Syllabus - Introduction to Radiology

Public perception of ionizing radiation, over the years, has been somewhat biased by the popular press. While I don't wish to de-emphasize the importance of the health risks of radiation, I believe it is important to keep a proper perspective on those effects. We have always been exposed to radiation in its many forms. We receive radiation exposure from the environment in the form of cosmic rays from the sun, from naturally occurring radioactive materials in the food chain, from the geology of the area and from radon, a naturally radioactive gas. The single largest contributor of man-made radiation is the medical profession. Over the years we have received significant radiation exposures from nuclear weapons testing as well as devices such as the shoe fluoroscope. This device was in wide use in the early to mid-1950s and delivered doses, according to the literature, of 10-12 rads per use. Recommendations were not to use the device, with children, more than three or four times per year. Even the radiation exposures associated with diagnostic radiology and nuclear medicine have been markedly reduced from those of years past.

Roentgen - unit of exposure dose. Defined only in air and for X- or gamma radiation.

rad - unit of absorbed radiation dose. Equal to 100 ergs of energy deposited per gram of absorbing material.

rem - unit of dose equivalence. Used to compare relative effectiveness of different radiations. Rem = Absorbed Dose (rads X Quality Factor where the Quality Factor is a measure of biologic effectiveness of a given radiation. Table 1 lists some quality factors for different radiations.

Gray - SI unit of absorbed radiation dose. One joule of energy absorbed from any ionizing radiation in one kilogram of any material. Equal to 100 rads.

Sievert - SI unit of dose equivalence. The absorbed dose in Gray is multiplied by the Quality Factor. Equal to 100 rems.

Everyone is exposed to some, though varying, levels of ionizing radiation throughout life. The chronic effects of radiation result from exposures to low levels of ionizing radiation such as we might receive in our everyday occupations, or even from appliances in our homes, as well as exposures from diagnostic radiography. These exposures are generally in the millirem (mr-A millirem is 1/1000 of a rem) range, and may be received over a short time interval, or more likely, over a much longer time period of years. For a perspective of the numbers involved, population exposure to radiation in most of the United States is a bit less than 400 mrems per year for each person in the population. About 70 mrems of this comes from so-called man-made sources, of which medical radiation is the largest contributor. Another 100 mrem/year is from naturally occurring radioactivity such as cosmic rays from the sun, or from geological structures. The remaining 200 mrems comes from exposure to inhaled radon gas and its daughter products. Some areas, such as Colorado, do have somewhat higher backgrounds because of their geology, but this number is a good estimate of the national average. As a numerical comparison, a chest radiograph (PA and lateral views) exposes a patient to approximately 20 mrem of radiation.

The single largest source of exposure to the population is radon. Radon is a naturally occurring radioactive gas first discovered in the 1920's. Chemically, radon is a noble gas with a behavior similar to helium or neon. Radon is a decay product of the most common form of uranium. The radon hazards do not come primarily from radon itself, but rather from radioactive products formed in the decay of radon-222. These products, called the "radon daughters," are also radioactive but, unlike radon, they are atoms of heavy metals and readily attach themselves to whatever they contact. the main health problems stem from the inhaling of these radon daughters, or dust particles carrying them, and the subsequent lodging of the radon daughters in the lung. These radioactive daughters decay with the emission of alpha particles with very high LETs and consequently very high Quality Factors. Thus the equivalent dose to the lung tissue is very large.

The effects of ionizing radiation on a given population are generally divided into two broad categories-acute, and chronic. The acute effects are considered to be those which happen in the immediate post irradiation period, i.e. from the time of radiation exposure up to six months to a year post exposure. Acute effects are generally the result of large radiation exposure delivered to the whole body, or at least a major part of it, in a very short time.

On the other hand, the chronic effects of radiation result from relatively low exposure levels delivered over long periods of time. These are the sort of effects that might result from occupational exposure, or to the background exposure levels mentioned above. These effects may be observed many years after the radiation exposure.

While the acute effects of radiation are of interest primarily from the academic standpoint, a basic knowledge of these effects may be valuable in dealing with a major radiation accident. Because these effects are associated with high (greater than 200 rems) doses delivered in a short period over the whole body, they are almost always seen in the accident situation, or, potentially, with nuclear weapons. Occasionally, however, a radiation therapy patient will also exhibit certain of these symptoms. There were some exposures of this magnitude associated with the development of nuclear weapons in the late 1940's. More recently, several accidents, beginning with the accident at the Chernobyl Power Station in the U.S.S.R. in 1986, have focused attention on this type of radiation effect. Accidents in Goiana, Brazil in late 1988 and in San Salvador in early 1989 have also been in this catagory and provided some additional patient exposure information.

For this lecture, however, because of the time constraints, we will concentrate on the chronic, or long term, effects of radiation. These are the effects most likely to have an impact on us, either as radiation workers, or as patients.

The chronic, or long term, effects of radiation are of most relevance to radiation workers today. Additionally, the chronic effects are of greater importance because of the types of possible damages and the large population involved. Everyone is exposed to low level radiation, and, consequently, potentially falls in this category. Radiation workers, for obvious reasons, are especially concerned with this category of injury. There are three major categories of radiation effects - cancer, genetic damage and birth defects. Before we look at these individually, there are some issues that relate to each of these potential effects.

While the potential study population is large, the incidence of radiation effects is very small compared to the natural incidence of these effects. For example, the natural incidence of cancer in the United States population is approximately one case in three individuals in the population. Radiation exposure causes an additional 1-2 cases per 10,000 people exposed per rad of exposure. Thus, either very large populations exposed to very small doses of radiation may be studied, or alternatively, small populations that have received relatively high level radiation exposures serve as study bases.

The largest radiation study population utilized at this time is the group of victims exposed to the nuclear weapons dropped on the Japanese cities of Hiroshima and Nagasaki during World War Two. In this population a variety of cancer types have been observed. Individuals exposed during the radiation accident in Chernobyl are presently under intensive study, but any significant data will not be available for some years yet.

Certain population groups have also been observed for specific cancers. These groups include individuals exposed both medically and occupationally. For example, an excess incidence of thyroid cancer has been observed in individuals exposed to radiation as children for a variety of conditions including acne, respiratory difficulties and tonsillitis. Breast cancer has been detected in greater than expected levels in women exposed to repeated fluoroscopy in the management of tuberculosis. In these populations and others the cancers are detected after relatively large exposures of selected small populations.

Certain occupations also have shown an increased incidence of disease related to cancer. Many of the early radiation workers succumbed to radiation induced disease. Miners working in uranium mines have shown an increased incidence of lung cancer. This, incidentally, was probably the first radiation induced cancer, though not recognized as such. Silver miners in the Erz Mountains of Germany in the sixteenth century were described as having a lung disease that we now would identify as radiation induced lung cancer. The radium dial painters of the 1920's also represent an occupationally exposed group. These workers, primarily young women, received large body burdens of radium through the ingestion of radium based paint used in luminescent instrument dials.

In attempting to investigate effects due to radiation, particularly at the very low exposure levels of occupationally exposed individuals, several problems arise.

First, there are no unique effects of radiation. No specific biologic end point, that is, effect, can be associated with radiation exposure alone. For example, radiation produces no damage that other agents, such as drugs or other chemicals, cannot also produce. Thus, any association of a particular biologic effect with an exposure to ionizing radiation must have with it a degree of uncertainty.

Additionally, low levels of radiation may produce little, if any, effect. This idea of a threshold will be discussed later as we look at dose response relationships.

Finally, the biologic effects that we usually ascribe to ionizing radiation already exist in the population at relatively high levels. Cancer, for example, occurs in roughly one in three individuals sometime during their life time. Genetic damage and birth defects also occur at significant levels within the general population. Thus we must always keep in mind these normal incidences of effects as we discuss radiation as a causative agent.

Another problem that we encounter in the study of low-level radiation effects is the latent period. The latent period is the time between the initial radiation exposure and the development of the biologic effect. In general, this latent period is approximately 20 years. This period may range, however, from a minimum of about two years for leukemia to the remaining life span for some types of cancer. Many generations may be required to observe detectable genetic change. This long latent period makes follow-up difficult in prospective studies, and complicates dose determinations in retrospective studies. Historically, this long latent period allowed significant numbers of individuals to be exposed to radiation before any correlation was noted between radiation exposure and injury.

Cancer is probably the most publicized of the effects of radiation. True, radiation causes cancer, but so do many other agents. With the single exception of chronic lymphocytic leukemia, all other forms of cancer have, at one time or another, been linked to radiation exposure. Cancer was certainly an occupational hazard for the early radiation workers. Skin cancers, loss of limbs from amputation during treatment of cancers and burns were almost the badge of the early radiologist. One must remember, however, that for many of these early workers, the average dose was perhaps the equivalent of one rad per day. Today, the Maximum Permissible Dose (MPD) is five rads per year with most workers getting considerably less than this. The following table lists some cancers associated with radiation exposure.

Leukemias and related blood disorders probably account for somewhat more than 10% of the radiation-induced cancers following whole-body radiation exposure. The minimum time between radiation exposure and first appearance of the disease seems to be about two years, with the average latent period being about 5.7 years. The increased risk of leukemia seems to then decline somewhat, though it is still present at a lower value for at least forty years post exposure. The data from the atomic bomb victims in Japan suggest that there is an apparent threshold for leukemia induction of about 75 rads in a single exposure. Protracted exposure increases the necessary induction dose. Below this figure, the likelihood of leukemia induction appears small.

Solid tumors account for a bit less than 90% of the radiation-induced cancers. The major sites of solid tumors induced by whole-body radiation are the breast in women, the thyroid, the lung, and some digestive organs. The incidence of radiation-induced breast and thyroid cancer is such that the total cancer risk is greater for women than for men. Breast cancer occurs almost exclusively in women, and absolute risk estimates for thyroid cancer induction by radiation are higher for women than for men, as is the case with the natural incidence. With respect to the other cancers, the radiation risks in the two sexes are approximately equal. There are some other points about these specific cancer forms that warrant further discussion.

Breast Cancer - Breast cancer represents an area where the concept of risk-benefit can be extremely well visualized. The 1994 Cancer Statistics of the American Cancer Society indicate that thirty two percent of all cancers in women, and 18% of all cancer deaths are due to breast cancer. Radiographic examinations of the breast have been found to be of considerable value in the diagnosis of breast cancer. This may be especially true in the asymptomatic patient without a palpable mass, or with a very small, less than one centimeter, lesion. Such cancers have a greater than 95% cure probability. These examinations, however, are associated with a possible risk of induction of breast cancer. Modern mammographic techniques subject patients to extremely low doses of radiation to the breast, i.e. in the range of 0.1 to 0.5 rem. Recent studies have shown an increased risk of breast cancer even at these low doses, and especially in the very young. The risk of breast cancer induction at such doses has been estimated to be approximately equal to smoking one cigarette, or riding 60 miles in an automobile. Many factors, however, enter into the likelihood of a woman developing breast cancer, besides a history of radiation exposure. One of these factors is age. For example, only two percent of all breast cancers develop before the age of 34 years, whereas 50% of breast cancers develop in 55 to 74 year olds. An additional factor is the relative radiosensitivity of the breast with regard to age. The breast tissue in the 30-35 year old range may be some 3-4 times as sensitive as in the over 50 population in regard to cancer induction. By combining this age incidence with radiation risks, general guidelines may be drawn regarding breast cancer and radiation exposure (mammography). These guidelines, as published by the American Cancer Society, recommend annual mammographic screening for all women over 50 years of age. For women in the age group 35-40 years, a base line study is recommended. Some authorities feel that annual mammography should begin at age 40, but most suggest mammograms every two years or upon the recommendation of their physician for women in the 40-49 age group. Between the ages of 25 and 34 years, mammograms are used only when there is a diagnostic problem and never on a periodic basis. Routine, screening mammograms are not advised on patients under 25 years of age.

Thyroid Disease - From the late 1920's through the early 1950's, a large number of people, primarily infants and children, were irradiated in the area of the head and neck for a variety of reasons including acne, ring worm, tonsillitis, and respiratory difficulties. Today, a significant number of these people have developed thyroid disease. In this particular case of radiation-induced disease, some additional points should be mentioned. First, the very young at time of exposure (less than 10 years) are at the greatest risk. Secondly, most of the disease develops in the second to third decade of life, that is, with a latent period of about 20 years. As this exposed population ages, however, the increased incidence of thyroid disease seems to remain in the population. Even at forty years post exposure there is an excess of cancer and other thyroid disease present in this group. While there is a high incidence of thyroid disease in these people, only about 20% of the radiation-induced thyroid disease is malignant disease.

Lung Cancer - Historically, cancer of the lung has long been associated with the mining industry, particularly pitchblende and uranium mining. Recent studies indicate that a significant proportion of this lung cancer is caused by exposure of the miners to radon and its daughter decay products. The Environmental Protection Agency has estimated that of the 136,000 deaths annually due to lung cancer, some 4-15% (5000-20000) may be due to radon exposure. While some scientists feel that this estimate may be too high, the fact remains that radon and its primary biological effect, lung cancer, may represent a significant public health concern.

The most recent summary of radiation-induced cancer is the National Academy of Sciences' 1990 report Health Effects of Exposure to Low Levels of Ionizing Radiation-BEIR V. This study stated "In this report it is estimated that if 100,000 persons of all ages received a whole body dose of 0.1 Gy (10 rads) of gamma radiation in a single brief exposure, about 800 extra cancer deaths would be expected to occur during their remaining lifetimes in addition to the nearly 20,000 cancer deaths that would occur in the absence of radiation. Because the extra cancer deaths would be indistinguishable from those that occurred naturally, even to obtain a measure of how many extra deaths occurred is a difficult statistical estimation problem." While this is not an insignificant increase, its significance must be measured against the normal risk and the benefit gained from the exposure. If there is no benefit, the risk is not warranted.

We know that radiation causes mutations, but in man we have no direct evidence of effects even at the high doses of radiation received by the Japanese during the bombings of Nagasaki and Hiroshima.

The most recent data from the children born to parents exposed during the bombings in Japan show no significant differences in the number of still births, birth weight, or congenital abnormalities. While there are anecdotal reports from Chernobyl and other locations, particularly within the old U.S.S.R., no hard dates exists for such effects. There is information relating to in utero exposure which we will discuss later.

Most of the genetic information that we have concerning radiation genetics comes from a large series of animal studies performed at Oak Ridge by the team of Russell and Russell. Currently, these experiments represent the best available data. These concepts of radiation genetics have been summarized by Hall as follows:

1. Different mutations vary significantly in the rate at which they are produced by a given dose.
2. There is a substantial dose-rate effect, so that spreading the radiation over time greatly reduces the genetic consequences of a given dose as compared to the consequences of an acute exposure.
3. The male is much more sensitive to radiation-induced mutation than is the female. For practical purposes, at low-dose rates almost all of the radiation-induced genetic burden in a population is carried by the males.
4. The genetic consequences of a given dose can be greatly reduced if a time interval is allowed between irradiation and conception. The exact time for humans is not known, but as a conservative estimate, six months to a year should be allowed to elapse before a planned conception follows a significant gonadal dose.
5. The amount of radiation required to double the natural, or spontaneous, mutation rate in man is between 20 and 200 rem over a generation.

The fetus is extremely sensitive to ionizing radiation. This sensitivity is due to the rapidly dividing cell populations that characterize the fetus. Because the sensitivity of the fetus changes during gestation, protection of the embryo/fetus requires consideration of the various portions of gestation.

Radiation exposure prior to implantation (day 9-14) generally results in an "all or nothing" response. This means that the pregnancy either self-terminates or proceeds with no apparent problems. The percentage of prenatal death declines rapidly after the first week or so of the pregnancy with the likelihood of in utero death after implantation being small. Beginning immediately after implantation of the embryo in the uterine wall, the organ systems start to develop. This period of organogenesis represents the period of greatest sensitivity for the development of congenital abnormalities.

Starting at implantation, the fetus becomes increasingly sensitive to the induction of congenital abnormalities until the peak sensitivity is reached somewhere around day 28-30 of gestation, counting from last menses. Radiation doses as low as 15-20 rads during this time may produce visible congenital anomalies. Unfortunately, during this period the woman quite often does not realize that she is pregnant, and consequently might be exposed to radiation for diagnostic purposes or other reasons. Thus, extreme care must be exercised in any radiation exposure of potentially pregnant women.

After this period of organogenesis, the overall sensitivity of the fetus declines, and remains relatively low throughout the rest of gestation. One major exception is that the developing central nervous system remains sensitive to radiation through much of gestation. Radiation may produce some developmental abnormalities including mental retardation and microcephaly during this time. In the Japanese atomic-bomb survivors who were irradiated in utero, the prevalence of radiation-related mental retardation was highest in those irradiated between 8 and 15 weeks after conception, decreased in those irradiated between 16 and 25 weeks, and was negligible in those irradiated before 8 weeks or later than 25 weeks. In those irradiated between weeks 8 and 15, the prevalence of mental retardation appeared to increase with dose in a manner consistent with a linear, no-threshold response, although the data do not exclude a threshold in the range of 0.2-0.4 Gy (20-40 rads).

Another area of concern with radiation and the fetus is the induction of cancer. The fetus appears to be very susceptible to cancer induction. Data from Stewart and others suggest that in utero radiation exposure may increase the likelihood of early childhood cancer by 50% or more depending on the given radiation dose. The cancers primarily involved are leukemia and tumors of the central nervous system. In these cases too, first trimester radiation exposure is more likely to result in damage than is second or third trimester exposure. The increased cancer risk appears to exist only through the first 8-10 years of life.

In these sessions, we have discussed some of the historical background and the supporting information that enters into our understanding of the biology of ionizing radiation. Exposure of patients and radiation workers to ionizing radiation requires knowledge of the potential risks as well as the benefits to be gained from such exposure. This information also provides the basis for the regulations that govern the use of radiation in the day to day operation of a radiology department or any radiation facility.

Hall, E.J., Radiation and Life, 2nd edition, Pergammon Press, New York, 1984.
Hall, E.J., Radiobiology for the Radiologist, 4rd edition, J.B. Lippincott, Philadelphia, 1994.
National Research Council, Health Effects of Exposure to Low Levels of Ionizing Radiation-BEIR V, National Academy Press, Washington D.C., 1990.
Nias, A.H.W., An Introduction to Radiobiology, John Wiley and Sons, New York, 1990.
Travis, E.L., Primer of Medical Radiobiology, 2nd edition, Yearbook Medical Publishers, Chicago, 1989.