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

开发氧化应激相关疾病的ESRI・MRI融合成像装置

基本信息

批准号：
13357019
负责人：
UTSUMI Hideo
金额：
$ 31.78万
依托单位：
Kyushu University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (A)
财政年份：
2001
资助国家：
日本
起止时间：
2001 至 2003
项目状态：
已结题

项目摘要

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

为了研究自由基产生与疾病发生和/或进展之间的关系，自由基产生的位置必须与特定的靶器官或组织相对应。在本研究中，我们开发了融合成像系统。将可可视化自由基分布的电子自旋共振成像（ESRI）与可提供解剖信息的磁共振成像（MRI）相结合，以分析氧化应激相关疾病，并将该系统应用于在为了构建联合配准系统，使用可以通过ESRI和MRI获得的图像可视化的硝酰自由基作为位置校准的标记，并通过模拟实验评估图像构建的最佳方法，因为对动物施用高精度的共同配准硝酰自由基溶液，获得的融合图像显示了不同给药途径硝酰自由基动力学的差异。并在探针处理前口服自由基生成剂正辛醇/水分配系数(Po/w)，并获得显示胃中自由基生成的图像。我们提出了体内ESR/。自旋探针技术作为一种无创、实时分析体内自由基反应的方法，在胃肠道损伤、糖尿病和脑缺血再灌注疾病的实验模型中评估了自由基产生的机制。伤害是选择作为氧化应激相关疾病的模型，并研究了自由基产生的位置和类型，提出使用几种不同Po/w的硝酰基自由基，在细胞内隔室中产生羟基自由基。吲哚美辛引起的胃损伤模型，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。根据这些发现，融合成像系统结合了ESRI和MRI被认为是清除体内靶器官和/或组织中自由基生成的有力工具，预计该系统的应用使我们能够阐明自由基的机制。氧化应激相关疾病的发生较少。