Radiation Risks from Exposure to Chest Computed Tomography

Biological Effects of Ionizing Radiation 

The passage of ionizing radiation (x-rays) through a cell results in liberation of free electrons. These free electrons may directly interact with the cellular DNA producing breaks in the double helix, or the electrons may first combine with other molecules to produce free radicals that, in turn, damage the DNA.3 Cellular defense mechanisms include free radical scavengers and antioxidants, DNA repair mechanisms, and apoptosis.4 Failure of the cellular repair mechanism may result in cell death and or loss of function. Some mutated cells may survive later to cause cancers in somatic cells or inheritable, genetic mutations in germ cells.5

Cell death may manifest as deterministic biological effects, such as skin burns or cataracts. Deterministic effects only occur when a finite, threshold dose is attained. The severity increases as the dose further exceeds threshold.5 Radiation doses associated with most diagnostic imaging procedures are insufficient to produce deterministic effects. Genetic mutations may lead to stochastic effects, such as cancers or inheritable, genetic defects. These effects do not have threshold doses. Instead, the probability of a stochastic effect increases directly with increasing dose.5 Stochastic effects, specifically cancers, are the primary risk associated with ionizing radiation exposure from diagnostic imaging.6

Radiation Dose Measurements 

Absorbed dose represents the amount of energy absorbed per unit mass within an object at a specific point7, 8, 9, 10 (Table 1). The unit for absorbed dose is the gray (1 Gy = 1 J/kg and 1 Gy = 100 rad). Absorbed dose can be estimated from Monte Carlo computer programs or from anthropomorphic phantom representations of an “average” patient.11 The equivalent dose for a given organ or tissue is expressed in sieverts (Sv). It is calculated by multiplying absorbed dose by a radiation weighting factor. In the case of x-rays, the radiation weighting factor is equal to 1. Therefore, the equivalent dose is equal to the absorbed dose.

Table 1. Radiation Dosimetry Units of Measure

	Term	Definition	Unit (SI)	How Measured/Derived
	Radiation exposure	Number of ions produced per unit mass of air	Coulombs per kilogram (C/kg)	Ion chamber
	Air kerma	Amount of energy released per unit mass of air	Coulombs per kilogram (C/kg)	Ion chamber
	Absorbed dose	Energy absorbed per unit mass	Gray (Gy)	Monte Carlo simulations Anthropomorphic phantoms
	Dose equivalent	Modification of absorbed dose to account for differing biological effects of different types of radiation	Sievert (Sv)	Absorbed dose × quality factor
	Effective dose (E)	Dose that the whole body would receive from a uniform exposure that would give the same cancer risk as the dose from a non-uniform exposure of various organs/tissues	Sievert (Sv)	Σ(tissue weighting factor × dose equivalent)

The concept of an effective dose (E) exists as a means to estimate an averaged whole body dose from an inhomogeneous exposure, such as a CT examination. The unit for effective dose is the Sv. The effective dose is a summation of all the respective organs' equivalent doses multiplied by their respective tissue weighting factors (ωT), which are measures of the organs' radiosensitivities.9 Tissue weighting factors are based upon statistical analyses of the tissue and organ specific cancer incidence rates in survivors of the atomic bomb blasts.12 The effective dose is a widely used means of comparing exposures between radiologic procedures and also estimating potential biological detriment (ie, carcinogenesis, life shortening, hereditary effects) from a particular radiation exposure.10, 13

A dose parameter specific to CT is the CT dose index 100 (CTDI100)14 (Table 2). The CTDI100 represents the dose measured in air or in a phantom, but it does not quantify patient risk.15 CT dose index weighted (CTDIw) represents two-thirds of the CTDI100 peripheral dose plus one-third of the CTDI100 central dose.

Table 2. Parameters Specific to CT

	CT Dose Parameter	Definition	Unit
	CT dose index 100(CTDI100)	The integral of the dose profile produced in a single axial scan along a line perpendicular to the imaging plane from −50 mm to +50 mm, divided by the product of the number of slices and the nominal collimation width.	Gray (Gy)
	CT dose index weighted (CTDIW)	2/3 of the CTDI 100 peripheral dose plus 1/3 of the CTDI100 central dose.	Gray (Gy)
	CTDI volume (CTDIvol)	The average dose over the total volume scanned: for axial scans, CTDIvol = [(N*T)/Δd]*CTDIw. where N is the number of slices in a single rotation, T is the slice thickness and Δd is the table travel in the Z direction. For helical scanning the CTDIvol is the CTDIw divided by pitch.	Gray (Gy)
	Dose-length product (DLP)	CTDIvol multiplied by scan length (cm)	mGy-cm
	Effective dose (E)	DLP multiplied by conversion coefficient	Sievert (Sv)

For helical scanning, dividing the CTDIW by the pitch yields the CTDI volume. CTDI volume is multiplied by the scan length (cm) to derive the dose-length product, which is expressed in milligray–centimeters (mGy–cm).9 Multiplying the dose-length product by a conversion coefficient specific to the body part imaged provides an estimate of the effective dose for a CT examination15, 16 (Fig. 1).

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Figure 1. Estimating effective dose from a chest CT scan (64-MDCT scanner (Lightspeed VCT; GE Medical Systems, Milwaukee, WI); 120 kVp, automated mA, 1.375 pitch, 5 mm slice thickness) for a model patient.

Limitations exist in calculating effective dose and in using it to estimate the probability of stochastic effects from medical imaging. Although a full discussion of these limitations is beyond the scope of this review, it is important to recognize that significant errors may occur as a result. Errors in the range of ±40% in the calculated effective dose and a factor of ±3 in derived risk for a reference patient are possible.17 Because of this wide variability, some experts argue that effective dose should not be used to assign a risk estimate to an individual patient.18

Risk estimates of radiation-induced cancer incidence and mortality at the relatively low levels used in medical imaging are based upon statistics derived from 100,000 survivors of the 1945 atomic bomb blasts over Hiroshima and Nagasaki, Japan.19, 20 Based upon the data collected from this cohort, several dose–response models have been proposed.21 A general consensus exists among several national and international agencies that “there is a linear, no threshold dose–response relationship between exposure to ionizing radiation and the development of cancer in humans” as stated by the BEIR VII Committee.22

The atomic bomb survivor cohort has demonstrated a statistically significant increased solid-cancer mortality rate in those exposed to 5-125 mSv with a mean exposure of 35 mSv and a statistically significant higher incidence rate at 5-100 mSv with a mean dose of 29 mSv.21 Similarly, data from multiple other cohorts exposed to medical radiation supports an association between radiation dose and the development of radiation-induced cancers.23, 24

Nevertheless, the application of the linear, no threshold model, and the extrapolation of data ranging from whole body exposures to anatomically limited exposures used in medical imaging have been challenged.4, 25 Disagreement results from uncertainty in calculations of the true radiation exposure received by the atomic bomb blast survivors, differences in the natural cancer risks in the Japanese population compared with other populations, and the different quality of the radiation emitted from the atomic bomb compared with that used with medical imaging.26

Growth of CT Imaging 

In comparison with 1993 when 18 million CT scans were performed in the United States, approximately 67 million were performed in 2006, which accounted for 15% of all radiologic and nuclear medicine imaging procedures.27 This corresponds to an annual growth rate of greater than 10%. During this same period, the annual growth rate of the United States population was less than 1%. The National Council of Radiation Protection reports that the growth of medical imaging, especially CT, contributed to a rise in the approximate annual per capita effective dose (background and medical) to 6.2 mSv in 2006.28 About 2.98 mSv could be attributed to medical imaging in general28 and 1.5 mSv of this medical radiation exposure was from CT examinations alone (Table 3).29 In contrast, the annual effective dose to the average American in 1982 was 3.6 mSv with all medical imaging procedures contributing just 0.54 mSv (15%) to this total.30 Similar trends are seen in the UK. In 1989, CT comprised just 2% of the diagnostic x-ray examinations and 20% of the collective medical radiation exposure, but by 1999 this had risen to 4% and 40%, respectively.31 Furthermore, approximately 3 million CT scans were performed in the UK in 2007-2008 in comparison with 0.25 million scans performed in 1980.32, 33

Table 3. Radiation Exposure in the United States Per Capita

Data source.27, 28, 29

a Collective effective dose estimated from NCRP Report No. 160.29

The growth in CT utilization encompasses all patient demographics. Mettler et al34 found that CTs performed on children under the age of 15 constituted about 11% of the total number of CTs performed between 1990 and 1999. Similarly, data from a major, American pediatric hospital demonstrated a 92% increase in CTs of the abdomen and pelvis performed on children under 15 years of age from 1996 to 1999.35 These findings are especially concerning because children are more sensitive to the effects of ionizing radiation. The effective dose delivered to a child is larger than that for an adult for a given CT examination. Children have a longer life expectancy and, thus, more time to develop a radiation-induced cancer. These concerns recently prompted the inception of the “Image Gently” campaign. Image Gently is a collaborative effort between multiple radiologic and medical subspecialty societies aimed at increasing awareness of pediatric radiation exposures and providing methods to reduce radiation doses in pediatric imaging.36

The rapid growth in CT utilization has not necessarily been accompanied by an increased awareness of the radiation doses associated with it. Studies have demonstrated that patients, ordering physicians, and radiologists tend to underestimate the radiation associated with CT examinations.37, 38, 39 An even larger percentage fail to recognize the potential associated cancer risks.38 As demonstrated in a study by Soye and Paterson40 and endorsed by the American College of Radiology, formal educational programs addressing radiation exposure to patients from diagnostic imaging result in an increased awareness of potential radiation risks among ordering providers.2 It remains to be seen whether this increased risk awareness will result in significant changes in referral patterns for these studies.

Cancer Risks Associated with CT 

The probability of developing cancer from all causes is approximately 420 out of 1,000.6 Because of this high, natural background incidence, difficulty exists in precisely quantifying excess risk attributable to the low levels of radiation used with most diagnostic imaging studies. Additionally, radiation-induced cancers occur in the same age range as spontaneous cancers, further complicating the task of attributing disease to radiation and not natural background risk.41

Data from the atomic bomb survivor cohort demonstrate that the risk of an individual dying from a radiation-induced cancer is small.12 However, recent analysis of incident cancer data by Preston et al19 found that approximately 11% of all solid cancers in the cohort were associated with atomic bomb radiation exposure. It should be noted that the individual excess risk demonstrated significant variation with respect to patient gender, attained age, and age at exposure. Nevertheless, when a small individual risk is applied to populations numbering in the tens of millions, the potential number of radiation-induced cancers becomes alarming and represents a public health problem. This rationale underlies the concern expressed over the growing use of medical imaging in the care of an ever-expanding patient population. Because of its increasing utilization and consequential population radiation burden, CT is at the forefront of this debate. A recent article claiming that CT may be responsible for 1.5%-2.0% of all cancers in the near future was widely publicized in the mainstream press.42

11.6 million (17.4%) of the 67 million CT scans performed in the United States in 2006 consisted of protocols evaluating the chest, total body for cancer screening, and the heart for calcium scoring or coronary angiography (Fig. 2).27 Furthermore, institutional data presented by Sodickson et al43 demonstrated that CT protocols embodying chest anatomy accounted for approximately 37% of the 190,712 CT examinations performed over a 22-year review period. The most likely target organs for radiation-induced cancers in adults are the breast and lung. The absorbed dose to the thyroid gland can potentially be among the highest organ absorbed doses depending on the CT protocol and field of view applied.44 However, the risk of radiation-induced thyroid cancer from CT examinations performed on adults is not considered to have the epidemiologic significance of breast and lung cancer. On the contrary, radiation-induced thyroid cancers resulting from routine CT imaging of pediatric patients, especially female patients, is of significant concern.35, 45

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Figure 2. Pie chart depicting the breakdown of CT scans by examinations performed in the United States in 2006, Mettler et al.27, 28, 29 (Color version of figure is available online.)

Cancers 

Approximately 11.1 million Americans live with cancer. In 2009, an estimated 1,479,350 people will likely be diagnosed with cancer in the United States with 562,340 expected cancer deaths.46 Lung cancer will likely be diagnosed in 116,090 men and 103,350 women, and 88,900 men and 70,490 women will likely die of their disease, making it the number one cause of cancer mortality.46 With the exception of nonmelanoma skin cancer, breast cancer is the most common form of cancer in women. In 2009, 192,370 women will be diagnosed with and 40,170 will die from breast cancer in the USA.46

The effects of radiation on breast cancer induction have been extensively studied in multiple cohorts, including the atomic bomb survivors and other patients including those patients subjected to frequent radiography or fluoroscopy for evaluation of scoliosis and tuberculosis; radiation treatment for benign breast diseases and post-partum mastitis; thymic radiation in infants; radiation treatment of skin hemangiomas; and radiation treatment for childhood and adult cancers.47, 48 In the atomic bomb survivor cohort, about 27% of breast cancer cases were attributed to radiation exposure with an excess relative risk (ERR) of 0.87 per Gy and an excess absolute risk (EAR) of 9.2 per Gy.19 The EAR represents an annual increase of 9.2 breast cancers per year per 10,000 people exposed to 1 Gy. Lung cancer was the second most common cancer in the cohort.19 One hundred seventeen excess cases of lung cancer (approximately 15% of cases) were attributable to radiation exposure. The ERR/Gy was 0.28 for men and 1.33 for women with an EAR/Gy of 6.0 and 9.1, respectively. Unlike other solid cancers, lung cancer risk increased with advancing age at exposure.49 Furthermore, the data suggested that smoking and radiation may have additive effects on lung cancer induction as proposed earlier by Pierce et al.19, 50

According to the BEIR VII report, a population of 100,000 persons consisting of all ages and sexes exposed to 0.1 Gy will sustain 210 deaths from radiation-induced lung cancer and 37 deaths from radiation-induced female breast cancer.49 These organ-specific cancer incidence and mortality statistics serve as the basis upon which cancer risks associated with medical imaging, including CT, are estimated.42, 51 For example, Berrington de Gonzalez and Darby52 calculated cancer risks by applying the BEIR VII report statistics to volumes and patterns of diagnostic x-ray use in 15 countries. They concluded the following: 5,695 (0.9%) and 700 (0.6%) of annual cancers in the United States and the UK, respectively, could be attributed to diagnostic imaging; 70 cancer cases per year in the UK could be attributed to CT scans alone; 21 (0.1%) and 40 (0.5%) of lung cancers per year in men and women, respectively, may be attributed to diagnostic imaging; and 29 (0.1%) of breast cancers could be attributed to medical imaging.

CT for Lung Cancer Screening 

Lung cancer is a major public health concern and the leading cause of cancer death in the United States. It is estimated that 219,440 new cases of lung cancer will be diagnosed in the United States in 2009 with 159,390 deaths.46 Lung cancer accounts for more deaths than breast, colorectal, and prostate cancers combined.53 Five-year survival for all lung cancers is only 16%. For non–small-cell lung cancers, however, detection of localized (stage I/II) disease results in 60%-70% 5-year survival whereas advanced (stage III or greater) disease is associated with a less than 10% 5-year survival.54 By the time that lung cancer presents clinically, it is usually at an advanced stage. Early-stage disease is almost always diagnosed incidentally on imaging studies performed for other indications.55 Therefore, there is an initiative to use CT for lung cancer screening (ie, in asymptomatic patients). CT screening for lung cancer is predicated upon the presumptions that cancers most commonly present as noncalcified pulmonary nodules, low-dose chest CT protocols accurately detect small pulmonary nodules, and detection of early-stage disease results in improved survival.56

Results from the largest, randomized, controlled studies undertaken to date are still pending. Observational lung cancer screening trials have revealed the following: (1) a large number of noncalcified pulmonary nodules are detected; (2) the vast majority of these are benign; (3) the lack of specificity of CT in characterizing nodules and the differing clinical approaches to their work up can lead to a high percentage of invasive procedures being performed; (4) a greater number of total lung cancers are detected than would be expected without screening; (5) of cancers detected, a large percentage are adenocarcinomas; (6) and a higher percentage of stage I cancers are found.54, 55, 57, 58, 59, 60, 61, 62, 63, 64 Results from the International Early Lung Cancer Action Program trial demonstrated that CT screening resulted in 85% of detected lung cancers being stage I with an estimated 10-year survival of 88% in this subgroup.65 However, these promising survival statistics are tempered by several biases (lead time, length time, and overdiagnosis bias) that are inherent to screening tests.66 To date, there is no evidence that CT screening leads to a reduction in advanced stage lung cancers or cancer-related mortality—the hallmarks of an effective screening test, although the latter may be partially attributed to insufficient follow-up periods.67 Therefore, the American College of Chest Physicians does not recommend the use of chest CT for lung cancer screening outside of clinical trials.59

One measure of an effective screening test is that it causes little morbidity.58 Because screened individuals are by definition asymptomatic and “healthy,” it is imperative that a screening test shows beneficial results without causing harm.68 Therefore, the non-negligible radiation risks associated with CT screening and morbidity associated with biopsies of benign nodules must be weighed against the potential benefits. The predominant risk of CT lung cancer screening is radiation-induced lung cancer. This is of concern because data from the atomic bomb survivors demonstrate that the risk of radiation-induced lung cancer does not decrease with increasing age, unlike other solid cancers. Instead, the risk peaks between the ages of 50-60 years, which roughly corresponds to the age range of the targeted screening population.49

The low-dose, chest CT techniques utilized in the larger screening studies vary with most employing 120-140 kVp, 20-40 mA, 5-10 mm collimation, and a pitch of 1.5-2.0 (Fig. 3).63 Swenson et al69 estimated an average effective dose of 0.65 mSv from screening chest CTs. Similarly, Diederich et al56 estimated effective doses of 0.6 mSv for men and 1.1 mSv for women from one low dose scan. Based on estimates from the International Commission on Radiological Protection, 3 (men) to 6 (women) cases of radiation-induced cancer would occur in every 100,000 screened individuals over 15-20 years. These estimates do not account for annual repeat or follow-up examinations.69

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Figure 3. Stable, noncalcified right middle lobe pulmonary nodule (arrows). (A) Representative axial image and dose report from a routine chest CT (120 kVp, 320 mA, 5.0 mm slice thickness, pitch 0.75). (B) Low-dose chest CT (120 kVp, 80 mA, 5.0 mm collimation, pitch 1.5) performed 2 years later demonstrates satisfactory visualization of the nodule and an approximately 90% reduction in dose over (A).

Using data from the ITALUNG screening trial, Mascalchi et al70 performed a risk-benefit analysis of CT lung cancer screening. They factored in additional examinations necessary for follow-up and interventional CTs for the management of indeterminate, suspicious nodules in calculating cumulative 4-year effective mean total body doses based on Early Lung Cancer Action Program follow-up criteria. They estimated effective doses of 3.3 mSv with MDCT and 5.8 with single-detector CT. These doses corresponded to an estimated 11.7 and 20.5 respective radiation-induced fatal cancers per 100,000, 50-70 year olds screened. The group concluded that the benefits of a 4-year screening program with a lung cancer specific mortality reduction of 10%-30% outweighs the risks posed to both male and female smokers. The data did not support screening of never-smokers, and it was indeterminate for the screening of former smokers. Therefore, if CT screening trials cannot demonstrate a significant reduction in overall lung cancer mortality, then risks associated with screening cannot be justified.70

Based upon techniques reported in multiple low-dose CT lung cancer screening trials, Brenner71 estimated the organ specific dose to the lung to be 5.2 mGy. Accounting for sex and smoking status and assuming that 18 of the 36 million current and former smokers complied with annual CT screening beginning at age 50 and continuing through age 75, he concluded that 36,000 lung cancers in the screened population would be radiation-induced. This represents a 1.8% (95% CI: 0.5%-5.5%) increase over the 1.9 million cases expected in the absence of screening. This risk could be reduced by increasing the minimum screening age to 60 or by instituting biannual screening.71

Whole Body CT Screening 

The idea of CT screening has expanded beyond the lungs and cancer to include whole body screening. A single CT examination is performed to evaluate for such diseases as lung cancer, coronary artery disease (CAD), colon cancer, cancers of the abdominal viscera, and aortic aneurysms. These examinations are mostly performed by private imaging groups, with the target population being asymptomatic, self-referred, self-paying individuals.

The concept of whole body screening has created debate. Proponents laud the ability to detect a wide array of disease processes. Critics complain about the lack of a proven benefit, high false-positive rates, lack of a standard technique, hypothetical medicolegal issues that may result, and associated radiation risks.72, 73, 74, 75 Burger et al76 surveyed radiologists' attitudes towards CT screening examinations. They found that the primary motivation for performing whole body examinations was to satisfy physician and patient requests whereas the primary reasons for not performing such examinations were the lack of a proven benefit and the high rate of incidental findings.

Because patients are frequently self-referred and there is no targeted age demographic, there can be high cumulative lifetime doses from decades of annual examinations.22 In contrast to the low-dose protocols utilized in lung cancer screening trials that take advantage of the inherent contrast provided by the aerated lung, whole body CT examinations may utilize regular dose protocols to aid in the detection of subtle, solid organ cancers. Therefore, the potential for significant whole body doses exists with wide variability between different scanners and manufacturers.77 Brenner and Elliston44 estimated the organ dose to the lung to be 15.5 mGy and the whole body effective dose to be 12 mSv for a typical scan. They concluded that radiation-induced lung cancer would be the dominant cause of cancer mortality from whole body CT examinations. In a more recent article, Hall and Brenner51 reduced these dose estimates to approximately 9 mGy and 7 mSv, respectively; but they still estimated a lifetime cancer mortality risk of 4.5 × 10−4 (1 in 2200) for a 45-year-old undergoing a single examination with even higher risks associated with multiple scans.

CT Coronary Angiography 

Initially restricted to electron-beam CT (EBCT) scanners, the field of cardiac CT has grown rapidly with improvements in CT technology over the past decade. Through the development of multidetector row technology and electrocardiography (ECG)-synchronized scanning and reconstruction techniques, barriers to high-quality cardiac imaging such as the need for rapid acquisition times and high spatial and temporal resolution have been overcome.78 CT now provides a noninvasive means of evaluating the coronary arteries. Previously, this was possible only by conventional angiography—a more invasive procedure compared with CT with serious risks. Additionally, CT coronary angiography (CTCA) is being used both to screen for CAD and to triage patients presenting with chest pain and risk factors for acute coronary syndrome.

Atherosclerosis is the major cause of CAD. CAD affects more than 24 million adults in the United States. It is the leading killer of Americans accounting for more than 650,000 deaths in 2005.79 Approximately 50% of patients with CAD present with a myocardial infarction as the initial manifestation. More than 50% of patients sustaining an acute MI will die within the subsequent month.80 Acute chest pain is the second most common reason for emergency room visits.81

Throughout much of the 1990s, cardiac CT was possible only with EBCT owing to its ability to acquire high resolution images in 100 milliseconds.82 EBCT gained wide acceptance as a screening tool for the detection of coronary artery calcifications, which serve as a measure of overall coronary plaque burden and a predictor of future CAD events.82 More recently, helical CTs with faster gantry rotation times and multidetector rows have been used for coronary artery calcium scoring. These noncontrast examinations are limited in that the noncalcified atherosclerotic plaque burden is not assessed. These noncalcified plaques may be more unstable and prone to rupture leading to acute coronary syndrome.83 Additionally, although detection of coronary artery calcifications is nearly 100% sensitive for predicting the presence of coronary artery atherosclerosis, it is nonspecific for identification of hemodynamically-significant lesions, thereby limiting coronary artery calcium scoring CT examinations.84

Contrast-enhanced CTCA provides a noninvasive means of evaluating for coronary artery stenosis, atherosclerotic plaque characterization, coronary artery anomalies, bypass graft patency, and stent patency.85 The clinical role of CTCA in the assessment of CAD continues to evolve. Consensus statements support its use in chest pain patients with a low to intermediate pre-test probability of CAD, patients with uninterpretable ECGs, and patients who cannot exercise.86, 87 Risk assessment in the appropriate triage of patients with suspected CAD to CTCA will undoubtedly improve as evidence-based algorithms for practice are performed. Of primary benefit is the exclusion of significant CAD in patients with chest pain, thus facilitating their earlier discharge and obviating the need for further expense and work-up.81 Early studies with 16-detector row CTCA found a high percentage of false positives and non-evaluable coronary artery segments.88 However, the improved spatial resolution and shorter acquisition times possible with 64-MDCT have improved diagnostic performance with a significant reduction in both the number of false positives and non-evaluable segments.89

The increasing utilization of cardiac CT as both a screening and diagnostic examination coupled with the lack of standardized protocols has raised concerns regarding the radiation risks associated with these examinations. Hunold et al90 estimated the effective dose from EBCT coronary calcium scoring examinations to be 1.0 mSv for men and 1.3 mSv for women. Coronary calcium scoring with MDCT results in effective doses ranging from 1.0-6.2 mSv with retrospective ECG-gating and 0.5-1.8 mSv with prospective ECG-gating.91 Effective doses from contrast-enhanced CTCA on average are higher (4.0-21.4 mSv) because of (1) wide dose variations between different protocols, (2) different scanning equipment, and (3) variable implementation of dose-savings techniques.91 In comparison, the mean effective dose from a dual isotope myocardial perfusion study and conventional angiography are approximately 29.2 and 7 mSv, respectively.91

Improvements in diagnostic performance from increasing detector rows come at the cost of higher effective doses delivered to patients.91, 92, 93 A recent, international, multicenter study of CTCA revealed that 96% of patients were examined on 64-MDCTs as opposed to 4% on 16-MDCTs.94 Effective doses calculated from dose length products for 64-MDCT examinations averaged 12 mSv with a range of 5-30 mSv across individual institutions, which reflects the variability in protocols and implementation of dose-saving strategies. Similar estimates of 11.7-13.0 mSv have been measured in phantom studies employing retrospective ECG-gating.95

With cardiac CT examinations, the lungs and breasts have among the highest absorbed doses because they are directly in the radiation beam.90 Einstein et al96 calculated respective equivalent doses to the lungs and breasts in females to be up to 80 and 91 mSv in CT angiography protocols that include the aorta (ie, “triple rule-out” examinations). They calculated the lifetime ERR of cancer in a 20-year-old female from a standard CTCA without ECG-controlled tube current modulation to be 0.70% or 1 in 143. Although the total risk of developing a radiation-induced cancer decreased with advancing age, breast and lung cancer combined accounted for a constant 80%-85% of the excess risk at all ages.

Hurwitz et al97 determined organ and effective dose measurements from an anthropomorphic female phantom undergoing ECG-controlled tube current modulation CTCA to calculate lifetime attributable cancer risk. Organ doses to the breasts and lungs with CTCA protocols with maximum tube currents of 500 mA (protocol 1) and 750 mA (protocol 2) were approximately 4.8 and 4.4 mGy and 9.1 and 6.9 mGy, respectively. Respective mean effective doses were 17.9 and 31.8 mSv. With these data, they concluded that a 25-year-old female undergoing a single CTCA examination would have respective ERRs of breast and lung cancer of 1.4% and 2.4% for protocol 1 and 2.6% and 3.8% for protocol 2.

Hall and Brenner51 estimate that 7000 radiation-induced lung cancer deaths would occur if all 61 million eligible Americans were screened for coronary artery calcium pursuant to the Screening for Heart Attack Prevention and Education guidelines with MDCT delivering a typical lung dose of 10 mGy. These estimates are tempered by a recent study by Schoepf et al98 in which the excess lifetime risk of cancer was calculated in an actual patient cohort undergoing cardiac CT. They found that in their population in which most patients were male (62%), overweight (median weight 92 kg), and older (median age 59 years) that the average lifetime risk for developing a radiation-induced cancer was a significantly lower 0.12%.

Multiple techniques to lower radiation dose exist (Fig. 4). These include ECG-controlled tube current modulation, reducing tube voltage, prospective sequential scanning, reducing scan length, and increasing pitch.94, 99, 100, 101 The highest doses with CTCA occur with retrospective ECG-gated acquisitions. With this technique, there is continuous radiation exposure as highly overlapping image sections are acquired at low pitch values (0.25 and 0.4) resulting in considerable overscanning.78 Because the diastolic phase is associated with the least cardiac motion, data from the diastolic phases of several cardiac cycles are reconstructed to optimize both spatial and temporal resolution. Therefore, a large portion of the data acquired and radiation delivered throughout the cardiac cycle falls outside of the desired diastolic interval and is not utilized in image generation (Fig. 5A).102

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Figure 4. Normal coronary arteries in a 43-year-old with chest pain scanned with prospective-ECG gating and breast shields in place. Axial images at the level of the left (A) and right (B) coronary artery origins and curved multiplanar reformatted images of the left main (single arrow) and left anterior descending (double arrows) (C) and the left circumflex artery (triple arrows) (D) demonstrate satisfactory opacification and visualization of the arterial lumina (120 kVp, 650 mA, 0.35-s rotation time, 64 × 0.625 collimation, center of the imaging window set at 75% of the R-R interval) with satisfactory image quality for interpretation.

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Figure 5. Schematic representations of CT coronary angiography techniques. Areas shaded in gray represent the time interval during which the CT beam is on. The distance above the ECG baseline represents the relative tube current. (A) Retrospective ECG Gating, (B) Retrospective Gating with ECG-controlled tube current modulation, and (C) Prospective ECG Gating. (Color version of figure is available online.)

An alternative to this technique is ECG-controlled tube current modulation (“ECG pulsing”). Here, tube output is maximized during the diastolic interval and reduced by 80% through a reduction in tube current during all other phases of the cardiac cycle (Fig. 5B).80 Reported dose reductions of up to 50% are possible with dose savings indirectly related to heart rate.44, 80, 92, 93 Increasing the pitch according to higher heart rates yields even greater dose reductions.80 ECG-controlled tube current modulation use in “triple rule out” CTCA protocols has been reported to reduce effective dose by more than 50% (18.0 ± 5.6 mSv without vs 8.75 ± 2.64 mSv with) with superior subjective image quality in comparison with examinations performed without tube current modulation.103

Prospective ECG-gated (“step and shoot”) scanning is another technique for dose reduction. Here, the beam is triggered during a predetermined phase of the cardiac cycle (usually diastole) and is turned off during the remainder (Fig. 5C). The table does not move while the beam is on, but instead advances approximately 1 detector length every other heart beat.104 The effective pitch is slightly less than 1 as a small (approximately 5 mm) overlap is built in to allow for potential differences in the heart position between beats.100 Such precision scanning is best attempted in patients with slow, regular heart rates. Patients with variable heart rates can still be imaged by scanning for a predetermined time interval around the center of acquisition—a technique known as “padding.” Although this accommodates for variability in heart rate, it increases radiation dose.105 Effective doses from prospective ECG-triggered examinations are on the order of 2.0-4.2 mSv in patients with slow and regular heart rates in contrast to 12-20 mSv with retrospective ECG-gating.94, 104, 105, 106 Furthermore, image quality and assessment of luminal obstruction with prospective ECG-gated techniques is comparable to retrospective ECG-gated protocols in patients with regular heart rates of 75 beats per minute or less.104, 106

Adjusting parameters (mAs and kVp) in accordance with body habitus and weight can yield substantial dose savings. Lower voltage settings of 80 and 100 kVp have been used successfully in CTCA studies. In addition to reduced doses, lower kV settings allow for decreased volume of contrast administration as the k-edge of iodine is closer to the mean beam energy producing greater intravascular enhancement.93 In a multicenter, prospective study of nearly 5,000 patients across Michigan, Raff et al107 found that a reduction of tube voltage from 120 kVp to 100 kVp was the strongest variable in reducing patients' radiation exposure. Coupling of ECG-controlled tube current modulation with lower tube voltage (80 kVp) resulted in an 88% reduction in dose in slim patients without significant impairment of image quality.99 Similarly, prospectively-gated acquisitions coupled with a low (100) kVp yielded a 90% effective dose reduction over retrospective ECG-gating at 120 kVp.105 Despite the effectiveness of such radiation dose-saving techniques, a study by Hausleiter et al94 demonstrated the use of these techniques across many institutions is variable resulting in widely variable patient doses at different sites and with different scanners. Moreover, there was also system-specific variability in radiation doses for institutions using identical equipment, implying improvements in the use of dose-reduction algorithms are achievable.

Recent advances in cardiac CT include dual-source CT scanners. These utilize 2 x-ray tubes and 2 sets of detectors mounted on the gantry at 90° to one another. This configuration reduces the effective scan time necessary to generate 1 image from one-half of a gantry rotation with single source MDCT to one-quarter of a rotation with dual-source CT, effectively improving temporal resolution by a factor of 2.99 This creates many advantages such as scanning patients with higher heart rates without the need for beta-blocker medications; scanning patients with irregular heart rates; using higher pitch values in patients with higher heart rates thereby reducing radiation doses; reducing motion artifact; and improving characterization of atherosclerotic plaques.108

Employing 2 x-ray sources has raised concern of increased radiation doses. In a phantom study by McCullough et al,109 doses on the order of those with single source CTs and up to 50% lower were possible through the use of a cardiac beam shaping filter, a dedicated reconstruction kernel that utilizes a 3D adaptive noise reconstruction algorithm, increased pitch values for higher heart rates, and ECG-gated tube current modulation with narrower diastolic intervals. Mean effective doses of 7.8-8.8 mSv with dual-source CTCA have been reported with ECG-tube current modulation, and even significantly lower doses are possible with higher pitch.110 In a study of 200 patients, Alkadhi et al111 achieved dose reductions of 86% by tailoring protocols (retrospective ECG-gating vs prospective ECG-triggering) to patients' heart rates and tailoring tube voltage and current in accordance with BMI while still maintaining diagnostic image quality.

CT Pulmonary Angiography 

Diagnosing a PE is clinically difficult as symptoms are often nonspecific. Failure to make the diagnosis and institute appropriate treatment may result in substantial morbidity and mortality. Traditionally, ventilation-perfusion (VQ) radionuclide pulmonary scintigraphy and pulmonary angiography served as the primary imaging modalities in the work-up of suspected PE.112 Both tests, however, have significant limitations. VQ scintigraphy results in a significant number of patients for whom the diagnosis of PE is neither established nor excluded (up to 75%) and significant differences (25%-30%) in interobserver interpretation.113, 114 Limitations of pulmonary angiography include significant variability in interobserver interpretation; false positive examinations due to mediastinal processes; incomplete or nondiagnostic examinations; and small, but real, procedure-related morbidity and mortality.112

CTPA has supplanted VQ scintigraphy and conventional angiography as the imaging modality of choice in patients with suspected PE. Advances in MDCT technology and protocols, high interobserver agreement, wide availability, clinical validity of a negative scan, its relatively noninvasive nature, and its ability to define alternative diagnoses are just a few of the factors behind the change.115, 116 These benefits coupled with decreasing thresholds by clinicians to image for PE have driven the rapid rise in CTPA utilization. Donohoo et al117 found a 227% increase in CTPA examinations per month following the installation of a 16-MDCT scanner in their institution's emergency room. The rise in CTPA utilization was accompanied by a drop in the percentage of tests positive for PE and alternative diagnoses. Prologo et al118 reported similar results in their study of CTPA utilization among both emergency department and hospitalized patients. The greater reliance upon CTPA by clinicians creates concern over the potential radiation risks to patients, especially reproductive-age females, who may be referred for minor symptoms or with low clinical suspicion for PE.

Radiation doses from CTPA vary widely between scanner manufacturers and institutional protocols. However, representative dose estimates have been reported in the literature. O'Neill et al119 estimated the average effective dose for CTPA performed on a single-slice CT to be 1.6 mSv (range, 1.4-1.9 mSv), which is comparable to 1.2 mSv with VQ scans but less than 3.2 mSv with conventional pulmonary angiography. Kuiper et al120 reported average effective doses of 4.2 mSv (range, 2.2-6.0 mSv) for 4-MDCT derived from the CTDI compared with 7.1 mSv (range, 3.3-17.3) for conventional pulmonary angiography. Similarly, Coche et al121 found the average dose at the middle of the chest of an anthropomorphic phantom to be 4 times higher with digital subtraction angiography than with 4- and 16-MDCT pulmonary angiography. Reported average effective doses with 16-MDCT pulmonary angiography range from 1.37-3.28 mSv.122, 123 The large increase in dose seen with 4-MDCT over single-detector CT has not been observed with the increase to 16-MDCT from 4-MDCT. Increased numbers of thinner detector rows improve detector efficiency and create smaller penumbral effects relative to the primary beam width.124

Similar to other CT examinations, many strategies exist to reduce radiation doses from CTPA examinations to include the use of automated tube current modulation, lower kVp, and shorter scan lengths.125 Automated tube current modulation programs reduce doses by 5%-20%.121 Lowering the tube voltage by 20 kVp (ie, 80 vs 100 or 100 vs 120) has been shown to reduce effective dose by approximately 44% without a significant loss of image quality.122, 123, 126 Furthermore, the beam energy at lower kVp settings more closely approximates the k-edge of iodine, thus resulting in greater intravascular enhancement and making diagnostic examinations possible with smaller contrast volumes.

Radiation risks associated with CT cancer screening and CTCA protocols have been discussed previously within this review. In contrast to these examinations that target diseases largely affecting an older population, are limited in availability, and have yet to be clinically validated; CTPA is used in patients of all ages, is implemented in the acute care setting, is widely available, and is the new study of choice in imaging for PE. Multiple epidemiologic studies have demonstrated an increased risk of breast cancer in women exposed to ionizing radiation with the degree of risk dependent upon dose, age at exposure, and attained age.47, 48, 127, 128, 129 Therefore, breast exposures in young females from CTPA have proved to be a cause for concern.116

Parker et al130 reported that 60% of CTPA examinations performed on their institution's 4-MDCT from May 2000 through December 2002 were on women, and 26.7% of the women imaged were less than 40 years of age. The calculated dose delivered to the average 60-kg woman in their study was 20 mGy per breast, which far exceeds the 3 mGy permitted with a two-view, screening mammogram and the 0.28 mGy from perfusion lung scintigraphy.116, 130 A phantom study by Hurwitz et al131 calculated breast doses of 40-60 mGy delivered by a 16-MDCT using their institution's protocol. Based upon these data, they estimated that a female less than 20 years old undergoing a single CTPA would have a relative risk of 1.68 of developing breast cancer before age 35 years. In a subsequent 64-MDCT phantom study, Hurwitz et al132 reported potential dose reductions of 55% and 45% to the breast and lungs, respectively, through the use of lower kVp (120 vs 140), automatic tube current modulation, and bismuth breast shields without degradation of image quality. Other studies have demonstrated respective dose reductions of 40%-57% and 29% to the adult and pediatric breasts by the use of bismuth shields (Fig. 6).133, 134, 135

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Figure 6. Bismuth breast shields. (A) Breast shields lay upon a thin layer of foam. (B) Breast shields interposed between 2 layers of foam applied to this 30-year-old female volunteer. (C) and (D) Axial CT images from a CT pulmonary angiography study in an actual 35-year-old female patient with breast shields demonstrate right lower lobe segmental (arrow) and peripheral subsegmental (curved arrows) artery emboli (120 kVp, auto mA, 1.0 pitch, 1.25 slice thickness). (Color version of figure is available online.)

Imaging of pregnant women with suspected PE has sparked debate. Pregnant women have a 5-fold increased risk of venous thromboembolic disease because of physiological changes associated with the pregnant state, and pulmonary emboli are a leading cause of preventable maternal morbidity and mortality.136 Additionally, the radiation risks are 2-fold in that the risks to the fetus and the increased radiosensitivity of the proliferating maternal breast tissue must be considered (Fig. 7).

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Figure 7. Axial CT image from a CT pulmonary angiography examination performed without breast shields on a 25-year-old post-partum patient demonstrates proliferative glandular breast tissue (120 kVp, auto mA, 1.0 pitch, 1.25 slice thickness).

The initial work-up for PE should include a chest radiograph to exclude other pulmonary processes followed by lower extremity ultrasound. If the ultrasound is positive, then no further imaging for pulmonary embolus is warranted as anticoagulation treatment can be initiated. In instances in which lower extremity ultrasound is negative, then further evaluation with CTPA or VQ scintigraphy may follow. Exposures to the fetus with CTPA are conflicting with doses on the order of or even below lung scintigraphy reported in the literature.116 Regardless, both modalities result in a fetal dose well below 1 mGy. In fact, a work-up entailing chest radiography, lung scintigraphy, CTPA, and conventional pulmonary angiography combined would result in a fetal dose of about 1.5 mGy, which is still well below the 50 mGy threshold for deterministic effects in the fetus and is comparable to natural background radiation doses.136 However, it should be noted that there is a statistically significant increased chance of a nondiagnostic CTPA in pregnant patients when standard protocols are employed.137

It is likely that judicious use of CTPA combined with risk stratification of patients suspected to have signs and symptoms attributable to PE (chest pain, shortness of breath, tachycardia, etc) will result in much higher specificity in the diagnosis of PE. For example, the use of a D-dimer assay combined with CTPA has high positive and negative predictive values.138, 139

Conclusions 

The current models of risks associated with radiation exposure from medical imaging are in evolution. It may be decades before long-term data proving or disproving the risk of radiation-induced cancers from the use of CT become available. Until then, controversy will surround claims of possible risks associated with CT imaging that are extrapolated from the data of other exposed cohorts.

There is no controversy, however, regarding the fact that the risks associated with the use of ionizing radiation in medical imaging are real.140 Failure on the part of the radiology community, and the medical community at large, to take a proactive approach in reducing radiation exposure cannot be justified especially when the implementation of dose saving techniques and shielding have been shown to significantly reduce exposures without sacrificing diagnostic image quality. Failure to act now to curtail population radiation burden will likely result in preventable, radiation-induced cancers.

With further advances in CT technology, the utilization of CT imaging will continue to grow. It is incumbent upon the radiology community to take the lead in protecting patients from unnecessary radiation. In doing so, we must also better educate referring providers about the potential risks associated with CT. Multiple radiologic and medical subspecialty societies have already embraced such an approach as exemplified by the increasingly popular “Image Gently” campaign. Moreover, there is widespread acceptance of the as low as is reasonably achievable (ALARA).141

Radiologists must function as both gate-keepers and imaging experts. The former requires that requested examinations are clinically appropriate and the potential benefits outweigh the risks. The latter insures that recommendations for alternative imaging modalities lacking ionizing radiation are used when possible. Finally, when CT scanning of the chest is appropriate, tailored examinations with low dose algorithms are mandatory to minimize patients' radiation exposure.