Electron paramagnetic resonance oxygen mapping (EPROM): Direct visualization of oxygen concentration in tissue
S. Sendhil Velan
Nuclear Magnetic Resonance Unit, National Institute on Aging, National Institutes of Health, Baltimore, Maryland
Search for more papers by this authorRichard G.S. Spencer
Nuclear Magnetic Resonance Unit, National Institute on Aging, National Institutes of Health, Baltimore, Maryland
Search for more papers by this authorJay L. Zweier
The EPR Center, Division of Cardiology, Department of Medicine, Johns Hopkins University, School of Medicine, Baltimore, Maryland
Search for more papers by this authorCorresponding Author
Periannan Kuppusamy
The EPR Center, Division of Cardiology, Department of Medicine, Johns Hopkins University, School of Medicine, Baltimore, Maryland
EPR Center, Johns Hopkins University, School of Medicine, 5501 Hopkins Bayview Circle, Baltimore, MD 21224===Search for more papers by this authorS. Sendhil Velan
Nuclear Magnetic Resonance Unit, National Institute on Aging, National Institutes of Health, Baltimore, Maryland
Search for more papers by this authorRichard G.S. Spencer
Nuclear Magnetic Resonance Unit, National Institute on Aging, National Institutes of Health, Baltimore, Maryland
Search for more papers by this authorJay L. Zweier
The EPR Center, Division of Cardiology, Department of Medicine, Johns Hopkins University, School of Medicine, Baltimore, Maryland
Search for more papers by this authorCorresponding Author
Periannan Kuppusamy
The EPR Center, Division of Cardiology, Department of Medicine, Johns Hopkins University, School of Medicine, Baltimore, Maryland
EPR Center, Johns Hopkins University, School of Medicine, 5501 Hopkins Bayview Circle, Baltimore, MD 21224===Search for more papers by this authorAbstract
Tissue oxygen content is a central parameter in physiology but is difficult to measure. We report a novel procedure for spatial mapping of oxygen by electron paramagnetic resonance (EPR) utilizing a spectral-spatial imaging data set, in which an EPR spectrum is obtained from each image volume element. From this data set, spatial maps corresponding to local spin density and maximum EPR spectral line amplitude are generated. A map of local EPR spectral linewidth is then computed. Because linewidth directly correlates with oxygen concentration, the linewidth image provides a map of oxygenation. This method avoids a difficulty inherent in other oxygen content mapping techniques using EPR, that is, the unwanted influence of local spin probe density on the image. We provide simulation results and data from phantom studies demonstrating the validity of this method. We then apply the method to map oxygen content in rat tail tissue and vasculature. This method provides a new, widely applicable, approach to direct visualization of oxygen concentration in living tissue. Magn Reson Med 43:804–809, 2000. © 2000 Wiley-Liss, Inc.
REFERENCES
- 1 Moslen MT, Smith CV. Free radical mechanisms of tissue injury. Boca Raton, FL: CRC Press, Inc.; 1992.
- 2 Lubbers DW, Huch R, Huch A. Problems of transcutaneous measurement of arterial blood gases. Adv Exp Med Biol 1973; 37A: 115–120.
- 3 Keizer HH, Jobsis-Vander Vleit FF, Lucas SS, Piantadosi CA, Sylvia AL. The near infrared (NIR) absorption band of cytochrome aa3 in purified enzyme, isolated mitochondria and in the intact brain in situ. Adv Exp Med Biol 1985; 191: 823–832.
- 4 Linsenmeier RA, Yancey CM. Improved fabrication of double-barreled recessed cathode O2 microelectrodes. J Appl Physiol 1987; 63: 2554–2557.
- 5 Fishman JE, Joseph PM, Carvlin MJ, Saadi-elmandjra M, Mukherji B, Sloviter HA. In vivo measurements of vascular oxygen tension in tumors using MRI of a fluorinated blood substitute. Invest Radiol 1989; 24: 65–71.
- 6 Swartz HM, Boyer S, Brown D, Chang K, Gast P, Glockner JF, Hu H, Liu KJ, Moussavi M, Nilges M, Norby SW, Smirnov A, Vahidi T, Walczak T, Wu M, Clarkson RB. The use of EPR for the measurement of the concentration of oxygen in vivo in tissues under physiologically pertinent conditions and concentrations. Adv Exp Med Biol 1992; 317: 221–228.
- 7 Halpern HJ, Yu C, Peric M, Barth E, Grdina DJ, Teicher BA. Oxymetry deep in tissues with low-frequency electron paramagnetic resonance. Proc Natl Acad Sci USA 1994; 91: 13047–13051.
- 8 Kuppusamy P, Afeworki M, Shankar RA, Coffin D, Krishna MC, Hahn SM, Mitchell JB, Zweier JL. In vivo electon paramagnetic resonance imaging of tumor heterogeneity and oxygenation in a murine model. Cancer Res 1998; 58: 1562–1568.
- 9 Kuppusamy P, Shankar RA, Zweier JL. In vivo measurement of arterial and venous oxygenation in the rat using 3D spectral-spatial electron paramagnetic resonance imaging. Phys Med Biol 1998; 43: 1837–1844.
- 10 Liu KJ, Gast P, Moussavi M, Norby SW, Vahidi N, Walczak T, Wu M, Swartz HM. Lithium phthalocyanine: a probe for electron paramagnetic resonance oximetry in viable biological systems. Proc Natl Acad Sci USA 1993; 90: 5438–5442.
- 11 Liu KJ, Bacic G, Hoopes PJ, Jiang J, Du H, Ou LC, Dunn JF, Swartz HM. Assessment of cerebral pO2 by EPR oximetry in rodents: effects of anesthesia, ischemia, and breathing gas. Brain Res 1995; 685: 91–98.
- 12 Glockner JF, Swartz HM. In vivo oximetry using two novel probes: fusinite and lithium phthalocyanine. Adv Exp Med Biol 1992; 317: 229–234.
- 13 Zweier JL, Chzhan M, Ewert U, Schneider G, Kuppusamy P. Development of a highly sensitive probe for measuring oxygen in biological tissues. J Magn Reson B 1994; 105: 52–57.
- 14 Glockner JF, Norby SW, Swartz HM. Simultaneous measurement of intracellular and extracellular oxygen concentrations using a nitroxide-liposome system. Magn Reson Med 1993; 29: 12–18.
- 15 Kuppusamy P, Wang P, Chzhan M, Zweier JL. High resolution electron paramagnetic resonance imaging of biological samples with a single line paramagnetic label. Magn Reson Med 1997; 37: 479–483.
- 16 Murugesan R, Cook JA, Devasahayam N, Afeworki M, Subramanian S, Tschudin R, Larsen JA, Mitchell JB, Russo A, Krishna MC. In vivo imaging of a stable paramagnetic probe by pulsed-radiofrequency electron paramagnetic resonance spectroscopy. Magn Reson Med 1997; 38: 409–414.
- 17 Eaton GR, Eaton SS, Ohno K. EPR imaging and in vivo EPR. Boca Raton, FL: CRC Press, Inc.; 1991.
- 18 Swartz HM, Glockner JF. Measurement of oxygen by EPRI and EPRS. In: GR Eaton, SS Eaton, K Ohno, editors. EPR imaging and in vivo EPR. Boca Raton, FL: CRC Press, Inc.; 1991. p 261–290.
- 19 Maltempo MM, Eaton SS, Eaton GR. Spectral-spatial two-dimensional EPR imaging. J Magn Reson 1987; 72: 449–455.
- 20 Kuppusamy P, Chzhan M, Vij K, Shteynbuk M, Lefer DJ, Giannella E, Zweir JL. Three-dimensional spectral-spatial EPR imaging of free radicals in the heart: a technique for imaging tissue metabolism and oxygenation. Proc Natl Acad Sci USA 1994; 91: 3388–3392.
- 21 Kuppusamy P, Chzhan M, Samouilov A, Wang P, Zweier JL. Mapping the spin-density and lineshape distribution of free radicals using 4D spectral-spatial EPR imaging. J Magn Reson B 1995; 107: 116–125.
- 22 Poole CP. Electron spin resonance, a comprehensive treatise on experimental techniques. New York: John Wiley & Sons; 1983.
- 23 Halpern HJ, Peric M, Yu C, Bales BL. Rapid quantitation of parameters from inhomogeneously broadened EPR spectra. J Magn Reson A 1993; 103: 13–22.
- 24 Zweier JL, Kuppusamy P. Electron paramagnetic resonance measurements of free radicals in the intact beating heart: a technique for detection and characterization of free radicals in whole biological tissues. Proc Natl Acad Sci USA 1988; 85: 5703–5707.
- 25 Chzhan M, Kuppusamy P, Zweier JL. Development of an electronically tunable L-band resonator for EPR spectroscopy and imaging of biological samples. J Magn Reson B 1995; 108: 67–72.
- 26 Kuppusamy P, Zweier JL. A forward-subtraction procedure for removing hyperfine artifacts in electron paramagnetic resonance imaging. Magn Reson Med 1996; 35: 316–322.
- 27 Wu Y, Jiji LM, Lemons DE, Weinbaum S. A non-uniform three-dimensional perfusion model of rat tail heat transfer. Phys Med Biol 1995; 40: 789–806.
- 28 Tsoref L, Shinar H, Seo Y, Eliav U, Navon G. Proton double-quantum filtered MRI—a new method for imaging ordered tissues. Magn Reson Med 1998; 40: 720–726.
- 29 Mason RP, Shukla H, Antich PP. In vivo oxygen tension and temperature: simultaneous determination using 19F NMR spectroscopy of perfluorocarbon. Magn Reson Med 1993; 29: 296–302.
- 30 Parhami P, Fung BM. Flourine-19 relaxation study of perfluoro chemicals as oxygen carriers. J Phys Chem 1983; 87: 1928–1931.
- 31 Taylor J, Deutsch C. 19F—Nuclear magnetic resonance:measurements of O2 and pH in biological systems. Biophys J 1988; 53: 227–233.
- 32 Mancini DM, Wilson JR, Bolinger L, Li H, Kendrick K, Chance B, Leigh JS. In vivo magnetic resonance spectroscopy measurement of deoxymyoglobin during excercise in patients with heart failure. Circulation 1994; 90: 500–508.
- 33 Zhu XH, Kim SG, Andersen P, Ogawa S, Ugurbil K, Chen W. Simultaneous oxygenation and perfusion imaging study of functional activity in primary visual cortex at different visual stimulation frequency: quantitative correlation between BOLD and CBF changes. Magn Reson Med 1998; 40: 703–711.