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.
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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