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中华脑血管病杂志(电子版) doi: 10.3877/cma.j.issn.1673-9248.XXXX.XX.XXX

基础研究

多模态磁共振成像技术在食蟹猴脑缺血再灌注模型建立中的应用价值
芮春朵1, 沈海林2, 杜红娣2, 邱志富3, 于乐林2, 李振凯2, 叶娟,2()   
  1. 1 214200 江苏 宜兴,江苏大学附属宜兴医院医学影像科
    2 215028 江苏 苏州,上海交通大学医学院苏州九龙医院医学影像科
    3 201400 上海浦灵生物科技有限公司
  • 收稿日期:2024-12-19
  • 通信作者: 叶娟
  • 基金资助:
    苏州市科技计划项目(SKY2022093); 苏州市医学会“姑苏医星”系列之“影像医星”科技项目“青年项目”(2022YX-Q04); 江苏大学医教协同创新基金项目(JDYY2023130); 苏州九龙医院院级预研基金项目(SZJL202301)

The application value of multimodal magnetic resonance imaging technology in establishing a cerebral ischemia-reperfusion model in cynomolgus monkeys

Chunduo Rui1, Hailin Shen2, Hongdi Du2, Zhifu Qiu3, Lelin Yu2, Zhenkai Li2, Juan Ye,2()   

  1. 1 Department of Radiology, the Affiliated Yixing Hospital of Jiangsu University, Yixing 214200, China
    2 Department of Radiology, Shanghai Jiao Tong University School of Medicine Suzhou Kowloon Hospital, Suzhou 215028, China
    3 Prisys Biotechnologies Co., Ltd., Shanghai 201400, China
  • Received:2024-12-19
  • Corresponding author: Juan Ye
引用本文:

芮春朵, 沈海林, 杜红娣, 邱志富, 于乐林, 李振凯, 叶娟. 多模态磁共振成像技术在食蟹猴脑缺血再灌注模型建立中的应用价值[J/OL]. 中华脑血管病杂志(电子版), doi: 10.3877/cma.j.issn.1673-9248.XXXX.XX.XXX.

Chunduo Rui, Hailin Shen, Hongdi Du, Zhifu Qiu, Lelin Yu, Zhenkai Li, Juan Ye. The application value of multimodal magnetic resonance imaging technology in establishing a cerebral ischemia-reperfusion model in cynomolgus monkeys[J/OL]. Chinese Journal of Cerebrovascular Diseases(Electronic Edition), doi: 10.3877/cma.j.issn.1673-9248.XXXX.XX.XXX.

目的

数字减影血管造影(DSA)引导下建立食蟹猴脑缺血再灌注(CIR)模型,探讨并评估多模态磁共振(MRI)成像技术在模型建立过程中的应用价值。

方法

选取8只成年食蟹猴,术前排除脑血管畸形及颅内占位性病变,DSA引导下成功栓塞食蟹猴大脑中动脉(MCA),建立CIR模型。术后1 h行颅脑多模态MRI扫描确认栓塞位置及脑缺血范围,并于术后2.5 h行阿替普酶(rt-PA)静脉溶栓治疗,分别后于术后4 h、24 h及7 d再次行颅脑多模态MRI扫描明确治疗后影像学变化。术后第8天处死动物取脑组织进行2,3,5-三苯基氯化四氮唑(TTC)染色。

结果

6只实验动物DSA下均证实栓塞成功。静脉溶栓再灌注治疗后4 h、24 h及7 d后弥散加权成像(DWI)异常高信号区相对面积逐渐减小,表观弥散系数(ADC)值持续升高,磁共振血管成像(MRA)显示MCA血流再通,血管信号强度逐渐增强,远端分支显影逐渐增多。脑组织TTC失染区相对面积较术后4 h DWI图像明显减小,与术后7 d MRI结果相符。

结论

DSA引导下可成功建立猴脑CIR模型。多模态MRI的DWI、ADC及MRA成像技术可评价CIR模型血管再通情况及脑缺血面积变化。

Objective

To establish a cerebral ischemia-reperfusion (CIR) model in cynomolgus monkeys under digital subtraction angiography (DSA) guidance and evaluate the utility of multimodal magnetic resonance imaging (MRI) in the modeling process.

Methods

Eight adult cynomolgus monkeys were selected, with cerebrovascular malformations and intracranial space-occupying lesions excluded preoperatively. The middle cerebral artery (MCA) was successfully embolized under DSA guidance to establish the CIR model. Multimodal MRI was performed at 1 h post-operation to confirm the embolization site and ischemic area. Intravenous thrombolysis with recombinant tissue plasminogen activator (rt-PA) was administered at 2.5 h, followed by serial multimodal MRI scans at 4 h, 24 h, and 7 d post-operation to assess therapeutic changes. Animals were sacrificed on day 8 for 2,3,5-triphenyltetrazolium chloride (TTC) staining of brain tissues.

Results

Successful embolization was angiographically confirmed in six animals. Following thrombolytic reperfusion, the relative area of hyperintensity on diffusion-weighted imaging (DWI) progressively decreased at 4 h, 24 h, and 7 d, accompanied by continuously increasing apparent diffusion coefficient (ADC) values. Magnetic resonance angiography (MRA) demonstrated MCA recanalization with gradual enhancement of vascular signal intensity and increased visualization of distal branches. The relative area of TTC-unstained regions was significantly reduced compared to 4 h DWI findings, correlating with 7 d MRI results.

Conclusion

Under DSA guidance, a cerebral ischemia-reperfusion (CIR) model in monkeys was successfully established. Multimodal MRI techniques, including diffusion-weighted imaging (DWI), apparent diffusion coefficient (ADC) mapping, and magnetic resonance angiography (MRA), could effectively evaluate vascular recanalization status and dynamic changes in cerebral ischemic area in the CIR model.

图1 不同时间点食蟹猴脑缺血再灌注模型MRI扫描脑组织缺氧缺血的变化过程。图a、b:基线状态下弥散加权成像(DWI)、表观弥散系数(ADC)图像;图c、d:栓塞术后1 h,DWI呈稍高信号,对应部位ADC稍低信号;图e、f:栓塞术后4 h,DWI呈明显异常高信号,对应部位ADC信号更低;图g~j:为栓塞术后24 h及7 d,MRI扫描显示DWI异常高信号相对面积明显逐渐变小,ADC信号部分恢复,血管信号强度逐渐增强
图2 不同时间点磁共振血管成像(MRA)图像变化评估食蟹猴缺血再灌注模型血管闭塞再通及侧支循环的变化过程。图a为基线状态下MRA序列图像,图b为栓塞术后1 h,MRA显示右侧大脑中动脉血流信号中断,图c、d、e分别为栓塞术后4 h、24 h及7 d,MRA显示大脑中动脉再通,血管信号强度逐渐增强,远端分支血管逐渐增多
图3 食蟹猴大脑中动脉栓塞模型脑组织2,3,5-三苯基四唑氯溶液染色图片,箭头示溶栓梗死病灶
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