Magnetic resonance imaging (MRI), an all-pervasive imaging modality, shows precise inner body architecture using nuclear magnetic resonance (NMR) theory coupled with gradient magnetic fields. MRI as an imaging technique depends on protons' spin density, along with the lengthening (T1) and slicing (T2) relaxation time to distinguish tissues.
The role of MRI contrast agents is crucial in enhancing this tissue contrast, enabling clearer delineation of structures. Metal-based nanoparticles, in particular, are a novel generation of MRI contrast agents because they are able to function magnetically, are biocompatible, and are functionalizable. Alfa Chemistry is exploring these nanoparticles' properties, uses, and classifications in detail for MRI applications in this article from Alfa Chemistry.
Gadolinium-based Nanoparticles
Gadolinium (Gd) contrast agents are some of the most popular contrast agents for MRI and mostly help with improving T1-weighted images by decreasing the T1 relaxation time. For clinical MRI contrast, gadolinium ions are the go-to choice, as they are highly magnetic sensitive and biocompatible. But gadolinium ions are extremely poisonous; the drugs are used in the form of chelates to minimize side effects. The classes of gadolinium-based agents include:
| Category | Description |
| Extracellular Fluid (ECF) Agents | Distributed primarily within extracellular spaces and commonly used for tissue differentiation. |
| Blood Pool Contrast Agents (BPCAs) | Remain within the vascular system, ideal for angiography and vascular imaging. |
| Organ-Specific Agents | Designed for specific organs such as the liver, where gadolinium can enhance the visualization of organ-specific pathologies. |
The effectiveness of gadolinium agents stems from their capacity to create high-contrast images by promoting proton relaxation, which brightens areas where these agents accumulate, thereby providing precise diagnostic insights.
Fig.1 Nanoparticle designs for amplifying MRI contrast: Preparation of nanogels incorporating Gd-chelates as cross-linkers through reverse emulsion[1].
Manganese-based Nanoparticles
Nanoparticles containing manganese (Mn) such as MnO have the potential as T1-weighted MRI agents. Manganese ions (Mn2+) are paramagnetic and will get into cells via calcium channels to sharpen MRI contrast and enable functional brain imaging. Manganese ions, in contrast to gadolinium, are more benign and do not require chelation, so don't need fancy chemical synthesis. This means that it can sometimes be used instead of gadolinium.
Manganese-enhanced MRI (MEMRI) has performed well in animal models (particularly in neuroimaging). It has been shown that manganese-doped graphene oxide composites can be formulated as potent contrast agents that are stable and bioavailable.
Fig.2 Manganese oxide nanoparticles for in vivo imaging. (A) Common modification strategy for improving the T1 relaxation rate and biocompatibility of Mn3O4 NPs. (B) Schematic illustration of the interaction between Mn3O4 NPs and water[2].
Iron Oxide Nanoparticles
MRI contrast agent with one of the most widespread uses is Iron oxide nanoparticles (Fe3O4/γ-Fe2O3). Nanoparticles of iron oxide are biocompactible and magnetic, and commonly deployed in T2-weighted imaging as superparamagnetic iron oxide (SPIO) and ultra-small superparamagnetic iron oxide (USPIO). These agents are colloidal suspensions of iron oxide nanoparticles that, when applied to MRI, darken the T2 signal in the tissue they're incorporated into, and hence the tissue darkens. SPIO and USPIO drugs are specifically suited for liver tissue, which is why they are so useful in liver tumor diagnosis.
| Classification Type | Details |
| Magnetic Property-Based | Classified as paramagnetic, superparamagnetic, and ferromagnetic agents. |
| Pharmacokinetics | Divided into non-specific extracellular, cell-associated, and blood pool agents. |
| Ionic Charge | Includes ionic and non-ionic agents depending on their charge, with ionic agents being more selective. |
The nanoscale size and spherical shape of the iron oxide particles provide unique biodistribution and allow for targeting applications that would be difficult to achieve using traditional agents. In addition, their water solubility and biocompatibility can be further enhanced by surface modifications such as polyethylene glycol (PEG) coatings.
Fig.3 Ultrasmall iron oxide nanoparticles are used as T1 (positive) contrast agents for magnetic resonance imaging[4].
Ferroplatinum (FePt) Nanoparticles
Bimetallic nanoparticles also show good promise. These alloy nanoparticles are not only highly biocompatible but can also be optimized for magnetic and biological functions by modulating the elemental distribution. Superparamagnetic iron-platinum nanoparticles (SIPPs) exhibit enhanced T2 relaxation properties compared to iron oxide, and SIPPs have been lipid-coated to form multifunctional micelles specifically targeting cancer cells (e.g., prostate cancer cells), making them a focal point for tumor-related imaging. Although promising, SIPP is still under investigation and has not yet been approved for human clinical use.
Fig.4 The cysteamine-capped FePt nanoparticles were used as a contrast agent for in vitro and in vivo MRI and CT evaluation for dual contrast enhancement[4].
Conclusion
Metal-based nanoparticle MRI contrast agents now offer significant enhancements in precision and specificity for medical imaging. Thanks to advances in nanotechnology, there are new nanoparticles, multifunctional agents, both therapeutic and diagnostic, being invented all the time. Such nanoparticles are promising not just in image contrast, but also in targeted imaging and therapy, notably in oncology and neurology.
References
- Advances in Gadolinium-based MRI Contrast Agent Designs for Monitoring Biological Processes in Vivo. Current Opinion in Chemical Biology (2018).
- Ultrahigh Relaxivity and Safe Probes of Manganese Oxide Nanoparticles for in Vivo Imaging. Scientific Reports (2013).
- Magnetic Iron Oxide Nanoparticles as T1 Contrast Agents for Magnetic Resonance Imaging. J. Mater. Chem. C (201I8).
- In Vitro and in Vivo Studies of FePt Nanoparticles for Dual Modal CT/MRI Molecular Imaging. Journal of the American Chemical Society (2010).
