Measurements of clinically significant doses of ionizing radiation using non-invasive In Vivo EPR spectroscopy of teeth in situThere are plausible circumstances (e.g. terrorism) in which populations could be exposed to doses of ionizing radiation that could cause direct clinical effects within days or weeks, but where there is no clear knowledge as to the magnitude of the exposure to individuals. The threshold for clinically significant doses is about 50 - 100 cGy). The measurement system needs to have an accuracy of about ±25 cGy and rely on changes that occur within the potentially exposed individual. About 50 years ago it was shown that the unpaired electrons induced in bones and teeth by ionizing radiation provide such a potential dosimeter, but that approach required removal of the teeth or bones for the assay. The development of in vivo EPR now makes it feasible to make such measurements in vivo. It is likely that many of the individuals will not have received clinically significant doses of radiation, while others may have been exposed to potentially life-threatening doses. A method is needed that can differentiate among doses 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. The lower frequency has greater tolerance for the presence of water and also has a relatively large sample volume. Our aim is to develop a method to obtain retrospective dose estimates for individuals sufficient to discriminate rapidly among exposures that are: 1. very unlikely to cause any acute symptoms (<50 cGy), 2. likely to lead to mild and delayed clinical symptomatology (75-150 cGy), 3. likely to lead to moderate to severe clinical symptomatology (150-300 cGy), 4. likely to lead to early severe clinical symptomatology with a potential for lethal outcome (>300 cGy), 5. very likely to lead to early death (>600 cGy) Methods The approach uses a lower frequency EPR spectrometer (1.2 GHz compared to the usual 9 GHz), which can accommodate a large object and, most importantly, does not cause unacceptable heating due to non-resonant absorption of the microwave. A resonator has been specially designed that can probe teeth in situ in the mouth, maximizing the amount of enamel that is probed, because most of the radiation-induced EPR signal is in the enamel. To permit rapid and comfortable positioning of the subject, we have developed a one-sided magnet system that comfortably and effectively can provide the required magnetic field in the teeth in the human head. Special data gathering and data processing procedures have been developed to maximize sensitivity and provide an output useable by modestly trained personnel. The challenges for the data gathering/processing aspects include the relatively low sensitivity of lower frequency EPR and the presence of a small but significant background signal in un-irradiated teeth. The components of the system have been designed to make it reasonably transportable by cart, with the total system weighing about 80 kg.
Figure 1: EPR spectra of human teeth at 1200 MHz. The spectra in the upper plot were obtained under the same conditions, after doses from 100 to 3,000 cGy. We also measured the signal of non-irradiated teeth and without any sample, which we term "Empty Resonator". In the lower plot are the spectra after subtraction of the background signals.
Figure 2: Normalization for variations in volume of teeth. Before normalization (left) the signal amplitude clearly correlates with tooth size. This can be compensated by applying a normalization factor hat is specific for each resonator (right).
Figure 3: Specialized resonators constructed for use with molar teeth (top row) and incisors (bottom row).
Figure 4: Signal/noise obtained on the same sample, in the same resonator, when placed inside the mouth of a volunteer, "intra oral", versus the same sample with the resonator in air, "extra oral".
Table 1: Comparison of S/N obtained from extra and intra oral measurements
Figure 5: Complete resonators for use with incisors (left) and molars (right), including the transmission arm, adjustable coupling, and automatic frequency control.
Figure 6: (left) The resonator for incisors installed in the mouth of a volunteer. (right) The resonator for molars installed on an irradiated human molar.
Figure 7: A special device was constructed to hold the head of a patient and position the resonator for tooth dosimetry. Summary of Dosimeter In its current state, the in vivo EPR dosimeter can provide estimates of absorbed dose of ± 25 cGy in the range of 100 - >1,000 cGy. This is expected to improve, with improvements in the resonator, the algorithm for calculating dose, and the uniformity of the magnetic field. It is sufficient for most applications related to terrorism or nuclear warfare, for decision-making for action for individuals in regard to acute effects from exposure to ionizing radiation. It should be emphasized that this approach is designed for the rapid triage of potentially exposed individuals into categories for which appropriate actions can be taken in regard to expected short term consequences of the exposure to ionizing radiation. In this respect this approach appears to have significant advantages over any other known approach because of its appropriate rapidity, sensitivity, and accuracy for the purpose. |