Quantitative Correlation of the MR-Angiography and Atherosclerosis Probe VSOP in Atherosclerotic Plaques with Markers for PlaqueInstability by Element Microscopy (LA-ICP-MS)

我们已经表明，超顺磁性非常小的氧化铁颗粒（VSOP）不仅非常适合磁共振血管造影术（MRA），但也允许非常灵敏的检测动脉粥样硬化斑块，他们已被发现是最适合与其他几个阴离子纳米粒子相比。与空间稳定的氧化铁纳米颗粒（例如，ferumoxytol，批准用于铁替代疗法）VSOP由于其快速动力学而具有在单个MR成像会话中在少于3小时内进行组合的MRA和斑块成像的潜力。普鲁士蓝铁染色，内源性组织铁非特异性）铕掺杂VSOP（Eu-VSOP）与激光消融电感耦合等离子体质谱（LA-ICP-MS）的组合首次允许选择性，灵敏度和定量鉴定组织切片中的氧化铁纳米颗粒。在拟议的项目中，我们打算使用这种组合来研究哪些典型的炎症和脆弱性标志物与动脉粥样硬化斑块中的VSOP积累相关，以及内源性或颗粒铁区域是否含有活性氧（ROS）。当用不同的镧系元素标记抗体时，该技术允许在相同的组织切片中同时关联几种标记物与Eu-VSOP（多路复用）。为了进行比较，计划进行常规免疫组织学染色，然后（取下盖玻片后）用LA-ICP-MS额外研究这些制剂。最后，通过在铕通道中应用ICP-MS，将Eu-VSOP用于非放射性测定器官分布。这些研究与了解VSOP在斑块中的蓄积和VSOP的临床转化高度相关。

We have shown that superparamagnetic very small iron oxide particles (VSOP) are not only well suited for magnetic resonance angiography (MRA) but also allow very sensitive detection of atherosclerotic plaques, for which they have been found to be most suitable compared with several other anionic nanoparticles. Unlike sterically stabilized iron oxide nanoparticles (e.g., ferumoxytol, approved for iron replacement therapy) VSOP have due to their fast kinetics the potential for performing combined MRA and plaque imaging in less than 3 hours in a single MR imaging session.Recently, we have shown that, in contrast to established methods, (e.g., Prussian blue iron staining, unspecific with endogenous tissue iron) the combination of Europium-doted VSOP (Eu-VSOP) with laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) for the first time allows selective, sensitive, and quantitative identification of iron oxide nanoparticles in tissue sections. In the proposed project, we intend to use this combination to investigate which typical markers of inflammation and vulnerability correlate with VSOP accumulation in atherosclerotic plaques and whether areas with endogenous or particle iron contain reactive oxygen species (ROS). When antibodies are labeled with different lanthanoids, this technique allows simultaneous correlation of several markers with Eu-VSOP in the same tissue section (multiplexing). For comparison, it is planned to perform conventional immunohistological staining and to then (after removal of the cover slips) additionally investigate these preparations with LA-ICP-MS. Finally, the Eu-VSOP will be used for nonradioactive determination of organ distribution by applying ICP-MS in the Europium channel. These investigations are highly relevant for understanding VSOP accumulation in plaques and for clinical translation of VSOP.