Clinical EPR: unique opportunities and some challenges

Abstract

Electron paramagnetic resonance (EPR) spectroscopy has been well established as a viable technique for measurement of free radicals and oxygen in biological systems, from in vitro cellular systems to in vivo small animal models of disease. However, the use of EPR in human subjects in the clinical setting, although attractive for a variety of important applications such as oxygen measurement, is challenged with several factors including the need for instrumentation customized for human subjects, probe, and regulatory constraints. This article describes the rationale and development of the first clinical EPR systems for two important clinical applications, namely, measurement of tissue oxygen (oximetry) and radiation dose (dosimetry) in humans. The clinical spectrometers operate at 1.2 GHz frequency and use surface-loop resonators capable of providing topical measurements up to 1 cm depth in tissues. Tissue pO2 measurements can be carried out noninvasively and repeatedly after placement of an oxygen-sensitive paramagnetic material (currently India ink) at the site of interest. Our EPR dosimetry system is capable of measuring radiation-induced free radicals in the tooth of irradiated human subjects to determine the exposure dose. These developments offer potential opportunities for clinical dosimetry and oximetry, which include guiding therapy for individual patients with tumors or vascular disease by monitoring of tissue oxygenation. Further work is in progress to translate this unique technology to routine clinical practice.

Keywords: Electron paramagnetic resonance; dosimetry; free radical; hyperoxygenation; oxygen; radiation therapy; tumor therapy.

Copyright © 2014 AUR. Published by Elsevier Inc. All rights reserved.

Figures

Figure 1. Clinical EPR system

(A) Our 1.2 GHz EPR spectrometer using a large-gap permanent magnet and surface loop resonator. Also shown is a moveable bed for patient positioning. (B) Measurement of tumor pO2 in a head & neck cancer patient suing surface loop resonator.

Figure 2. Implantable resonator design

Photograph of a 25-cm-long implantable resonator made of 34-AWG enamel-coated copper wire containing PDMS-encapsulated LiNc-BuO sensor at one end (Probe tip) and coupling loop at the other end. The inset shows an EPR spectrum obtained using the resonator.

Figure 3. In vivo tooth dosimetry using deployable EPR dosimeter

(A) 1.15 GHz EPR dosimeter setup. (B) Magnet, modulation coil, and resonator assembly. (C) Surface-loop resonator (~9-mm diameter loop). (D) Side view of the dosimeter with the person undergoing tooth measurement.

Figure 4. Photographs illustrating the position of fingers in resonators for in vivo nail dosimetry

(A) SRA resonator, (B) rectangular TE102 cavity aperture resonator (AR), and (C) hemispherical TE121 AR.