Normal tissue oxygen levels are critical to maintain homeostasis. Significant divergence from expected levels could serve as an indicator or confirmation of an underlying condition that may require intervention or more diligent monitoring. Despite the clinical significance and importance of tissue oxygenation levels in the diagnosis, prognosis, and treatment of several pathologies, there is clearly an unmet need for technologies to quantify tissue oxygen levels with a reasonable degree of accuracy, reliability, and robustness. The overall objective of this proposal is to bring the precision and consistency of electron paramagnetic resonance (EPR) oximetry to the clinical realm for easily-translatable measurements in cardiovascular, cancer, and cutaneous applications. In the past funding periods, we have discovered unique solid-state implants (probes) and procedures that enable unsurpassed accuracy and repeated interrogation of tissue oxygen levels at specific sites over a period of time, extending to months or longer. However, these measurements are limited primarily to laboratory research involving cells and small animals, the latter of which have known drawbacks in simulating human physiology. In the proposed funding period, we intend to build upon these innovations to translate this promising technology to the clinical realm. As a first ste toward this translation, we plan to develop at least three types of probes and procedures specifically intended for pO2 measurements in transcutaneous, subcutaneous, and deep tissue/organs. We will evaluate and validate the methods in pre- clinical, large animal models, and humans. We also propose to perform rigorous biocompatibility testing using a number of ISO/ASTM guidelines for implantable devices. The following specific aims are proposed: (i) Development of oxygen-sensing chips for continuous or long-term monitoring of pO2 in humans;(ii) Biocompatibility evaluation of oxygen-sensing chips for use in humans;(iii) Evaluation of oxygen-sensing chips for repeated pO2 measurements in preclinical animal models of disease and in humans;and (iv) Enabling technologies for making simultaneous oximetry measurements from multiple sites. When complete, the results from the proposed work will pave the way for subsequent clinical trials applying these innovative technologies for pO2 monitoring.
Disease and injury produce numerous changes in homeostasis, or the maintenance of a normal, healthy condition. One such change is the oxygen level in the affected tissues. Measurement of tissue oxygen is important in terms of diagnosis, long-term tracking, and treatment in a number of applications, including wound healing, cancer, and myocardial infarction (a heart attack). In this proposal, we intend to characterize and test several new, topical and implantable sensors designed for use in human patients to obtain information on the local oxygen level in tissues and organs.
|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 812:81-6|
|Swartz, Harold M; Williams, Benjamin B; Zaki, Bassem I et al. (2014) Clinical EPR: unique opportunities and some challenges. Acad Radiol 21:197-206|
|Swartz, Harold M; Hou, Huagang; Khan, Nadeem et al. (2014) Advances in probes and methods for clinical EPR oximetry. Adv Exp Med Biol 812:73-9|
|Madan, Esha; Gogna, Rajan; Kuppusamy, Periannan et al. (2013) SCO2 induces p53-mediated apoptosis by Thr845 phosphorylation of ASK-1 and dissociation of the ASK-1-Trx complex. Mol Cell Biol 33:1285-302|
|Gogna, R; Madan, E; Kuppusamy, P et al. (2012) Re-oxygenation causes hypoxic tumor regression through restoration of p53 wild-type conformation and post-translational modifications. Cell Death Dis 3:e286|
|Pandian, Ramasamy P; Chacko, Simi M; Kuppusamy, M Lakshmi et al. (2011) Evaluation of lithium naphthalocyanine (LiNc) microcrystals for biological EPR oximetry. Adv Exp Med Biol 701:29-36|
|Pandian, Ramasamy P; Meenakshisundaram, Guruguhan; Bratasz, Anna et al. (2010) An implantable Teflon chip holding lithium naphthalocyanine microcrystals for secure, safe, and repeated measurements of pO2 in tissues. Biomed Microdevices 12:381-7|
|Meenakshisundaram, Guruguhan; Eteshola, Edward; Blank, Aharon et al. (2010) A molecular paramagnetic spin-doped biopolymeric oxygen sensor. Biosens Bioelectron 25:2283-9|
|Sliman, Sean M; Eubank, Timothy D; Kotha, Sainath R et al. (2010) Hyperglycemic oxoaldehyde, glyoxal, causes barrier dysfunction, cytoskeletal alterations, and inhibition of angiogenesis in vascular endothelial cells: aminoguanidine protection. Mol Cell Biochem 333:9-26|
|Vikram, Deepti S; Rivera, Brian K; Kuppusamy, Periannan (2010) In vivo imaging of free radicals and oxygen. Methods Mol Biol 610:3-27|
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