Oxygen is one of the most important molecules in biological systems since it is involved as either a reactant or a product in a vast number of biochemical processes. The element is found in most biomolecules that are essential to living organisms, and plays a crucial role in cellular respiration and the electron transport chain in the mitochondria of living cells. Any imbalance in oxygen levels, which can occur due to altered supply or utilization of oxygen, may affect metabolic homeostasis and lead to pathophysiology. Thus, a means by which to evaluate and track changes in tissue oxygen levels will be of paramount importance in our ability to understand the mechanisms of pathogenesis and to develop effective strategies to correct the imbalance. This would require methods capable of quantifying the levels of tissue oxygenation with good spatial and temporal resolution. Ideally, these measurements should be obtained through minimally invasive or noninvasive means. Thus, the overall objective of this proposal is to develop safe, implantable oxygen-sensing probes (OxyChips) for electron paramagnetic resonance (EPR) oximetry that can be used in clinical applications. The probes will be designed to be implanted in the tissue of interest, permitting repeated measurements of tissue oxygenation from the same site by noninvasive means. This new class of EPR probes will be based on oxygen-sensitive particulate probes embedded in an oxygen-permeable biocompatible substrate, polydimethylsiloxane (PDMS). Using this approach, OxyChip implants of various shapes, sizes, and dimensions will be fabricated and characterized. The robustness of the probes will also be tested to ensure that they will perform as expected. Biocompatibility testing and validation of the probe applicability will then be performed in several clinically-relevant animal models of human disease. The following specific aims are proposed: 1) Encapsulation of particulate EPR probes and fabrication of OxyChips; 2) Biostability and biocompatibility evaluation of encapsulated EPR particulates; 3) Toxicity, immunological response, and safety evaluation of OxyChips, and 4) In vivo implantation and testing of OxyChips in clinically-relevant animal models of disease. The information gained from these devices will provide a better understanding of various metabolic and disease states (e.g. cancer and peripheral vascular disease) and help in making effective clinical decisions regarding treatment and therapy. The long-term objective of this proposal is to develop implantable, oxygen-sensing probes for use in clinical electron paramagnetic resonance (EPR) oximetry. Oxygen is found in most biomolecules that are essential to living organisms, and plays a role in a number of processes in both normal and altered physiology. Once implanted, the new probes will permit repeated, noninvasive measurement of oxygen concentration in tissues. The probes could be used to track growth and/or death of tumor tissues, progression of peripheral arterial disease and muscular atrophy, and wound healing response. ? ? ?
The long-term objective of this proposal is to develop implantable, oxygen-sensing probes for use in clinical electron paramagnetic resonance (EPR) oximetry. Oxygen is found in most biomolecules that are essential to living organisms, and plays a role in a number of processes in both normal and altered physiology. Once implanted, the new probes will permit repeated, noninvasive measurement of oxygen concentration in tissues. The probes could be used to track growth and/or death of tumor tissues, progression of peripheral arterial disease and muscular atrophy, and wound healing response.
| Hou, Huagang; Khan, Nadeem; Gohain, Sangeeta et al. (2018) Pre-clinical evaluation of OxyChip for long-term EPR oximetry. Biomed Microdevices 20:29 |
| Hou, Huagang; Khan, Nadeem; Gohain, Sangeeta et al. (2017) Dynamic EPR Oximetry of Changes in Intracerebral Oxygen Tension During Induced Thromboembolism. Cell Biochem Biophys 75:285-294 |
| Caston, Rose M; Schreiber, Wilson; Hou, Huagang et al. (2017) Development of the Implantable Resonator System for Clinical EPR Oximetry. Cell Biochem Biophys 75:275-283 |
| Hou, H; Khan, N; Nagane, M et al. (2016) Skeletal Muscle Oxygenation Measured by EPR Oximetry Using a Highly Sensitive Polymer-Encapsulated Paramagnetic Sensor. Adv Exp Med Biol 923:351-357 |
| Swartz, Harold M; Williams, Benjamin B; Hou, Huagang et al. (2016) Direct and Repeated Clinical Measurements of pO2 for Enhancing Cancer Therapy and Other Applications. Adv Exp Med Biol 923:95-104 |
| Khan, Nadeem; Hou, Huagang; Swartz, Harold M et al. (2015) Direct and Repeated Measurement of Heart and Brain Oxygenation Using In Vivo EPR Oximetry. Methods Enzymol 564:529-52 |
| Ohanyan, Vahagn; Yin, Liya; Bardakjian, Raffi et al. (2015) Requisite Role of Kv1.5 Channels in Coronary Metabolic Dilation. Circ Res 117:612-621 |
| Khan, Nadeem; Hou, Huagang; Eskey, Clifford J et al. (2015) Deep-tissue oxygen monitoring in the brain of rabbits for stroke research. Stroke 46:e62-6 |
| Swartz, Harold M; Williams, Benjamin B; Zaki, Bassem I et al. (2014) Clinical EPR: unique opportunities and some challenges. Acad Radiol 21:197-206 |
| Rivera, Brian K; Naidu, Shan K; Subramanian, Kamal et al. (2014) Real-time, in vivo determination of dynamic changes in lung and heart tissue oxygenation using EPR oximetry. Adv Exp Med Biol 812:81-86 |
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