Magnetic particle imaging

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Magnetic particle imaging (MPI) is an emerging non-invasive tomographic technique that directly detects superparamagnetic nanoparticle tracers. The technology has potential applications in diagnostic imaging and material science. Currently, it is used in medical research to measure the 3-D location and concentration of nanoparticles. Imaging does not use ionizing radiation and can produce a signal at any depth within the body. MPI was first conceived in 2001 by scientists working at the Royal Philips Research lab in Hamburg. The first system was established and reported in 2005. Since then, the technology has been advanced by academic researchers at several universities around the world. The first commercial MPI scanners have recently become available from Magnetic Insight and Bruker Biospin.

Contents

The hardware used for MPI is very different from MRI. MPI systems use changing magnetic fields to generate a signal from superparamagnetic iron oxide (SPIO) nanoparticles. These fields are specifically designed to produce a single magnetic field free region. A signal is only generated in this region. An image is generated by moving this region across a sample. Since there is no natural SPIO in tissue, a signal is only detected from the administered tracer. This provides images without background. MPI is often used in combination with anatomical imaging techniques (such as CT or MRI) providing information on the location of the tracer.

Applications

Magnetic particle imaging combines high tracer sensitivity with submillimeter resolution. Imaging is performed in a range of milliseconds to seconds. The iron oxide tracer used with MPI are cleared naturally by the body through the mononuclear phagocyte system. The iron oxide nanoparticles are broken down in the liver, where the iron is stored and used to produce hemoglobin. SPIOs have previously been used in humans for iron supplementation and liver imaging.

Blood pool imaging

Cardiovascular

The first in vivo MPI results provided images of a beating mouse heart in 2009. With further research, this could eventually be used for real-time cardiac imaging. [1]

Oncology

MPI has numerous applications to the field of oncology research. Accumulation of a tracer within solid tumors can occur through the enhanced permeability and retention effect. This has been successfully used to detect tumor sites within rats. [2] The high sensitivity of the technique means it may also be possible to image micro-metastasis through the development of nanoparticles targeted to cancer cells. MPI is being investigated as a clinical alternative screening technique to nuclear medicine in order to reduce radiation exposure in at-risk populations.

Cell tracking

By tagging therapeutic cells with iron oxide nanoparticles, MPI allows them to be tracked throughout the body. This has applications in regenerative medicine and cancer immunotherapy. Imaging can be used to improve the success of stem cell therapy by following the movement of these cells in the body. [3] The tracer is stable while tagged to a cell and remains detectable past 87 days. [4]

Functional brain imaging

MPI has been proposed as a promising platform for functional brain imaging that requires highly sensitive imaging as well as short scan times for sufficient temporal resolution. For this, MPI is used to detect the increase of cerebral blood volume (CBV) arising from neuroactivation. Functional neuroimaging using MPI has been successfully demonstrated [5] in rodents and has a promising sensitivity advantage compared to other imaging modalities. In the long perspective, this could potentially allow to study functional neuroactivation on a single-patient level and thus bring functional neuroimaging to clinical diagnostics.

Superparamagnetic tracer

The tracers used in magnetic particle imaging (MPI) are superparamagnetic iron oxide nanoparticles (SPIONs). They are composed of a magnetite (Fe3O4) or maghemite (Fe2O3) core surrounded by a surface coating (commonly dextran, carboxydextran, or polyethylene glycol). [6] [7] [8] [9]

The SPION tracer is detectable within biological fluids, such as the blood. This fluid is very responsive to even weak magnetic fields, and all of the magnetic moments will line up in the direction of an induced magnetic field. These particles can be used because the human body does not contain anything which will create magnetic interference in imaging. As the sole tracer, the properties of SPIONs are of key importance to the signal intensity and resolution of MPI. Iron oxide nanoparticles, due to their magnetic dipoles, exhibit a spontaneous magnetization that can be controlled by an applied magnetic field. Therefore, the performance of SPIONs in MPI is critically dependent on their magnetic properties, such as saturation magnetization, magnetic diameter, and relaxation mechanism. Upon application of an external magnetic field, the relaxation of SPIONs can be governed by two mechanisms, Néel, and Brownian relaxation. When the entire particle rotates with respect to the environment, it is following Brownian relaxation, which is affected by the physical diameter. When only the magnetic dipole rotates within the particles, the mechanism is called Néel relaxation, which is affected by the magnetic diameter. According to the Langevin model of superparamagnetism, the spatial resolution of MPI should improve cubically with the magnetics diameter, which can be obtained by fitting magnetization versus magnetic field curve to a Langevin model. [10] However, more recent calculations suggest that there exists an optimal SPIONs magnetic size range (~26 nm) for MPI. [6] This is because of blurring caused by Brownian relaxation of large magnetics size SPIONs. Although magnetic size critically affects the MPI performance, it is often poorly analyzed in publications reporting applications of MPI using SPIONs. Often, commercially available tracers or home-made tracers are used without thorough magnetic characterization. Importantly, due to spin canting and disorder at the surface, or due to the formation of mixed-phase nanoparticles, the equivalent magnetic diameter can be smaller than the physical diameter. And magnetic diameter is critical because of the response of particles to an applied magnetic field dependent on the magnetic diameter, not physical diameter. The largest equivalent magnetic diameter can be the same as the physical diameter. A recent review paper by Chandrasekharan et al. summarizes properties of various iron oxide contrast agents and their MPI performance measured using their in-house Magnetic Particle Spectrometer, shown in the picture here. It should be pointed out that the core diameter listed in the table is not necessarily the magnetic diameter. The table provides a comparison of all current published SPIONs for MPI contrast agents. As seen in the table, LS017, with a SPION core size of 28.7 nm and synthesized through heating up thermal decomposition with post-synthesis oxidation, has the best resolution compared with others with lower core size. Resovist (Ferucarbotran), consisting of iron oxide made via coprecipitation, is the most commonly used and commercially available tracer. However, as suggested by Gleich et al., only 3% of the total iron mass from Resovist contributes to the MPI signal due to its polydispersity, leading to relatively low MPI sensitivity. The signal intensity of MPI is influenced by both the magnetic core diameter and the size distribution of SPIONs. Comparing the MPI sensitivity listed in the above table, LS017 has the highest signal intensity (54.57 V/g of Fe) as particles are monodisperse and possess a large magnetic diameter compared with others.

The surface coating also plays a key role in determining the behavior of the SPIONs. It minimizes unwanted interactions between the iron oxide cores (for example, counteracting attractive forces between the particles to prevent aggregation), increases stability and compatibility with the biological environment, and can also be used to tailor SPION performance to particular imaging applications. [9] [11] Different coatings cause changes in cellular uptake, blood circulation, and interactions with the immune system, influencing how the tracer becomes distributed throughout the body over time. [11] For example, SPIONs coated with carboxydextran have been shown to clear to the liver almost immediately after injection, while those with a polyethylene glycol (PEG) coating remain in circulation for hours before being cleared from the blood. These behaviors make the carboxydextran-coated SPION tracer better optimized for liver imaging and the PEG-coated SPION tracer more suitable for vascular imaging. [6] [7]

Advantages

Signal enhancement

Passive dual coil resonator

A device that provides frequency-selective signal enhancement was recently developed at RWTH Aachen University. The passive dual coil resonator (pDCR) is a purely passive receive coil insert for a preclinical MPI system. The pDCR aims to enhance the frequency components associated with high mixing orders, which are critical to achieve a high spatial resolution. [12]

Congresses, workshops

Related Research Articles

<span class="mw-page-title-main">Superparamagnetism</span>

Superparamagnetism is a form of magnetism which appears in small ferromagnetic or ferrimagnetic nanoparticles. In sufficiently small nanoparticles, magnetization can randomly flip direction under the influence of temperature. The typical time between two flips is called the Néel relaxation time. In the absence of an external magnetic field, when the time used to measure the magnetization of the nanoparticles is much longer than the Néel relaxation time, their magnetization appears to be in average zero; they are said to be in the superparamagnetic state. In this state, an external magnetic field is able to magnetize the nanoparticles, similarly to a paramagnet. However, their magnetic susceptibility is much larger than that of paramagnets.

<span class="mw-page-title-main">Magnetite</span> Iron ore mineral

Magnetite is a mineral and one of the main iron ores, with the chemical formula Fe2+Fe3+2O4. It is one of the oxides of iron, and is ferrimagnetic; it is attracted to a magnet and can be magnetized to become a permanent magnet itself. With the exception of extremely rare native iron deposits, it is the most magnetic of all the naturally occurring minerals on Earth. Naturally magnetized pieces of magnetite, called lodestone, will attract small pieces of iron, which is how ancient peoples first discovered the property of magnetism.

<span class="mw-page-title-main">Ferrofluid</span> Special type of liquid which is attracted by poles of a magnet

Ferrofluid is a liquid that is attracted to the poles of a magnet. It is a colloidal liquid made of nanoscale ferromagnetic or ferrimagnetic particles suspended in a carrier fluid. Each magnetic particle is thoroughly coated with a surfactant to inhibit clumping. Large ferromagnetic particles can be ripped out of the homogeneous colloidal mixture, forming a separate clump of magnetic dust when exposed to strong magnetic fields. The magnetic attraction of tiny nanoparticles is weak enough that the surfactant's Van der Waals force is sufficient to prevent magnetic clumping or agglomeration. Ferrofluids usually do not retain magnetization in the absence of an externally applied field and thus are often classified as "superparamagnets" rather than ferromagnets.

<span class="mw-page-title-main">Nanoparticle</span> Particle with size less than 100 nm

A nanoparticle or ultrafine particle is usually defined as a particle of matter that is between 1 and 100 nanometres (nm) in diameter. The term is sometimes used for larger particles, up to 500 nm, or fibers and tubes that are less than 100 nm in only two directions. At the lowest range, metal particles smaller than 1 nm are usually called atom clusters instead.

<span class="mw-page-title-main">Iron(II,III) oxide</span> Chemical compound

Iron(II,III) oxide, or black iron oxide, is the chemical compound with formula Fe3O4. It occurs in nature as the mineral magnetite. It is one of a number of iron oxides, the others being iron(II) oxide (FeO), which is rare, and iron(III) oxide (Fe2O3) which also occurs naturally as the mineral hematite. It contains both Fe2+ and Fe3+ ions and is sometimes formulated as FeO ∙ Fe2O3. This iron oxide is encountered in the laboratory as a black powder. It exhibits permanent magnetism and is ferrimagnetic, but is sometimes incorrectly described as ferromagnetic. Its most extensive use is as a black pigment (see: Mars Black). For this purpose, it is synthesized rather than being extracted from the naturally occurring mineral as the particle size and shape can be varied by the method of production.

<span class="mw-page-title-main">Gadolinium(III) oxide</span> Chemical compound

Gadolinium(III) oxide (archaically gadolinia) is an inorganic compound with the formula Gd2O3. It is one of the most commonly available forms of the rare-earth element gadolinium, derivatives of which are potential contrast agents for magnetic resonance imaging.

Magnetofection is a transfection method that uses magnetic fields to concentrate particles containing vectors to target cells in the body. Magnetofection has been adapted to a variety of vectors, including nucleic acids, non-viral transfection systems, and viruses. This method offers advantages such as high transfection efficiency and biocompatibility which are balanced with limitations.

MRI contrast agents are contrast agents used to improve the visibility of internal body structures in magnetic resonance imaging (MRI). The most commonly used compounds for contrast enhancement are gadolinium-based contrast agents (GBCAs). Such MRI contrast agents shorten the relaxation times of nuclei within body tissues following oral or intravenous administration.

Magnetic-targeted carriers, also known as MTCs or magnetic vehicles, are micro- or nanoparticles that carry an anticancer drug to the target site by using an external magnetic field and field gradient to direct the desired drug. Usually, the complex involves microscopic beads of activated carbon, which bind the anticancer drug. A magnet applied from outside the body then can direct the drug to the tumor site. This can keep a larger dose of the drug at the tumor site for a longer period of time, and help protect healthy tissue from the side effects of chemotherapy.

<span class="mw-page-title-main">Janus particles</span> Type of nanoparticle or microparticle

Janus particles are special types of nanoparticles or microparticles whose surfaces have two or more distinct physical properties. This unique surface of Janus particles allows two different types of chemistry to occur on the same particle. The simplest case of a Janus particle is achieved by dividing the particle into two distinct parts, each of them either made of a different material, or bearing different functional groups. For example, a Janus particle may have one-half of its surface composed of hydrophilic groups and the other half hydrophobic groups, the particles might have two surfaces of different color, fluorescence, or magnetic properties. This gives these particles unique properties related to their asymmetric structure and/or functionalization.

Magnetic Nanorings are a form of magnetic nanoparticles, typically made of iron oxide in the shape of a ring. They have multiple applications in the medical field and computer engineering. In experimental trials, they provide a more localized form of cancer treatment by attacking individual cells instead of a general cancerous region of the body, as well as a clearer image of tumors by improving accuracy of cancer cell identification. They also allow for a more efficient and smaller, MRAM, which helps reduce the size of the technology houses it. Magnetic nanorings can be produced in various compositions, shapes, and sizes by using hematite nanorings as the base structure.

Magnetic nanoparticles are a class of nanoparticle that can be manipulated using magnetic fields. Such particles commonly consist of two components, a magnetic material, often iron, nickel and cobalt, and a chemical component that has functionality. While nanoparticles are smaller than 1 micrometer in diameter, the larger microbeads are 0.5–500 micrometer in diameter. Magnetic nanoparticle clusters that are composed of a number of individual magnetic nanoparticles are known as magnetic nanobeads with a diameter of 50–200 nanometers. Magnetic nanoparticle clusters are a basis for their further magnetic assembly into magnetic nanochains. The magnetic nanoparticles have been the focus of much research recently because they possess attractive properties which could see potential use in catalysis including nanomaterial-based catalysts, biomedicine and tissue specific targeting, magnetically tunable colloidal photonic crystals, microfluidics, magnetic resonance imaging, magnetic particle imaging, data storage, environmental remediation, nanofluids, optical filters, defect sensor, magnetic cooling and cation sensors.

Magnet-assisted transfection is a transfection method which uses magnetic interactions to deliver DNA into target cells. Nucleic acids are associated with magnetic nanoparticles, and magnetic fields drive the nucleic acid-particle complexes into target cells, where the nucleic acids are released.

<span class="mw-page-title-main">Iron oxide nanoparticle</span>

Iron oxide nanoparticles are iron oxide particles with diameters between about 1 and 100 nanometers. The two main forms are composed of magnetite and its oxidized form maghemite. They have attracted extensive interest due to their superparamagnetic properties and their potential applications in many fields including molecular imaging.

Biomagnetics is a field of biotechnology. It has actively been researched since at least 2004. Although the majority of structures found in living organisms are diamagnetic, the magnetic field itself, as well as magnetic nanoparticles, microstructures and paramagnetic molecules can influence specific physiological functions of organisms under certain conditions. The effect of magnetic fields on biosystems is a topic of research that falls under the biomagnetic umbrella, as well as the construction of magnetic structures or systems that are either biocompatible, biodegradable or biomimetic. Magnetic nanoparticles and magnetic microparticles are known to interact with certain prokaryotes and certain eukaryotes.

Magnetogenetics refers to a biological technique that involves the use of magnetic fields to remotely control cell activity.

Magnetic nanoparticle-based drug delivery is a means in which magnetic particles such as iron oxide nanoparticles are a component of a delivery vehicle for magnetic drug delivery, due to the simplicity with which the particles can be drawn to (external) magnetopuissant targets. Magnetic nanoparticles can impart imaging and controlled release capabilities to drug delivery materials such as micelles, liposomes, and polymers.

Superparamagnetic relaxometry (SPMR) is a technology combining the use of sensitive magnetic sensors and the superparamagnetic properties of magnetite nanoparticles (NP). For NP of a sufficiently small size, on the order of tens of nanometers (nm), the NP exhibit paramagnetic properties, i.e., they have little or no magnetic moment. When they are exposed to a small external magnetic field, on the order of a few millitesla (mT), the NP align with that field and exhibit ferromagnetic properties with large magnetic moments. Following removal of the magnetizing field, the NP slowly become thermalized, decaying with a distinct time constant from the ferromagnetic state back to the paramagnetic state. This time constant depends strongly upon the NP diameter and whether they are unbound or bound to an external surface such as a cell. Measurement of this decaying magnetic field is typically done by superconducting quantum interference detectors (SQUIDs). The magnitude of the field during the decay process determines the magnetic moment of the NPs in the source. A spatial contour map of the field distribution determines the location of the source in three dimensions as well as the magnetic moment.

Magnetoelastic filaments are one-dimensional composite structures that exhibit both magnetic and elastic properties. Interest in these materials tends to focus on the ability to precisely control mechanical events using an external magnetic field. Like piezoelectricity materials, they can be used as actuators, but do not need to be physically connected to a power source. The conformations adopted by magnetoelastic filaments are dictated by the competition between its elastic and magnetic properties.

<i>T</i>2*-weighted imaging Type of neuroimaging

T2*-weighted imaging is an MRI sequence to quantify observable or effective T2. In this sequence, hemorrhages and hemosiderin deposits become hypointense.

References

  1. ↑ Weizenecker, J.; Gleich, B.; Rahmer, J.; Dahnke, H.; Borgert, J. (2009-01-01). "Three-dimensional real-time in vivo magnetic particle imaging". Physics in Medicine and Biology. 54 (5): L1–L10. Bibcode:2009PMB....54L...1W. doi:10.1088/0031-9155/54/5/L01. ISSN   0031-9155. PMID   19204385. S2CID   2635545.
  2. ↑ Yu, Elaine Y.; Bishop, Mindy; Zheng, Bo; Ferguson, R. Matthew; Khandhar, Amit P.; Kemp, Scott J.; Krishnan, Kannan M.; Goodwill, Patrick W.; Conolly, Steven M. (2017-03-08). "Magnetic Particle Imaging: A Novel in Vivo Imaging Platform for Cancer Detection". Nano Letters. 17 (3): 1648–1654. Bibcode:2017NanoL..17.1648Y. doi:10.1021/acs.nanolett.6b04865. ISSN   1530-6984. PMC   5724561 . PMID   28206771.
  3. ↑ Zheng, Bo; See, Marc P. von; Yu, Elaine; Gunel, Beliz; Lu, Kuan; Vazin, Tandis; Schaffer, David V.; Goodwill, Patrick W.; Conolly, Steven M. (2016). "Quantitative Magnetic Particle Imaging Monitors the Transplantation, Biodistribution, and Clearance of Stem Cells In Vivo". Theranostics. 6 (3): 291–301. doi:10.7150/thno.13728. PMC   4737718 . PMID   26909106.
  4. ↑ Zheng, Bo; Vazin, Tandis; Goodwill, Patrick W.; Conway, Anthony; Verma, Aradhana; Saritas, Emine Ulku; Schaffer, David; Conolly, Steven M. (2015-09-11). "Magnetic Particle Imaging tracks the long-term fate of in vivo neural cell implants with high image contrast". Scientific Reports. 5 (1): 14055. Bibcode:2015NatSR...514055Z. doi:10.1038/srep14055. ISSN   2045-2322. PMC   4566119 . PMID   26358296.
  5. ↑ Herb, Konstantin; Mason, Erica; Mattingly, Eli; Mandeville, Joseph; Mandeville, Emiri; Cooley, Clarissa; Wald, Lawrence (2020). "Functional MPI (fMPI) of hypercapnia in rodent brain with MPI time-series imaging". International Journal on Magnetic Particle Imaging. 6 (2/1). doi:10.18416/IJMPI.2020.2009009.
  6. 1 2 3 Chandrasekharan, Prashant; Tay, Zhi Wei; Zhou, Xinyi Yedda; Yu, Elaine; Orendorff, Ryan; Hensley, Daniel; Huynh, Quincy; Fung, K. L. Barry; VanHook, Caylin Colson; Goodwill, Patrick; Zheng, Bo (November 2018). "A perspective on a rapid and radiation-free tracer imaging modality, magnetic particle imaging, with promise for clinical translation". The British Journal of Radiology. 91 (1091): 20180326. doi:10.1259/bjr.20180326. ISSN   1748-880X. PMC   6475963 . PMID   29888968.
  7. 1 2 Keselman, Paul; Yu, Elaine Y.; Zhou, Xinyi Y.; Goodwill, Patrick W.; Chandrasekharan, Prashant; Ferguson, R. Matthew; Khandhar, Amit P.; Kemp, Scott J.; Krishnan, Kannan M.; Zheng, Bo; Conolly, Steven M. (2017-05-07). "Tracking short-term biodistribution and long-term clearance of SPIO tracers in magnetic particle imaging". Physics in Medicine and Biology. 62 (9): 3440–3453. Bibcode:2017PMB....62.3440K. doi:10.1088/1361-6560/aa5f48. ISSN   1361-6560. PMC   5739049 . PMID   28177301.
  8. ↑ Makela, Ashley V.; Gaudet, Jeffrey M.; Murrell, Donna H.; Mansfield, James R.; Wintermark, Max; Contag, Christopher H. (2021-10-15). "Mind Over Magnets - How Magnetic Particle Imaging is Changing the Way We Think About the Future of Neuroscience". Neuroscience. 474: 100–109. doi:10.1016/j.neuroscience.2020.10.036. ISSN   1873-7544. PMID   33197498. S2CID   226842684.
  9. 1 2 Talebloo, Nazanin; Gudi, Mithil; Robertson, Neil; Wang, Ping (2020). "Magnetic Particle Imaging: Current Applications in Biomedical Research". Journal of Magnetic Resonance Imaging. 51 (6): 1659–1668. doi:10.1002/jmri.26875. ISSN   1522-2586. PMID   31332868. S2CID   198169801.
  10. ↑ Goodwill, Patrick (2012). "X-Space MPI: Magnetic Nanoparticles for Safe Medical Imaging". Advanced Materials. 24 (28): 3870–7. Bibcode:2012AdM....24.3870G. doi:10.1002/adma.201200221. hdl: 11693/53587 . PMID   22988557. S2CID   554405.
  11. 1 2 Billings, Caroline; Langley, Mitchell; Warrington, Gavin; Mashali, Farzin; Johnson, Jacqueline Anne (January 2021). "Magnetic Particle Imaging: Current and Future Applications, Magnetic Nanoparticle Synthesis Methods and Safety Measures". International Journal of Molecular Sciences. 22 (14): 7651. doi: 10.3390/ijms22147651 . PMC   8306580 . PMID   34299271.
  12. ↑ Pantke, Dennis; Mueller, Florian; Reinartz, Sebastian; Philipps, Jonas; Mohammadali Dadfar, Seyed; Peters, Maximilian; Franke, Jochen; Schrank, Franziska; Kiessling, Fabian; Schulz, Volkmar (2022-05-17). "Frequency-selective signal enhancement by a passive dual coil resonator for magnetic particle imaging". Physics in Medicine & Biology. 67 (11): 115004. Bibcode:2022PMB....67k5004P. doi:10.1088/1361-6560/ac6a9f. ISSN   0031-9155. PMID   35472698. S2CID   248404124.

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