Tooth Dosimetry

Tooth Dosimetry

A method is needed that can differentiate among doses of radiation sufficiently to classify individuals into subclasses for appropriate action and advice. Our approach is based on electron paramagnetic resonance (EPR), which specifically and sensitively responds to the presence of unpaired electrons. Ionizing radiation generates large numbers of unpaired electron species. While most of these react immediately and disappear, in some materials where diffusion is limited, the unpaired electrons can persist for long periods. Teeth are especially attractive because the signal intensity is strong, because of the high amount of crystalline matrix in enamel. With the recent development of lower frequency EPR (e.g. 1 GHz) for making measurements in vivo with good sensitivity, it becomes possible to assess the amount of irradiated dose in vivo.

Ex Vivo Fingernail Dosimetry

Clipped Fingernail Dosimetry

Fingernails are another attractive choice for a natural dosimeter. Like tooth enamel, the keratin in fingernails enables the measurement of radiation induced free radicals long after exposure. An individual's fingernails may be clipped and measured with EPR spectrometer, allowing measurements to be made with less direct involvement of the subject. Unfortunately, in addition to the radiation induced signal, there exist mechanically induced signals generated by the process of the clipping the fingernails. Being able to distinguish between these two sets of signals is one of the primary tasks of fingernail dosimetry. Currently, methods are being explored to separate the signals using different decomposition techniques, based on the kinetics, power saturation and line shapes of the signals.

In Vivo Fingernail Dosimetry

In Vivo Fingernail Dosimetry

Given that distinguishing between the radiation induced signal and the signals generated by clipping the nails is one of the main problems of fingernail dosimetry, the ability to be able to make measurements in vivo without needing to clip the nails is very attractive. Unfortunately, the small size of the samples and the close proximity of the lossy tissue of the finger make obtaining a sufficiently large signal difficult. Novel resonator designs, which limit the effects of the nearby tissue, have shown promise in the execution of these measurements.

Tumor Oximetry

Oximetry for Tumor Therapy

The concentration or partial pressure of oxygen (pO2) is a crucial factor affecting the response of tumors to irradiation and other cytotoxic treatments. Over the past decade, clinical studies using oxygen microelectrodes have demonstrated the potential value of measuring the pO2 in tumors in order to determine the probability that the tumors will respond to conventional radiation therapy. While these studies have demonstrated the clinical potential for such measurements, they also have shown the limitations of doing these measurements with oxygen electrodes. Such electrodes are difficult to use, involve a significant degree of invasiveness, have limited sensitivity, and, importantly, cannot be used for repeated measurements. As has been demonstrated in animals and humans, EPR oximetry can overcome all of these limitations; therefore, it may be the clinical tool of choice for such measurements.

Oximetry for Peripheral Vascular Disease

Oximetry for Peripheral Vascular Disease

The oxygen tension (pO2) in the tissues at risk in the diabetic foot is the parameter of greatest clinical importance. Currently there is no reliable method available to measure it, however, making it very difficult to evaluate the state of the disease and the response to therapeutic measures. The ability of EPR oximetry to make repeated non-invasive measurements of oxygen at several sites (after the initial placement of the paramagnetic material, India ink, at the sites of interest) would provide an important new way to improve the management of this disease, making it feasible to characterize the status of the disease, and to determine the effects of therapeutic intervention and progression of disease, based on the pO2 at critical sites. We have begun measurements in the human foot at the site of greatest risk in patients with diabetic peripheral vascular diseases.

Oximetry for Wound Healing

Oximetry for Wound Healing

There is a great need to improve wound healing in many patients, and this is likely to occur through a better understanding of key factors affecting the process. Oxygen is perhaps the most important variable in the healing of wounds, as has been shown empirically in patients and more specifically in animal models. With appropriate methods, animal models can be used to understand the fundamental molecular biology and physiology that affects wound healing. In collaboration with groups at UCSF and The U. of Texas Medical Branch at Galveston, we have been using the capabilities of EPR oximetry to measure oxygen in wounds repeatedly to understand basic phenomena involved in wound healing. It has become clear that in addition to being a very useful technique for studying wounds in animal models, it is quite feasible to adapt the technique to clinical applications.

EPR Hardware

Instrumental Development

Numerous hardware developments have been made in order to facilitate the above EPR measurements. Innovative L-band bridge designs allow for some of the only in vivo EPR measurements in the world. Great efforts have also been made to automate the task of taking EPR measurements. Automatic tuning and coupling will help to allow measurements to be made by non-expert users. For oximetry, the development of implantable resonators allows measurements on non-superficial tissues.