Deep-Tissue Oxygen Monitoring in the Brain of Rabbits for Stroke Research

Khan, Nadeem; Hou, Huagang; Eskey, Clifford J.; Moodie, Karen L; Gohain, Sangeeta; Du, Gaixin; Hodge, Sassan; Culp, William C.; Kuppusamy, Periannan; Swartz, Harold M.

doi:10.1161/strokeaha.114.007324

Cited by 22 publications

(24 citation statements)

References 20 publications

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“…We have previously reported the effect of breathing hypoxic (10-15% O 2 ) and hyperoxic (100% O 2 , carbogen and hyperbaric oxygen therapy) challenges on the brain pO 2 in rats and rabbits with the goal to understand the sensitivity of IRs to local changes of brain pO 2 and how improved oxygen levels protect brain from ischemic stroke in the brain [28,29,32,33]. …”

Section: Resultsmentioning

confidence: 99%

“…The entire resonator was coated with a gas-permeable and biocompatible Teflon AF2400 [38]. The implantable resonators are well tolerated by the animals (mice, rats, or rabbits) [32, 39-42]. The mean area of the oximetry probe at the surface of each sensor loop was 1.3 - 1.6 mm 2 .…”

Section: Methodsmentioning

confidence: 99%

“…EPR oximetry, therefore, samples a region that includes many capillary segments and provides average pO 2 at the site of the sensor loop [5, 26]. We have recently described the procedures for the placement of the implantable resonator and EPR oximetry in rabbits [42]. The diameter and the number of sensors, the length of the transmissions lines and the distance between sensors can be adjusted based on the experimental requirements.…”

Section: Methodsmentioning

confidence: 99%

“…We have developed EPR oximetry using implantable oxygen sensors to repeatedly measure cerebral pO 2 in the regions directly affected by ischemic stroke as well as the contralateral regions of the rat brain [32]. We have also systematically developed sensors that can be used to assess pO 2 at depths greater than 10 mm from the surface [33]. In this paper, we report the application of an implantable resonator (IR) with four sensory tips to assess the dynamic changes in the regional oxygen levels at different depths (10 mm and 15 mm) in rabbit cerebral tissue for 4 weeks.…”

Section: Introductionmentioning

confidence: 99%

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Dynamic EPR Oximetry of Changes in Intracerebral Oxygen Tension During Induced Thromboembolism

Hou

Khan

Gohain

et al. 2017

Cell Biochem Biophys

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Cerebral tissue oxygenation (oxygen tension, pO2) is a critical parameter that is closely linked to brain metabolism, function, and pathophysiology. In this work, we have used electron paramagnetic resonance (EPR) oximetry with a deep-tissue multi-site oxygen-sensing probe, called implantable resonator (IR), to monitor temporal changes in cerebral pO2 simultaneously at 4 sites in a rabbit model of ischemic stroke induced by embolic clot. The pO2 values in healthy brain were not significantly different among the 4 the sites measured over a period of 4 weeks. During exposure to 15% O2 (hypoxia), a sudden and significant decrease in pO2 was observed in all four sites. On the other hand, brief exposure to breathing carbogen gas (95% O2 + 5% CO2) showed a significant increase in the cerebral pO2 from baseline value. During ischemic stroke, induced by embolic clot in the left brain, a significant decline in the pO2 of the left cortex (ischemic core) was observed without any change in the contralateral sites. While the pO2 in the non-infarct regions returned to baseline at 24-h post-stroke, pO2 in the infarct core was consistently lower compared to the baseline and other regions of the brain. The results demonstrated that EPR oximetry with the IR can repeatedly and simultaneously report temporal changes in cerebral pO2 at multiple sites. This oximetry approach can be used to develop interventions to rescue hypoxic/ischemic tissue by modulating cerebral pO2 during hypoxic and stroke injury.

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Dynamic EPR Oximetry of Changes in Intracerebral Oxygen Tension During Induced Thromboembolism

Hou

Khan

Gohain

et al. 2017

Cell Biochem Biophys

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“…Studies in animals have demonstrated the reliability and repeatability of measurements obtained from IRs in vivo [14–20]. These studies have demonstrated feasibility and have also led to improvements in the utility of the IR system.…”

Section: Introductionmentioning

confidence: 99%

Development of the Implantable Resonator System for Clinical EPR Oximetry

Caston

Schreiber

Hou

et al. 2017

Cell Biochem Biophys

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Hypoxic tumors are more resistant to radiotherapy and chemotherapy, which decreases the efficacy of these common forms of treatment. We have been developing implantable paramagnetic particulates to measure oxygen in vivo using electron paramagnetic resonance. Once implanted, oxygen can be measured repeatedly and non-invasively in superficial tissues (<3 cm deep), using an electron paramagnetic resonance spectrometer and an external surface-loop resonator. To significantly extend the clinical applications of electron paramagnetic resonance oximetry, we developed an implantable resonator system to obtain measurements at deeper sites. This system has been used to successfully obtain oxygen measurements in animal studies for several years. We report here on recent developments needed to meet the regulatory requirements to make this technology available for clinical use. radio frequency heating is discussed and magnetic resonance compatibility testing of the device has been carried out by a Good Laboratory Practice-certified laboratory. The geometry of the implantable resonator has been modified to meet our focused goal of verifying safety and efficacy for the proposed use of intracranial measurements and also for future use in tissue sites other than the brain. We have encapsulated the device within a smooth cylindrical-shaped silicone elastomer to prevent tissues from adhering to the device and to limit perturbation of tissue during implantation and removal. We have modified the configuration for simultaneously measuring oxygen at multiple sites by developing a linear array of oxygen sensing probes, which each provide independent measurements. If positive results are obtained in additional studies which evaluate bio-compatibility and chemical characterization, we believe the implantable resonator will be at a suitable stage for initial testing in human subjects.

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Measuring Flap Oxygen Using Electron Paramagnetic Resonance Oximetry

et al. 2019

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Objectives/Hypothesis To determine if electron paramagnetic resonance (EPR) oximetry is a viable technology to aid in flap monitoring. Study Design Prospective cohort. Methods This was a cohort study assessing accuracy and speed of EPR oximetry in detecting ischemia of a saphenous artery–based flap in a rat model, using transcutaneous oximetry as a control. Measurements were obtained under both resting and ischemic conditions for nine Sprague Dawley rats (18 flaps), for 3 postoperative days following flap elevation. Results The mean partial pressure of oxygen prior to tourniquet application was 66.9 ± 8.9 mm Hg with EPR oximetry and 64.7 ± 5.2 mm Hg with transcutaneous oximetry (P = .45). Mean partial pressures of oxygen during tourniquet application were 8.9 ± 3.2 mm Hg and 8.5 ± 2.9 mm Hg for EPR oximetry and transcutaneous oximetry, respectively (P = .48), and 67.2 ± 6.9 mm Hg and 65.3 ± 6.1 mm Hg after tourniquet release for EPR oximetry and transcutaneous oximetry, respectively (P = .44). The mean ischemia detection time of EPR oximetry was 49 ± 21 seconds. Conclusions Offering timely, accurate, and noninvasive tissue oxygen measurements, EPR oximetry is a promising adjunct in flap monitoring. Level of Evidence NA Laryngoscope, 129:E415–E419, 2019

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Deep-Tissue Oxygen Monitoring in the Brain of Rabbits for Stroke Research

Cited by 22 publications

References 20 publications

Dynamic EPR Oximetry of Changes in Intracerebral Oxygen Tension During Induced Thromboembolism

Dynamic EPR Oximetry of Changes in Intracerebral Oxygen Tension During Induced Thromboembolism

Development of the Implantable Resonator System for Clinical EPR Oximetry

Measuring Flap Oxygen Using Electron Paramagnetic Resonance Oximetry

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