在一个人性化的小鼠模型中,对HIV-1相关的神经代谢障碍的CEST MRI评估
Gabriel C Gauthier1, Micah Summerlin2, Balasrinivasa R Sajja1
1Department of Radiology, University of Nebraska Medical Center, Omaha, NE, USA.
概括
化学交换和转移 (CEST) MRI检测了由HIV-1感染引起的大脑代谢变化,并显示了抗逆转录病毒疗法 (ART) 的改善. 这种成像技术对监测神经艾滋病病毒的进展和治疗反应有希望.
科学领域:
- 神经科学是一个神经科学.
- 医疗成像医学成像
- 生物化学 生物化学
背景情况:
- 人类免疫缺陷病毒1 (HIV-1) 相关的神经认知障碍 (HAND) 持续存在,尽管抗逆转录病毒治疗 (ART).
- 持续的神经炎症和代谢功能障碍驱动HAND.
- 需要新的生物标志物来监测神经HIV的疾病进展和治疗反应.
研究的目的:
- 评估化学交换和转移 (CEST) 核磁共振能否检测HIV-1诱导的神经代谢障碍.
- 评估CESTMRI能否检测到在神经HIV的人性化小鼠模型中ART介导的改善.
- 确定CESTMRI作为神经HIV潜在的非侵入性生物标志物.
主要方法:
- 被HIV-1感染的人性化CD34-NSG小鼠在基线,感染后6周和ART或载体治疗后12周接受了CESTMRI.
- 测量CEST对比度为2ppm (与肌相关),3ppm (与谷氨酸相关) 和-3.5ppm (核Overhauser效应,NOE).
- 通过免疫组织化学和qPCR评估神经炎症和病毒载量.
主要成果:
- 艾滋病毒-1感染降低了2ppm的CEST对比度,并在感染后6周增加了NOE.
- 车辆治疗导致12周后多个大脑区域的3ppm和2ppmCEST对比度下降.
- 在特定的大脑区域,ART恢复了CEST对比度,与减少病毒负荷和神经炎症相关.
结论:
- 在HIV-1感染中,CEST MRI有效地检测出特定区域的代谢异常.
- CEST MRI 显示了 ART 的特定区域代谢恢复,反映了病毒载量降低和神经炎症.
- CEST MRI 是一个有前途的非侵入性生物标志物,用于监测神经艾滋病病毒的进展和治疗反应.
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