Development of ESRI・MRI fused imaging device for oxidative stress-related diseases

自由基产生的位置必须与特定的靶器官或组织相对应，以便研究自由基产生与疾病的发生和/或进展之间的关系。在本研究中，我们将能够显示自由基分布的电子自旋共振成像（ESRI）与能够提供解剖信息的磁共振成像（MRI）相结合，开发了融合成像系统，用于分析氧化应激相关疾病，并将该系统应用于体内测量。采用ESRI和MRI获得的图像均可可视化的方法作为位置校准的标记，并通过模拟实验评价图像构建的最佳方法，因为该方法具有高精度的配准。给动物注射氮氧自由基溶液，获得融合图像 ...更多信息 这些图像证明了硝酰基自由基的动力学随给药途径和正辛醇/水分配系数（Po/w）的差异。自由基产生试剂在探针治疗前口服给药，并获得图像，显示胃中的自由基产生，我们提出了一种体内ESR/自旋探针技术作为一种非侵入性和实时分析体内自由基反应的方法，并评估了疾病的实验模型中的自由基产生机制。本研究选择胃肠道损伤、糖尿病和脑缺血再灌注损伤作为氧化应激相关疾病的模型，探讨自由基产生的部位和种类。结果表明，在吲哚美辛胃损伤模型中，不同Po/w的硝酰基自由基在细胞内产生羟自由基，在脑缺血再灌注损伤模型中，脑血管细胞膜表面产生脂质自由基。ESRI与MRI相结合的融合成像系统被认为是清除靶器官和/或组织体内自由基生成的有力工具。在不久的将来，这一系统的应用有望使我们能够阐明氧化应激相关疾病中自由基产生的机制。少

It is essential that the location of free radical generation corresponds to the specific target organ or tissue in order to investigate the relationship between the free radical generation and the initiation and/or progression of diseases. In this study, we developed the fused imaging system by the combination of Electron Spin Resonance Imaging(ESRI), which can visualize the free radical distribution, with Magnetic Resonance Imaging(MRI), which can provide anatomical information, for the purpose of analysis of oxidative stress-related diseases, and applied the system to in vivo measurement.To build the co-registration system, a nitroxyl radical, which could be visualized by both images obtained using ESRI and MRI as a marker for positional calibration, was used, and the optimal methods in image construction were evaluated by simulation experiment because of the co-registration with high-precision. Nitroxyl radical solutions were administered to animals, and the fused images were obtain … More ed. These images demonstrate the differences in kinetics of nitroxyl radicals by the administration routes and the n-octanol/water partition coefficients(Po/w). Free radical generating reagents were orally administered just before the probe treatment, and the images, showing the free radical generation in stomach, were obtained.We proposed an in vivo ESR/spin probe technique as a method for non-invasive and real-time analysis of in vivo free radical reaction and have evaluated the mechanism of free radical generation in the experimental models of diseases. In this study, gastrointestinal injury, diabetes and brain ischemia-reperfusion injury were selected as the models of oxidative stress-related diseases, and the location and kind of free radical generation were investigated. It was suggested that, using several kinds of nitroxyl radicals with different Po/w, hydroxyl radical was generated in an intracellular compartment in the model of indomethacin-induced gastric lesion injury and lipid radical was generated on the surfaces of cerebrovascular cell membranes in the model of brain ischemia-reperfusion injury.From these findings, the fused imaging system by the combination of ESRI and MRI is thought to be the powerful tool to clear the in vivo free radical generation in the target organ and/or tissue. In the near future, it is expected that the application of this system enables us to elucidate the mechanism of free radical generation in oxidative stress-related diseases. Less