用内源性对比 MRI 成像检测短寿命活性氧（ROS）。
Imaging short-lived reactive oxygen species (ROS) with endogenous contrast MRI.
机构信息
Department of Radiology, College of Medicine, University of Illinois at Chicago, Chicago, Illinois, USA.
Center for MR Research, University of Illinois at Chicago, Chicago, Illinois, USA.
出版信息
J Magn Reson Imaging. 2018 Jan;47(1):222-229. doi: 10.1002/jmri.25763. Epub 2017 May 15.
PURPOSE
To characterize the relaxation properties of reactive oxygen species (ROS) for the development of endogenous ROS contrast magnetic resonance imaging (MRI).
MATERIALS AND METHODS
ROS-producing phantoms and animal models were imaged at 9.4T MRI to obtain T and T maps. Egg white samples treated with varied concentrations of hydrogen peroxide (H O ) were used to evaluate the effect of produced ROS in T and T for up to 4 hours. pH and temperature changes due to H O treatment in egg white were also monitored. The influences from H O itself and oxygen were evaluated in bovine serum albumin (BSA) solution producing no ROS. In addition, dynamic temporal changes of T in H O -treated egg white samples were used to estimate ROS concentration over time and hence the detection sensitivity of relaxation-based endogenous ROS MRI. The relaxivity of ROS was compared with that of Gd-DTPA as a reference. Finally, the feasibility of in vivo ROS MRI with T mapping acquired using an inversion recovery sequence was demonstrated with a well-established rotenone-treated mouse model (n = 6).
RESULTS
pH and temperature changes in treated egg white samples were insignificant (<0.1 unit and <1°C, respectively). T relaxation time in the H O -treated egg white was reduced significantly (P < 0.05), while there was only small reduction in T (<10%). In the H O -treated BSA solution that produce no ROS, there was a small change in T due to H O itself (±1%), although a significant T -shortening effect was observed (>10%, P < 0.05). Also, there was a small reduction in T (13 ± 1%) and T (1 ± 2%) from molecular oxygen. The detection sensitivity of ROS MRI was estimated around 10 pM. The T relaxivity of ROS was found to be much higher than that of Gd-DTPA (3.4 × 10 vs. 0.9 s ·mM ). Finally, significantly reduced T was observed in rotenone-treated mouse brain (5.1 ± 2.5%, P < 0.05).
CONCLUSION
We demonstrated in the study that endogenous ROS MRI based on the paramagnetic effect has sensitivity for in vitro and in vivo applications.
LEVEL OF EVIDENCE
2 Technical Efficacy Stage: 2 J. Magn. Reson. Imaging 2018;47:222-229.
目的
为了开发内源性活性氧（ROS）对比磁共振成像（MRI），对活性氧的弛豫特性进行研究。
材料与方法
在 9.4T MRI 下对产生 ROS 的模型和动物模型进行成像，以获得 T1 和 T2 图。使用经过不同浓度过氧化氢（H2O2）处理的蛋清样本，评估产生的 ROS 在 4 小时内对 T1 和 T2 的影响。还监测了 H2O2 处理蛋清导致的 pH 值和温度变化。在不产生 ROS 的牛血清白蛋白（BSA）溶液中，评估了 H2O2 本身和氧气的影响。此外，还利用 H2O2 处理的蛋清样品的 T1 动态时间变化来估算 ROS 浓度随时间的变化，从而评估基于弛豫的内源性 ROS MRI 的检测灵敏度。将 ROS 的弛豫率与作为参考的 Gd-DTPA 进行了比较。最后，通过使用反转恢复序列获得 T 映射，在已建立的鱼藤酮处理的小鼠模型（n=6）中验证了体内 ROS MRI 的可行性。
结果
处理蛋清样本的 pH 值和温度变化很小（分别<0.1 个单位和<1°C）。H2O2 处理的蛋清中的 T1 弛豫时间明显缩短（P<0.05），而 T2 弛豫时间只有很小的缩短（<10%）。在不产生 ROS 的 H2O2 处理的 BSA 溶液中，由于 H2O2 本身的影响，T1 有很小的变化（±1%），尽管观察到 T1 缩短的效果非常显著（>10%，P<0.05）。另外，由于分子氧的存在，T1（13±1%）和 T2（1±2%）也有很小的减少。ROS MRI 的检测灵敏度估计约为 10pM。ROS 的 T1 弛豫率明显高于 Gd-DTPA（3.4×10 比 0.9 s·mM-1）。最后，在鱼藤酮处理的小鼠大脑中观察到 T 弛豫率明显降低（5.1±2.5%，P<0.05）。
结论
本研究证明了基于顺磁效应的内源性 ROS MRI 具有体外和体内应用的灵敏度。
证据水平
2 技术功效分期：2 J. Magn. Reson. Imaging 2018;47:222-229.
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