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Electron resonance imaging

From Wikipedia, the free encyclopedia

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.

Origin

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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]

In vivo applications

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Oxygen imaging

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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]

Redox status and oxidative stress

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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]

Pharmacokinetics

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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]

Spin probes

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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.

References

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  1. ^ Utsumi H, Muto E, Masuda S, Hamada A. In vivo ESR measurement of free radicals in whole mice. Biochem Biophys Res Commun. 1990;172(3):1342–8.
  2. ^ a b c Eaton GR, Eaton SS. Introduction to EPR imaging using magnetic-field gradients. Concepts Magn Reson. 1995;7(1):49–67.
  3. ^ Kotecha, Mrignayani, Boris Epel, Sriram Ravindran, Deborah Dorcemus, Syam Nukavarapu, and Howard Halpern. (2018). "Noninvasive Absolute Electron Paramagnetic Resonance Oxygen Imaging for the Assessment of Tissue Graft Oxygenation". Tissue Engineering Part C: Methods. 24 (1): 14–19. doi:10.1089/ten.TEC.2017.0236. PMC 5756934. PMID 28844179.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  4. ^ Yan G, Lei P, Shuangquan JI, Liang L, Bottle SE. Spin probes for electron paramagnetic resonance imaging. Chinese Science Bulletin 53(24):3777-3789. December 2008.
  5. ^ a b M. Gonet, M. Baranowski, T. Czechowski, M. Kucinska, A. Plewinski, P. Szczepanik, S. Jurga, M. Murias Multiharmonic electron paramagnetic resonance imaging as an innovative approach for in vivo studies. Free Radic. Biolo. And Medic. 152, 271-279, (2020)
  6. ^ a b c d M. Baranowski, M. Gonet, T. Czechowski, M. Kucinska, A. Plewinski, P. Szczepanik, M. Murias Dynamic electron paramagnetic resonance imaing: modern technique for biodistribution and pharmacokinetic imaging. J. Phys. Chem. C 124, 19743-19752, (2020)
  7. ^ Bobko AA, Eubank TD, Driesschaert B, Khramtsov VV. In Vivo EPR Assessment of pH, pO2, Redox Status, and Concentrations of Phosphate and Glutathione in the Tumor Microenvironment. J Vis Exp. 2018 Mar 16;(133).
  8. ^ Lawrence J. Berliner, Narasimham L. Parinandi (2020). Measuring oxidants and oxidative stress in biological systems, Biological Magnetic Resonance 34 (2020). Biological Magnetic Resonance. Vol. 34. doi:10.1007/978-3-030-47318-1. ISBN 978-3-030-47317-4. PMID 33411425. S2CID 221071036.
  9. ^ Tseytlin M, Stolin AV, Guggilapu P, Bobko AA, Khramtsov VV, Tseytlin O, Raylman RR. A combined positron emission tomography (PET)-electron paramagnetic resonance imaging (EPRI) system: initial evaluation of a prototype scanner. Phys Med Biol. 2018;63(10):105010.
  10. ^ Zavoisky E. Spin-magnetic resonance in paramagnetics. J Phys Acad Sci USSR. 1945;9:211–45.
  11. ^ Purcell E, Torrey H, Pound R. Resonance absorption by nuclear magnetic moments in a solid. Phys Rev. 1946;69:37–338.
  12. ^ Elas M, Bell R, Hleihel D, Barth ED, McFaul C, Haney CR, Bielanska J, Pustelny K, Ahn K-H, Pelizzari CA, Kocherginsky M, Halpern HJ. Electron Paramagnetic Resonance Oxygen Image Hypoxic Fraction Plus Radiation Dose Strongly Correlates With Tumor Cure in FSa Fibrosarcomas. Int J Radiat Oncol. 2008;71(2):542–9.
  13. ^ Halpern, H. J., C. Yu, M. Peric, E. Barth, D. J. Grdina, and B. A. Teicher. (20 December 1994). "Oxymetry Deep in Tissues with Low-Frequency Electron Paramagnetic Resonance." Proceedings of the National Academy of Sciences of the United States of America 91, no. 26 (December 20, 1994): 13047–51". Proceedings of the National Academy of Sciences. 91 (26): 13047–13051. doi:10.1073/pnas.91.26.13047. PMC 45578. PMID 7809170.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  14. ^ Elas M, et al. EPR oxygen images predict tumor control by a 50% tumor control radiation dose. Cancer Res. 2013 Sep 1;73(17):5328-35.
  15. ^ Epel, Boris, Matthew C. Maggio, Eugene D. Barth, Richard C. Miller, Charles A. Pelizzari, Martyna Krzykawska-Serda, Subramanian V. Sundramoorthy. (March 2019). "Oxygen-Guided Radiation Therapy." International Journal of Radiation Oncology, Biology, Physics 103, no. 4 (15 2019): 977–84". International Journal of Radiation Oncology, Biology, Physics. 103 (4): 977–984. doi:10.1016/j.ijrobp.2018.10.041. PMC 6478443. PMID 30414912.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  16. ^ Tormyshev, Victor M., Alexander M. Genaev, Georgy E. Sal’nikov, Olga Yu Rogozhnikova, Tatiana I. Troitskaya, Dmitry V. Trukhin, Victor I. Mamatyuk, Dmitry S. Fadeev, and Howard J. Halpern. (2012). "Triarylmethanols Bearing Bulky Aryl Groups and the NOESY/EXSY Experimental Observation of Two-Ring-Flip Mechanism for Helicity Reversal of Molecular Propellers." European Journal of Organic Chemistry 2012, no. 3 (January 2012)". European Journal of Organic Chemistry. 2012 (3): 623–629. doi:10.1002/ejoc.201101243. PMC 3843112. PMID 24294110.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  17. ^ Gomberg, M. (1897). "Tetraphenylmethan". Berichte der Deutschen Chemischen Gesellschaft. 30 (2): 2043–2047. doi:10.1002/cber.189703002177.
  18. ^ Emoto MC, Matsuoka Y, Yamada KI, Sato-Akaba H4, Fujii HG. Non-invasive imaging of the levels and effects of glutathione on the redox status of mouse brain using electron paramagnetic resonance imaging. Biochem Biophys Res Commun. 2017 Apr 15;485(4):802-806.
  19. ^ Elas M, Ichikawa K, Halpern HJ. Oxidative stress imaging in live animals with techniques based on electron paramagnetic resonance. Radiat Res. 2012;177(4):514–23.
  20. ^ Fujii H, Sato-Akaba H, Kawanishi K, Hirata H. Mapping of redox status in a brain-disease mouse model by three-dimensional EPR imaging: EPR Imaging of Nitroxides in Mouse Head. Magn Reson Med. 2011;65(1):295–303.
  21. ^ Vanea E, Charlier N, Dewever J, Dinguizli M, Feron O, Baurain J-F, Gallez B. Molecular electron paramagnetic resonance imaging of melanin in melanomas: a proof-of-concept. NMR Biomed. 2008;21(3):296–300.
  22. ^ Charlier N, Desoil M, Gossuin Y, Gillis P, Gallez B. Electron Paramagnetic Resonance Imaging of Melanin in Honey Bee. Cell Biochem Biophys. 2020
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