Radiation Protection Dosimetry Advance Access published April 16, 2015 Radiation Protection Dosimetry (2015), pp. 1–6
doi:10.1093/rpd/ncv165
ENVIRONMENTAL MICRODOSIMETRY: MICRODOSIMETRIC CHARACTERISATION OF LOW-DOSE EXPOSURES A. J. Waker*, T. Mahilrajan and H. Sandhu Faculty of Energy Systems and Nuclear Science, UOIT, 2000 Simcoe Street North, Oshawa, ON, Canada L1H 7K4 *Corresponding author: [email protected]
INTRODUCTION Beginning from the early days of experimental microdosimetry, the importance of the event frequency or the mean number of events per unit dose, w, as a measure of the stochastic character of radiation interaction was recognised and reported along with other microdosimetric averages such as the frequency mean and dose mean of the specific energy(1). To promote a wider understanding of low-dose exposures in general, others have emphasised the use of microdosimetric concepts and quantities to reveal the stochastic characteristics of radiation interaction on the cellular scale(2), and recently, the International Commission on Radiation Units and Measurements has recommended that in cases where the energy distribution of particle irradiance cannot be deduced or measured, lineal energy and energy deposition event rates may be the best way to quantify low-dose and other heterogeneous exposures(3). The concepts of microdosimetry are not necessarily self-evident to the general health physics community, and this article seeks to examine the microdosimetric basis of low-dose exposure within the framework of conventional internal dosimetry and to determine their compatibility. The examples used are low-dose exposure to radioactive isotopes of iodine such that can be released into the environment from reactor accidents and spent-fuel reprocessing activities. BACKGROUND Macroscopic dose expressed in microdosimetric terms Absorbed dose is an average non-stochastic quantity, which nevertheless, can be expressed in terms of averaged stochastic quantities such as the mean number of
individual energy deposition events or ‘hits’ experienced by micro-masses or ‘cells’ in a given tissue, as well as the fraction of these micro-masses in the tissue that actually experience these events for a given exposure of a given radiation quality or type. Following Bond, Feinendegen and Booz(2), D ¼ h d F1 ;
ð1Þ
where h is the mean number of hits in sites that have experienced at least one hit, d is the mean specific energy from single events in micro-masses of specified size—the micro-dose and F1 is the fraction of micromasses in the exposed tissue experiencing at least one event during the exposure that leads to the tissue dose of D. Derivation of Equation 1 is given in the Appendix; Table 1 shows the outcome of applying Equation 1. In this example, the dose mean specific energy has been obtained from measured single-event spectra for 60Co and low-energy neutrons for 8 mm diameter micro-masses. This site size was chosen as representative of the mammalian cell nuclear diameter. The mean specific energy used for 60Co was actually for a site size of 7.7 mm(4), and the mean specific energy for the low-energy neutrons was obtained by extrapolating experimental data beyond those reported for site diameters between 0.25 and 4 mm(5). From Table 1, the effect of radiation quality on the stochastic nature of the exposures is clearly seen. For high-energy gamma rays at an exposure of 5 mSv, all the micro-masses experience at least one hit and above that dose the mean hit number for each cell nucleus increases proportionately with the dose. For low-energy neutrons, such that may be encountered in a nuclear workplace environment, it is not until an exposure of around 100 mSv that all micro-volumes are
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A number of researchers, as well as the International Commission on Radiation Units and Measurements, have described how concepts and quantities used in microdosimetry best capture the stochastic nature of low-level exposures in terms of cell hits and the fraction of cells affected within a tissue. However, the concepts of microdosimetry are not generally intuitive to the public or indeed to health physicists. In this article, the methods of conventional internal dosimetry was applied to different forms of radioactive iodine to derive cell-hit numbers and cell fractions affected by low-level exposures, and it is shown that microdosimetric analysis is compatible with conventional dosimetry but has the advantage of underscoring the stochastic nature of ionising radiation at low dose. The microdosimetric description of low-dose exposures derived in this work could be improved with the use of Monte Carlo track structure codes and more realistic models of different tissues and their cellular structure.
A. J. WAKER ET AL. Table 1. Mean event numbers and fractions of cells receiving at least one ‘hit’ for two different qualities of radiation (60Co gamma rays and fast neutrons) for macroscopic doses ranging from 0.1 to 500 mGy. 60 Co 8 mm d (mGy)
440 keV neutrons 8 mm d (mGy)
0.816
30.47
D (mGy) h F1
0.1 1.06 0.12
0.18 1.1 0.20
0.5 1.3 0.46
1 1.7 0.71
3 3.8 0.97
5 6.1 1.00
10 12.3 1.00
50 61.3 1.00
100 122.5 1.00
500 612.7 1.00
D (mGy) h F1
0.1 1.00 0.003
0.18 1.00 0.006
0.5 1.01 0.016
1 1.02 0.032
3 1.05 0.094
5 1.08 0.151
10 1.17 0.280
50 2.04 0.806
100 3.41 0.962
500 16.41 1.000
Table 2. Classification of exposures to 60Co low-LET radiation in terms of the fraction of the cell population receiving at least one hit, F1, and the mean number of events in each hit cell, h.
Microdosimetric classification of low-dose exposure
Dose (mGy)
Describing the macroscopic adsorbed dose in microdosimetric terms also provides a useful means of classifying different levels of exposure in a manner that captures the stochastic properties inherent in the exposure. Applying Equation 1 to three commonly considered exposure levels, namely; (a) the lowest dose at which there is evidence of elevated carcinogenic risk for acute exposure to high-energy gamma rays, 50 mSv(6); (b) typical background radiation levels of around 3 mSv and (c) natural environmental exposure to K-40, around 0.18 mSv(7). As shown in Table 2, F1 and h values derived from experimental data for 60Co gamma rays for a site size of 8 mm change considerably between exposures that have yielded meaningful epidemiological data and exposures at background or environmental levels. Natural environmental exposure to K-40, for example, results on average in only 20 % of the micromass population receiving only one hit compared with all micro-masses being hit on average some 60 times for a 50 mSv exposure. These extremes of lowlevel exposure also impact on the discussion concerning non-targeted effects where ‘bystander effects’ are reserved for exposure situations where the radiation dose is low enough to spare some cells in the population from direct energy deposition and ‘cohort effects’ for exposures where all cells are multiply hit in the course of the exposure(8). Another factor of crucial importance in describing the stochastic nature of radiation will be the dose rate, which will determine the average time between events in cells. MICRODOSIMETRY AND INTERNAL DOSIMETRY Test cases: 129I and 131I 129 I and 131I are two radioactive isotopes that can make their way into the environment as a result of nuclear power operations. 129I is a very long-lived fission product that is mainly of concern in
0.18 3 50
Fraction of cells ‘hit’ (F1)
Mean number of events (d)
0.2 0.97 1.0
1.1 3.8 61.3
discussions around the safe storage or reprocessing of spent nuclear fuel, whereas 131I is a short-lived fission product released into the environment as a result of reactor accidents such as the Windscale fire (1956), Chernobyl (1986) and Fukushima (2011). The standard method for calculating the committed effective dose (CED) from intakes of radioactive isotopes is to employ an internal dosimetry code that uses internationally agreed biokinetic models to estimate the uptake by various organs of the body. The committed equivalent dose is first calculated for each organ from the isotopic emissions and the total number of disintegrations occurring in a particular organ. When these committed equivalent doses are weighted by the appropriate tissue weighting factors for each organ and summed over all organs, the CED is obtained. An internal dosimetry code often employed for internal dosimetry calculations and used extensively in Canadian nuclear utilities is Integrated Modules for Bioassay Analysis (IMBA)(9). Using IMBA and the derived values for the thyroid uptake resulting in a whole-body CED of 1 mSv, the total number of disintegrations of the iodine isotopes in the thyroid has been estimated, and from these values, mean cell-hit numbers have been derived along with the fraction of the thyroid cell population affected by the exposure. These results are then compared with the same quantities derived directly from microdosimetric analysis. An exposure of 1 mSv was chosen as a test case as this represents a public dose limit. A more realistic scenario of a radioactive iodine exposure would be one related to a power reactor melt-down, consequently cell-hit numbers and cell population fractions of hit cells have also been estimated for
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hit at least once and the mean hit number is only around 3 compared with 122 in the case of gamma rays.
ENVIRONMENTAL MICRODOSIMETRY
reported exposures to Fukushima incident.
131
I as a result of the
1mSv Public Dose Limit Exposure: 129I and 131I
Table 3. Physical and biological data for thyroid gland. 129
I Effective decay constant, lE ¼ 1` 1027 s21 b ¼ 50 keV E Rbav ¼ 43.2 mm Cells hit per beta decay (43.2/15) ¼ 2.9 131
I Effective decay constant, lE ¼ 1.1` 1026 s21 b ¼ 202 keV E Rbav ¼ 448 mm Cells hit per beta decay (448/15) ¼ 29
129
I,
131
I and the
Thyroid mass ¼ 20 g Thyroid volume 18.7 cm3 Average cell diameter 15 mm No of thyroid cells ¼ 1.03` 1010
The Fukushima exposure: 131I Given the agreement obtained earlier, it is interesting to apply the same methods to a more realistic environmental exposure such as resulted from the reactor releases from Fukushima. Thyroid equivalent doses at Ibraki, Japan, have been estimated by Priest (10) to be 5.9 mSv. Using IMBA, a thyroid equivalent dose of 5.9 mSv results from a thyroid uptake of 10.96 kBq. Using the same methods as outlined earlier and the same values for biological and microdosimetric parameters for 131I, a mean cell-hit number of 28 is obtained from conventional internal dosimetry and from microdosimetry 16, with all cells in the thyroid receiving at least one hit. Again, a similar discrepancy was seen between the two values that, as stated earlier, most likely results from the overestimation of the number of cells hit by a single beta particle. It is interesting to note that even at environmental exposure levels of 131I, resulting in CEDs of about 0.3 mSv, such as at Ibraki, the whole thyroid cell population is affected with each cell experiencing multiple beta particle interactions. Clearly, dose rate will be a significant issue concerning the response of the tissue to these multiple events, and this will be discussed briefly later in the Discussion section.
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The 129I intake for a whole-body committed effective does of 1 mSv given by IMBA is 2.72` 104 Bq, which results in a thyroid uptake of 1.06` 104 Bq (39 %). Using the physical and biological data given in ~ in Table 3, the total number of 129I disintegrations, A, thyroid tissue is estimated to be 1.06` 1011, where ~ ¼ Að0Þ=lE , A(0) is the initial activity and lE is the A effective decay constant of 129I in the body. The number of cells in the thyroid has been estimated to be 1.03` 1010 by dividing the volume of the thyroid by the volume of an individual follicular cell with an assumed diameter of 15 mm. Finally, the mean number of hits per cell has been calculated by taking the number of 129I disintegrations over the exposure period multiplied by the number of cells hit by each beta particle, 2.9 (estimated by dividing the range of the beta particle by the cell diameter) and dividing the resulting ‘number of cells hit’ by the total number of cells in the thyroid. This estimate gives the mean number of hits per cell in the thyroid for the whole-body exposure of 1 mSv as 30. The microdosimetric calculation of the same quantity can be arrived at in the following manner. With the assumption that the only tissue affected by the iodine intake is the thyroid and using a tissue weighting factor WT of 0.05, the equivalent dose to the thyroid for an exposure resulting in a whole-body effective dose of 1 mSv is 20 mSv. With a macroscopic dose of 20 mGy (WR ¼ 1 for beta particles) and a mean specific energy of 0.852 mGy (estimated by extrapolating measured yF values for 36 keV photons(4) to a simulated diameters of 15 mm) the fraction of thyroid cells receiving at least one hit is obtained using the Poisson statistics with F1 ¼(12e2D/d) and is 1, which in turn gives a value for the mean number of hits per cell as D/dF1 ¼ 23.5. Thus, the agreement between the internal dose calculation and the microdosimetric
analysis is reasonable when considering the assumptions and simplifications made in the analysis. A similar calculation both by internal dosimetry and microdosimetric analysis was carried out for 131I; the physical and biological data for this calculation are also given in Table 3. The total number of disintegrations derived from IMBA for the 1 mSv 131I CED was estimated to be of 3.4` 1010. The mean number of hits per cell derived from the internal dosimetry calculation was found to be 96, whereas the mean number of hits per cell derived from microdosimetry was calculated to be 55; once again, a value for the mean specific energy was obtained by extrapolation of experimental data of Kliauga and Dvorak(4). Although the agreement in cell-hit numbers is less good, the values are of the same order and the difference is most likely accountable by the fact that in the internal dosimetry calculation the mean number of cells hit by a single beta particle is estimated by dividing the range of the beta particle by the cell diameter. This estimation takes no account of the actual track structure and is likely to be less precise as the range of the beta particle increases beyond a few cell diameters. Overall, however, the agreement between conventional dosimetry and microdosimetry is reasonable and provides some confidence that measured microdosimetric parameters such as the frequency mean specific energy can be used to gain insight into the stochastic nature of a given low-dose exposure.
A. J. WAKER ET AL.
TISSUE AND TRACK MODELLING
Figure 1. The tissue model constructed with a 5` 5` 5 array of hexagonally close-packed array of cells 20 mm in diameter and each containing an 8 mm diameter nucleus. Table 4. Results from modelling 48 keV electron tracks emitted at the centre of the hexagonally close-packed cellular array depicted in Figure 1. Total cellular volume Total extra-cellular volume Mean number of hits per hit cell Per cent nucleus hits to whole-cell hits Extra-cellular space hits to whole-cell hits
5.2` 105 mm3 3.7` 105 mm3 3.34 12.2 % 29 %
DISCUSSION AND CONCLUSIONS In this article, it has been shown that a microdosimetric description of low-dose exposures is compatible with more conventional internal dosimetric analysis and that using measurable microdosimetric quantities low-dose exposures can be classified into categories representing different levels of cell-hit numbers and fractions of the tissue cell population experiencing at least one event. Thus, microdosimetric descriptions of low-dose exposures reveal the underlying stochastics of radiation interaction that will be important in determining the biological outcome (tissue response) of the irradiation. In this context, it is useful to be reminded that when it comes to environmental exposures, the general public do not necessarily think in a stochastic manner or that a tissue response might be completely different than at higher doses where radiation energy is more or less spread evenly among all cells within the tissue. This lack of use of stochastic information is also the case in conventional internal dosimetry where sophisticated biokinetic models and mathematical phantoms nevertheless calculate only the total energy deposited in a given organ and hence the average quantity absorbed dose to that organ. This approach is quite reasonable for acute exposures that lead to all cells being hit multiple times, more or less at the same time as was the case for atomic bomb survivors, from which current radiation risk factors are mainly derived. Conventional dosimetry becomes more questionable, however, for exposures where the dose is low enough that only a small fraction of cells within a tissue are hit and on average not much more than once. In this article, the issue of dose rate has not been directly addressed. Referring to Table 2 one could argue that for situations where few cells are hit and never more than once or where all cells are hit, but again on average not much more than once that dose rate is not likely to be a significant factor in the final tissue response. However, for exposures where all cells are hit multiple times, dose rate is very likely to be a factor. Consider a 50 mSv exposure to high-energy gamma rays where all cells are hit on average 60 times, with a Poisson probability distribution encompassing
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In the derivation of Equation 1 given in the Appendix, the tissue block is divided into an integer number of micro-masses with no interstitial spaces. This is not a particularly realistic description of tissue, and as it has been already noted, there is also an error associated with unrealistic descriptions of beta particle track lengths. Both these deficiencies need to be addressed by more realistic models of tissue and particle tracks. To investigate more realistic radiation –tissue interactions, a tissue model has been constructed consisting of a 5` 5` array of hexagonally close-packed spherical cells of 20 mm in diameter with each cell containing a spherical nucleus of 8 mm in diameter and the Monte Carlo code Penelope(11) has been used to model the interaction of 48 keV electron tracks emitted at the centre of the cell cluster. Figure 1 shows the tissue model used, and Table 4 gives the results of the track modelling. From Table 4, it is clear that the simple division of a tissue mass into equal micro-masses is inadequate. The extra-cellular volume is significant and accounts
for 71 % of the total volume occupied by the ‘cells’, but the number of hits in this inter-cellular space is only about a third of the number hits experienced by the cellular micro-masses, so surface area as well as volume must be significant in determining the number of events within a given micro-mass or other tissue compartment. It is also interesting to note from Table 4 that the fraction of hits to cell nuclei is only some 12 % of the total number of whole-cell hits for this particular tissue model. Such information will have an impact on discussions concerning targeted and non-targeted effects and the overall tissue response.
ENVIRONMENTAL MICRODOSIMETRY
(1) To date, most microdosimetric measurements have been carried out for simulated diameters of 1 –2 mm, and apart from a few early studies, there are little or no data for site sizes of nuclear or cellular dimensions, 8 –25 mm say, for different radiation qualities. (2) More realistic tissue models are required along with Monte Carlo track structure simulations to compute more geometrically realistic microdosimetric parameters. This information is required not only to compare with experimental microdosimetric methods but also to be used in cases where direct measurements may not be possible or very difficult such as with low-energy beta particles. (3) Novel radiobiological experiments are required that investigate the effect of exposures that mimic the partial or fractional irradiation of tissue at low dose compared with exposures where all cells within the tissue are hit multiple times. (4) Under exposure conditions where all cells within a tissue are hit multiple times, radiobiological experiments are required that can investigate dose rate and the significance of the time interval between the individual events within cells.
4. Kliauga, P. and Dvorak, R. Microdosimetric measurements of ionization by monoenergetic photons. Radiat. Res. 73(1), 1 –20 (1978). 5. Srdoc, D. and Marino, S. Microdosimetry of monoenergetic neutrons. Radiat. Res. 146(4), 466– 474 (1996). 6. Brenner, D. J. et al. Cancer risks attributable to low doses of ionizing radiation: assessing what we really know. PNAS. 100(24), 13761– 13766 (2003). 7. Peterson, J., MacDonell, M., Haroun, L. and Monette, F. Radiological and Chemical Fact Sheets to Support Health Risk Analyses for Contaminated Areas – Potassium 40. Argonne National laboratory Environmental Sciences Division (2007). Available on http://www.remm.nlm. gov/ANL_ContaminantFactSheets_All_070418.pdf (Last accessed on April 2015). 8. Blyth, B. J. and Sykes, P. J. Radiation-induced bystander effects: what are they, and how relevant are they to human radiation exposures? Radiat. Res. 176, 139–157 (2011). 9. IMBAw Professional Plus Internal Dosimetry Software. Public Health England.Available on https://www.pheprotectionservices.org.uk/imba/ (Last accessed on April 2015) 10. Priest, N. D. Radiation doses received by adult Japanese populations living outside Fukushima prefecture during March 2011, following the Fukushima 1 nuclear power plant failures. J. Environ. Radioact. 114, 162–170 (2012). 11. Salvat, S., Fernandez-Varea, J. M. and Sempau, J. PENELOPE-2011: A Code System for Monte-Carlo Simulation of Electron and Photon Transport. OECD, Nuclear Energy Agency (2011). Available on http:// www.oecd-nea.org/tools/abstract/detail/nea-1525 (Last accessed on April 2015).
APPENDIX Relationship between absorbed dose, D; frequency mean specific energy, d and fraction of micro-masses experiencing at least one event F1. Consider a block of tissue subdivided into N micromasses each of mass m (kg).
ACKNOWLEDGEMENTS Funding for this work has been provided by the University Network of Excellence in Nuclear Engineering (UNENE), the Natural Sciences and Engineering Research Council of Canada and the Ontario Research Fund. A number of undergraduate students at UOIT are thanked for their early contributions to the problem of low-dose exposures and in particular Anupama Bulkan, David Wallace and Manirul Islam.
The absorbed dose (J kg – 1) to the tissue slab is given by
REFERENCES 1. Ellet, W. H. and Braby, L. A. The microdosimetry of 250 kVp and 65 kVp x-rays, 60Co gamma rays and tritium beta particles. Radiat. Res. 51(2), 229–243 (1972). 2. Bond, V. P., Feinendegen, L. E. and Booz, J. What is a low dose of radiation? Int. J. Radiat. Biol. 53(1), 1–12 (1988). 3. ICRU Report No. 86, Quantification and reporting of low-dose and other heterogeneous exposures. Journal of the ICRU. 11(2), 61–63 (2011).
D¼
S1 ; N:m
where e is the imparted energy [J] to a tissue micromass, and N is the total number of such micro-masses or ‘cells’. 1 will depend on the mean number of energy deposition events, h, in a cell and on the size of the energy
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this mean value resulting in some cells receiving considerably more than 60 hits. It is not unreasonable to think that the biological outcome may be different between a population exposed acutely to 50 mSv and an environmental or occupational exposure over the course of a year say where on average the cells receive one hit every 146 h, which is very long compared with the time constants associated with common cellular repair mechanisms. The relatively straightforward microdosimetric analysis described in this article highlights a number of topics that would benefit from further research effort. These are as follows:
A. J. WAKER ET AL.
deposition. It is convenient to write Se as
Substituting into the expression for absorbed dose,
h:NH
S1 ; h NH
D¼
where (S1/h.NH) is the mean imparted energy per event per hit cell, and [(S1/ h.NH)/m] is the mean specific energy per event per hit cell, d (J kg – 1).
ðh NH dÞ ; N
and NH/N is the fraction of cells in the tissue receiving at least one ‘hit’, F1, and so D ¼ h d F1 :
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doi:10.1093/rpd/ncv165
ENVIRONMENTAL MICRODOSIMETRY: MICRODOSIMETRIC CHARACTERISATION OF LOW-DOSE EXPOSURES A. J. Waker*, T. Mahilrajan and H. Sandhu Faculty of Energy Systems and Nuclear Science, UOIT, 2000 Simcoe Street North, Oshawa, ON, Canada L1H 7K4 *Corresponding author: [email protected]
INTRODUCTION Beginning from the early days of experimental microdosimetry, the importance of the event frequency or the mean number of events per unit dose, w, as a measure of the stochastic character of radiation interaction was recognised and reported along with other microdosimetric averages such as the frequency mean and dose mean of the specific energy(1). To promote a wider understanding of low-dose exposures in general, others have emphasised the use of microdosimetric concepts and quantities to reveal the stochastic characteristics of radiation interaction on the cellular scale(2), and recently, the International Commission on Radiation Units and Measurements has recommended that in cases where the energy distribution of particle irradiance cannot be deduced or measured, lineal energy and energy deposition event rates may be the best way to quantify low-dose and other heterogeneous exposures(3). The concepts of microdosimetry are not necessarily self-evident to the general health physics community, and this article seeks to examine the microdosimetric basis of low-dose exposure within the framework of conventional internal dosimetry and to determine their compatibility. The examples used are low-dose exposure to radioactive isotopes of iodine such that can be released into the environment from reactor accidents and spent-fuel reprocessing activities. BACKGROUND Macroscopic dose expressed in microdosimetric terms Absorbed dose is an average non-stochastic quantity, which nevertheless, can be expressed in terms of averaged stochastic quantities such as the mean number of
individual energy deposition events or ‘hits’ experienced by micro-masses or ‘cells’ in a given tissue, as well as the fraction of these micro-masses in the tissue that actually experience these events for a given exposure of a given radiation quality or type. Following Bond, Feinendegen and Booz(2), D ¼ h d F1 ;
ð1Þ
where h is the mean number of hits in sites that have experienced at least one hit, d is the mean specific energy from single events in micro-masses of specified size—the micro-dose and F1 is the fraction of micromasses in the exposed tissue experiencing at least one event during the exposure that leads to the tissue dose of D. Derivation of Equation 1 is given in the Appendix; Table 1 shows the outcome of applying Equation 1. In this example, the dose mean specific energy has been obtained from measured single-event spectra for 60Co and low-energy neutrons for 8 mm diameter micro-masses. This site size was chosen as representative of the mammalian cell nuclear diameter. The mean specific energy used for 60Co was actually for a site size of 7.7 mm(4), and the mean specific energy for the low-energy neutrons was obtained by extrapolating experimental data beyond those reported for site diameters between 0.25 and 4 mm(5). From Table 1, the effect of radiation quality on the stochastic nature of the exposures is clearly seen. For high-energy gamma rays at an exposure of 5 mSv, all the micro-masses experience at least one hit and above that dose the mean hit number for each cell nucleus increases proportionately with the dose. For low-energy neutrons, such that may be encountered in a nuclear workplace environment, it is not until an exposure of around 100 mSv that all micro-volumes are
# The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: [email protected]
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A number of researchers, as well as the International Commission on Radiation Units and Measurements, have described how concepts and quantities used in microdosimetry best capture the stochastic nature of low-level exposures in terms of cell hits and the fraction of cells affected within a tissue. However, the concepts of microdosimetry are not generally intuitive to the public or indeed to health physicists. In this article, the methods of conventional internal dosimetry was applied to different forms of radioactive iodine to derive cell-hit numbers and cell fractions affected by low-level exposures, and it is shown that microdosimetric analysis is compatible with conventional dosimetry but has the advantage of underscoring the stochastic nature of ionising radiation at low dose. The microdosimetric description of low-dose exposures derived in this work could be improved with the use of Monte Carlo track structure codes and more realistic models of different tissues and their cellular structure.
A. J. WAKER ET AL. Table 1. Mean event numbers and fractions of cells receiving at least one ‘hit’ for two different qualities of radiation (60Co gamma rays and fast neutrons) for macroscopic doses ranging from 0.1 to 500 mGy. 60 Co 8 mm d (mGy)
440 keV neutrons 8 mm d (mGy)
0.816
30.47
D (mGy) h F1
0.1 1.06 0.12
0.18 1.1 0.20
0.5 1.3 0.46
1 1.7 0.71
3 3.8 0.97
5 6.1 1.00
10 12.3 1.00
50 61.3 1.00
100 122.5 1.00
500 612.7 1.00
D (mGy) h F1
0.1 1.00 0.003
0.18 1.00 0.006
0.5 1.01 0.016
1 1.02 0.032
3 1.05 0.094
5 1.08 0.151
10 1.17 0.280
50 2.04 0.806
100 3.41 0.962
500 16.41 1.000
Table 2. Classification of exposures to 60Co low-LET radiation in terms of the fraction of the cell population receiving at least one hit, F1, and the mean number of events in each hit cell, h.
Microdosimetric classification of low-dose exposure
Dose (mGy)
Describing the macroscopic adsorbed dose in microdosimetric terms also provides a useful means of classifying different levels of exposure in a manner that captures the stochastic properties inherent in the exposure. Applying Equation 1 to three commonly considered exposure levels, namely; (a) the lowest dose at which there is evidence of elevated carcinogenic risk for acute exposure to high-energy gamma rays, 50 mSv(6); (b) typical background radiation levels of around 3 mSv and (c) natural environmental exposure to K-40, around 0.18 mSv(7). As shown in Table 2, F1 and h values derived from experimental data for 60Co gamma rays for a site size of 8 mm change considerably between exposures that have yielded meaningful epidemiological data and exposures at background or environmental levels. Natural environmental exposure to K-40, for example, results on average in only 20 % of the micromass population receiving only one hit compared with all micro-masses being hit on average some 60 times for a 50 mSv exposure. These extremes of lowlevel exposure also impact on the discussion concerning non-targeted effects where ‘bystander effects’ are reserved for exposure situations where the radiation dose is low enough to spare some cells in the population from direct energy deposition and ‘cohort effects’ for exposures where all cells are multiply hit in the course of the exposure(8). Another factor of crucial importance in describing the stochastic nature of radiation will be the dose rate, which will determine the average time between events in cells. MICRODOSIMETRY AND INTERNAL DOSIMETRY Test cases: 129I and 131I 129 I and 131I are two radioactive isotopes that can make their way into the environment as a result of nuclear power operations. 129I is a very long-lived fission product that is mainly of concern in
0.18 3 50
Fraction of cells ‘hit’ (F1)
Mean number of events (d)
0.2 0.97 1.0
1.1 3.8 61.3
discussions around the safe storage or reprocessing of spent nuclear fuel, whereas 131I is a short-lived fission product released into the environment as a result of reactor accidents such as the Windscale fire (1956), Chernobyl (1986) and Fukushima (2011). The standard method for calculating the committed effective dose (CED) from intakes of radioactive isotopes is to employ an internal dosimetry code that uses internationally agreed biokinetic models to estimate the uptake by various organs of the body. The committed equivalent dose is first calculated for each organ from the isotopic emissions and the total number of disintegrations occurring in a particular organ. When these committed equivalent doses are weighted by the appropriate tissue weighting factors for each organ and summed over all organs, the CED is obtained. An internal dosimetry code often employed for internal dosimetry calculations and used extensively in Canadian nuclear utilities is Integrated Modules for Bioassay Analysis (IMBA)(9). Using IMBA and the derived values for the thyroid uptake resulting in a whole-body CED of 1 mSv, the total number of disintegrations of the iodine isotopes in the thyroid has been estimated, and from these values, mean cell-hit numbers have been derived along with the fraction of the thyroid cell population affected by the exposure. These results are then compared with the same quantities derived directly from microdosimetric analysis. An exposure of 1 mSv was chosen as a test case as this represents a public dose limit. A more realistic scenario of a radioactive iodine exposure would be one related to a power reactor melt-down, consequently cell-hit numbers and cell population fractions of hit cells have also been estimated for
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hit at least once and the mean hit number is only around 3 compared with 122 in the case of gamma rays.
ENVIRONMENTAL MICRODOSIMETRY
reported exposures to Fukushima incident.
131
I as a result of the
1mSv Public Dose Limit Exposure: 129I and 131I
Table 3. Physical and biological data for thyroid gland. 129
I Effective decay constant, lE ¼ 1` 1027 s21 b ¼ 50 keV E Rbav ¼ 43.2 mm Cells hit per beta decay (43.2/15) ¼ 2.9 131
I Effective decay constant, lE ¼ 1.1` 1026 s21 b ¼ 202 keV E Rbav ¼ 448 mm Cells hit per beta decay (448/15) ¼ 29
129
I,
131
I and the
Thyroid mass ¼ 20 g Thyroid volume 18.7 cm3 Average cell diameter 15 mm No of thyroid cells ¼ 1.03` 1010
The Fukushima exposure: 131I Given the agreement obtained earlier, it is interesting to apply the same methods to a more realistic environmental exposure such as resulted from the reactor releases from Fukushima. Thyroid equivalent doses at Ibraki, Japan, have been estimated by Priest (10) to be 5.9 mSv. Using IMBA, a thyroid equivalent dose of 5.9 mSv results from a thyroid uptake of 10.96 kBq. Using the same methods as outlined earlier and the same values for biological and microdosimetric parameters for 131I, a mean cell-hit number of 28 is obtained from conventional internal dosimetry and from microdosimetry 16, with all cells in the thyroid receiving at least one hit. Again, a similar discrepancy was seen between the two values that, as stated earlier, most likely results from the overestimation of the number of cells hit by a single beta particle. It is interesting to note that even at environmental exposure levels of 131I, resulting in CEDs of about 0.3 mSv, such as at Ibraki, the whole thyroid cell population is affected with each cell experiencing multiple beta particle interactions. Clearly, dose rate will be a significant issue concerning the response of the tissue to these multiple events, and this will be discussed briefly later in the Discussion section.
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The 129I intake for a whole-body committed effective does of 1 mSv given by IMBA is 2.72` 104 Bq, which results in a thyroid uptake of 1.06` 104 Bq (39 %). Using the physical and biological data given in ~ in Table 3, the total number of 129I disintegrations, A, thyroid tissue is estimated to be 1.06` 1011, where ~ ¼ Að0Þ=lE , A(0) is the initial activity and lE is the A effective decay constant of 129I in the body. The number of cells in the thyroid has been estimated to be 1.03` 1010 by dividing the volume of the thyroid by the volume of an individual follicular cell with an assumed diameter of 15 mm. Finally, the mean number of hits per cell has been calculated by taking the number of 129I disintegrations over the exposure period multiplied by the number of cells hit by each beta particle, 2.9 (estimated by dividing the range of the beta particle by the cell diameter) and dividing the resulting ‘number of cells hit’ by the total number of cells in the thyroid. This estimate gives the mean number of hits per cell in the thyroid for the whole-body exposure of 1 mSv as 30. The microdosimetric calculation of the same quantity can be arrived at in the following manner. With the assumption that the only tissue affected by the iodine intake is the thyroid and using a tissue weighting factor WT of 0.05, the equivalent dose to the thyroid for an exposure resulting in a whole-body effective dose of 1 mSv is 20 mSv. With a macroscopic dose of 20 mGy (WR ¼ 1 for beta particles) and a mean specific energy of 0.852 mGy (estimated by extrapolating measured yF values for 36 keV photons(4) to a simulated diameters of 15 mm) the fraction of thyroid cells receiving at least one hit is obtained using the Poisson statistics with F1 ¼(12e2D/d) and is 1, which in turn gives a value for the mean number of hits per cell as D/dF1 ¼ 23.5. Thus, the agreement between the internal dose calculation and the microdosimetric
analysis is reasonable when considering the assumptions and simplifications made in the analysis. A similar calculation both by internal dosimetry and microdosimetric analysis was carried out for 131I; the physical and biological data for this calculation are also given in Table 3. The total number of disintegrations derived from IMBA for the 1 mSv 131I CED was estimated to be of 3.4` 1010. The mean number of hits per cell derived from the internal dosimetry calculation was found to be 96, whereas the mean number of hits per cell derived from microdosimetry was calculated to be 55; once again, a value for the mean specific energy was obtained by extrapolation of experimental data of Kliauga and Dvorak(4). Although the agreement in cell-hit numbers is less good, the values are of the same order and the difference is most likely accountable by the fact that in the internal dosimetry calculation the mean number of cells hit by a single beta particle is estimated by dividing the range of the beta particle by the cell diameter. This estimation takes no account of the actual track structure and is likely to be less precise as the range of the beta particle increases beyond a few cell diameters. Overall, however, the agreement between conventional dosimetry and microdosimetry is reasonable and provides some confidence that measured microdosimetric parameters such as the frequency mean specific energy can be used to gain insight into the stochastic nature of a given low-dose exposure.
A. J. WAKER ET AL.
TISSUE AND TRACK MODELLING
Figure 1. The tissue model constructed with a 5` 5` 5 array of hexagonally close-packed array of cells 20 mm in diameter and each containing an 8 mm diameter nucleus. Table 4. Results from modelling 48 keV electron tracks emitted at the centre of the hexagonally close-packed cellular array depicted in Figure 1. Total cellular volume Total extra-cellular volume Mean number of hits per hit cell Per cent nucleus hits to whole-cell hits Extra-cellular space hits to whole-cell hits
5.2` 105 mm3 3.7` 105 mm3 3.34 12.2 % 29 %
DISCUSSION AND CONCLUSIONS In this article, it has been shown that a microdosimetric description of low-dose exposures is compatible with more conventional internal dosimetric analysis and that using measurable microdosimetric quantities low-dose exposures can be classified into categories representing different levels of cell-hit numbers and fractions of the tissue cell population experiencing at least one event. Thus, microdosimetric descriptions of low-dose exposures reveal the underlying stochastics of radiation interaction that will be important in determining the biological outcome (tissue response) of the irradiation. In this context, it is useful to be reminded that when it comes to environmental exposures, the general public do not necessarily think in a stochastic manner or that a tissue response might be completely different than at higher doses where radiation energy is more or less spread evenly among all cells within the tissue. This lack of use of stochastic information is also the case in conventional internal dosimetry where sophisticated biokinetic models and mathematical phantoms nevertheless calculate only the total energy deposited in a given organ and hence the average quantity absorbed dose to that organ. This approach is quite reasonable for acute exposures that lead to all cells being hit multiple times, more or less at the same time as was the case for atomic bomb survivors, from which current radiation risk factors are mainly derived. Conventional dosimetry becomes more questionable, however, for exposures where the dose is low enough that only a small fraction of cells within a tissue are hit and on average not much more than once. In this article, the issue of dose rate has not been directly addressed. Referring to Table 2 one could argue that for situations where few cells are hit and never more than once or where all cells are hit, but again on average not much more than once that dose rate is not likely to be a significant factor in the final tissue response. However, for exposures where all cells are hit multiple times, dose rate is very likely to be a factor. Consider a 50 mSv exposure to high-energy gamma rays where all cells are hit on average 60 times, with a Poisson probability distribution encompassing
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In the derivation of Equation 1 given in the Appendix, the tissue block is divided into an integer number of micro-masses with no interstitial spaces. This is not a particularly realistic description of tissue, and as it has been already noted, there is also an error associated with unrealistic descriptions of beta particle track lengths. Both these deficiencies need to be addressed by more realistic models of tissue and particle tracks. To investigate more realistic radiation –tissue interactions, a tissue model has been constructed consisting of a 5` 5` array of hexagonally close-packed spherical cells of 20 mm in diameter with each cell containing a spherical nucleus of 8 mm in diameter and the Monte Carlo code Penelope(11) has been used to model the interaction of 48 keV electron tracks emitted at the centre of the cell cluster. Figure 1 shows the tissue model used, and Table 4 gives the results of the track modelling. From Table 4, it is clear that the simple division of a tissue mass into equal micro-masses is inadequate. The extra-cellular volume is significant and accounts
for 71 % of the total volume occupied by the ‘cells’, but the number of hits in this inter-cellular space is only about a third of the number hits experienced by the cellular micro-masses, so surface area as well as volume must be significant in determining the number of events within a given micro-mass or other tissue compartment. It is also interesting to note from Table 4 that the fraction of hits to cell nuclei is only some 12 % of the total number of whole-cell hits for this particular tissue model. Such information will have an impact on discussions concerning targeted and non-targeted effects and the overall tissue response.
ENVIRONMENTAL MICRODOSIMETRY
(1) To date, most microdosimetric measurements have been carried out for simulated diameters of 1 –2 mm, and apart from a few early studies, there are little or no data for site sizes of nuclear or cellular dimensions, 8 –25 mm say, for different radiation qualities. (2) More realistic tissue models are required along with Monte Carlo track structure simulations to compute more geometrically realistic microdosimetric parameters. This information is required not only to compare with experimental microdosimetric methods but also to be used in cases where direct measurements may not be possible or very difficult such as with low-energy beta particles. (3) Novel radiobiological experiments are required that investigate the effect of exposures that mimic the partial or fractional irradiation of tissue at low dose compared with exposures where all cells within the tissue are hit multiple times. (4) Under exposure conditions where all cells within a tissue are hit multiple times, radiobiological experiments are required that can investigate dose rate and the significance of the time interval between the individual events within cells.
4. Kliauga, P. and Dvorak, R. Microdosimetric measurements of ionization by monoenergetic photons. Radiat. Res. 73(1), 1 –20 (1978). 5. Srdoc, D. and Marino, S. Microdosimetry of monoenergetic neutrons. Radiat. Res. 146(4), 466– 474 (1996). 6. Brenner, D. J. et al. Cancer risks attributable to low doses of ionizing radiation: assessing what we really know. PNAS. 100(24), 13761– 13766 (2003). 7. Peterson, J., MacDonell, M., Haroun, L. and Monette, F. Radiological and Chemical Fact Sheets to Support Health Risk Analyses for Contaminated Areas – Potassium 40. Argonne National laboratory Environmental Sciences Division (2007). Available on http://www.remm.nlm. gov/ANL_ContaminantFactSheets_All_070418.pdf (Last accessed on April 2015). 8. Blyth, B. J. and Sykes, P. J. Radiation-induced bystander effects: what are they, and how relevant are they to human radiation exposures? Radiat. Res. 176, 139–157 (2011). 9. IMBAw Professional Plus Internal Dosimetry Software. Public Health England.Available on https://www.pheprotectionservices.org.uk/imba/ (Last accessed on April 2015) 10. Priest, N. D. Radiation doses received by adult Japanese populations living outside Fukushima prefecture during March 2011, following the Fukushima 1 nuclear power plant failures. J. Environ. Radioact. 114, 162–170 (2012). 11. Salvat, S., Fernandez-Varea, J. M. and Sempau, J. PENELOPE-2011: A Code System for Monte-Carlo Simulation of Electron and Photon Transport. OECD, Nuclear Energy Agency (2011). Available on http:// www.oecd-nea.org/tools/abstract/detail/nea-1525 (Last accessed on April 2015).
APPENDIX Relationship between absorbed dose, D; frequency mean specific energy, d and fraction of micro-masses experiencing at least one event F1. Consider a block of tissue subdivided into N micromasses each of mass m (kg).
ACKNOWLEDGEMENTS Funding for this work has been provided by the University Network of Excellence in Nuclear Engineering (UNENE), the Natural Sciences and Engineering Research Council of Canada and the Ontario Research Fund. A number of undergraduate students at UOIT are thanked for their early contributions to the problem of low-dose exposures and in particular Anupama Bulkan, David Wallace and Manirul Islam.
The absorbed dose (J kg – 1) to the tissue slab is given by
REFERENCES 1. Ellet, W. H. and Braby, L. A. The microdosimetry of 250 kVp and 65 kVp x-rays, 60Co gamma rays and tritium beta particles. Radiat. Res. 51(2), 229–243 (1972). 2. Bond, V. P., Feinendegen, L. E. and Booz, J. What is a low dose of radiation? Int. J. Radiat. Biol. 53(1), 1–12 (1988). 3. ICRU Report No. 86, Quantification and reporting of low-dose and other heterogeneous exposures. Journal of the ICRU. 11(2), 61–63 (2011).
D¼
S1 ; N:m
where e is the imparted energy [J] to a tissue micromass, and N is the total number of such micro-masses or ‘cells’. 1 will depend on the mean number of energy deposition events, h, in a cell and on the size of the energy
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this mean value resulting in some cells receiving considerably more than 60 hits. It is not unreasonable to think that the biological outcome may be different between a population exposed acutely to 50 mSv and an environmental or occupational exposure over the course of a year say where on average the cells receive one hit every 146 h, which is very long compared with the time constants associated with common cellular repair mechanisms. The relatively straightforward microdosimetric analysis described in this article highlights a number of topics that would benefit from further research effort. These are as follows:
A. J. WAKER ET AL.
deposition. It is convenient to write Se as
Substituting into the expression for absorbed dose,
h:NH
S1 ; h NH
D¼
where (S1/h.NH) is the mean imparted energy per event per hit cell, and [(S1/ h.NH)/m] is the mean specific energy per event per hit cell, d (J kg – 1).
ðh NH dÞ ; N
and NH/N is the fraction of cells in the tissue receiving at least one ‘hit’, F1, and so D ¼ h d F1 :
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