Electron resonance imaging

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Electron resonance imaging (ERI) is a preclinical imaging method, together with positron emission tomography (PET), computed tomography scan (CT scan), magnetic resonance imaging (MRI), and other techniques. ERI is dedicated to imaging small laboratory animals and its unique feature is the ability to detect free radicals. [1] [2] This technique could also be used for other purposes such as material science, quality of food, etc. [3]

Contents

For in vivo imaging purposes, ERI is a minimally invasive method. It requires an intravenous injection of the external substances, called spin probes [4] (usually nitroxide or triarylmethyl compounds). The main advantage of ERI modality is the ability of mapping the tissue microenvironment parameters e.g. oxygen partial pressure (pO2), redox status, oxidative stress, thiol concentration, pH, inorganic phosphorus, viscosity, etc. [5] [6] [7] [8] ERI is commonly used to research in the areas of oncology, neurodegenerative disorders and drug development.

Origin

ERI is a preclinical application of electron paramagnetic resonance imaging (EPRI). [9] [2] The term "ERI" was introduced in order to distinguish a commercial device from EPRI devices that are normally used in the academic domain.

Electron paramagnetic resonance (EPR) spectroscopy is dedicated to the research of substances with unpaired electrons. It was first introduced in 1944, approximately the same time as the similar phenomenon - nuclear magnetic resonance (NMR). [10] [11] Owing to hardware and software limitations, EPR was not developing as rapidly as NMR. This led to a huge gap between these two methods. Therefore, to underline a breakthrough in preclinical imaging, by presenting EPRI as a complementary method to the present ones, the term "ERI" was introduced. [5] [6]

In vivo applications

Oxygen imaging

One of the many possible applications of ERI is the ability to measure the absolute value of oxygen. [12] The width of the EPR signal from oxygen-sensitive spin probes depends linearly from the oxygen concentration in tissues. [13] Therefore, the information about the oxygen value is collected directly from the examined areas. Oxygen mapping is commonly used for planning and improving the effectiveness of radiotherapy treatments. [14] [15] Trityl spin probes are the most suitable for the use in oxygen imaging. [16] [17]

Redox status and oxidative stress

The unique property of ERI is the ability to track reactive oxygen species (ROS). [18] Those particles are versatile and are constantly generated in living organisms. ROS plays a special role in oxidative and reduction mechanisms. In a normal physiological state, the number of ROS is controlled by antioxidants. Factors that increase the number of ROS (e.g. ionizing radiation, metal ions, etc.) will cause their overproduction. This state leads to an imbalance between those particles and is therefore called the oxidative stress. [19] [20]

Pharmacokinetics

ERI allows for dynamic measurements and 3D tracking of the spin probe. [6] In this case, the term "dynamics" refers to the fast repetition of the imaging process, and the tracking of changes in the signal intensity for each location that is imaged over time. Owing to the high temporal resolution and sensitivity of the method, it is possible to distinguish both the inflow and outflow phases of the spin probe, the bio-distribution, and the time to reach a maximum concentration of the spin probe. [6]

Spin probes

In natural conditions, free radicals are characterised with an extremely short lifespan, so in order to capture the EPR signal, an external molecule with a stable free radical must be delivered. Usually it happens by injection into the animal's body. There are two main classes of spin probes used for imaging: nitroxide and triarylmethyl (TAM, trityl) radicals.

Nitroxide radicals are sensitive to oxygen concentration, pH, thiol concentrations, viscosity and polarity. [2] The issue with these type of spin probes is their fast reduction, which sometimes leads to loss of the EPR signal. Triarylmethyl radicals are characterised by a far longer lifespan, and an increased stability towards reducing and oxidising biological agents. They are perfect for measuring the oxygen concentration, pH, thiol concentrations, inorganic phosphate and redox status.

Although, the aforementioned spin probes are the most popular choice, there are many more that can be used in ERI. One of many examples is melanin – a polymeric pigment that contains a mixture of eumelanin and pheomelanin. [21] [22] This is the only substance that occurs in natural conditions and allows for the registration of the EPR signal, without the need to deliver extraneous spin probes.

Related Research Articles

Paramagnetism Weak, attractive magnetism possessed by most elements and some compounds

Paramagnetism is a form of magnetism whereby some materials are weakly attracted by an externally applied magnetic field, and form internal, induced magnetic fields in the direction of the applied magnetic field. In contrast with this behavior, diamagnetic materials are repelled by magnetic fields and form induced magnetic fields in the direction opposite to that of the applied magnetic field. Paramagnetic materials include most chemical elements and some compounds; they have a relative magnetic permeability slightly greater than 1 and hence are attracted to magnetic fields. The magnetic moment induced by the applied field is linear in the field strength and rather weak. It typically requires a sensitive analytical balance to detect the effect and modern measurements on paramagnetic materials are often conducted with a SQUID magnetometer.

Site-directed spin labeling (SDSL) is a technique for investigating the structure and local dynamics of proteins using electron spin resonance. The theory of SDSL is based on the specific reaction of spin labels with amino acids. A spin label's built-in protein structure can be detected by EPR spectroscopy. SDSL is also a useful tool in examinations of the protein folding process.

Microwave spectroscopy is the spectroscopy method that employs microwaves, i.e. electromagnetic radiation at GHz frequencies, for the study of matter.

Singlet oxygen Oxygen with all of its electrons spin paired

Singlet oxygen, systematically named dioxygen(singlet) and dioxidene, is a gaseous inorganic chemical with the formula O=O, which is in a quantum state where all electrons are spin paired. It is kinetically unstable at ambient temperature, but the rate of decay is slow.

Electron paramagnetic resonance

Electron paramagnetic resonance (EPR) or electron spin resonance (ESR) spectroscopy is a method for studying materials with unpaired electrons. The basic concepts of EPR are analogous to those of nuclear magnetic resonance (NMR), but the spins excited are those of the electrons instead of the atomic nuclei. EPR spectroscopy is particularly useful for studying metal complexes and organic radicals. EPR was first observed in Kazan State University by Soviet physicist Yevgeny Zavoisky in 1944, and was developed independently at the same time by Brebis Bleaney at the University of Oxford.

Ferromagnetic resonance, or FMR, is coupling between an electromagnetic wave and the magnetization of a medium through which it passes. This coupling induces a significant loss of power of the wave. The power is absorbed by the precessing magnetization of the material and lost as heat. For this coupling to occur, the frequency of the incident wave must be equal to the precession frequency of the magnetization and the polarization of the wave must match the orientation of the magnetization.

Spin trapping

Spin trapping is an analytical technique employed in chemistry and biology for the detection and identification of short-lived free radicals through the use of electron paramagnetic resonance (EPR) spectroscopy. EPR spectroscopy detects paramagnetic species such as the unpaired electrons of free radicals. However, when the half-life of radicals is too short to detect with EPR, compounds known as spin traps are used to react covalently with the radical products and form more stable adduct that will also have paramagnetic resonance spectra detectable by EPR spectroscopy. The use of radical-addition reactions to detect short-lived radicals was developed by several independent groups by 1968.

Radical (chemistry) Atom, molecule, or ion that has an unpaired valence electron; typically highly reactive

In chemistry, a radical is an atom, molecule, or ion that has at least one unpaired valence electron. With some exceptions, these unpaired electrons make radicals highly chemically reactive. Many radicals spontaneously dimerize. Most organic radicals have short lifetimes.

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Acoustic paramagnetic resonance (APR) is a phenomenon of resonant absorption of sound by a system of magnetic particles placed in an external magnetic field. It occurs when the energy of the sound wave quantum becomes equal to the splitting of the energy levels of the particles, the splitting being induced by the magnetic field. APR is a variation of electron paramagnetic resonance (EPR) where the acoustic rather than electromagnetic waves are absorbed by the studied sample. APR was theoretically predicted in 1952, independently by Semen Altshuler and Alfred Kastler, and was experimentally observed by W. G. Proctor and W. H. Tanttila in 1955.

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Alexander Kovarski

Alexander L’vovich Kovarski is a Russian physical chemist, professor, member of Russian Academy of Natural Sciences, and member of American Chemical Society. His main research area is physical chemistry of polymers and composites, magnetic resonance of free radicals and nano-sized systems.

James S. Hyde is an American biophysicist. He holds the James S. Hyde chair in Biophysics at the Medical College of Wisconsin (MCW) where he specializes in magnetic resonance instrumentation and methodology development in two distinct areas: electron paramagnetic resonance (EPR) spectroscopy and magnetic resonance imaging (MRI). He is senior author of the widely cited 1995 paper by B.B. Biswal et al. reporting the discovery of resting state functional connectivity (fcMRI) in the human brain. He also serves as Director of the National Biomedical EPR Center, a Research Resource supported by the National Institutes of Health. He is author or more than 400 peer-reviewed papers and review articles and holds 35 U.S. Patents. He has been recognized by Festschrifts in both EPR and fcMRI.

Sandra Eaton is an American chemist and Professor at the University of Denver, known for her work on electron paramagnetic resonance.

Wolfgang Lubitz

Wolfgang Lubitz is a German chemist and biophysicist. He is currently a director emeritus at the Max Planck Institute for Chemical Energy Conversion. He is well known for his work on bacterial photosynthetic reaction centres, hydrogenase enzymes, and the oxygen-evolving complex using a variety of biophysical techniques. He has been recognized by a Festschrift for his contributions to electron paramagnetic resonance (EPR) and its applications to chemical and biological systems.

Spectroelectrochemistry

Spectroelectrochemistry (SEC) is a set of multi-response analytical techniques in which complementary chemical information is obtained in a single experiment. Spectroelectrochemistry provides a whole vision of the phenomena that take place in the electrode process. The first spectroelectrochemical experiment was carried out by Theodore Kuwana, PhD, in 1964.

Mohindar Singh Seehra is an Indian-American Physicist, academic and researcher. He is Eberly Distinguished Professor Emeritus at West Virginia University (WVU).

R. David Britt is the Winston Ko Chair and Distinguished Professor of Chemistry at the University of California, Davis. Britt uses electron paramagnetic resonance (EPR) spectroscopy to study metalloenzymes and enzymes containing organic radicals in their active sites. Britt is the recipient of multiple awards for his research, including the Bioinorganic Chemistry Award in 2019 and the Bruker Prize in 2015 from the Royal Society of Chemistry. He has received a Gold Medal from the International EPR Society (2014), and the Zavoisky Award from the Kazan Scientific Center of the Russian Academy of Sciences (2018). He is a Fellow of the American Association for the Advancement of Science and of the Royal Society of Chemistry.

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