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]
For in vivo imaging purposes, ERI is a minimally invasive method. It requires an intravenous injection of external substances called spin probes [4] (usually nitroxide or triarylmethyl compounds). The main advantage of ERI modality is the ability to map 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.
ERI is a preclinical application of electron paramagnetic resonance imaging (EPRI). [9] [2] The term "ERI" was introduced to distinguish a commercial device from EPRI devices normally used in the academic domain.
Electron paramagnetic resonance (EPR) spectroscopy is dedicated to researching substances with unpaired electrons. It was first introduced in 1944, approximately the same time as a 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]
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 on tissue oxygen concentration. [13] Therefore, the information about the oxygen value is collected directly from the examined areas. Oxygen mapping is commonly used to plan and improve the effectiveness of radiotherapy treatments. [14] [15] Trityl spin probes are the most suitable for use in oxygen imaging. [16] [17]
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. Therefore, this state leads to an imbalance between those particles and is called oxidative stress. [19] [20]
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 imaged over time. Due to the method's high temporal resolution and sensitivity, 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]
In natural conditions, free radicals are characterised by an extremely short lifespan, so to capture the EPR signal, an external molecule with a stable free radical must be delivered. Usually, it happens when an injection is made into the animal's body. Two main classes of spin probes are used for imaging: nitroxide and triaryl methyl (TAM, trityl) radicals.
Nitroxide radicals are sensitive to oxygen concentration, pH, thiol concentrations, viscosity, and polarity. [2] The issue with these spin probes is their fast reduction, which sometimes leads to loss of the EPR signal. Triarylmethyl radicals are characterised by far longer lifespans and increased stability towards reducing and oxidising biological agents. They are perfect for measuring oxygen concentration, pH, thiol concentrations, inorganic phosphate, and redox status.
Although the aforementioned spin probes are the most popular choice, many more 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.
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.
In chemistry and biology, reactive oxygen species (ROS) are highly reactive chemicals formed from diatomic oxygen (O2), water, and hydrogen peroxide. Some prominent ROS are hydroperoxide (O2H), superoxide (O2-), hydroxyl radical (OH.), and singlet oxygen. ROS are pervasive because they are readily produced from O2, which is abundant. ROS are important in many ways, both beneficial and otherwise. ROS function as signals, that turn on and off biological functions. They are intermediates in the redox behavior of O2, which is central to fuel cells. ROS are central to the photodegradation of organic pollutants in the atmosphere. Most often however, ROS are discussed in a biological context, ranging from their effects on aging and their role in causing dangerous genetic mutations.
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.
Singlet oxygen, systematically named dioxygen(singlet) and dioxidene, is a gaseous inorganic chemical with the formula O=O (also written as 1
[O
2] or 1
O
2), 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 (EPR) or electron spin resonance (ESR) spectroscopy is a method for studying materials that have 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.
Frémy's salt is a chemical compound with the formula (K4[ON(SO3)2]2), sometimes written as (K2[NO(SO3)2]). It is a bright yellowish-brown solid, but its aqueous solutions are bright violet. The related sodium salt, disodium nitrosodisulfonate (NDS, Na2ON(SO3)2, CAS 29554-37-8) is also referred to as Frémy's salt.
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 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.
In chemistry, a radical, also known as a free 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.
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.
Electron nuclear double resonance (ENDOR) is a magnetic resonance technique for elucidating the molecular and electronic structure of paramagnetic species. The technique was first introduced to resolve interactions in electron paramagnetic resonance (EPR) spectra. It is currently practiced in a variety of modalities, mainly in the areas of biophysics and heterogeneous catalysis.
William Dale Phillips was an American chemist, nuclear magnetic resonance spectroscopist, federal science policy advisor and member of the National Academy of Sciences. He was born October 10, 1925, in Kansas City, Missouri and died in St. Louis, Missouri, on December 15, 1993.
Magnetochemistry is concerned with the magnetic properties of chemical compounds. Magnetic properties arise from the spin and orbital angular momentum of the electrons contained in a compound. Compounds are diamagnetic when they contain no unpaired electrons. Molecular compounds that contain one or more unpaired electrons are paramagnetic. The magnitude of the paramagnetism is expressed as an effective magnetic moment, μeff. For first-row transition metals the magnitude of μeff is, to a first approximation, a simple function of the number of unpaired electrons, the spin-only formula. In general, spin–orbit coupling causes μeff to deviate from the spin-only formula. For the heavier transition metals, lanthanides and actinides, spin–orbit coupling cannot be ignored. Exchange interaction can occur in clusters and infinite lattices, resulting in ferromagnetism, antiferromagnetism or ferrimagnetism depending on the relative orientations of the individual spins.
Pulsed electron paramagnetic resonance (EPR) is an electron paramagnetic resonance technique that involves the alignment of the net magnetization vector of the electron spins in a constant magnetic field. This alignment is perturbed by applying a short oscillating field, usually a microwave pulse. One can then measure the emitted microwave signal which is created by the sample magnetization. Fourier transformation of the microwave signal yields an EPR spectrum in the frequency domain. With a vast variety of pulse sequences it is possible to gain extensive knowledge on structural and dynamical properties of paramagnetic compounds. Pulsed EPR techniques such as electron spin echo envelope modulation (ESEEM) or pulsed electron nuclear double resonance (ENDOR) can reveal the interactions of the electron spin with its surrounding nuclear spins.
James S. Hyde was an American biophysicist. He held the James S. Hyde chair in Biophysics at the Medical College of Wisconsin (MCW) where he specialized 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 served as Director of the National Biomedical EPR Center, a Research Resource supported by the National Institutes of Health. He was author of more than 400 peer-reviewed papers and review articles and held 35 U.S. Patents. He was 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 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 (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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