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 Medical imaging is the technique and process of imaging the interior of a body for clinical analysis and medical intervention, as well as visual representation of the function of some organs or tissues ( physiology). Medical imaging seeks to r ...

and material science. Currently, it is used in

medical research Medical research (or biomedical research), also known as experimental medicine, encompasses a wide array of research, extending from " basic research" (also called ''bench science'' or ''bench research''), – involving fundamental scienti ...

to measure the 3-D location and concentration of

nanoparticle 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 10 ...

s. Imaging does not use

ionizing radiation Ionizing radiation (or ionising radiation), including nuclear radiation, consists of subatomic particles or electromagnetic waves that have sufficient energy to ionize atoms or molecules by detaching electrons from them. Some particles can travel ...

and can produce a signal at any depth within the body. MPI was first conceived in 2001 by

scientist A scientist is a person who conducts scientific research to advance knowledge in an area of the natural sciences. In classical antiquity, there was no real ancient analog of a modern scientist. Instead, philosophers engaged in the philosop ...

s working at the Royal

Philips Research The Philips Natuurkundig Laboratorium (English translation: ''Philips Physics Laboratory'') or NatLab was the Dutch section of the Philips research department, which did research for the product divisions of that company. Originally located in t ...

lab in

Hamburg Hamburg (, ; nds, label=Hamburg German, Low Saxon, Hamborg ), officially the Free and Hanseatic City of Hamburg (german: Freie und Hansestadt Hamburg; nds, label=Low Saxon, Friee un Hansestadt Hamborg),. is the List of cities in Germany by popul ...

. 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 fro
Magnetic Insight
an

The hardware used for MPI is very different from MRI. MPI systems use changing

magnetic field A magnetic field is a vector field that describes the magnetic influence on moving electric charges, electric currents, and magnetic materials. A moving charge in a magnetic field experiences a force perpendicular to its own velocity and to ...

s 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 Iron oxides are chemical compounds composed of iron and oxygen. Several iron oxides are recognized. All are black magnetic solids. Often they are non-stoichiometric. Oxyhydroxides are a related class of compounds, perhaps the best known of wh ...

tracer used with MPI are cleared naturally by the body through the

mononuclear phagocyte system In immunology, the mononuclear phagocyte system or mononuclear phagocytic system (MPS) also known as the reticuloendothelial system or macrophage system is a part of the immune system that consists of the phagocytic cells located in reticular co ...

. The iron oxide nanoparticles are broken down in the

liver The liver is a major organ only found in vertebrates which performs many essential biological functions such as detoxification of the organism, and the synthesis of proteins and biochemicals necessary for digestion and growth. In humans, it i ...

, where the iron is stored and used to produce hemoglobin. SPIOs have previously been used in humans for

iron supplement Iron supplements, also known as iron salts and iron pills, are a number of iron formulations used to treat and prevent iron deficiency including iron deficiency anemia. For prevention they are only recommended in those with poor absorption, h ...

ation and

imaging.

Blood pool imaging

Cardiovascular

The first ''in vivo'' MPI results provided images of a beating mouse

heart The heart is a muscular Organ (biology), organ in most animals. This organ pumps blood through the blood vessels of the circulatory system. The pumped blood carries oxygen and nutrients to the body, while carrying metabolic waste such as ca ...

in 2009. With further research, this could eventually be used for real-time

cardiac imaging Cardiac imaging refers to non-invasive imaging of the heart using ultrasound, magnetic resonance imaging (MRI), computed tomography (CT), or nuclear medicine (NM) imaging with PET or SPECT. These cardiac techniques are otherwise referred to as ec ...

Oncology

MPI has numerous applications to the field of oncology research. Accumulation of a tracer within

solid tumors A neoplasm () is a type of abnormal and excessive growth of tissue. The process that occurs to form or produce a neoplasm is called neoplasia. The growth of a neoplasm is uncoordinated with that of the normal surrounding tissue, and persists ...

can occur through the enhanced permeability and retention effect. This has been successfully used to detect tumor sites within rats. The high sensitivity of the technique means it may also be possible to image micro-metastasis through the development of nanoparticles targeted to

cancer Cancer is a group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body. These contrast with benign tumors, which do not spread. Possible signs and symptoms include a lump, abnormal b ...

cells. MPI is being investigated as a clinical alternative screening technique to

nuclear medicine Nuclear medicine or nucleology is a medical specialty involving the application of radioactive substances in the diagnosis and treatment of disease. Nuclear imaging, in a sense, is " radiology done inside out" because it records radiation emi ...

in order to reduce

radiation exposure Radiation is a moving form of energy, classified into ionizing and non-ionizing type. Ionizing radiation is further categorized into electromagnetic radiation (without matter) and particulate radiation (with matter). Electromagnetic radiation con ...

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 Regenerative medicine deals with the "process of replacing, engineering or regenerating human or animal cells, tissues or organs to restore or establish normal function". This field holds the promise of engineering damaged tissues and organs by st ...

and

cancer immunotherapy Cancer immunotherapy (sometimes called immuno-oncology) is the stimulation of the immune system to treat cancer, improving on the immune system's natural ability to fight the disease. It is an application of the fundamental research of cancer ...

. Imaging can be used to improve the success of

stem cell In multicellular organisms, stem cells are undifferentiated or partially differentiated cells that can differentiate into various types of cells and proliferate indefinitely to produce more of the same stem cell. They are the earliest type of ...

therapy by following the movement of these cells in the body. The tracer is stable while tagged to a cell and remains detectable past 87 days.

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 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 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 ...

(Fe₃O₄) or

maghemite Maghemite (Fe2O3, γ-Fe2O3) is a member of the family of iron oxides. It has the same spinel ferrite structure as magnetite and is also ferrimagnetic. It is sometimes spelled as "maghaemite". ''Maghemite'' can be considered as an Fe(II)-deficie ...

(Fe₂O₃) core surrounded by a surface coating (commonly

dextran Dextran is a complex branched glucan ( polysaccharide derived from the condensation of glucose), originally derived from wine. IUPAC defines dextrans as "Branched poly-α-d-glucosides of microbial origin having glycosidic bonds predominantly C- ...

, carboxydextran, or

polyethylene glycol Polyethylene glycol (PEG; ) is a polyether compound derived from petroleum with many applications, from industrial manufacturing to medicine. PEG is also known as polyethylene oxide (PEO) or polyoxyethylene (POE), depending on its molecular we ...

). The SPION tracer is detectable within biological fluids, such as the

blood Blood is a body fluid in the circulatory system of humans and other vertebrates that delivers necessary substances such as nutrients and oxygen to the cells, and transports metabolic waste products away from those same cells. Blood in the cir ...

. This fluid is very responsive to even weak

s, 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. However, more recent calculations suggest that there exists an optimal SPIONs magnetic size range (~26 nm) for MPI. 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. 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. For example, SPIONs coated with carboxydextran have been shown to clear to the liver almost immediately after injection, while those with a

(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.

Advantages

*High resolution (~0.4 mm) *Fast image results (~20 ms) *No radiation *No iodine *No background noise (high contrast)

Signal enhancement

Passive dual coil resonator

A device that provides frequency-selective signal enhancement was recently developed at

RWTH Aachen University RWTH Aachen University (), also known as North Rhine-Westphalia Technical University of Aachen, Rhine-Westphalia Technical University of Aachen, Technical University of Aachen, University of Aachen, or ''Rheinisch-Westfälische Technische Hoch ...

. 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 In physics and geosciences, the term spatial resolution refers to distance between independent measurements, or the physical dimension that represents a pixel of the image. While in some instruments, like cameras and telescopes, spatial resolut ...

.{{Cite journal , last1=Pantke , first1=Dennis , last2=Mueller , first2=Florian , last3=Reinartz , first3=Sebastian , last4=Philipps , first4=Jonas , last5=Mohammadali Dadfar , first5=Seyed , last6=Peters , first6=Maximilian , last7=Franke , first7=Jochen , last8=Schrank , first8=Franziska , last9=Kiessling , first9=Fabian , last10=Schulz , first10=Volkmar , date=2022-05-17 , title=Frequency-selective signal enhancement by a passive dual coil resonator for magnetic particle imaging , url=https://iopscience.iop.org/article/10.1088/1361-6560/ac6a9f , journal=Physics in Medicine & Biology , language=en , volume=67 , issue=11 , pages=115004 , doi=10.1088/1361-6560/ac6a9f , bibcode=2022PMB....67k5004P , s2cid=248404124 , issn=0031-9155

Congresses, workshops

WMIS MPI Interest Group Meeting

Homepage of the Annual International Workshop on MPI

References

External links

Magnetic Insight, Inc. - Commercializing MPI technology originally developed at the University of California, Berkeley 11/2014

Understanding Magnetic Particle Imaging

The MOMENTUM Magnetic Particle Imaging System

J.-P. Gehrcke. ''Characterization of the Magnetic Particle Imaging Signal Based on Theory, Simulation, and Experiment''. M. Sc. thesis, University of Würzburg, 2010.Magnetic particle imaging: moving ahead, medicalphysicsweb.org Apr 12, 2011"Traveling Wave MPI at University of Würzburg""Magnetic Particle Imaging (MPI) at RWTH Aachen University"

"MPI work at University of California, Berkeley"

"MPI research at University of Lübeck"

"Philips announces breakthrough in medical imaging technology"

What you see is what you've got

Breaking New Ground in Molecular Imaging

Flipping Good Imaging. Radiology Today May 2017
Imaging