Deep-Tissue Oxygen Monitoring in the Brain of Rabbits for Stroke Research
2015; Lippincott Williams & Wilkins; Volume: 46; Issue: 3 Linguagem: Inglês
10.1161/strokeaha.114.007324
ISSN1524-4628
AutoresNadeem Khan, Huagang Hou, Clifford J. Eskey, Karen L Moodie, Sangeeta Gohain, Gaixin Du, Sassan Hodge, William C. Culp, Periannan Kuppusamy, Harold M. Swartz,
Tópico(s)Electron Spin Resonance Studies
ResumoHomeStrokeVol. 46, No. 3Deep-Tissue Oxygen Monitoring in the Brain of Rabbits for Stroke Research Free AccessResearch ArticlePDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessResearch ArticlePDF/EPUBDeep-Tissue Oxygen Monitoring in the Brain of Rabbits for Stroke Research Nadeem Khan, PhD, Huagang Hou, MD, Clifford J. Eskey, MD, Karen Moodie, MSc, Sangeeta Gohain, MSc, Gaixin Du, MSc, Sassan Hodge, PhD, William C. Culp, MD, Periannan Kuppusamy, PhD and Harold M. Swartz, MD, PhD Nadeem KhanNadeem Khan From the Department of Radiology, EPR Center for the Study of Viable Systems, Geisel School of Medicine at Dartmouth, Hanover, NH (N.K., H.H., S.G., G.D., S.H., P.K., H.M.S.); Norris Cotton Cancer Center, Dartmouth-Hitchcock Medical Center, Lebanon, NH (N.K., H.H., S.G., P.K., H.M.S.); Department of Radiology, Dartmouth-Hitchcock Medical Center, Lebanon, NH (C.J.E.); Center for Comparative Medicine and Research, Dartmouth College, Hanover, NH (K.M.); and Department of Radiology, Interventional Radiology, University of Arkansas for Medical Sciences, Little Rock (W.C.C.). , Huagang HouHuagang Hou From the Department of Radiology, EPR Center for the Study of Viable Systems, Geisel School of Medicine at Dartmouth, Hanover, NH (N.K., H.H., S.G., G.D., S.H., P.K., H.M.S.); Norris Cotton Cancer Center, Dartmouth-Hitchcock Medical Center, Lebanon, NH (N.K., H.H., S.G., P.K., H.M.S.); Department of Radiology, Dartmouth-Hitchcock Medical Center, Lebanon, NH (C.J.E.); Center for Comparative Medicine and Research, Dartmouth College, Hanover, NH (K.M.); and Department of Radiology, Interventional Radiology, University of Arkansas for Medical Sciences, Little Rock (W.C.C.). , Clifford J. EskeyClifford J. Eskey From the Department of Radiology, EPR Center for the Study of Viable Systems, Geisel School of Medicine at Dartmouth, Hanover, NH (N.K., H.H., S.G., G.D., S.H., P.K., H.M.S.); Norris Cotton Cancer Center, Dartmouth-Hitchcock Medical Center, Lebanon, NH (N.K., H.H., S.G., P.K., H.M.S.); Department of Radiology, Dartmouth-Hitchcock Medical Center, Lebanon, NH (C.J.E.); Center for Comparative Medicine and Research, Dartmouth College, Hanover, NH (K.M.); and Department of Radiology, Interventional Radiology, University of Arkansas for Medical Sciences, Little Rock (W.C.C.). , Karen MoodieKaren Moodie From the Department of Radiology, EPR Center for the Study of Viable Systems, Geisel School of Medicine at Dartmouth, Hanover, NH (N.K., H.H., S.G., G.D., S.H., P.K., H.M.S.); Norris Cotton Cancer Center, Dartmouth-Hitchcock Medical Center, Lebanon, NH (N.K., H.H., S.G., P.K., H.M.S.); Department of Radiology, Dartmouth-Hitchcock Medical Center, Lebanon, NH (C.J.E.); Center for Comparative Medicine and Research, Dartmouth College, Hanover, NH (K.M.); and Department of Radiology, Interventional Radiology, University of Arkansas for Medical Sciences, Little Rock (W.C.C.). , Sangeeta GohainSangeeta Gohain From the Department of Radiology, EPR Center for the Study of Viable Systems, Geisel School of Medicine at Dartmouth, Hanover, NH (N.K., H.H., S.G., G.D., S.H., P.K., H.M.S.); Norris Cotton Cancer Center, Dartmouth-Hitchcock Medical Center, Lebanon, NH (N.K., H.H., S.G., P.K., H.M.S.); Department of Radiology, Dartmouth-Hitchcock Medical Center, Lebanon, NH (C.J.E.); Center for Comparative Medicine and Research, Dartmouth College, Hanover, NH (K.M.); and Department of Radiology, Interventional Radiology, University of Arkansas for Medical Sciences, Little Rock (W.C.C.). , Gaixin DuGaixin Du From the Department of Radiology, EPR Center for the Study of Viable Systems, Geisel School of Medicine at Dartmouth, Hanover, NH (N.K., H.H., S.G., G.D., S.H., P.K., H.M.S.); Norris Cotton Cancer Center, Dartmouth-Hitchcock Medical Center, Lebanon, NH (N.K., H.H., S.G., P.K., H.M.S.); Department of Radiology, Dartmouth-Hitchcock Medical Center, Lebanon, NH (C.J.E.); Center for Comparative Medicine and Research, Dartmouth College, Hanover, NH (K.M.); and Department of Radiology, Interventional Radiology, University of Arkansas for Medical Sciences, Little Rock (W.C.C.). , Sassan HodgeSassan Hodge From the Department of Radiology, EPR Center for the Study of Viable Systems, Geisel School of Medicine at Dartmouth, Hanover, NH (N.K., H.H., S.G., G.D., S.H., P.K., H.M.S.); Norris Cotton Cancer Center, Dartmouth-Hitchcock Medical Center, Lebanon, NH (N.K., H.H., S.G., P.K., H.M.S.); Department of Radiology, Dartmouth-Hitchcock Medical Center, Lebanon, NH (C.J.E.); Center for Comparative Medicine and Research, Dartmouth College, Hanover, NH (K.M.); and Department of Radiology, Interventional Radiology, University of Arkansas for Medical Sciences, Little Rock (W.C.C.). , William C. CulpWilliam C. Culp From the Department of Radiology, EPR Center for the Study of Viable Systems, Geisel School of Medicine at Dartmouth, Hanover, NH (N.K., H.H., S.G., G.D., S.H., P.K., H.M.S.); Norris Cotton Cancer Center, Dartmouth-Hitchcock Medical Center, Lebanon, NH (N.K., H.H., S.G., P.K., H.M.S.); Department of Radiology, Dartmouth-Hitchcock Medical Center, Lebanon, NH (C.J.E.); Center for Comparative Medicine and Research, Dartmouth College, Hanover, NH (K.M.); and Department of Radiology, Interventional Radiology, University of Arkansas for Medical Sciences, Little Rock (W.C.C.). , Periannan KuppusamyPeriannan Kuppusamy From the Department of Radiology, EPR Center for the Study of Viable Systems, Geisel School of Medicine at Dartmouth, Hanover, NH (N.K., H.H., S.G., G.D., S.H., P.K., H.M.S.); Norris Cotton Cancer Center, Dartmouth-Hitchcock Medical Center, Lebanon, NH (N.K., H.H., S.G., P.K., H.M.S.); Department of Radiology, Dartmouth-Hitchcock Medical Center, Lebanon, NH (C.J.E.); Center for Comparative Medicine and Research, Dartmouth College, Hanover, NH (K.M.); and Department of Radiology, Interventional Radiology, University of Arkansas for Medical Sciences, Little Rock (W.C.C.). and Harold M. SwartzHarold M. Swartz From the Department of Radiology, EPR Center for the Study of Viable Systems, Geisel School of Medicine at Dartmouth, Hanover, NH (N.K., H.H., S.G., G.D., S.H., P.K., H.M.S.); Norris Cotton Cancer Center, Dartmouth-Hitchcock Medical Center, Lebanon, NH (N.K., H.H., S.G., P.K., H.M.S.); Department of Radiology, Dartmouth-Hitchcock Medical Center, Lebanon, NH (C.J.E.); Center for Comparative Medicine and Research, Dartmouth College, Hanover, NH (K.M.); and Department of Radiology, Interventional Radiology, University of Arkansas for Medical Sciences, Little Rock (W.C.C.). Originally published22 Jan 2015https://doi.org/10.1161/STROKEAHA.114.007324Stroke. 2015;46:e62–e66Other version(s) of this articleYou are viewing the most recent version of this article. Previous versions: January 1, 2015: Previous Version 1 The primary event in the ischemic stroke is a rapid decline in the oxygen levels after the loss of blood flow in specific areas of the brain. Subsequent pathological processes results in a central core area of severely ischemic tissue surrounded by a region of moderate ischemic tissue (penumbra) with a preserved cellular metabolism. The outcome of an ischemic stroke depends on the size of the infarct core and the potential to salvage the cells in the penumbra, which is hypoperfused, and therefore, at risk of infarction but still viable. Such viable penumbral tissue can be rescued by quick interventions that can increase oxygen levels or slow metabolism in the ischemic area to minimize oxidative injury on reperfusion.Several strategies have been investigated to rescue ischemic tissue using experimental models, especially rodents, but largely failed in subsequent clinical trials. The rabbit model of ischemic stroke using embolic clot is a promising model for developing effective strategies. This model first led to the prediction of the clinical response of recombinant tissue-type plasminogen activator to restore blood flow in patients.1 The drug is currently recommended for administration within 3 hours for best outcomes and has also shown modest benefit when administered within 4.5 to 6 hours of clinical onset.2 The rabbit model of embolic clot is now considered as a pertinent model for translational research by the Stroke Therapy Academic Industry Roundtable recommendations.3To rationally develop effectual therapies, it is important to understand the effect of ischemic stroke on oxygen levels (partial pressure of oxygen [pO2]) in the regions directly affected by the pathology, as well as contralateral regions of the rabbit brain. The potential changes in tissue po2 of contralateral regions may provide crucial information on adaptive response, if any, of the brain to counteract ischemic stroke. Such research will greatly benefit from the availability of oximetry techniques that can directly and repeatedly measure tissue pO2 in several regions of the brain.Several methods are currently available for the assessment of brain pO2, including oxygen electrodes.4,5 However, their limited capability to directly and repeatedly measure brain pO2 in a minimally invasive manner has restricted their effective application in ischemic stroke where monitoring oxygen levels are crucial for the development, and optimization of novel strategies for clinical translation. We report electron paramagnetic resonance (EPR) oximetry using implantable resonators to monitor brain pO2 in rabbit with the goal to develop and test novel strategies that can significantly reduce brain loss in ischemic stroke. EPR oximetry using particulate probes, such as lithium phthalocyanine crystals or its derivatives, have been used to study tissue pO2 in a wide range of experimental systems, including muscle, heart, brain, kidney, and liver in rodents6–9 and is now being developed for clinical applications.10,11 Despite the benefits of EPR oximetry, the currently available hardware technology limits pO2 measurement to a depth of 1 cm at L-band frequencies (1.2 GHz). This is largely because of nonresonant losses of the microwave energy in the tissue of interest. The penetration of microwave energy can be increased up to ≈7 cm by using lower frequencies but this decreases the signal/noise (S/N) ratio of the EPR signal, thus compromising the accuracy of measurements.12 To resolve this problem, we have pioneered an innovative design of implantable resonators for pO2 measurement at depths >1 cm (Figure 1). We have implemented this approach to monitor tissue pO2 at 2 sites in each hemisphere of the rabbit brain simultaneously. Our overall goal is to optimize the outcome of ischemic stroke for clinical translation. To the best of our knowledge, this is the first report of monitoring brain pO2 in multiple sites and at depths >1 cm from the skull in rabbit by EPR oximetry.Download figureDownload PowerPointFigure 1. A, Implantable resonator with 10- and 15-mm length of transmission line for pO2 measurement at different depths. B, Schematic representation of a surface loop resonator coupled to the implantable resonator for pO2 measurement at 4 sites in a rabbit brain. C, Typical electron paramagnetic resonance spectra acquired from the implantable resonator with sensor loops (SL1–SL4) perfused with N2, 5% O2, and 21% O2 for the purpose of calibration. D, Change in line width (LW) with pO2 (calibration) of each sensor loop from left to right.Description of the InnovationImplantable ResonatorThe implantable resonator is assembled with thin nonmagnetic copper wire (0.3-mm wire gauge) and consists of a coupling loop (12–16 mm diameter) at one end and a transmission line with sensor loops (0.4–0.5 mm inner diameter) at the other end (Figure 1A). The sensor loops (or tips) are loaded with 30 to 50 μg of lithium phthalocyanine (LiPc, oximetry probe)13 crystals. The length of the transmission lines defines the depth and can be varied as needed for the experiment. The number of sensor loops and the distance between them can also be varied to measure pO2 at ≥1 sites in the brain of rabbits. The entire resonator is coated with a gas permeable and biocompatible Teflon AF2400.14 The mean area of the oximetry probe at the surface of each sensor loop is estimated to be 1.3 to 1.6 mm2; EPR oximetry, therefore, samples a region that includes many capillary segments and provides average pO2 at the site of sensor loop.8,15 Histological examination of the cerebral tissue in the rabbit euthanized 4 weeks after the placement of implantable resonator did not show any obvious accumulation of inflammatory cells or blood cells surrounding the sensor loops. Similar results were also evident as early as 7 days after the placement of implantable resonator with 6-mm length of transmission lines in the brain of rats.16Procedure for the Placement of Implantable Resonator in the Brain of RabbitsThe surgical procedure for the placement of implantable resonator in the brain of rabbit was in strict accordance with the National Institutes of Health Guide for the Care and Use of Laboratory Animals and approved by the Institutional Animal Care and Use Committee of Geisel School of Medicine at Dartmouth. The head of the anesthetized rabbit was antiseptically treated with Betadine, and 70% alcohol scrubs. A small incision (2–3 cm) was made on the skin and burr holes were gently created by using 18-gauge needle on the skull at predefined coordinates (anterior–posterior from bregma, −2.0 mm; medial–lateral from midline, 4 and 8 mm on each hemisphere; dorsal–ventral from surface of skull, 15 and 10 mm in each hemisphere). The sensor loops, SL1 and SL4, were located in the parietal cortex, whereas SL2 and SL3 were located in the subcortex (basal forebrain/internal capsule) region of the brain. The position of the sensor loops can be altered depending on the coordinates of the compromised tissue after ischemic stroke. The sensor loops were placed at the desired depth and the coupling loop was placed on the skull below the skin, to allow inductive coupling with the external surface loop resonator of the EPR spectrometer (Figure 1B). The incision on the skin was closed with nonabsorbable 3-0 nylon suture and the rabbit was monitored for recovery as per the Institutional Animal Care and Use Committee protocol. The repeated measurements of brain pO2 by EPR oximetry was started 72 hours (day 3) after the placement of implantable resonator and the measurements were repeated for 4 weeks.In Vivo EPR OximetryEPR oximetry requires one-time implantation of the oxygen probes (LiPc or implantable resonator), but rest of the procedure for pO2 measurement is entirely noninvasive and can be repeated as desired.8,17–19 The basis of oximetry is the paramagnetic nature of oxygen, which broadens the EPR signal of the probe in proportion to the amount of oxygen. EPR oximetry has unique capabilities and advantages compared with other techniques, such as (1) direct measurement of absolute pO2 in the tissue of interest, (2) pO2 is quantified through a physical interaction of oxygen with the probe (does not require oxygen consumption), (3) pO2 measurements can be made continuously and repeatedly as desired, without a confounding influence of previous measurements, (4) The oxygen sensors are metabolically inert and coated with Teflon, therefore, do not perturb the tissue microenvironment, including oxygen content, and (5) there is no other technique available at present to make repeated measurement of tissue pO2 without the need to reintroduce the probe for each measurement.A 1.2-GHz EPR spectrometer equipped with a surface loop resonator and a set of gradient coil for multisite oximetry was used for monitoring brain pO2 in the rabbit. The anesthetized rabbit (2.5% isoflurane in 30% O2) was positioned in the EPR magnet and the external surface loop resonator was gently placed over the head region. A magnetic field gradient of 1.7 G/cm per ampere was used to separate the EPR spectra from each sensor loop for simultaneous multisite oximetry.20 The peak-to-peak line widths of the EPR spectra were used to determine pO2 by using the calibration of implantable resonator (Figure 1C and 1D). The rabbit was maintained at 38±1.0°C (monitored via a rectal probe) by keeping the animal under warm air during the EPR measurements. The EPR settings were as follows: incident microwave power, 0.4 to 1.2 mW; modulation frequency, 24 kHz; magnetic field center, 410 G; scan time, 10 s, scan range, 8 to 12 G, and modulation amplitude not exceeding one third of the line width. The implantable resonator appears as a signal void in T1-weighted MRI scans, which can be used to confirm their position in the brain of rabbits.ResultsBrain pO2 was measured for 20 to 25 minutes on day 3 and the measurements were repeated on days 5, 7, 14, 21, and 28 (Figure 2). The mean (SD) baseline pO2 at each site (SL1–SL4) in the brain on day 3 was 39.2 (2.2), 41.6 (1.4), 41.3 (1.7), and 43.6 (2.0) mm Hg, respectively, and only a modest variation was observed in the measurements repeated subsequently for ≤4 weeks. To mimic the ischemic situation with low levels of oxygen and test the response of implantable resonator, the breathing gas was switched to 15% O2 for 15 minutes and then returned to 30% O2, (Figure 3A). To test the potential effect of hyperoxia on brain pO2, the breathing gas was switched to carbogen (95% O2+5% CO2) for 20 to 25 minutes and then returned to 30% O2, (Figure 3B). These experiments were performed on days 7, 14, 21, and 28. The brain pO2 measured at 4 sites decreased by ≈30% from baseline in rabbit breathing 15% O2. However, brain pO2 measured at 4 sites increased significantly by ≥75% during carbogen breathing. An exponential quadratic function of time was used to determine minimum pO2 (PO2min) attained during 15% O2 on each day and the time to reach the PO2min (Tmin) (Figure 4). Similar analysis was used to determine maximal pO2 (PO2max) attained on each day and the time to reach maximum pO2 (Tmax) during carbogen inhalation. These analyses suggest that it took 10 to 14 minutes to reach a minimal or maximal pO2 when the breathing gas was switched from 30% O2 to 15% O2 or carbogen, respectively. A similar time scale was noted for the brain pO2 to return to the baseline level when the breathing gas was switched from 15% O2 or carbogen to 30% O2. We anticipate that such temporal pO2 information will be extremely useful in designing hyperoxic therapies to modulate oxygen levels in ischemic stroke.Download figureDownload PowerPointFigure 2. Tissue pO2 in the rabbit brain at 2 sites in each hemisphere measured simultaneously by multisite electron paramagnetic resonance oximetry. The sensor loops (SL) 1 and SL4 were at a depth of 10 mm; SL2 and SL3 were at a depth of 15 mm in the left and right hemisphere, respectively. The brain pO2 measurements were repeated on days 3, 5, 7, 14, 21, and 28.Download figureDownload PowerPointFigure 3. Typical changes in tissue pO2 of the rabbit brain at 2 sites in each hemisphere during (A) 30% O2 (baseline), 15% O2, and return to 30% O2 breathing, (B) 30% O2, carbogen and return to 30% O2 breathing. The experiment was repeated for 4 consecutive weeks.Download figureDownload PowerPointFigure 4. A, Baseline (base), minimum (min), and maximum (max) brain pO2 determined using exponential quadratic function in rabbit breathing 30% O2, 15% O2, and carbogen, respectively. B, Time required to reach minimal pO2 on 15% O2 breathing (Tmin), maximal pO2 on carbogen breathing (Tmax), time required to return to baseline pO2 when the gas was switched from 15% O2 to 30% O2 (*Tbase), and time required to return to baseline pO2 when the gas was switched from carbogen to 30% O2 (**Tbase) in the experiments repeated on days 7, 14, 21, and 28. The pO2 obtained from all the sensor loops were pooled on each day to obtain average brain pO2 for these analyses.DiscussionTo fully comprehend the pathology of stroke and rationally develop strategies to rescue ischemic tissue, there is an unmet need to understand the complex temporal changes in tissue pO2 that occur during the course of ischemic stroke, a capability that previously has not been available. The results highlight the ability of EPR oximetry using implantable resonator for pO2 measurements at 4 sites simultaneously in the brain of a rabbit. The pO2 measurements can be repeated as desired. A rapid decline in tissue pO2 during 15% O2 breathing potentially highlights the immediate changes in the oxygen levels that may occur in ischemic stroke. The extent of increase in tissue pO2 during carbogen breathing is encouraging and can be potentially used as a therapeutic strategy to improve oxygen levels and thus save vital tissue loss in ischemic stroke.For the multisite oximetry approach, the position of sensor loops should be carefully selected so that they are located in the region of interest, that is, infarct core and penumbra after ischemic stroke. The design of the implantable resonator, including the length of transmission lines, number, and distance between the sensor loops can be modified as needed for a particular experiment. A stable brain pO2 was observed from day 3, which suggest that the experiments to investigate ischemic stroke can be initiated as early as 3 days after the placement of implantable resonator in the brain of rabbits. The measurement of tissue pO2 in the nonischemic contralateral brain can be used as internal control and investigate adaptive response of the brain to ischemic stroke. The brain pO2 data presented here was obtained in a rabbit to illustrate the capability of temporal monitoring by EPR oximetry. We are currently implementing this technique to investigate temporal changes in the brain pO2 in additional rabbits during hyperoxia and ischemic stroke.ConclusionsWe have demonstrated a direct and longitudinal measurement of absolute tissue pO2 at several sites simultaneously in the brain of rabbit by EPR oximetry using implantable resonators, a capability, which was not available hitherto. Dynamic information of cerebral pO2 can be used to test and to optimize strategies for improving treatment outcome of ischemic stroke. EPR oximetry with implantable resonators should also be useful to investigate the effect of other pathologies, such as traumatic brain injury and cold injury, on the oxygen levels in the brain of clinically pertinent animal models.Sources of FundingNational Institutes of Health grants R21NS082585 to Dr Khan, R01EB004031 to Dr Kuppusamy, and the Electron Paramagnetic Resonance Center, Geisel School of Medicine at Dartmouth, Lebanon, NH.DisclosuresNone.FootnotesCorrespondence to Nadeem Khan, PhD, EPR Center for the Study of Viable Systems, Geisel School of Medicine at Dartmouth, 48 Lafayette St, Lebanon, NH 03766. E-mail [email protected]References1. Lapchak PA. Translational stroke research using a rabbit embolic stroke model: a correlative analysis hypothesis for novel therapy development.Transl Stroke Res. 2010; 1:96–107. doi: 10.1007/s12975-010-0018-4.CrossrefMedlineGoogle Scholar2. Wardlaw JM, Murray V, Berge E, del Zoppo G, Sandercock P, Lindley RL, et al. Recombinant tissue plasminogen activator for acute ischaemic stroke: an updated systematic review and meta-analysis.Lancet. 2012; 379:2364–2372. doi: 10.1016/S0140-6736(12)60738-7.CrossrefMedlineGoogle Scholar3. Albers GW, Goldstein LB, Hess DC, Wechsler LR, Furie KL, Gorelick PB, et al; STAIR VII Consortium. Stroke Treatment Academic Industry Roundtable (STAIR) recommendations for maximizing the use of intravenous thrombolytics and expanding treatment options with intra-arterial and neuroprotective therapies.Stroke. 2011; 42:2645–2650. doi: 10.1161/STROKEAHA.111.618850.LinkGoogle Scholar4. Fisher M. The ischemic penumbra: a new opportunity for neuroprotection.Cerebrovasc Dis. 2006; 21(suppl 2):64–70. doi: 10.1159/000091705.CrossrefMedlineGoogle Scholar5. Dengl M, Jaeger M, Renner C, Meixensberger J. Comparing brain tissue oxygen measurements and derived autoregulation parameters from different probes (Licox vs. Raumedic).Acta Neurochir Suppl. 2012; 114:165–168. doi: 10.1007/978-3-7091-0956-4_31.CrossrefMedlineGoogle Scholar6. Helisch A, Wagner S, Khan N, Drinane M, Wolfram S, Heil M, et al. Impact of mouse strain differences in innate hindlimb collateral vasculature.Arterioscler Thromb Vasc Biol. 2006; 26:520–526. doi: 10.1161/01.ATV.0000202677.55012.a0.LinkGoogle Scholar7. Jiang J, Nakashima T, Liu KJ, Goda F, Shima T, Swartz HM. Measurement of po2 in liver using EPR oximetry.J Appl Physiol (1985). 1996; 80:552–558.CrossrefMedlineGoogle Scholar8. Khan N, Williams BB, Hou H, Li H, Swartz HM. Repetitive tissue pO2 measurements by electron paramagnetic resonance oximetry: current status and future potential for experimental and clinical studies.Antioxid Redox Signal. 2007; 9:1169–1182. doi: 10.1089/ars.2007.1635.CrossrefMedlineGoogle Scholar9. Towner RA, Sturgeon SA, Khan N, Hou H, Swartz HM. In vivo assessment of nodularin-induced hepatotoxicity in the rat using magnetic resonance techniques (MRI, MRS and EPR oximetry).Chem Biol Interact. 2002; 139:231–250.CrossrefMedlineGoogle Scholar10. Swartz HM, Williams BB, Zaki BI, Hartford AC, Jarvis LA, Chen EY, et al. Clinical EPR: unique opportunities and some challenges.Acad Radiol. 2014; 21:197–206. doi: 10.1016/j.acra.2013.10.011.CrossrefMedlineGoogle Scholar11. Swartz HM, Hou H, Khan N, Jarvis LA, Chen EY, Williams BB, et al. Advances in probes and methods for clinical EPR oximetry.Adv Exp Med Biol. 2014; 812:73–79. doi: 10.1007/978-1-4939-0620-8_10.CrossrefMedlineGoogle Scholar12. 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 U S A. 1994; 91:13047–13051.CrossrefMedlineGoogle Scholar13. Liu KJ, Gast P, Moussavi M, Norby SW, Vahidi N, Walczak T, et al. Lithium phthalocyanine: a probe for electron paramagnetic resonance oximetry in viable biological systems.Proc Natl Acad Sci U S A. 1993; 90:5438–5442.CrossrefMedlineGoogle Scholar14. Dinguizli M, Jeumont S, Beghein N, He J, Walczak T, Lesniewski PN, et al. Development and evaluation of biocompatible films of polytetrafluoroethylene polymers holding lithium phthalocyanine crystals for their use in EPR oximetry.Biosens Bioelectron. 2006; 21:1015–1022. doi: 10.1016/j.bios.2005.03.009.CrossrefMedlineGoogle Scholar15. O'Hara JA, Hou H, Demidenko E, Springett RJ, Khan N, Swartz HM. Simultaneous measurement of rat brain cortex pO2 using EPR oximetry and a fluorescence fiber-optic sensor during normoxia and hyperoxia.Physiol Meas. 2005; 26:203–213. doi: 10.1088/0967-3334/26/3/006.CrossrefMedlineGoogle Scholar16. Hou H, Dong R, Li H, Williams B, Lariviere JP, Hekmatyar SK, et al. Dynamic changes in oxygenation of intracranial tumor and contralateral brain during tumor growth and carbogen breathing: a multisite EPR oximetry with implantable resonators.J Magn Reson. 2012; 214:22–28. doi: 10.1016/j.jmr.2011.09.043.CrossrefMedlineGoogle Scholar17. Ahmad R, Kuppusamy P. Theory, instrumentation, and applications of electron paramagnetic resonance oximetry.Chem Rev. 2010; 110:3212–3236. doi: 10.1021/cr900396q.CrossrefMedlineGoogle Scholar18. Khan N, Mupparaju S, Hou H, Williams BB, Swartz H. Repeated assessment of orthotopic glioma pO(2) by multi-site EPR oximetry: a technique with the potential to guide therapeutic optimization by repeated measurements of oxygen.J Neurosci Methods. 2012; 204:111–117. doi: 10.1016/j.jneumeth.2011.10.026.CrossrefMedlineGoogle Scholar19. Dunn JF, Swartz HM. In vivo electron paramagnetic resonance oximetry with particulate materials.Methods (San Diego, Calif). 2003; 30:159–166.CrossrefMedlineGoogle Scholar20. Smirnov AI, Norby SW, Clarkson RB, Walczak T, Swartz HM. Simultaneous multi-site EPR spectroscopy in vivo.Magn Reson Med. 1993; 30:213–220.CrossrefMedlineGoogle Scholar Previous Back to top Next FiguresReferencesRelatedDetailsCited By Chen E, Tse D, Hou H, Schreiber W, Schaner P, Kmiec M, Hebert K, Kuppusamy P, Swartz H and Williams B (2021) Evaluation of a Refined Implantable Resonator for Deep-Tissue EPR Oximetry in the Clinic, Applied Magnetic Resonance, 10.1007/s00723-021-01376-5, 52:10, (1321-1342), Online publication date: 1-Oct-2021. Pla L, Berdún S, Mir M, Rivas L, Miserere S, Dulay S, Samitier J, Eixarch E, Illa M and Gratacós E (2021) Non-invasive monitoring of pH and oxygen using miniaturized electrochemical sensors in an animal model of acute hypoxia, Journal of Translational Medicine, 10.1186/s12967-021-02715-7, 19:1, Online publication date: 1-Dec-2021. Kuppusamy P (2020) Sense and Sensibility of Oxygen in Pathophysiology Using EPR Oximetry Measuring Oxidants and Oxidative Stress in Biological Systems, 10.1007/978-3-030-47318-1_9, (135-187), . Hirata H, Petryakov S and Schreiber W (2020) Resonators for Clinical Electron Paramagnetic Resonance (EPR) Measuring Oxidants and Oxidative Stress in Biological Systems, 10.1007/978-3-030-47318-1_10, (189-219), . Tseytlin O, Guggilapu P, Bobko A, AlAhmad H, Xu X, Epel B, O'Connell R, Hoblitzell E, Eubank T, Khramtsov V, Driesschaert B, Kazkaz E and Tseytlin M (2019) Modular imaging system: Rapid scan EPR at 800 MHz, Journal of Magnetic Resonance, 10.1016/j.jmr.2019.06.003, 305, (94-103), Online publication date: 1-Aug-2019. Kmiec M, Tse D, Mast J, Ahmad R and Kuppusamy P (2019) Implantable microchip containing oxygen-sensing paramagnetic crystals for long-term, repeated, and multisite in vivo oximetry, Biomedical Microdevices, 10.1007/s10544-019-0421-x, 21:3, Online publication date: 1-Sep-2019. Kmiec M, Hou H, Lakshmi Kuppusamy M, Drews T, Prabhat A, Petryakov S, Demidenko E, Schaner P, Buckey J, Blank A and Kuppusamy P (2018) Transcutaneous oxygen measurement in humans using a paramagnetic skin adhesive film, Magnetic Resonance in Medicine, 10.1002/mrm.27445, 81:2, (781-794), Online publication date: 1-Feb-2019. Baek J and Buehler P (2019) Can molecular markers of oxygen homeostasis and the measurement of tissue oxygen be leveraged to optimize red blood cell transfusions?, Current Opinion in Hematology, 10.1097/MOH.0000000000000533, 26:6, (453-460), Online publication date: 1-Nov-2019. Vidya Shankar R and Kodibagkar V (2019) A faster PISTOL for 1 H MR‐based quantitative tissue oximetry , NMR in Biomedicine, 10.1002/nbm.4076, 32:5, Online publication date: 1-May-2019. Polacco M, Hou H, Kuppusamy P and Chen E (2019) Measuring Flap Oxygen Using Electron Paramagnetic Resonance Oximetry, The Laryngoscope, 10.1002/lary.28043, 129:12, Online publication date: 1-Dec-2019. Enomoto A, Qian C, Devasahayam N, Kishimoto S, Oshima N, Blackman B, Swenson R, Mitchell J, Koretsky A and Krishna M (2018) Wireless implantable coil with parametric amplification for in vivo electron paramagnetic resonance oximetric applications, Magnetic Resonance in Medicine, 10.1002/mrm.27185, 80:5, (2288-2298), Online publication date: 1-Nov-2018. Tokunaga Y, Nakao M, Naganuma T and Ichikawa K (2017) Construction of 0.15 Tesla Overhauser Enhanced MRI Oxygen Transport to Tissue XXXIX, 10.1007/978-3-319-55231-6_51, (393-398), . Hou H, Khan N, Gohain S, Eskey C, Moodie K, Maurer K, Swartz H and Kuppusamy P (2017) Dynamic EPR Oximetry of Changes in Intracerebral Oxygen Tension During Induced Thromboembolism, Cell Biochemistry and Biophysics, 10.1007/s12013-017-0798-1, 75:3-4, (285-294), Online publication date: 1-Dec-2017. Caston R, Schreiber W, Hou H, Williams B, Chen E, Schaner P, Jarvis L, Flood A, Petryakov S, Kmiec M, Kuppusamy P and Swartz H (2017) Development of the Implantable Resonator System for Clinical EPR Oximetry, Cell Biochemistry and Biophysics, 10.1007/s12013-017-0809-2, 75:3-4, (275-283), Online publication date: 1-Dec-2017. Gallez B (2016) Contribution of Harold M. Swartz to In Vivo EPR and EPR Dosimetry , Radiation Protection Dosimetry, 10.1093/rpd/ncw157, 172:1-3, (16-37), Online publication date: 1-Dec-2016. Khan N, Hou H, Swartz H and Kuppusamy P (2015) Direct and Repeated Measurement of Heart and Brain Oxygenation Using In Vivo EPR Oximetry Electron Paramagnetic Resonance Investigations of Biological Systems by Using Spin Labels, Spin Probes, and Intrinsic Metal Ions, Part B, 10.1016/bs.mie.2015.06.023, (529-552), . Abou Khouzam R, Brodaczewska K, Filipiak A, Zeinelabdin N, Buart S, Szczylik C, Kieda C and Chouaib S (2021) Tumor Hypoxia Regulates Immune Escape/Invasion: Influence on Angiogenesis and Potential Impact of Hypoxic Biomarkers on Cancer Therapies, Frontiers in Immunology, 10.3389/fimmu.2020.613114, 11 March 2015Vol 46, Issue 3 Advertisement Article InformationMetrics © 2015 American Heart Association, Inc.https://doi.org/10.1161/STROKEAHA.114.007324PMID: 25613304 Manuscript receivedDecember 4, 2014Manuscript acceptedDecember 22, 2014Originally publishedJanuary 22, 2015Manuscript revisedDecember 4, 2014 KeywordsEPR oximetryhyperoxiacarbogenpO2strokeimplantable resonatorischemiaPDF download Advertisement SubjectsAnimal Models of Human DiseaseImaging
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