半花菁染料用于分子影像的研究进展

分子影像广泛用于基本的生物学过程研究,众多疾病诊断、治疗策略设计以及疗效评估.半花菁染料具有良好的光物理性质、生物相容性和对生物系统的低毒性,是一种比较理想的生物成像试剂.近年来,出现了大量基于半花菁染料的探针用于分子成像的研究工作.该文系统地介绍了基于半花菁染料的探针用于荧光和多模态成像的研究进展,详细地介绍了这些可...     

Multimodal Functional Imaging for Cancer/Tumor Microenvironments Based on MRI,EPRI, and PET

Radiation therapy is one of the main modalities to treat cancer/tumor. The response to radiation therapy, however, can be influenced by physiological and/or pathological conditions in the target tissues, especially by the low partial oxygen pressure and altered redox status in cancer/tumor tissues. Visualizing such cancer/tumor patho-physiological microenvironment would be a useful not only for planning radiotherapy but also to detect cancer/tumor in an earlier stage. Tumor hypoxia could be sensed by positron emission tomography (PET), electron paramagnetic resonance (EPR) oxygen mapping, and in vivo dynamic nuclear polarization (DNP) MRI. Tissue oxygenation could be visualized on a real-time basis by blood oxygen level dependent (BOLD) and/or tissue oxygen level dependent (TOLD) MRI signal. EPR imaging (EPRI) and/or T₁-weighted MRI techniques can visualize tissue redox status non-invasively based on paramagnetic and diamagnetic conversions of nitroxyl radical contrast agent. ¹³C-DNP MRI can visualize glycometabolism of tumor/cancer tissues. Accurate co-registration of those multimodal images could make mechanisms of drug and/or relation of resulted biological effects clear. A multimodal instrument, such as PET-MRI, may have another possibility to link multiple functions. Functional imaging techniques individually developed to date have been converged on the concept of theranostics.     

Multimodality Imaging Agents with PET as the Fundamental Pillar

Positron emission tomography (PET) provides quantitative information in vivo with ultra‐high sensitivity but is limited by its relatively low spatial resolution. Therefore, PET has been combined with other imaging modalities, and commercial systems such as PET/computed tomography (CT) and PET/magnetic resonance (MR) have become available. Inspired by the emerging field of nanomedicine, many PET‐based multimodality nanoparticle imaging agents have been developed in recent years. This Minireview highlights recent progress in the design of PET‐based multimodality imaging nanoprobes with an aim to overview the major advances and key challenges in this field and substantially improve our knowledge of this fertile research area.     

超小金纳米簇用于荧光及CT双模态成像的研究

基于金纳米簇强烈的量子限制效应（strong quantum confinement effect,SQCE）,采用一步合成法,制备了同时具有高效近红外荧光与CT双模态成像能力的超小金纳米簇.实验表明,通过优化合成比例以及合成条件,所合成的超小金纳米簇具有很大的斯托克斯（Stokes）位移、较高的荧光强度和X射线吸收效率.除此之外,该超小金纳米簇具有良好的单分散性、稳定性和生物相容性.4T1肿瘤细胞荧光成像实验结果表明,该纳米粒子可被肿瘤细胞快速、高效地摄取.     

基于散射信号的超分辨光学相减显微镜

现有的光学超分辨显微成像技术主要依赖于特殊的荧光标记物,其对于大多数非荧光样品的超分辨成像就变得无能为力。因此我们提出将光学相减显微技术应用到非荧光样品的成像当中,利用普通共聚焦光斑和面包圈型光斑分别激发样品的散射光成像,从而得到样品同一区域的两幅图像,再通过图像相减的方法提高了图像空间分辨率。不同于一般的超分辨成像方法,这种光学相减显微镜不需要特殊的样品预处理过程,同时两次成像的激发光强度可以保持在一个较低水平,避免了样品损伤的影响。随后金纳米小球和有机聚合物微丝的散射成像实验证明了光学相减显微镜可以将空间分辨率提高到215 nm (0.33λ, 1λ = 650 nm),并且通过探测散射信号得到更多的样品细节信息。     

Facile preparation of holmium(III)-doped carbon nanodots for fluorescence/magnetic resonance dual-modal bioimaging

Holmium(III)-doped carbon nanodots (HoBCDs) were synthesized for the first time via hydrothermal treatment of citrate acid (CA), branched-polyethylenimine (BPEI) and diethylenetriamine pentaacetic acid hydrate holmium(III) dihydrogen salt (Ho-DTPA), and their dual-modality bioimaging applications were demonstrated by the use of HeLa cells. The as-prepared nanoprobes exhibited bright fluorescence with an absolute quantum yield of 8% and apparent contrast enhancement in T₁-weighted images.     

A Hg(II)-specific probe for imaging application in living systems and quantitative analysis in environmental/food samples

Mercury ions are highly toxic and can accumulate along food chains in water, soil, crops and animals. Effective detection of mercury ions in various media is of great significance for maintaining the ecological environment and protecting people’s health. In this work, a mercury ions specific fluorescent probe was developed by a simple one-step reaction of commercial substrates of 4-chloro-7-nitro-2,1,3-benzoxadiazole and 1-(2-aminoethyl)-4-methylpiperazine. Investigation on sensing behavior showed that this probe had high sensitivity and selectivity towards mercury ions. Furthermore, this probe could be used as a tool to track the level of mercury ions in living system. In living cells, the probe with green emission emitted a bright red fluorescence when it was bound to mercury ions. In Arabidopsis thaliana, similar red emission could be detected from the root tip and stalk when A. thaliana was grown in culture medium containing mercury ions. The imaging in zebrafish showed that mercury ions were mainly concentrated in the stomach and head of zebrafish. Especially, this probe could be applied in quantitative analysis of mercury ions in tap water, green tea, sea shrimp and soil. This work provided a practical tool for the detection of mercury ions in living systems and quantitative analysis in real samples.     

成像技术的回顾与展望

阐述了成像技术发展的3个阶段:机械电子化、自动化、数字成像阶段.具体包括胶片式向磁记录式的转变,胶片式与数字式的兼容,数字式的空间、辐射、光谱和时间分辨率成像的前沿技术.提出由部件到系统的成像自动处理控制理论,并阐述了未来成像技术的发展趋势.     

A review of recent trends in polymer characterization using non-destructive vibrational spectroscopic modalities and chemical imaging

This review focuses on the recent developments in vibrational spectroscopy and chemical imaging (i.e. Raman, Near Infrared, Mid Infrared) to characterize polymers in diverse forms, their behaviour and transient phenomenon. First, important polymeric properties and traditional methods of their characterization are outlined. Then relative advantages & disadvantages have been presented of different characterization methods are presented. This is followed by a detailed review of applications of chemical imaging and spectroscopic techniques in polymer characterization, including the limitations encountered. The article ends with a discussion on the future of chemical imaging with regards to polymer characterization.     

Inhalable Thioflavin S for the Detection of Amyloid Beta Deposits in the Retina

We present an integrated delivery technology herein employing the aerosolized method to repurpose thioflavin S for imaging amyloid beta (Abeta) deposits in the retina as a surrogate of Abeta in the brain for early detection of Alzheimer’s disease. The data showed that wild type (WT) mice also have Abeta deposits in the retinae, albeit much less than 5XFAD mice. Further, only in 5XFAD mice, significant Abeta deposits were found associated with retinal ganglion cells (RGCs) in whole-mount and cross-section data. Furthermore, the fluorescent signal depicted from thioflavin S corroborates with Abeta immunohistochemistry staining information. Overall, this probe delivery via inhalation method is also applicable to other Abeta-binding molecules, such as Congo red, curcumin, and thioflavin T. The advantage of imaging retinal amyloid deposits compared to the brain counterparts is that the eye is easily accessible by in vivo imaging and it reduces the effort to design a probe that must cross the formidable blood-brain barrier.     

细菌感染成像的研究进展

由致病菌或条件致病菌侵入机体繁殖而产生的毒素和其它代谢产物所引起的感染性疾病是目前全球范围内的主要死亡原因之一. 感染性疾病的早期诊断是对其进行有效治疗与控制的重要途径. 分子影像技术的快速发展给体内细菌感染的评估带来了前所未有的变化和机遇. 本文综合评述了计算机断层扫描、 正电子发射断层扫描、 超声成像、 磁共振成像、 荧光成像及光声成像等成像方式在细菌感染体内成像中的研究进展、 不足和发展方向等, 以期为活体细菌感染检测方法的发展提供参考.     

成像技术在食品安全与质量控制中的研究进展

食品质量与安全是政府、食品行业以及消费者十分关注的问题。为了保证食品质量与安全，需要对食品中的风险因子进行检测。传统的分析方法如生物化学方法和仪器分析方法（色谱法、色谱-质谱法）存在前处理比较复杂，耗时，对样品具有破坏性及无法获取目标物空间信息等缺点。因此，开发快速，无损，实时和可视化的检测技术十分重要，这也是食品领域研究的热点。近年来，高光谱成像技术融合了成像和光谱两种技术，可以作为一种用于食品质量和安全评估的非破坏性和实时检测的工具。拉曼光谱成像技术可以同时获得待测物的光谱和空间信息，具有快速，无损和低成本等优点，在食品安全评价和质量控制中也得到了成功应用。质谱成像技术不需要标记和染色，即可实现样品组织表面待测物的可视化和高通量分析。它作为一种分子可视化技术，可以获得食品中营养成分及内、外源性有害物质的空间分布信息，在食品领域也表现出良好的应用前景。本文检索了近几年国内外发表的成像技术在食品研究中的相关文献，介绍了高光谱成像技术、拉曼光谱成像技术和质谱成像技术的原理，并综述了它们在食品安全与质量控制中的应用。此外，本文分析和讨论了这几种成像技术的优缺点，并对成像技术在食品领域的发展前景做出了展望。     

BODIPY: A Highly Versatile Platform for the Design of Bimodal Imaging Probes

In molecular imaging, multimodal imaging agents can provide complementary information, for improving the accuracy of disease diagnosis or enhancing patient management. In particular, optical/nuclear imaging may find important preclinical and clinical applications. To simplify the preparation of dual‐labeled imaging agents, we prepared versatile monomolecular multimodal imaging probe (MOMIP) platforms containing both a fluorescent dye (BODIPY) and a metal chelator (polyazamacrocycle). One of the MOMIP was conjugated to a cyclopeptide (i.e., octreotide) and radiolabeled with ¹¹¹In. In vitro and in vivo studies of the resulting bioconjugate were conducted, highlighting the potential of these BODIPY‐based bimodal probes. This work also confirmed that the biovector and/or the bimodal probes must be chosen carefully, due to the impact of the MOMIP on the overall properties of the resulting imaging agent.     

Advanced Nanomaterials for Multimodal Molecular Imaging

The development of multimodal molecular imaging contrast agents based on versatile nanomaterials has recently attracted much attention in disease diagnosis and therapeutic delivery. Contrast agents made from nanoparticles and used for multimodal imaging in vivo provide a multidimensional pathophysiological overview of diseases. This review summarizes recently developed advanced nanomaterials for multimodal molecular imaging. We comprehensively discuss these nanoparticle contrast agents in terms of their targeting modalities, limitations in clinical translation and future directions.     

Organic Nanoprobes for Fluorescence and 19F Magnetic Resonance Dual‐Modality Imaging

Multimodal imaging techniques have been demonstrated to be greatly advantageous in achieving accurate diagnosis and gained increasing attention in recent decades. Herein, we present a new strategy to integrate the complementary modalities of ¹⁹F magnetic resonance imaging (¹⁹F MRI) and fluorescence imaging (FI) into a polymer nanoprobe composed of hydrophobic fluorescent organic core and hydrophilic fluorinated polymer shell. The alkyne‐terminated fluorinated copolymer (Pn) of 2,2,2‐trifluoroethyl acrylate (TFEA) and poly(ethylene glycol) methyl ether acrylate (PEGA) was first prepared via atom transfer radical polymerization (ATRP). The PEGA plays an important role in both improving ¹⁹F signal and modulating the hydrophilicity of Pn. The alkynyl tail in Pn is readily conjugated with azide modified tetra‐phenylethylene (TPE) through click chemistry to form azo polymer (TPE‐azo‐Pn). The core‐shell nanoprobes (TPE‐P3N) with an average particle size of 57.2 ± 8.8 nm are obtained via self‐assembly with ultrasonication in aqueous solution. These nanoprobes demonstrate high water stability, good biocompatibility, strong fluorescence and good ¹⁹F MRI performance, which present great potentials for simultaneous fluorescence imaging and ¹⁹F–MR imaging.     

Dual‐Frequency Calcium‐Responsive MRI Agents

Responsive or smart magnetic resonance imaging (MRI) contrast agents are molecular sensors that alter the MRI signal upon changes in a particular parameter in their microenvironment. Consequently, they could be exploited for visualization of various biochemical events that take place at molecular and cellular levels. In this study, a set of dual‐frequency calcium‐responsive MRI agents are reported. These are paramagnetic, fluorine‐containing complexes that produce remarkably high MRI signal changes at the ¹H and ¹⁹F frequencies at varying Ca²⁺ concentrations. The nature of the processes triggered by Ca²⁺ was revealed, allowing a better understanding of these complex systems and their further improvement. The findings indicate that these double‐frequency tracers hold great promise for development of novel functional MRI methods.     

Tuning Phenols with Intra‐Molecular Bond Shifted HYdrogens (IM‐SHY) as diaCEST MRI Contrast Agents

The optimal exchange properties for chemical exchange saturation transfer (CEST) contrast agents on 3 T clinical scanners were characterized using continuous wave saturation transfer, and it was demonstrated that the exchangeable protons in phenols can be tuned to reach these criteria through proper ring substitution. Systematic modification allows the chemical shift of the exchangeable protons to be positioned between 4.8 to 12 ppm from water and enables adjustment of the proton exchange rate to maximize CEST contrast at these shifts. In particular, 44 hydrogen‐bonded phenols are investigated for their potential as CEST MRI contrast agents and the stereoelectronic effects on their CEST properties are summarized. Furthermore, a pair of compounds, 2,5‐dihydroxyterephthalic acid and 4,6‐dihydroxyisophthalic acid, were identified which produce the highest sensitivity through incorporating two exchangeable protons per ring.     

Suitability of infrared spectroscopic imaging as an intraoperative tool in cerebral glioma surgery

Infrared spectroscopic imaging is a promising intraoperative tool which enables rapid, on-site diagnosis of brain tumors during neurosurgery. A classification model was recently developed using infrared spectroscopic images from thin tissue sections to grade malignant gliomas, the most frequent class of primary brain tumor. In this study the model was applied to 54 specimens from six patients with inhomogeneous gliomas composed of regions with different tumor density and morphology. The resection was controlled using neuronavigation which transfers the findings obtained by preoperative magnetic resonance imaging (MRI) into the operating field. For comparison, all specimens were independently evaluated by histopathology after hematoxylin and eosin staining. The infrared-derived grading agreed with histopathology and MRI findings for almost all specimens. With regard to histopathological assessment, sensitivities of 100% (22/22) and 93.1% (27/29) and specificities of 96.9% (31/32) and 88.0% (22/25) were achieved, depending on whether the classification was based on the predominant or maximal tumor grade, respectively, in the specimen. Altogether, in 98% (53/54) of all specimens the decision to continue or not continue tumor resection could have been made according to the infrared spectroscopic classification. This retrospective study clearly demonstrates that infrared spectroscopic imaging may help to define tumor margins intraoperatively and to detect high-grade tumor residues for achieving more radical tumor resection. MRT-guided tumor resection (left) is combined with infrared spectroscopy-based tissue classification (middle, right). With regard to histopathological assessment, sensitivities of 100% and 93.1% and specificities of 96.9% and 88.0% were achieved for 54 specimens. (TIF 47.1 KB)