Non-uniform Exposure Research Articles

Radiation-Induced Chromosome Aberration Yields Following an Accidental Non-Uniform Exposure

Chromosomal aberration yields were obtained from short term lymphocyte cultures made at various times after an accidental partial body exposure to 192 Ir gamma rays. A rapid decline in the frequency of chromosomal aberrations (CA) has been observed during the first year of follow-up. Dicentric frequencies reduced to one-half, one-third and one-fourth of the original values at 160 days, 240 days and 1 year post-irradiation respectively. The decay of dicentric frequency occurred with a half-life of approximately 168 ± 32 days. A non-Poisson distribution of dicentrics and the presence of a few multi-aberrant cells were consistent with the non-uniform localised exposure

Recent controversy in radiation dosimetry

The correspondence between Drs. Macleod and Kemp [1] and Drs. Johansson et al. [2] in this issue is an example of the controversy that has arisen over use of the quantities effective dose equivalent (EDE) [3] and effective dose (E) [4]. Johansson et al. correctly point out the interpretations of these quantities, as well as their intended applications. The EDE was originally defined for use in radiation protection programs for situations in which nonstochastic effects do not occur. The adaptation to medical uses of radiation, including radiology and nuclear medicine, has been made by authors other than Johansson et al. [5, 6, 7] and advocated by the ICRP in ICRP Publication 53 [8]. Nonetheless, some people remain opposed to the use of the unit in medicine. The traditional approach to the characterization of radiation dosimetry in medical uses of radiation has been to report individual organ absorbed doses and a quantity called "total body" (or "whole body ") dose. Thus, radiation use committees, regulatory agencies, physicians, manufacturers, and others have become focused on calculation of "critical organ" dose and "total body" dose. As noted by Johansson et al., one accepted way to evaluate a patient's risk from stochastic effects would be to consider the average doses and radiation sensitivities of all organs. In principle, the EDE permits this evaluation to be made for different radiopharmaceuticals, as well as different modalities of ionizing radiation exposure, with the results being directly comparable. Furthermore, the EDE is designed to represent the uniform wholebody exposure that would carry the same risk as the actual nonuniform exposure received. The quantity "total body" dose, on the other hand, is usually calculated by dividing all of the energy absorbed in all tissues from a given exposure by the total body mass. This quantity is completely meaningless when a nonuniform distribution of radioactivity occurs. "Total body" dose is clearly inappropriate for evaluating the risk from nuclear medicine examinations and should not be the basis for decision-making or comparison of agents or procedures. The question becomes whether an effective dose equivalent or effective dose can be a suitable substitute for "total body" dose (or, more appropriately, "total body" dose equivalent). The effective dose contains by definition two sets of so-called "weighting factors," which are introduced through multiplication. The first are the "radiation weighting factors" (formerly quality factors), which express the relative effectiveness of different types of radiations at producing biological damage. Multiplication of a tissue absorbed dose (DT,R) (Gy, mGy, rad, etc.) by the appropriate radiation weighting factor (WR) (including all radiations) produces the tissue equivalent dose (HT) (formerly called dose equivalent) (Sv, mSv, rem, etc.):

Technical note: compensation for field non-uniformity on a mammographic X-ray unit.

A well observed phenomenon in diagnostic radiology is that of the anode heel effect. The heel effect is caused by target absorption of X rays emitted from an electron impact site at angles more nearly parallel to the anode face (Curry et al, 1984). This has the consequence of producing a non-uniform exposure profile in the image plane (Figure 1). Other non-uniformities may be caused by imperfections in any pre-filtration foils (IPSM, 1989). Although non-uniformity is tolerated and to a large extent is of no clinical concern, there are applications where a uniform field exposure is required. One such area is where quantitative measurements need to be made at different spatial positions. Additionally it may prove advantageous to use a flat field exposure in mammographic examination of women with very large breasts where areas towards the breast periphery may get a significantly lower exposure than at the chest wall, reducing image contrast in that region. As part of a Department of Health evaluation into the use of computed radiography (CR) in mammography (see, for example, Takeno et al, 1987) the authors have been investigating the mammographic imaging performance of CR using quantitative measurement techniques. One such technique is noise power spectrum analysis. Because this technique requires uniform exposure distribution over a large field area (12 cm × 12 cm) it was necessary to develop a technique to compensate for X-ray beam non-uniformity on a clinical mammography unit (Philips Diagnost UC).

Tumour induction in mouse epidermal cells irradiated by hot particles.

We have shown elsewhere that highly non-uniform exposure to ionizing radiation from authentic Chernobyl-released and artificially-produced hot particles (fragments of nuclear fuel) transform fibroblastic 10T1/2 cells in vitro effectively. We have also shown that hot-particle exposure leads to mutation and overexpression of the tumour suppressor gene p53 (and some other growth-related genes) in mouse skin in vivo at a high frequency. In the present paper it is shown that hot-particles produced by irradiating natural uranium with slow neutrons, when implanted (immobilized) under the skin of hairless and nude mice, induce epidermal tumours in excess compared with the conventional non-threshold stochastic model of radiation-induced cancer. One explanation for the effectiveness of the hot-particle exposure, under the present assay conditions, is that the same cells in which specific radiation-induced DNA damage is most likely to occur, are forced into sustained mitotic activity in the chronic wound which develops around the radiation source (combined genotoxic and nongenotoxic effects). The results are consistent with a role for cell proliferation in multistage carcinogenesis in mouse skin.

Radiation Risk to the Patient: A Case Study Involving Multiple Diagnostic X Ray Exposures Given Over a Period of 25 Years

Since diagnostic X ray examinations constitute the largest source of man-made radiation exposure to the population of Canada, the cumulative effect of many such exposures on the individual is of considerable interest. The somatic dose index (SDI) for a diagnostic radiology procedure is the uniform whole-body dose which has the same somatic detriment as the non-uniform exposure resulting from the diagnostic X ray examination. The cumulative SDI for a number of diagnostic X ray examinations was made for a 60 year old male. The history of diagnostic X ray exposure for this patient from 1957 to 1983 showed 29 diagnostic X ray examinations including more than 100 films and 15 minutes of fluoroscopy. The total cumulative SDI to this patient was 214 mGy (about 21 rad). More than half this dose, 142 Gy, was contributed from upper GI and barium enema examinations which used fluoroscopy, with 88 mGy from the fluoroscopy alone. Using the recently revised risk coefficient for fatal cancer following whole-body irradiation of adult workers recommended by the International Commission on Radiological Protection in 1990, we estimate a 0.9% cancer mortality risk to this patient resulting from the 29 diagnostic X ray examinations.

Nonuniform Irradiation of the Canine Intestine: I. Effects

To investigate the effects of nonuniform irradiation on the small intestine, we prepared 24 dogs for continent isoperistaltic ileostomies under aseptic surgical conditions and general anesthesia. After a 3-week recovery period, the ileum was catheterized with a fiberoptic endoscope to observe the intestinal mucosa and to harvest mucosal biopsies. The baseline macroscopic and microscopic appearance of the intestinal mucosa was determined. Two weeks later, the ileum was catheterized with a 100-cm soft tube containing 40 groups of three thermoluminescent dosimeters placed at equally spaced intervals, and a dose of either 4.5, 8, 10, 11, or 15 Gy 60Co gamma rays was delivered to the right abdomen (nonuniform exposure). This method allowed a direct and precise assessment of the dose received at 40 sites located in the 100-cm intestinal segment. The intestinal mucosa was again evaluated 1, 4, and 6 days after irradiation. All animals exposed to 4.5 and 8 Gy survived, whereas none survived after 11 and 15 Gy. After exposure to 10 Gy, 60% of the animals died within 4-6 days and 40% survived with symptoms associated with both the intestinal and the hematopoietic syndromes. Crypt cell necrosis, blunting of villi, and reduction of the mucosal lining increased between 1 and 4 days after irradiation, and mucosal damage was correlated with intraintestinal dosimetry at Day 6. The granulocyte counts at Day 4 were significantly lower than baseline level in animals that died within 4-6 days but not in survivors. The present model appears to be realistic and clinically relevant, allowing the concurrent study of the intestinal and hematopoietic effects of high-dose nonuniform irradiation similar to that received by patients during radiation therapy as well as by radiation accident victims.

Skin carcinogenesis following uniform and nonuniform beta irradiation.

In practical situations where workers or the general public may be exposed to ionizing radiation, the resulting irradiation is rarely uniform. The risk figures and dose limits recommended by the International Commission on Radiological Protection (ICRP) are based largely on clinical and epidemiological studies of reasonably uniform irradiated organs. The paucity of clinical or experimental data for highly nonuniform exposures has prevented the ICRP from providing adequate recommendations applicable to this practical situation. This weakness has led on a number of occasions to the postulate that highly nonuniform exposures of organs, such as the lung or the skin, could be 100,000 times more carcinogenic than ICRP risk figures would predict. This so-called "hot-particle hypothesis" found little support among reputable radiobiologists, but could not be clearly and definitively refuted on the basis of experiment. An experiment design, based on skin tumour induction in mouse skin, is described which was developed to test the "hot-particle hypothesis." In collaboration with the Radiobiology Department of St. Bartholomew's Hospital Medical College, London, the skin of 1200 SAS/4 male mice has been exposed to a range of uniform and nonuniform sources of the beta emitter 170Th (Emax 1 MeV). Nonuniform exposures were produced using arrays of 32 or 8 2-mm-diameter sources distributed over the same 8-cm2 area as a uniform control source. Average skin doses varied from 2-100 Gy. The results for the nonuniform sources show a 30% reduction in tumour incidence by the 32-point array at the lower mean doses compared with the response from uniform sources. The eight-point array showed an order-of-magnitude reduction in tumour incidence compared to uniform irradiation at low doses. These results, in direct contradiction to the "hot-particle hypothesis," indicate that nonuniform exposures produce significantly fewer tumours than uniform exposures.

The Biological Bases of Radiological Protection Criteria for Superficial, Low Penetrating Radiation Exposure

When the body is exposed to low penetrating radiation such as beta or low energy X rays, the skin, eyes and sometimes testes may be the most highly irradiated organs of the body. In order to assess the biological response following such exposures it is necessary to understand the radiobiology of the specific organs and, in particular, the identity and depth of the most radiosensitive cells. This information is also directly relevant to the needs of those responsible for calculating and measuring doses to personnel. Up to date information on the identification and depth of cells at risk, and the biological response following non-uniform exposures will be reviewed. One of the aims of this paper is to identify the limitations in this knowledge which are creating problems for dosimetric applications so that radiobiology programmes can then be evaluated and tailored to meet these practical needs.

A new approach to proximity effect correction

The proximity effect in electron beam lithography, arising from electron scattering in the resist and substrate, results in non-uniform exposure. In order to improve the developed pattern contour by applying dose corrected exposure, a new proximity effect correction technique for high accuracy resist exposure, denoted as Enhanced Proximity Effect Correction (EPEC), has been developed and succesfully implemented. The mathematical model for this technique and results have been given in this paper.

Lung tumour induction in mice after uniform and non-uniform external thoracic X-irradiation.

The aim of this study was to investigate the validity of the ICRP procedure of using average tissue/organ dose in estimating carcinogenic risk. It has been suggested that highly non-uniform exposure ('hot spots') is much more carcinogenic than an equivalent dose delivered uniformly. In a series of experiments, mice were irradiated with X-rays either uniformly to the thorax or non-uniformly with 72 1-mm microbeams which irradiated approximately 20 per cent of the total lung volume. Two experiments involving uniform irradiation showed a peaked tumour incidence curve with a maximum at 5 Gy. The first 'microbeam' study also produced a pronounced peak in the dose response with a maximum tumour incidence at 1 Gy average lung dose or 5 Gy to the irradiated lung tissue. This implied the use of average tissue dose might underestimate the carcinogenic hazard of non-uniform exposure. Later, more extensive, microbeam experiments failed to replicate this finding. The results were nearly similar to those for uniform irradiation, with a slight increase in tumour incidence from 2.5-5.0 Gy average lung dose. These results imply that for these irradiation conditions the ICRP dose averaging procedure remains valid.

Proximity Correction Enhancements for 1-µm Dense Circuits

The proximity effect in electron-beam lithography, which is due to electron scattering in the resist and wafer, results in nonuniform exposure and development for patterns in which the incident doses of all the shapes are the same. Correction for this effect has been accomplished in the past primarily by varying the incident doses of all the shapes in order to achieve an equal average resultant dose per unit area for all shapes. We show that in the case of dense circuits with linewidths of about 1 µm or smaller, two enhancements to the proximity correction technique can be easily implemented. One of these is a simple approach to shape breakup (partitioning) to enable dose correction to be applied nonuniformly within the original design shapes. The other technique is a new type of algorithm for forming subsets of the design to perform self-consistent dose correction. These two enhancements are applied to LSI chip data for dense circuits and are shown to permit fabrication of circuits which would be more difficult to process using the proximity correction techniques described previously, due to the particular geometries present in these circuit designs. We also show the application of step and repeat pattern recognition algorithms to compact the resulting data, and consequently to reduce the amount of data by an amount which is greater than the increase in the number of shapes caused by partitioning.

Chromosomal differentiation and adaptation to human environments in the Anopheles gambiae complex

Speciation in the Anopheles gambiae complex is reviewed and discussed with emphasis on the patterns of chromosomal differentiation, particularly at the intraspecific level. The significance of inversion polymorphism in gambiae and arabiensis (the two species of greatest medical importance) is evaluated with reference to recent field investigations carried out in Nigeria. In both sibling species some of the inversions show clinal geographical changes in frequencies, with evident correlations with climatic conditions and vegetation zones. Microgeographical variations in species distribution and in intraspecific inversion frequencies are also present, which appear mostly related to man-made environmental contrasts. Parallel indoor/outdoor collections of samples from polymorphic populations of arabiensis and gambiae show that adult mosquitoes carrying certain inversion karyotypes do not distribute at random in relation to the human environment, being significantly more frequent in outdoor than in indoor samples, or vice-versa. Optimal habitat choice appears to be involved in such variations of indoor resting behaviour, since the chromosomal types carried by less endophilic individuals are those more adapted to humid climates, i.e. those which tend to avoid the higher nocturnal saturation deficit of the indoor environment. This phenomenon, producing non-uniform exposure of the vector population to residual insecticides sprayed in houses, might explain the mediocrity of the results of malaria control projects based on house-spraying against endophilic vectors in the African savannas.

Proformance of Galvanized Reinforcement in Calcium Hydroxide Solution

Galvanized steel is passivated by the saturated calcium hydroxide solution contained in moist concrete. Inherent corrosion currents develop, however, at excessive chloride contents and under conditions of nonuniform exposure. These currents lead to local chloride accumulation with intensive pitting, regardless of existing passivation films. The corrosion resistance of galvanized steel reinforcement has been compared with that of bare steel.

Introduction of ICRP Publication 14 “Radiosensitivity and Spatial Distribution of Dose”

The ICRP Publication 14 contains two reports made by two Task Groups to Committee I. The first report is concerned with the spatial distribution of dose. In this report, many problems related to the basic concepts of radiation protection and inconsistency of the currently recommended dose limit are discussed. A scheme of dose limit for non-uniform exposure based on the risk estimate is presented tentatively. The second report is concerned with the relative radiosensitivity of different tissues and organs. In this report, risks of differnt kinds of biological damages by radiation are reviewed fully. A formal scheme for deriving dose limit for partial exposure of the body is presented. And, according to the data obtained from exposed populations, numerical values for dose limit to tumour induction are derived as an example for discussion. At present, the effect of radiation is not clear sufficiently, but it is suggested that the dose limit specified by ICRP for exposure of part of the body other than the lens and the gonads should be revised.In the present paper, the formal scheme for deriving dose limit and the example for the numerical derivation of dose limit are introduced somewhat in detail.

Active Bone-Marrow Dose Related to Hematological Changes in Whole-Body and Partial-Body60Co Gamma Radiation Exposures

This study investigates active bone marrow dose as a parameter for hematological changes resulting from whole-body and partial-body exposures. Dose distributions in active bone marrow were measured in a tissue-equivalent human phantom. Dose equivalents for the partial-body exposure conditions were determined by applying the phantom marrow dose distributions to a model for nonuniform exposure based on stem-cell dose-survival curves. The model was extended to predict hematological changes which agreed favorably with the observed clinical changes.

Efficiency of Photochromic Gratings

A method for computing the diffraction efficiency of photochromic, transmission holographic gratings is developed. The nonuniform exposure through the depth of the material is taken into account. The efficiency depends strongly on the modulation of the refractive index. The diffraction efficiency of some typical photochromic gratings is calculated, and efficiencies of up to 10% are predicted.

Cytogenetic effects of strontium-90 on the bone marrow of the Chinese hamster.

NUMEROUS studies have been made with the ultimate goal of establishing dose effect models that will enable quantitative assessments of the damage inflicted by various types of radiation exposures. In most, the animals were exposed to whole body gamma or X-irradiation delivered at high dose rates. The number of chromosome aberrations changes as a function of total radiation dose, radiation dose rate and time after exposure1–3, so it is not clear how these criteria apply in interpreting aberrations produced by internally deposited radionuclides which give low, continuous and non-uniform radiation dose rate exposures. Several workers have used in vivo or in vitro exposure to internal emitters and in vitro cell sampling to determine radiation damage4–7. These are relatively indirect, so we have tried to evaluate the influence of an internally deposited radionuclide on the frequency of chromosome aberrations produced and sampled in vivo. We selected 90Sr (in equilibrium with its daughter 90Y) because it exists in abundance in a number of nuclear processes, and localizes selectively in osseous tissues, resulting in beta irradiation of both bone and bone marrow. Aberrations in bone marrow cells are readily studied in vivo and may also be significant in the development of haematopoietic tissue neoplasms. We took two time periods, 2 and 14 days after injection, because differences in the aberration frequency which may be observed as a function of the total radiation dose and dose rate change with time.

A Mortality Determinant in Nonuniform Exposures of the Mammal

It is widely accepted that survival in most mammals exposed uniformly to penetrating radiation in the LD50(30) (hematological syndrome) range depends primarily on maintenance of a critical level of neutrophils and platelets in the peripheral blood. This minimum level depends in turn on the survival or proliferative integrity of a critical number or fraction of the stem cells in the total active bone marrow mass (1). From dose-survival curves established for bone marrow stem cells in the mammal (2-4), it appears that the dose-effect curve is closely approximated by an exponential function over a range of exposures that more than spans the LD50(30) range. It is reasonable to assume that subunits of the total marrow mass have the same number of stem cells per unit mass, and that the stem cells of each subunit, considered independently, are subject to the same exponential dose-effect relationship as that for the total marrow. It is further reasonable to assume that a surviving stem cell will, after irradiation, contribute mature cells to the peripheral blood at a rate that is independent of its location in the marrow. The foregoing statements form a logical basis for a stem cell model for survival; that is, survival of the animal depends on the same critical surviving fraction of stem cells, whether following uniform or nonuniform exposure. This fraction can be calculated from values for (1) the relative amounts of active bone marrow (stem cells) in different parts of the body; (2) the doses to these parts; and (3) the dosesurvival curve for stem cells.