Cell Tracking with Caged Xenon: Using Cryptophanes as MRI Reporters upon Cellular Internalization

Caged xenon has great potential in overcoming sensitivity limitations for solution‐state NMR detection of dilute molecules. However, no application of such a system as a magnetic resonance imaging (MRI) contrast agent has yet been performed with live cells. We demonstrate MRI localization of cells labeled with caged xenon in a packed‐bed bioreactor working under perfusion with hyperpolarized‐xenon‐saturated medium. Xenon hosts enable NMR/MRI experiments with switchable contrast and selectivity for cell‐associated versus unbound cages. We present MR images with 10³‐fold sensitivity enhancement for cell‐internalized, dual‐mode (fluorescence/MRI) xenon hosts at low micromolar concentrations. Our results illustrate the capability of functionalized xenon to act as a highly sensitive cell tracer for MRI detection even without signal averaging. The method will bridge the challenging gap for translation to in vivo studies for the optimization of targeted biosensors and their multiplexing applications.     

A Bis(pyridine N‐oxide) Analogue of DOTA: Relaxometric Properties of the GdIII Complex and Efficient Sensitization of Visible and NIR‐Emitting Lanthanide(III) Cations Including PrIII and HoIII

We report the synthesis of a cyclen‐based ligand (4,10‐bis[(1‐oxidopyridin‐2‐yl)methyl]‐1,4,7,10‐tetraazacyclododecane‐1,7‐diacetic acid= L1 ) containing two acetate and two 2‐methylpyridine N‐oxide arms anchored on the nitrogen atoms of the cyclen platform, which has been designed for stable complexation of lanthanide(III) ions in aqueous solution. Relaxometric studies suggest that the thermodynamic stability and kinetic inertness of the Gd^III complex may be sufficient for biological applications. A detailed structural study of the complexes by ¹H NMR spectroscopy and DFT calculations indicates that they adopt an anti‐Δ(λλλλ) conformation in aqueous solution, that is, an anti‐square antiprismatic (anti‐SAP) isomeric form, as demonstrated by analysis of the ¹H NMR paramagnetic shifts induced by Yb^III. The water‐exchange rate of the Gd^III complex is ${k{{298\hfill \atop {\rm ex}\hfill}}}$ =6.7×10⁶ s^?1, about a quarter of that for the mono‐oxidopyridine analogue, but still about 50 % higher than the ${k{{298\hfill \atop {\rm ex}\hfill}}}$ of GdDOTA (DOTA=1,4,7,10‐tetraazacyclododecane‐1,4,7,10‐tetraacetic acid). The 2‐methylpyridine N‐oxide chromophores can be used to sensitize a wide range of Ln^III ions emitting in both the visible (Eu^III and Tb^III) and NIR (Pr^III, Nd^III, Ho^III, Yb^III) spectral regions. The emission quantum yield determined for the Yb^III complex (${Q{{{\rm L}\hfill \atop {\rm Yb}\hfill}}}$ =7.3(1)×10^?3) is among the highest ever reported for complexes of this metal ion in aqueous solution. The sensitization ability of the ligand, together with the spectroscopic and relaxometric properties of its complexes, constitute a useful step forward on the way to efficient dual probes for optical imaging (OI) and MRI.     

Unprecedented Kinetic Inertness for a Mn2+‐Bispidine Chelate: A Novel Structural Entry for Mn2+‐Based Imaging Agents

The search for more biocompatible alternatives to Gd³⁺‐based MRI agents, and the interest in ⁵²Mn for PET imaging call for ligands that form inert Mn²⁺ chelates. Given the labile nature of Mn²⁺, high inertness is challenging to achieve. The strongly preorganized structure of the 2,4‐pyridyl‐disubstituted bispidol ligand L₁ endows its Mn²⁺ complex with exceptional kinetic inertness. Indeed, MnL₁ did not show any dissociation for 140 days in the presence of 50 equiv. of Zn²⁺ (37 °C, pH 6), while recently reported potential MRI agents MnPyC3A and MnPC2A‐EA have dissociation half‐lives of 0.285 h and 54.4 h under similar conditions. In addition, the relaxivity of MnL₁ (4.28 mm ^?1 s^?1 at 25 °C, 20 MHz) is remarkable for a monohydrated, small Mn²⁺ chelate. In vivo MRI experiments in mice and determination of the tissue Mn content evidence rapid renal clearance of MnL₁. Additionally, L₁ could be radiolabeled with ⁵²Mn and the complex revealed good stability in biological media.     

Synthesis and relaxivity of polyamide paramagnetic metal complexes for magnetic resonance imaging

A new class of paramagnetic macromolecular magnetic resonance imaging contrast agents has been developed. Eight new polyamide ligands were synthesized by copolymerization of ethylenediaminetetraacetic acid dianhydride or diethylenetriaminepentaacetic acid dianhydride and diamine monomers. Their gadolinium(III), manganese(II) and iron(III) complexes were also synthesized. All polyamide ligands and metal complexes were characterized by ¹H nuclear magnetic resonance, infrared spectra and elemental analyses. Relaxivity studies showed that the polyamide paramagnetic metal complexes had obviously higher relaxation effectiveness as compared to corresponding simple monomeric paramagnetic metal complexes.     

带有双X型铁心框架的超导MRI磁体的设计

文中对带有双X型铁心框架的MR I用高温和低温超导磁体的设计进行了介绍,包括项目的市场需求、磁体的基本参数和系统热负荷的预设计结果等。     

基于级联卷积神经网络的前列腺磁共振图像分类

针对深度学习训练成本高,以及基于磁共振图像的前列腺癌临床诊断需要大量医学常识且极为耗时的问题,本文提出了一种基于级联卷积神经网络（Convolutional Neural Network,CNN）和磁共振图像的前列腺癌（Prostate Cancer,PCa）自动分类诊断方法,该网络以Faster-RCNN作为前网络,对前列腺区域进行提取分割,用于排除前列腺附近组织器官的干扰;以基于ResNet改进的网络结构CNN40_bottleneck作为后网络,用于对前列腺区域病变进行分类.后网络由瓶颈结构串联组成,其中使用批量标准化（Batch Normalization,BN）、全局平均池化（Global Average Pooling,GAP）进行优化.实验结果证明,本文方法对前列腺癌诊断结果较好,而且缩减了训练时间和参数量,有效降低了训练成本.     

Magnetically modified bentonite as a possible contrast agent in MRI of gastrointestinal tract

A composite of iron oxide nanoparticles and mineral matrix has been studied by XRD, Mössbauer spectroscopy, and TEM. Magnetite and superparamagnetic magnetite have been identified by Mössbauer spectroscopy in the nanocomposite. A relationship between the hyperfine parameters and iron oxide particle size has been confirmed by TEM. The optimal concentration of “magnetite—bentonite” composite, when the MRI signal is fully reduced, was found for using this composite as a negative contrast agent.     

基于竞争配位的Ca2+特异性响应1H/19F磁共振成像分子探针

合成了一种含~(19)F的Mn~(2+)配合物3,12-二(2-氧代-2-((2,2,2-三氟乙基)氨基)乙基)-6,9-二氧杂-3,12-二氮杂十四烷酸锰(Ⅱ)(Mn(Ⅱ)-L,1),可实现对Ca~(2+)特异响应的~1H/~(19)F磁共振成像分析。~(19)F核在近距离的顺磁性Mn~(2+)影响下产生了顺磁弛豫增强作用,使~(19)F的横向弛豫时间T_2急剧缩短而磁共振信号锐减。当有Ca~(2+)存在时,与配体L的竞争配位使得~(19)F远离Mn~(2+)离子,从而~(19)F磁共振信号得到恢复。同时,由于Mn~(2+)离子从配合态变为游离态,水配位数增加使得其对~1H的纵向弛豫时间T_1弛豫性能增加,从而~1H磁共振成像信号也增强。相关实验的结果证实了该配合物是一种能对Ca~(2+)特异性响应的~1H/~(19)F磁共振成像探针。     

LF-NMR和MRI对干制虾仁复水过程水分状态及品质变化的研究

采用低场核磁(LF-NMR)及其成像技术(MRI)研究干制虾仁在25℃复水过程中的水分含量、分布及状态变化,并通过线性回归分析不同复水时间干制虾仁的LF-NMR参数与质构特性及复水率的相关性。实验结果表明,干制虾仁复水过程中存在结合水、不可移动水和自由水3个组分峰,随着复水时间的增加,结合水无明显变化,而自由水、不易流动水含量增加,且自由度增加,流动性增大。LF-NMR参数(T_(22)、T_(23)、A_(22)、A_(23)和A_(Total))和硬度、咀嚼性、弹性、凝聚性以及复水率有极显著的相关性(R~2≥0.613),为干制虾仁复水过程中品质的快速无损预测提供了一种新方法。