Donald P. Frush and Thomas L. Slovis

Trends in Medical Radiation Exposure to Children

Approximately 4 billion imaging examinations using ionizing radiation (i.e., radiography, fluoroscopy/angiography, CT, and nuclear imaging) are performed annually worldwide.⁵ In the United States, medical imaging currently accounts for a significant percentage of the annual radiation exposure to the population (Fig. 1-2),⁶ and most sources demonstrate continued increased use during the past decade. For example, one study showed a fivefold increase in CT examinations in the pediatric acute care setting from 1995 to 2008.⁷ Natural or background sources account for about 50% of the annual radiation exposure in the United States, and diagnostic medical radiation accounts for most of the remainder, an approximately sixfold increase during the past 30 years. CT alone accounts for nearly 25% of all radiation exposure to the U.S. population.⁶ Many reasons exist for the increased use of diagnostic medical radiation, and much use of such radiation is based on sound medical decision making. However, other factors determine use as well, including defensive medicine.

Pathophysiology of Radiation Effects

Hall⁸ has written an excellent review of radiobiology for the radiologist. The biologic effects of radiation result primarily from damage to deoxyribonucleic acid (DNA)—the critical target. The first step in the absorption of x-rays is that the x-ray particle, the photon, gives up its energy to produce a fast recoil electron. The electron may damage DNA directly, but the electron also can interact with a molecule of water to produce a free radical (Fig. 1-3). A free radical is a highly reactive atom or molecule with an unpaired electron in the outer shell:

where the asterisk indicates a free radical.

The hydroxyl radical (OH) can diffuse a short distance to cause DNA damage. The fact that two thirds of x-ray damage occurs via OH suggests that someday this component of radiation damage might be reduced through the use of chemical radioprotectants. The topic of radioprotectants was recently well reviewed.⁹

The biologic effects of radiation result primarily from damage to double-stranded DNA as opposed to single-strand injury (see Fig. 1-3). Single-strand breaks of DNA are readily repaired and are presumed to have a negligible effect. Breaks in both DNA strands that are opposite or separated by a few base pairs are much more difficult to repair. These double-strand breaks can cause important biologic effects, including genetic mutations, carcinogenesis, and cell death. Dicentric and fragmented breaks typically result in cell death, whereas nonlethal translocation repairs may cause impaired cellular function, including development of an oncogene.⁸

The biochemical and physiologic damage produced by radiation generally occurs within hours or days, but the impact of these changes, such as the induction of cancer, can take decades to manifest. This carcinogenesis process has several steps. Aberrations in chromosomes (e.g., deletions, translocations, or aneuploidy) are produced by DNA damage. Because these impaired cells survive, they become “stable aberrations” (some with neoplastic transformation), a morphologic change that is the first step of a multistep process to radiation-induced carcinogenesis. The second step of the process is cellular immortality. That is, most cancer cells are descendents of a single cell that originally underwent neoplastic transformation. The third step is tumorgenicity. The radiation exposure induces a cellular genomic instability that is transmitted to progeny, which Little¹⁰ described as “a persistent enhancement in the rate of which genetic changes arise in the descendents of the irradiated cells after many generations of replication … [this process] has been termed a nontargeted effect of radiation as genomic damage occurs in the cells that in themselves receive no direct radiation exposure.”

Most childhood tumors (about 85%) occur sporadically, but in 15% of the cases, a strong family association and genetic basis for radiation sensitivity are present. Persons with certain diseases are uniquely sensitive to radiation-induced cancers, although the exact mechanism is unclear (Box 1-1).

Types of Radiation Bioeffects

The two types of biologic effects from radiation are deterministic and stochastic (random). Deterministic bioeffects are characterized by a threshold dose, and the severity of the effect is dose dependent. For example, cataracts traditionally are reported not to occur with less than a 2.0 Gy exposure, although recent data suggest that this threshold is below 1.0 Gy.¹¹ Table 1-1 shows some of the doses for deterministic effect. In general, deterministic effects from the doses used in diagnostic imaging are extremely rare. Recent exceptions with head perfusion CT scanning in adults have been reported.¹² Deterministic effects such as skin ulcers and burns should never occur from diagnostic imaging, but they are seen with relatively lengthy interventional procedures.

Stochastic effects are more of a concern because they have the potential to occur at any dose, and the severity of the effect is independent of the dose. No threshold exists with stochastic effects, but the probability of an effect (e.g., cancer) increases with increasing doses.

Fetuses and Children Have Greater Radiation Risks

From a public health perspective, all ionizing radiation from medical imaging is considered to be potentially harmful because we assume that no threshold exists below which radiation is safe (i.e., no harmful effects will occur). This “linear no threshold” model is applied to low-level radiation exposure.13,14

The effects of radiation are greatest on rapidly developing organisms—that is, fetuses, infants, and young children. In pregnancy, the major biologic effects of fetal demise, growth restriction, organ malformations, and cognitive deficits are seen only with doses far in excess of routine diagnostic imaging.¹⁵ The risk of developing cancer from exposure of a fetus to radiation is uncertain, as it is with exposure of a child to radiation; potential effects could be seen with uterine doses that occur as a result of relatively high direct exposures (e.g., a pelvis CT scan for possible appendicitis). No data in humans indicate that genetic effects result from diagnostic levels of radiation.

Compared with middle-aged adults, children have been reported to be from 2 to 15 times more sensitive to radiation-induced carcinogenesis.16,17 However, Shuryak et al¹⁸ recently noted that the cancer induction risk (greater at younger ages) must be balanced with the radiation-induced promotion of premalignant damage (greater in middle age), which may differ for certain types of cancer. Thus cancer risks may be higher in the adult population than traditionally believed.¹⁸

Low-dose effects have been described by Pierce and Preston,¹⁹ who studied the data from atomic bomb survivors reported by the Radiation Effects Research Foundation. Among persons who had received dosages of 0.005 to 0.2 sievert (500 mrad to 20 rad), 35,000 people survived, and 5000 cases of cancer developed. The authors made the following conclusions: first, the solid cancer risk persists for more than 50 years. Second, there is a 10% increase over the expected cancer rate.¹⁹ Low-dose relative risk factors are shown in Figure 1-4.

The overall risk of cancer for the entire population suggested by the International Commission on Radiological Protection is 5% per sievert for low doses and low-dose rate. However, this value is an average value. For adults in late middle age, the risk decreases to only 1% per sievert, whereas for children in the first decade of life, the risk may be as high as 16% per sievert for girls and 12% per sievert for boys. The female dose is higher because of the greater incidence of breast and thyroid cancers (Fig. 1-5). Radiation risks from diagnostic imaging low-level radiation were reviewed recently.²⁰ Two excellent reviews also recently were published by Linet et al^21,22 (Table 1-2). At this point, we have cautious uncertainty regarding cancer risk and low-level radiation. As Hricak et al²³