Author: Maciej M. Kmiec, Periannan Kuppusamy, Ryan C. O'Connell, Sergey V. Petryakov, Conner Ubert 👨🔬
Affiliation: Dartmouth College 🌍
Purpose: The rigid needle-like EPR sensor, OxyTrack, was developed to provide minimally invasive, reliable, and quantitative measurements of oxygen distribution (pO2) in deep tissues. EPR oximetry's current in-vivo applications are confined to measurements of approximately 2 centimeter in depth, owing to biological tissues' off-resonance absorption of RF waves. Improved EPR depth measurement from this sensor allows for a more accurate assessment of tumor hypoxia, potentially leading to better cancer treatment strategies.
Methods: The OxyTrack utilizes a stiff brass body shaped like a needle, housing a coaxial cable; the cable forms a small loop to hold the FDA-approved oxygen probe (OxyChip) to measure pO2. Calibration results showed exceptionally high accuracy and outstanding linearity, exhibiting a standard error of inverse prediction < ±1 mmHg pO2. Murine muscle tissue and a canine osteogenic sarcoma were used in live animal studies. EPR spectra were recorded using a custom-built L-band spectrometer, with the OxyTrack being inserted percutaneously.
Results: Measurements of pO2 in about 1 cm of mouse muscle tissue were obtained using the OxyTrack. The signal-to-noise ratios (SNR) in these measurements were exceptionally high (~50). Canine experiments demonstrated the sensor's capacity to penetrate the tumor, which proved its effectiveness. It penetrated to a depth of ~4 cm (depth limited by the tissue environment) and reported tissue oxygen heterogeneity across tumor sub-volumes. Of note, despite breathing 100% O2, an significant hypoxia persisted within the large tumor. The sensor's reusability was confirmed because its calibration curve remained stable following insertion.
Conclusion: OxyTrack's pO2 measurements were reliable up to approximately 4 cm in-vivo, while maintaining a high SNR, exceeding the current standard EPR oximetry. This highly sensitive pO2 sensor could assist many researcher and clinician investigations of tumor hypoxia, thereby informing and improving personalized cancer treatment.