Cancer Research UK and Medical Research Council Oxford Institute for Radiation Oncology, Department of Oncology, University of Oxford, Oxford, UK,
Institute of Biomedical Engineering, Department of Engineering Sciences, University of Oxford, Oxford, UK.
Int J Nanomedicine. 2018 Jul 25;13:4345-4359. doi: 10.2147/IJN.S158071. eCollection 2018.
Molecular MRI is an evolving field of research with strong translational potential. Selection of the appropriate MRI sequence, field strength and contrast agent depend largely on the application. The primary aims of the current study were to: 1) assess the sensitivity of different MRI sequences for detection of iron oxide particles in mouse brain; 2) determine the effect of magnetic field strength on detection of iron oxide particles in vivo; and 3) compare the sensitivity of targeted microparticles of iron oxide (MPIO) or ultra-small superparamagnetic iron oxide (USPIO) for detection of vascular cell adhesion molecule-1 (VCAM-1) in vivo.
Mice were injected intrastriatally with interleukin 1β to induce VCAM-1 expression on the cerebral vasculature. Subsequently, animals were injected intravenously with either VCAM-MPIO or VCAM-USPIO and imaged 1 or 13 hours post-injection, respectively. MRI was performed at 4.7, 7.0, or 9.4 T, using three different *-weighted sequences: single gradient echo 3D (GE3D), multi-gradient echo 3D (MGE3D) and balanced steady-state free precession 3D (bSSFP3D).
MGE3D yielded the highest signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) for the detection of iron oxide particles. All sequences showed a significant increase in SNR and CNR from 4.7 to 7.0 T, but no further improvement at 9.4 T. However, whilst targeted MPIO enabled sensitive detection of VCAM-1 expression on the cerebral vasculature, the long half-life (16.5 h vs 1.2 min) and lower relaxivity per particle (1.29×10 vs 1.18×10 Hz L/particle) of USPIO vs. MPIO rendered them impractical for molecular MRI.
These findings demonstrate clear advantages of MPIO compared to USPIO for molecularly-targeted MRI, and indicate that the MGE3D sequence is optimal for MPIO detection. Moreover, higher field strengths (7.0/9.4 T) showed enhanced sensitivity over lower field strengths (4.7 T). With the development of biodegradable MPIO, these agents hold promise for clinical translation.
分子 MRI 是一个具有强大转化潜力的新兴研究领域。MRI 序列、场强和对比剂的选择在很大程度上取决于应用。本研究的主要目的是：1）评估不同 MRI 序列检测小鼠脑内氧化铁颗粒的灵敏度；2）确定磁场强度对体内氧化铁颗粒检测的影响；3）比较靶向氧化铁微球（MPIO）或超小超顺磁性氧化铁（USPIO）检测血管细胞间黏附分子-1（VCAM-1）的灵敏度。
向纹状体注射白细胞介素 1β，诱导血管内皮细胞表达 VCAM-1。随后，分别向动物静脉内注射 VCAM-MPIO 或 VCAM-USPIO，并在注射后 1 或 13 小时进行 MRI 检查。MRI 在 4.7、7.0 和 9.4 T 下进行，使用三种不同的 T1 加权序列：单梯度回波 3D（GE3D）、多梯度回波 3D（MGE3D）和平衡稳态自由进动 3D（bSSFP3D）。
MGE3D 产生的氧化铁颗粒检测信号与噪声比（SNR）和对比噪声比（CNR）最高。所有序列在从 4.7 T 到 7.0 T 时 SNR 和 CNR 均有显著提高，但在 9.4 T 时无进一步提高。然而，虽然靶向 MPIO 能够灵敏地检测血管内皮细胞上的 VCAM-1 表达，但 USPIO 相对于 MPIO 的半衰期较长（16.5 h 比 1.2 min）和每颗粒弛豫率较低（1.29×10 比 1.18×10 Hz L/particle），使其不适合用于分子 MRI。
这些发现表明，MPIO 相对于 USPIO 具有明显的分子靶向 MRI 优势，并且表明 MGE3D 序列是 MPIO 检测的最佳选择。此外，较高的场强（7.0/9.4 T）比较低的场强（4.7 T）具有更高的灵敏度。随着可生物降解 MPIO 的发展，这些试剂有望在临床转化中得到应用。
