Clinical applications of in vivo EPR: Rationale and initial results

Abstract

In vivo electron paramagnetic resonance (EPR) has been very useful for studies in animals, and these results suggest that tbere are some very attractive potential applications in human subjects. In this article, we describe our rationale for the clinical application of in vivo EPR, some of the principal technical challenges, the initial results in human subjeets, and our evaluation of the areas where in vivo EPR is likely to play ah important clinical role in the near future. The most obvious area of very high potential for clinical applications is tissue oximetry, where in vivo EPR can provide repeated and accurate measurements of tissue pO 2, a type of measurement tbat cannot be obtained by other techniques. Oximetry is capable of providing clinieians with information that can impact directly on diagnosis and therapy, especiaUy for peripheral vascular disease, oncology, and wound healing. The other area of great immediate importance is the ability of in vivo EPR to measure clinically significant exposures to ionizing radiation after the fact, which may occur due to accidents, terrorist activity, or nuclear war. The results obtained already from human subjects demonstrate the feasibility of the use of in vivo EPR for measurements in human subjects. We anticipate that in vivo EPR will play a vital role in the clinical management of various pathologies in the years to come. Rationale and Our Approaeh for the Clinical Applications of In Vivo EPRIn vivo electron paramagnetic resonance (EPR) has been apptied successfully and extensively to measure important physiologic parameters in animal models such as tissue pO 2, free radicals, pH, perfusion, and redox status [1]. It seems clear that measurements of many of these parameters could be utilized effectively to advance medical care, with the potential to improve significantly diagnosis and therapy. We therefore have undertaken an active research program to determine fully the methodology needed to make such measurements and to establish the usefulness of such measurements.We believe that the key step for the successful clinical use of in vivo EPR is to establish application(s) where EPR has clear advantages, either by providing unique information or by demonstrating that it can provide information more

Repetitive Tissue pO2 Measurements by Electron Paramagnetic Resonance Oximetry: Current Status and Future Potential for Experimental and Clinical Studies

“…Results indicate that the SAR measured in our clinical setup is well below the established limits (53). We have initiated the clinical studies using India ink as an oximetry probe, which is sensitive to tissue pO 2 , is very stable in tissue, and already has been approved for use in human subjects (8,37,38,61). This ink is prepared using components that are already in use in various pharmaceutical preparations.…”

“…These are metabolically inert and are very sensitive for measuring low levels of oxygen. Once introduced in the tissue of interest, they allow repeated measurement of pO 2 at the same site for up to years after implantation (37,38,61). The region of the sample that is measured directly is that immediately surrounding the paramagnetic material.…”

Tissue oxygenation in a murine SCC VII tumor after X-ray irradiation as determined by EPR spectroscopy

“…This is especially needed because it is now feasible to measure tumor pO 2 in patients [14,15]. In this study we measured the reoxygenation response in SCC VII tumors of mice after X-ray irradiation at various doses.…”

Burn trauma in skeletal muscle results in oxidative stress as assessed by in vivo electron paramagnetic resonance

“…The development of low frequency (1200 MHz and below) EPR spectrometers has led to the in vivo application of the technique in a variety of animal models. The most extensive applications of in vivo EPR have been repeated non-invasive measurements of oxygen, nitric oxide, free radicals, pH and tissue redox status (1)(2)(3)(4)(5)(6)(7)(8)(9). EPR in vivo has significantly contributed to the understanding of various pathological changes, and has the potential to become an important clinical tool (4,9).…”

“…The potential significance of our findings include the in vivo non-invasive nature of the EPR measurements, which can serve to follow tissue pathology and to monitor the effectiveness of antioxidant agents in order to alleviate the symptoms of severe burn trauma. With the development and application of in vivo EPR oximetry in clinical settings (4,9), its potential application in the clinical management of burn injury, alongside NMR, might also prove to be very useful.…”