Clinical Electron Paramagnetic Resonance (EPR) Oximetry Using India Ink

Small vessel disease is associated with white-matter (WM) magnetic resonance imaging (MRI) hyperintensities (WMHs) in patients with vascular cognitive impairment (VCI) and subsequent damage to the WM. Although WM is vulnerable to hypoxic-ischemic injury and O2 is critical in brain physiology, tissue O2 level in the WM has not been measured and explored in vivo. We hypothesized that spontaneously hypertensive stroke-prone rat (SHR/SP) fed a Japanese permissive diet (JPD) and subjected to unilateral carotid artery occlusion (UCAO), a model to study VCI, would lead to reduced tissue oxygen (pO2) in the deep WM. We tested this hypothesis by monitoring WM tissue pO2 using in vivo electron paramagnetic resonance (EPR) oximetry in SHR/SP rats over weeks before and after JPD/UCAO. The SHR/SP rats experienced an increase in WM pO2 from 9 to 12 weeks with a maximal 32% increase at week 12, followed by a dramatic decrease in WM pO2 to near hypoxic conditions during weeks 13 to 16 after JPD/UCAO. The decreased WM pO2 was accompanied with WM damage and hemorrhages surrounding microvessels. Our findings suggest that changes in WM pO2 may contribute to WM damage in SHR/SP rat model, and that EPR oximetry can monitor brain pO2 in the WM of small animals.

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First-In-Human Study in Cancer Patients Establishing the Feasibility of Oxygen Measurements in Tumors Using Electron Paramagnetic Resonance With the OxyChip

Frontiers in Oncology ◽

10.3389/fonc.2021.743256 ◽

2021 ◽

Vol 11 ◽

Author(s):

Philip E. Schaner ◽

Benjamin B. Williams ◽

Eunice Y. Chen ◽

Jason R. Pettus ◽

Wilson A. Schreiber ◽

...

Keyword(s):

Electron Paramagnetic Resonance ◽

Neoadjuvant Therapy ◽

Cancer Patients ◽

Human Study ◽

Tumor Oxygenation ◽

Paramagnetic Resonance ◽

Epr Oximetry ◽

Care Surgery ◽

Electron Paramagnetic ◽

Oxygen Measurements

ObjectiveThe overall objective of this clinical study was to validate an implantable oxygen sensor, called the ‘OxyChip’, as a clinically feasible technology that would allow individualized tumor-oxygen assessments in cancer patients prior to and during hypoxia-modification interventions such as hyperoxygen breathing.MethodsPatients with any solid tumor at ≤3-cm depth from the skin-surface scheduled to undergo surgical resection (with or without neoadjuvant therapy) were considered eligible for the study. The OxyChip was implanted in the tumor and subsequently removed during standard-of-care surgery. Partial pressure of oxygen (pO2) at the implant location was assessed using electron paramagnetic resonance (EPR) oximetry.ResultsTwenty-three cancer patients underwent OxyChip implantation in their tumors. Six patients received neoadjuvant therapy while the OxyChip was implanted. Median implant duration was 30 days (range 4–128 days). Forty-five successful oxygen measurements were made in 15 patients. Baseline pO2 values were variable with overall median 15.7 mmHg (range 0.6–73.1 mmHg); 33% of the values were below 10 mmHg. After hyperoxygenation, the overall median pO2 was 31.8 mmHg (range 1.5–144.6 mmHg). In 83% of the measurements, there was a statistically significant (p ≤ 0.05) response to hyperoxygenation.ConclusionsMeasurement of baseline pO2 and response to hyperoxygenation using EPR oximetry with the OxyChip is clinically feasible in a variety of tumor types. Tumor oxygen at baseline differed significantly among patients. Although most tumors responded to a hyperoxygenation intervention, some were non-responders. These data demonstrated the need for individualized assessment of tumor oxygenation in the context of planned hyperoxygenation interventions to optimize clinical outcomes.

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Measurement of the Partial Pressure of Oxygen in Cutaneous Tumors Using Electron Paramagnetic Resonance (EPR) Oximetry

Case Medical Research ◽

10.31525/ct1-nct04112342 ◽

2019 ◽

Author(s):

Keyword(s):

Electron Paramagnetic Resonance ◽

Partial Pressure ◽

Partial Pressure Of Oxygen ◽

Paramagnetic Resonance ◽

Epr Oximetry ◽

Electron Paramagnetic

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Measurement of PO2 in liver using EPR oximetry

Journal of Applied Physiology ◽

10.1152/jappl.1996.80.2.552 ◽

1996 ◽

Vol 80 (2) ◽

pp. 552-558 ◽

Cited By ~ 33

Author(s):

J. Jiang ◽

T. Nakashima ◽

K. J. Liu ◽

F. Goda ◽

T. Shima ◽

...

Keyword(s):

Blood Flow ◽

Kupffer Cells ◽

Oxygen Electrode ◽

Mean Value ◽

Paramagnetic Resonance ◽

India Ink ◽

Epr Oximetry ◽

Unanesthetized Animals ◽

Electron Paramagnetic

With the use of India ink and lithium phthalocyanine (LiPc) as electron paramagnetic resonance (EPR) oximetry probes, the PO2 of the liver was investigated in mice. Because India ink was taken up by the Kupffer cells of the liver, the EPR signal of the India ink reflected the average PO2 in phagocytic vesicles of these cells. The mean value of PO2 in the Kupffer cells measured by India ink was 15.3 +/- 4.4 Torr in unanesthetized animals. LiPc was administered as a macroscopic crystal and therefore reflected the PO2 of the overall liver. The PO2 measured by LiPc was 23.4 +/- 4.4 Torr, which is consistent with the median value of 23.5 Torr reported previously with the use of an oxygen electrode. Anesthesia (injection of 60 mg/kg ip pentobarbital sodium) decreased the average PO2 in both Kupffer cells and the overall liver. The effects of perturbing the blood flow were studied by reversible blockage of the portal vein and hepatic artery in anesthetized mice; the PO2 in both Kupffer cells (measured with India ink) and in overall liver (measured with LiPc) decreased with obstruction of the blood flow and returned toward normal with reperfusion. These results indicate that the PO2 in different locations in the liver can be significantly different under both normal conditions and after perturbation by either anesthesia or ischemia. These results also demonstrate that EPR oximetry can provide sensitive measurements of PO2 in the liver in vivo under various conditions.

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