Magnetic Resonance Imaging

Magnetic resonance imaging (MRI) is a technology that uses the principle of nuclear magnetic resonance (NMR) plus a gradient magnetic field to detect emitted electromagnetic waves and draw images of the internal structure of objects. The principle of MRI can be simply summarized as follows: the sample is divided into several thin layers according to the needs. Each layer can be divided into a small volume called a voxel. A marker is calibrated for each voxel, a process called encoding or spatial localization. After applying radio frequency pulses to a certain layer, the NMR signal of this layer is received and decoded to obtain the nuclear magnetic resonance signal of each voxel. Finally, according to the corresponding relationship between the voxel and the coded voxel, the size of the voxel signal is obtained and displayed on the corresponding pixel of the screen. Among them, the signal size is represented by different gray levels. A pixel with a large signal has a high brightness, and a pixel with a small signal has a low brightness. In this way, an image reflecting the size of the NMR signal of each voxel, that is, an MRI image, can be obtained.

MRI is a medical diagnostic technology that has developed rapidly in recent years and has been widely used in the discovery and early diagnosis of various diseases. Among them, magnetic resonance imaging contrast agent is an important part of this technology. The contrast in MR depends on proton spin density, as well as longitudinal (T1) and transverse (T2) relaxation times (Fig. 1), and contrast agents can significantly enhance T1-weighted or T2-weighted images. Clinically used gadolinium chelates shorten T1, thereby increasing the concentration-dependent relaxivity r1 (reciprocal of T1), resulting in a brightening effect in MR. Alternatively, superparamagnetic iron oxide nanoparticles can shorten T2 (increase r2), resulting in a decrease in signal and thus a darkening effect. There is also a subtractive effect from magnetic field inhomogeneities, called T2, which is usually shorter than T1.

Figure 1. Interaction of gadolinium complexes with water, resulting in relaxation of water protons

Magnetic Resonance Imaging Contrast Agent

Commonly used MRI contrast agents and their basic classifications are summarized below.

• Gadolinium-Based Contrast Agent

Gadolinium(III)-based contrast agents fall into three broad categories: extracellular fluid (ECF) contrast agents, blood pool contrast agents (BPCAs), and organ-specific contrast agents.

• Manganese-Based Contrast Agent

Manganese-enhanced MRI (MEMRI) uses manganese ions (Mn2+), a contrast agent used in animal experiments. Mn2+ enters cells through calcium (Ca2+) channels, therefore, this group of contrast agents can be used for functional brain imaging. A previous MRI study showed that Mn2+ carbon nanostructured composites of graphene oxide nanosheets and graphene oxide nanoribbons are very effective MRI contrast agents.

• Iron Oxide Contrast Agent

There are two types of iron oxide contrast agents: superparamagnetic iron oxide (SPIO) and ultrasmall superparamagnetic iron oxide (USPIO). Superparamagnetic contrast agents consist of suspended colloids of iron oxide nanoparticles. When applied during imaging, they reduce the intensity of the T2 signal in tissue that absorbs the contrast agent. SPIO and USPIO have achieved successful results in the diagnosis of some liver tumors.

The nanometer size and particle shape of this group of contrast agents allow for diverse biodistribution and applications not observed with other contrast agents. Currently, nanoparticulate iron oxide is a popular and unique nanoparticulate agent used in clinical practice. However, other nanoparticles have also received increased attention as potential MRI contrast agents due to sophisticated modern molecular and cellular imaging techniques that have made disease-specific biomarkers visible at the microscopic and molecular levels. Owing to the tremendous advances in nanotechnology, new nanoparticle MRI contrast agents have been developed with further enhancements in their contrast agent capabilities as well as other functionalities.

• Iron Platinum Contrast Agent

Compared with iron oxide nanoparticles, superparamagnetic iron-platinum particles (SIPPs) have significantly improved T2 relaxation properties. SIPP has been encapsulated by phospholipids to create multifunctional SIPP stealth immune micelles to specifically target human prostate cancer cells. To our knowledge, these contrast agents are still being researched and have not been studied in humans.

In general, there are three basic types of MRI contrast agents, which are classified according to different criteria.

1. According to the magnetic center of MRI contrast agents, MRI contrast agents can be divided into three categories: paramagnetic substances, superparamagnetic substances, and ferromagnetic substances.

2. According to pharmacokinetic characteristics, MRI contrast agents can be divided into the following three categories: non-specific extracellular contrast agents, cell-bound and intracellular contrast agents, and blood pool contrast agents.

3. According to whether the contrast agent is charged or not, the paramagnetic resonance imaging contrast agent can be divided into the following two types: non-ionic contrast agent and ionic contrast agent.

References

1. Colombo, M. , Carregalromero, S. , Casula, M. F. , Gutiérrez L, Morales, M. P. , & Böhm IB, et al. (2012). Biological applications of magnetic nanoparticles. Pharmaceutical Research, 41(11), 4306. https://doi.org/10.1039/C2CS15337H

2. Meng, X., Seton, H. C., Lu, L. T., Prior, I. A., Thanh, N. T. K., & Song, B. . (2011). Magnetic copt nanoparticles as MRI contrast agent for transplanted neural stem cells detection. NANOSCALE, 3(3), 977-0.https://doi.org/10.1039/C0NR00846J

3. Pablico-Lansigan, M. H., Hickling, W. J., Japp, E. A., Rodriguez, O. C., Ghosh, A., Albanese, C., ... & Stoll, S. L. (2013). Magnetic nanobeads as potential contrast agents for magnetic resonance imaging. ACS nano, 7(10), 9040-9048.https://doi.org/10.1021/nn403647t

4. Xiao, Y. D., Paudel, R., Liu, J., Ma, C., Zhang, Z. S., & Zhou, S. K. (2016). MRI contrast agents: classification and application (review). International Journal of Molecular Medicine, 38(5). https://doi.org/10.3892/ijmm.2016.2744

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