Department of Radiology, Dartmouth-Hitchcock Medical Center, Lebanon, NH 03756, United States of America. Geisel School of Medicine, Dartmouth College, Hanover, NH 03755, United States of America. Thayer School of Engineering, Dartmouth College, Hanover, NH 03755, United States of America. Department of Physics, Dartmouth College, Hanover, NH 03755, United States of America. Author to whom any correspondence should be addressed.
Phys Med Biol. 2020 Jun 11;65(12):125003. doi: 10.1088/1361-6560/ab8afd.
We are developing magnetic nanoparticle (NP) methods to characterize inflammation and infection in vivo. Peritoneal infection in C57BL/6 mice was used as a biological model. An intraperitoneal NP injection was followed by measurement of magnetic nanoparticle spectroscopy of Brownian rotation (MSB) spectra taken over time. MSB measures the magnetization of NPs in a low frequency alternating magnetic field. Two groups of three mice were studied; each group had two infected mice and one control with no infection. The raw MSB signal was compared with two derived metrics: the NP relaxation time and number of NPs present in the sensitive volume of the receive coil. A four compartment dynamic model was used to relate those physical properties to the relevant biological processes including phagocytic activity and migration. The relaxation time increased over time for all of the mice as the NPs were absorbed. The NP number decreased over time as the NPs were cleared from the sensitive volume of the receive coil. The composite p-values for all three rate constants were significant: raw signal, 0.0002, relaxation, <10 and local NP clearance, <10. However, not all the individual mice had significant changes: Only half the infected mice had significantly different rate constants for raw signal reduction. All infected mice had significantly smaller relaxation time constants. All but one of the infected mice had significantly lower rate constants for local clearance. Relaxation is affected by both phagocytic activity, edema and temperature changes and it should be possible to better isolate those effects to more completely characterize inflammation using more advanced MSB methods. The MSB NP signal can be used to identify inflammation in vivo because it has the unique ability to monitor phagocytic absorption through relaxation measurements.
我们正在开发磁性纳米粒子 (NP) 方法来对体内炎症和感染进行特征分析。以 C57BL/6 小鼠的腹腔感染作为生物模型。对 NP 进行腹腔内注射后，随着时间推移测量布朗旋转磁纳米粒子光谱（MSB）的光谱。MSB 测量 NPs 在低频交变磁场中的磁化。研究了两组共三只小鼠；每组有两只感染小鼠和一只未感染对照鼠。对原始 MSB 信号与两个衍生指标进行了比较：NP 弛豫时间和位于接收线圈灵敏体积中的 NP 数量。采用四室动力学模型将这些物理特性与相关生物过程（包括吞噬活性和迁移）相关联。随着 NPs 的吸收，所有小鼠的弛豫时间都随时间延长而增加。随着 NPs 从接收线圈灵敏体积中清除，NP 数量随时间减少。所有三个速率常数的综合 P 值均有统计学意义：原始信号，0.0002；弛豫，<10；局部 NP 清除，<10。然而，并非所有的小鼠都有明显的变化：只有一半感染小鼠的原始信号减少的速率常数有显著差异。所有感染小鼠的弛豫时间常数均显著减小。除了一只感染小鼠外，其余感染小鼠的局部清除率常数均显著降低。弛豫受吞噬活性、水肿和温度变化的影响，使用更先进的 MSB 方法应该有可能更好地分离这些影响，从而更全面地描述炎症。MSB NP 信号可用于体内识别炎症，因为它具有通过弛豫测量监测吞噬吸收的独特能力。
