Magnetic Beads (MBs) for Magnetic Resonance Imaging

  • Magnetic resonance imaging (MRI) is considered to be one of the most powerful techniques in diagnostics, clinical medicine and biomedical research. In MRI, the contrast agents are the key point because if without them, biological and functionally informative images cannot be obtained. Among different forms of probes, magnetic beads, which possess iron oxide magnetic cores, are the first and most widely used contrast agents due to their chemical stability, non-toxicity and biodegradability.

    MRI Principles

    Magnetic resonance imaging (MRI) is a non-invasive technique that uses magnetic fields to produce high-resolution and high-contrast images of tissue structure and function. It uses the magnetic properties of hydrogen atoms present in the human body such as water, membranes, lipids and proteins, as well as their interaction with magnetic fields.

     

    Fig. 1 Principles of Magnetic resonance imaging. (Journal of magnetism and magnetic materials 2014, 369, 176-183)

    Under normal circumstances, the arrangement of nuclei spin is irregular, but when the nuclei protons are placed in an external magnetic field, their spatial orientation transits from disorder to order. In this way, the nuclei will simultaneously precess at the angle between the spin axis and the direction of the applied magnetic field, which is known as the Larmor precession. The frequency of precession is related to the strength of magnetic field and is called the Larmor frequency (Fig. 1a). When a certain frequency of radio is introduced to the nuclear spin system, the protons absorb energy from the oscillating magnetic field and are excited to a higher energy state. After the radio frequency pulse is switched off, the excited nuclei cannot maintain the excited state, but will return to the equilibrium state, thereby releasing energy and emitting radio signals (Fig. 1b).

    The process of returning the nuclei from the excited state to the equilibrium state is called the relaxation process. There are two principal relaxation processes that characterize MRI signals. One is known as T1 or longitudinal relaxation, which involves the energy exchange between the rotating nucleus and the surrounding environment (e.g. lattice), thereby the magnetization (Mz) parallel to magnetic field can be recovered to the initial state (Fig. 1c). The other is known as T2 or transverse relaxation, which involves the energy exchange between rotating nuclei, so that the induced magnetization transverse to the static magnetic field (Mxy) will gradually decay (Fig. 1d).

    Magnetic Beads (MBs) as MRI Contrast Agents

    MRI offers several advantages including excellent temporal and spatial resolution, no radiation exposure, rapid in vivo acquisition of images, and a long effective imaging window. However, MRI is much less sensitive than nuclear medicine or fluorescence imaging, so more than 40% of all MRI examinations rely on contrast agents. Among various contrast agents, MBs with iron oxide cores (like γ-Fe2O3 or Fe3O4) and shells of polymers (like dextran or polyethylene glycol) are widely used for MRI application due to their high magnetization, chemical stability, non-toxicity and biodegradability.

    Basic Requirements of Magnetic Beads (MBs) in MRI

    Contrast Mechanism of Magnetic Beads (MBs)

    MBs are the types of T2 contrast agents for that they can produce local field distributions with very high T2 relaxivity, displaying superior T2 shortening effects even at low concentrations. In the human body, different tissues will absorb different amounts of MBs, showing different T2 values and specific images. When MRI is applied for the diagnosis of tumor cells, because the tumor cells do not have an effective reticuloendothelial system of healthy cells, so the contrast agent does not change their relaxation time, thus distinguishing them from the surrounding healthy cells. With the help of MBs contrast agents, great progresses have been made with MRI in gene delivery, cell tracking, drug delivery, tumor diagnosis and many other fields.

     

    Fig. 2 Illustration of signal enhancement in MRI by using MBs as contrast agent.

    The contrast properties mainly depend on several parameters, such as particle composition, particle size, structure morphology, hydrophilicity and magnetic field. In general, a single MB with a larger size has a higher T2 relaxivity, as long as its particle size is smaller than 20 nm to keep its superparamagnetic properties. Aggregates of multiple MBs were also found to have a much greater impact on T2, making it more sensitive.

    Adaptation Diseases

    • Nervous system diseases

    The adaptive diseases of MRI include neurological diseases such as cerebral infarction, brain tumors, inflammation, degenerative diseases, congenital malformations, trauma, etc. MRI is more accurate for the location and qualitative diagnosis of lesions.

    • Cardiovascular system

    MRI can be used for the diagnosis of heart disease, cardiomyopathy, pericardial tumor, pericardial effusion, mural thrombus, dissection of inner membrane, etc.

    • Thoracic lesions

    MRI can show the tumors in the mediastinum, lymph nodes and pleural lesions, etc.

    1. Abdominal organs

    MRI can be used for the diagnosis of liver cancer, liver hemangioma, liver cysts, intra-abdominal masses, especially retroperitoneal lesions.

    • Bone and joints

    MRI can also be used to diagnose intraosseous infections, tumors, trauma, especially some subtle changes such as bone contusion, etc.

    1. And many more …

    References

    1. Shokrollahi, H.; Khorramdin, A.; et al.Magnetic resonance imaging by using nano-magnetic particles. Journal of magnetism and magnetic materials2014, 369, 176-183.
    2. Weinstein, J. S.; Varallyay, C. G.; et al. Superparamagnetic iron oxide nanoparticles: diagnostic magnetic resonance imaging and potential therapeutic applications in neurooncology and central nervous system inflammatory pathologies, a review. Journal of Cerebral Blood Flow & Metabolism2010, 30 (1), 15-35.
    3. Shokrollahi, H., Contrast agents for MRI. Materials Science and Engineering: C2013, 33 (8), 4485-4497.
    4. Hola, K.; Markova, Z.; et al.Tailored functionalization of iron oxide nanoparticles for MRI, drug delivery, magnetic separation and immobilization of biosubstances. Biotechnol Adv 2015, 33 (6 Pt 2), 1162-76.