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

• 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
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13357019/
• 关键词: ESR; free radical; oxidative stress; reactive oxygen species; MRI; disease analysis; gastrointestinal injury; ischemic-reperfusion injury; ESRI・MRI; スピンプローブ; 生体計測ESR; 糖尿病; 胃潰瘍; スピントラップ; 活性窒素; 心不全

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

为了研究自由基的产生与疾病的发生和发展之间的关系，自由基产生的位置必须与特定的靶器官或组织相对应。本研究将电子自旋共振成像(ESRI)技术与核磁共振成像(MRI)技术相结合，开发出可显示自由基分布的融合成像系统，用于氧化应激相关疾病的分析，并将其应用于活体测量。为了建立联合配准系统，使用ESRI和MRI获得的图像都可以可视化的氮氧自由基作为位置标定的标志，并通过模拟实验评估了最优的图像构建方法。将氮氧自由基溶液注入动物体内，得到融合图像的…更多的爱德。这些图像显示了不同给药途径和正辛醇/水分配系数(Po/w)在硝基自由基动力学上的差异。在探针治疗前，口服自由基产生试剂，并获得显示胃内自由基产生的图像。我们提出了一种体内ESR/自旋探针技术，作为一种无创和实时分析体内自由基反应的方法，并在疾病的实验模型中评估了自由基产生的机制。本研究选择胃肠损伤、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，对自由基产生的部位和种类进行了研究。提示在消炎痛诱导的胃损伤模型中，几种不同Po/w的硝基自由基在细胞内产生羟基自由基，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。因此，ESRI与MRI相结合的融合成像系统被认为是清除体内靶器官和/或组织中自由基产生的有力工具。在不久的将来，该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的产生机制。较少

项目成果

Yasukawa K., Kasazaki K., Hyodo F., Utsumi H.: "Non-invasive analysis of reactive oxygen species generated toxin rats with water immersion restrain-induced gastric lesions using in vivo electron spin resonance spectroscopy"Free Radical Research. 38. 147-1

Yasukawa K.、Kasazaki K.、Hyodo F.、Utsumi H.：“使用体内电子自旋共振光谱法对水浸抑制大鼠胃损伤产生的活性氧产生的毒素进行非侵入性分析”自由基研究。

Utsumi H., Yamada K.: "In vivo electron spin resonance-computed tomography/nitroxyl probe technique for non-invasive analysis of oxidative injuries"Archives of Biochemistry an d Biophysics. 416. 1-8 (2003)

Utsumi H.、Yamada K.：“用于氧化损伤非侵入性分析的体内电子自旋共振计算机断层扫描/硝酰探针技术”生物化学和生物物理学档案。

Ksasazaki, K., Yasukawa, K., Sano, H., Yamada, K-i., Utsumi, H.: "Application of in vivo ESR spectroscopy to pharmaceutical sciences-Evaluation of in vivo inhibitory mechanism of anti-gastric lesion drugs-"Appl Magn Reson. (in press).

Ksasazaki, K.、Yasukawa, K.、Sano, H.、Yamada, K-i.、Utsumi, H.：“体内ESR光谱在药物科学中的应用-抗胃损伤药物体内抑制机制的评估-”

Ksasazaki, K., Yasukawa, K., Sano, H., Utsumi, H.: "Non-invasive analysis of reactive oxygen species generated in NH_4OH-induced gastric lesions of rats using a 300 MHz in vivo ESR technique"Free Radic Res. (in press).

Ksasazaki, K.、Yasukawa, K.、Sano, H.、Utsumi, H.：“使用 300 MHz 体内 ESR 技术对 NH_4OH 诱导的大鼠胃损伤中产生的活性氧进行非侵入性分析”Free Radic Res

Kasazaki K., Yasukawa K., Sano H., Utsumi H.: "Non-invasive analysis of reactive oxygen species generated in NH_4OH-induced gastric lesions of rats using a 300 MHz in vivo ESR technique"Free Radical Research. 37. 757-766 (2003)

Kasazaki K.、Yasukawa K.、Sano H.、Utsumi H.：“使用 300 MHz 体内 ESR 技术对 NH_4OH 诱导的大鼠胃损伤中产生的活性氧进行非侵入性分析”自由基研究。