PROJECT SUMMARY Knowledge of tissue oxygen levels has enormous clinical significance for accurate prognosis and treatment of several pathologies including cardiovascular diseases, stroke, wound healing, and cancer. Currently, there is an unmet need for devices that can measure oxygen reliably in the clinical settings. Although several methods are promising for clinical oximetry, they lack the ability to make reliable and repeated measurements of absolute values of oxygen, for example pO2, during or post-therapy. Oximetry based on electron paramagnetic resonance (EPR) offers certain unique advantages including accuracy, direct detection and high sensitivity and specificity to molecular oxygen (O2). Unfortunately, the adaptation of EPR oximetry for clinical measurements is faced with certain limitations, most notably due to restrictions that arise from the existing hardware. The conventional EPR systems are large, bulky units with restrictive spacing between the magnet poles (for patient placement) and require the patient to be transported to the EPR facility for measurements. Major changes in the hardware and more importantly out-side-the-box approaches in the overall design are needed to make the EPR technology a viable tool for use by bedside or at treatment site for successful clinical adaptation and implementation. The overall goal of this project is to develop an innovative device for on-site monitoring of pO2 in patients. We propose to construct a unique self-contained ultra-small, needle-shaped EPR probe-head, namely OxyTrack that can be used on-site, in the clinic or procedure room. In contrast to the existing EPR systems that contain a formidably large magnet thereby necessitating the patients transported to the EPR magnet, our innovative approach will use an extremely miniaturized magnet that is tightly integrated with resonator and oxygen-sensing probe, making a single unit (sensor). The integrated unit will be built inside the tip of a 21G syringe needle for minimally invasive insertion into tissues of interest. The EPR spectrometer, an external device connected to the OxyTrack needle, will be built based on state-of-the-art software-defined-radio (SDR) technology. We will assess the efficacy, reliability, and safety of the OxyTrack using tissue models and animals and validate the system performance using existing methods for oximetry. The specific aims of this project include: (i) Design and construction of an OxyTrack needle with built-in magnet, resonator, and oxygen sensor; (ii) Development of a compact spectrometer to work with the OxyTrack sensor; and (iii) Testing and validation of the OxyTrack system performance in vitro and in vivo. The OxyTrack oxygen sensor, when established as intended, will be a very valuable clinical tool for clinical conditions where tissue oxygen is a critical variable for decision making, e.g., cancer patients and patients with diabetic peripheral vascular diseases.

PROJECT NARRATIVE Ability to measure tissue oxygen levels has enormous clinical significance for reliable prognosis and treatment of several diseases, including cancer and vascular diseases. We propose to develop an innovative oxygen measurement device called OxyTrack for use in the clinic. The new device will be a valuable tool for clinical conditions where tissue oxygen is a critical variable for decision making, e.g., cancer patients and patients with diabetic peripheral vascular diseases.