion rates over very short spatial scales that are more specific for detecting changes in intracellular structure that may precede changes in cellularity. Results from a study of orthotopic 9L gliomas in rat brains indicate that this method can detect changes as early as 24 h following treatment with 1,3-bis(2-chloroethyl)-1-nitrosourea, when conventional approaches do not find significant effects. These studies suggest that diffusion imaging using oscillating gradients may be used to obtain an earlier indication of treatment efficacy than previous magnetic resonance imaging methods.     

Histopathological analysis of a bladder cancer stalk observed on MRI

Papillary transitional cell carcinoma of the bladder has a loose connective tissue stalk. For staging of bladder cancer on magnetic resonance imaging (MRI), it is important to clearly separate the cancer from the bladder wall. It is possible to distinguish a stalk from the cancer by the difference of intensity on the using MRI. Sixteen stalks of 20 polypoid bladder tumors on any of the T(2)W(I), dynamic images and delayed enhanced images were demonstrated. Most of the stalks show lower signal intensity than the tumors on T(2)W(I), less enhancement on dynamic images and stronger enhancement on delayed enhanced images. The stalk consisted of fibrous connective tissue, capillary blood vessels, inflammatory cell infiltration and edema. This stalk extended from the bladder wall to the center of the tumor. Some of the superficial muscular bundles were pulled into the stalk. These histopathological findings were compatible with the patterns of signal intensities on MRI. The identification of the stalk of a polypoid tumor may be an important observation to exclude bladder wall invasion by tumor.     

Perfusion MR imaging and proton MR spectroscopic imaging in differentiating necrotizing cerebritis from glioblastoma multiforme

We describe a lesion with the magnetic resonance imaging (MRI) characteristics of a glioblastoma mutiforme and demonstrate how perfusion MRI and proton MR spectroscopic imaging can be used to differentiate necrotizing cerebritis from what appeared to be a high-grade glioma. A 43-year-old woman presented to her physician complaining of progressive visual disturbance and headache for several weeks. Conventional MRI demonstrated a parietal peripherally enhancing mass with central necrosis and moderate to severe surrounding T2 hyperintensity, suggesting an infiltrating high-grade glioma. However, advanced imaging, including dynamic susceptibility contrast MRI (DSC MRI) and magnetic resonance spectroscopic imaging (MRSI), suggested a nonneoplastic lesion. The DSC MRI data demonstrated no hyperperfusion within the lesion and surrounding T2 signal abnormality, and the MRSI data showed overall decrease in metabolites in this region, except for lactate. Because of the aggressive appearance to the lesion and the patients' worsening symptoms, a biopsy was performed. The pathologic diagnosis was necrotizing cerebritis. After the commencement of steroid therapy, imaging findings and patient symptoms improved. This report will review the utility of advanced imaging for differentiating inflammatory from neoplastic appearing lesions on conventional imaging.     

Promise and pitfalls of quantitative imaging in oncology clinical trials

Quantitative imaging using computed tomography, magnetic resonance imaging and positron emission tomography modalities will play an increasingly important role in the design of oncology trials addressing molecularly targeted, personalized therapies. The advent of molecularly targeted therapies, exemplified by antiangiogenic drugs, creates new complexities in the assessment of response. The Quantitative Imaging Network addresses the need for imaging modalities which can accurately and reproducibly measure not just change in tumor size but changes in relevant metabolic parameters, modulation of relevant signaling pathways, drug delivery to tumor and differentiation of apoptotic cell death from other changes in tumor volume. This article provides an overview of the applications of quantitative imaging to phase 0 through phase 3 oncology trials. We describe the use of a range of quantitative imaging modalities in specific tumor types including malignant gliomas, lung cancer, head and neck cancer, lymphoma, breast cancer, prostate cancer and sarcoma. In the concluding section, we discuss potential constraints on clinical trials using quantitative imaging, including complexity of trial conduct, impact on subject recruitment, incremental costs and institutional barriers. Strategies for overcoming these constraints are presented.     

Real-time exercise stress cardiac MRI with Fourier-series reconstruction from golden-angle radial data

Magnetic resonance imaging (MRI) can measure cardiac response to exercise stress for evaluating and managing heart patients in the practice of clinical cardiology. However, exercise stress cardiac MRI have been clinically limited by the ability of available MRI techniques to quantitatively measure fast and unstable cardiac dynamics during exercise. The presented work is to develop a new real-time MRI technique for improved quantitative performance of exercise stress cardiac MRI. This technique seeks to represent real-time cardiac images as a sparse Fourier-series along the time. With golden-angle radial acquisition, parallel imaging and compressed sensing can be integrated into a linear system of equations for resolving Fourier coefficients that are in turn used to generate real-time cardiac images from the Fourier-series representation. Fourier-series reconstruction from golden-angle radial data can effectively address data insufficiency due to MRI speed limitation, providing a real-time approach to exercise stress cardiac MRI. To demonstrate the feasibility, an exercise stress cardiac MRI experiment was run to investigate biventricular response to in-scanner biking exercise in a cohort of sixteen healthy volunteers. It was found that Fourier-series reconstruction from golden-angle radial data effectively detected exercise-induced increase in stroke volume and ejection fraction in a healthy heart. The presented work will improve the applications of exercise stress cardiac MRI in the practice of clinical cardiology.     

Image-guided optical spectroscopy provides molecular-specific information in vivo: MRI-guided spectroscopy of breast cancer hemoglobin, water, and scatterer size

A multimodality instrument that integrated optical or near-infrared spectroscopy into a magnetic resonance imaging (MRI) breast coil was used to perform a pilot study of image-guided spectroscopy on cancerous breast tissue. These results are believed to be the first multiwavelength spectroscopic images of breast cancer using MRI-guided constraints, and they show the cancer tumor to have high hemoglobin and water values, decreased oxygen saturation, and increased subcellular granularity. The use of frequency-domain diffuse tomography methods at many wavelengths provides the spectroscopy required for recovering maps of absorbers and scattering spectra, but the integration with MRI allows these data to be recovered on an image field that preserves high resolution and fuses the two data sets together. Integration of molecular spectroscopy into standard clinical MRI can be achieved with this approach to spectral tomography.     

近红外影像诊断的物理基础和乳腺癌的早期诊断

乳腺癌的早期诊断是提高妇女生活品质、降低死亡率的重要环节.作为乳腺癌主流诊断技术的钼靶软X射线诊断（mammography）对人体具有射线损伤,而近红外影像诊断（CDI）是无损伤、可反复检查的新诊断技术,但假阳性率偏高,目前受到医学界的质疑.文章从影像诊断的物理基础入手,讨论了癌症病变组织的生长、转移和血管分布异常对于近红外光透过率的影响,分析了CDI的优缺点,并从理论上得出了该技术满足影像诊断三要素的结论.文章作者还评述了市场竞争因素对于这一技术发展的影响,最后简单提及物理学在与生命科学交叉领域的研究课题和发展机会.     

High-resolution near-infrared tomographic imaging simulations of the rat cranium by use of a priori magnetic resonance imaging structural information

Near-infrared (NIR) optical image reconstruction that incorporates magnetic resonance image (MRI) structural data was tested in a series of simulated reconstructions. NIR diffuse tomography generally suffers from comparatively low spatial resolution. By using the fine structural detail that is available with MRI, combined with the functional information of NIR spectroscopy, it is possible to design a new image-reconstruction methodology that provides high-resolution images that are correlated with hemoglobin concentration and oxygen saturation. To test this concept a MRI spin-echo image of a rat cranium was used to obtain an outline of the bone, brain, and muscle tissues, and this information was incorporated into an iterative-based diffuse tomography reconstruction. These simulations represent what is believed to be the first attempt at evaluating a spatially constrained iterative-reconstruction MRI-NIR imaging modality for brain tissue.     

The prospects for high resolution optical brain imaging: the magnetic resonance perspective

Various analogs of NMR and MRI are now technically possible in optics; specifically, high-resolution laser-pulse shaping and complex pulse sequence generation with well-defined phase shifts has been demonstrated. Here we summarize this technology and discuss the potential for these methods to enhance optical functional imaging, competing with (and surpassing?) what is possible by functional MRI.     

Identification of epsilon martensite in a Fe-based shape memory alloy by means of EBSD

Ferrous shape memory alloys (SMAs) are often thought to become a new, important group of SMAs. The shape memory effect in these alloys is based on the reversible, stress-induced martensitic transformation of austenite to epsilon martensite. The identification and quantification of epsilon martensite is crucial when evaluating the shape memory behaviour of this material. Previous work displayed that promising results were obtained when studying the evolution of the amount of epsilon martensite after different processing steps with Electron BackScatter Diffraction (EBSD). The present work will discuss in detail, on the one hand, the challenges and opportunities arising during the identification of epsilon martensite by means of EBSD and, on the other hand, the possible interpretations that might be given to these findings. It will be illustrated that although the specific nature of the austenite to epsilon martensite transformation can still cause some points of discussion, EBSD has a high potential for identifying epsilon martensite.     

Rapid and recoverable in vivo magnetic resonance imaging of the adult zebrafish at 7T

Increasing scientific interest in the zebrafish as a model organism across a range of biomedical and biological research areas raises the need for the development of in vivo imaging tools appropriate to this subject. Development of the embryonic and early stage forms of the subject can currently be assessed using optical based techniques due to the transparent nature of the species at these early stages. However this is not an option during the juvenile and adult stages when the subjects become opaque. Magnetic resonance imaging (MRI) techniques would allow for the longitudinal and non-invasive assessment of development and health in these later life stages. However, the small size of the zebrafish and its aquatic environment represent considerable challenges for the technique. We have developed a suitable flow cell system that incorporates a dedicated MRI imaging coil to solve these challenges. The system maintains and monitors a zebrafish during a scan and allows for it to be fully recovered. The imaging properties of this system compare well with those of other preclinical MRI coils used in rodent models. This enables the rapid acquisition of MRI data which are comparable in terms of quality and acquisition time. This would allow the many unique opportunities of the zebrafish as a model organism to be combined with the benefits of non-invasive MRI.     

Plexiform neurofibroma of the pelvis: CT and MRI findings

We present a case of plexiform neurofibroma of the pelvis in a patient with neurofibromatosis using magnetic resonance imaging (MRI) with computed tomography (CT) correlation. We discovered an extensive pelvic mass with a slightly greater signal intensity than muscle in T1-weighted images and a marked increased signal intensity in T2-weighted images. Multiple hypointense septations were identified throughout the tumor, particularly in the T2-weighted images. The MR appearance of pelvic plexiform neurofibroma is identical to those found in spinal and paraspinal locations. In the presence of an extensive pelvic mass in a patient with neurofibromatosis, MRI is recommended in evaluating and diagnosing plexiform neurofibroma. Since the MRI appearance of this tumor is characteristic, other lesions can possibly be ruled out. In addition, MRI's multiplanar capability is ideally suited to demonstrate the extension of these large tumors.