Andrew J. Einstein

Exposure to Low-Dose Ionizing Radiation from Medical Imaging Procedures

BACKGROUND The growing use of imaging procedures in the United States has raised concerns about exposure to low-dose ionizing radiation in the general population. METHODS We identified 952,420 nonelderly adults (between 18 and 64 years of age) in five health care markets across the United States between January 1, 2005, and December 31, 2007. Utilization data were used to estimate cumulative effective doses of radiation from imaging procedures and to calculate population-based rates of exposure, with annual effective doses defined as low (< or = 3 mSv), moderate (> 3 to 20 mSv), high (> 20 to 50 mSv), or very high (> 50 mSv). RESULTS During the study period, 655,613 enrollees (68.8%) underwent at least one imaging procedure associated with radiation exposure. The mean (+/-SD) cumulative effective dose from imaging procedures was 2.4+/-6.0 mSv per enrollee per year; however, a wide distribution was noted, with a median effective dose of 0.1 mSv per enrollee per year (interquartile range, 0.0 to 1.7). Overall, moderate effective doses of radiation were incurred in 193.8 enrollees per 1000 per year, whereas high and very high doses were incurred in 18.6 and 1.9 enrollees per 1000 per year, respectively. In general, cumulative effective doses of radiation from imaging procedures increased with advancing age and were higher in women than in men. Computed tomographic and nuclear imaging accounted for 75.4% of the cumulative effective dose, with 81.8% of the total administered in outpatient settings. CONCLUSIONS Imaging procedures are an important source of exposure to ionizing radiation in the United States and can result in high cumulative effective doses of radiation.

Radiation Dose to Patients From Cardiac Diagnostic Imaging

The volume of cardiac diagnostic procedures involving the use of ionizing radiation has increased rapidly in recent years. Whereas in 1990, fewer than 3 million nuclear cardiology studies were performed in the United States, by 2002 this figure more than tripled to 9.9 million.1 Cardiac computed tomographic (CT) volume doubled between 2002 and 2003, to 485 000 cases,2 and has continued to grow since then. The volume of procedures performed in cardiac catheterization labs increased from 2.45 million in 1993 to 3.85 million in 2002.3 The powerful diagnostic and risk-stratification data provided by these procedures play a central role in clinical cardiology and have contributed to the decrease in morbidity and mortality from coronary heart disease. Nevertheless, performance of any diagnostic test requires a careful assessment of the risks and benefits of the test and optimization of protocols to minimize risks to patients, staff members, and the public. Procedures that utilize ionizing radiation should be performed in accordance with the As Low As Reasonably Achievable (ALARA) philosophy. Thus, physicians ordering and performing cardiac imaging should be very familiar with the dosage of radiation from cardiac diagnostic tests and ways in which dose can be minimized. In this report we discuss the measurement of radiation and the dosimetry of commonly performed cardiac diagnostic imaging tests, including nuclear scintigraphy, CT for calcium scoring and coronary angiography (CTCA), and conventional coronary angiography (CCA). For each modality, we address the terminology and methodology used to quantify radiation received by patients, doses to patients with typical protocols, and dose-reduction techniques. Biological effects of ionizing radiation can be classified as deterministic or stochastic. Deterministic effects such as skin injuries and cataract formation occur predictably when dose exceeds a certain threshold, whereas stochastic effects such as cancer incidence and germ cell mutations occur with …

Cumulative Exposure to Ionizing Radiation from Diagnostic and Therapeutic Cardiac Imaging Procedures: A Population-Based Analysis

OBJECTIVES The purpose of this study was to describe radiation exposure from cardiac imaging procedures over time in a general population. BACKGROUND Cardiac imaging procedures frequently expose patients to ionizing radiation, but their contribution to effective doses of radiation in the general population is unknown. METHODS We used administrative claims to identify cardiac imaging procedures performed from 2005 to 2007 in 952,420 nonelderly insured adults in 5 U.S. health care markets. We estimated 3-year cumulative effective doses of radiation in millisieverts from these procedures We then calculated population-based annual rates of radiation exposure to effective doses < or =3 mSv/year (background level of radiation from natural sources), >3 to 20 mSv/year, or >20 mSv/year (upper annual limit for occupational exposure averaged over 5 years). RESULTS A total of 90,121 (9.5%) individuals underwent at least 1 cardiac imaging procedure using radiation. Among patients who underwent > or =1 cardiac imaging procedures, the mean cumulative effective dose over 3 years was 23.1 mSv (range 1.5 to 543.7 mSv). Myocardial perfusion imaging accounted for 74% of the cumulative effective dose. Overall, 47.8% of cardiac imaging procedures were performed in physician offices; this proportion was higher for myocardial perfusion imaging (74.8%) and cardiac computed tomography studies (76.5%). The annual population-based rate of receiving an effective dose of >3 to 20 mSv/year was 89.0 per 1,000; and 3.3 per 1,000 for cumulative doses >20 mSv/year. Annual effective doses increased with age and were generally higher among men. CONCLUSIONS Cardiac imaging procedures lead to substantial radiation exposure and effective doses for many patients in the U.S.

Multiple testing, cumulative radiation dose, and clinical indications in patients undergoing myocardial perfusion imaging.

CONTEXT Myocardial perfusion imaging (MPI) is the single medical test with the highest radiation burden to the US population. Although many patients undergoing MPI receive repeat MPI testing, or additional procedures involving ionizing radiation, no data are available characterizing their total longitudinal radiation burden and relating radiation burden with reasons for testing. OBJECTIVES To characterize procedure counts, cumulative estimated effective doses of radiation, and clinical indications for patients undergoing MPI. DESIGN, SETTING, AND PATIENTS A retrospective cohort study of 1097 consecutive patients undergoing index MPI during the first 100 days of 2006 (January 1-April 10) at Columbia University Medical Center, New York, New York, that evaluated all preceding medical imaging procedures involving ionizing radiation undergone beginning October 1988, and all subsequent procedures through June 2008, at the center. MAIN OUTCOME MEASURES Cumulative estimated effective dose of radiation, number of procedures involving radiation, and indications for testing. RESULTS Patients underwent a median of 15 (interquartile range [IQR], 6-32; mean, 23.9) procedures involving radiation exposure; of which 4 (IQR, 2-8; mean, 6.5) were high-dose procedures (≥3 mSv; ie, 1 years background radiation), including 1 (IQR, 1-2; mean, 1.8) MPI study per patient. A total of 344 patients (31.4%) received cumulative estimated effective dose from all medical sources of more than 100 mSv. Multiple MPIs were performed in 424 patients (38.6%), for whom cumulative estimated effective dose was 121 mSv (IQR, 81-189; mean, 149 mSv). Men and white patients had higher cumulative estimated effective doses. More than 80% of initial and 90% of repeat MPI examinations were performed in patients with known cardiac disease or symptoms consistent with it. CONCLUSION In this institution, multiple testing with MPI was common and in many patients associated with high cumulative estimated doses of radiation.

Use of Medical Imaging Procedures With Ionizing Radiation in Children: A Population-Based Study

OBJECTIVE To determine population-based rates of the use of diagnostic imaging procedures with ionizing radiation in children, stratified by age and sex. DESIGN Retrospective cohort analysis. SETTING All settings using imaging procedures with ionizing radiation. PATIENTS Individuals younger than 18 years, alive, and continuously enrolled in UnitedHealthcare between January 1, 2005, and December 31, 2007, in 5 large US health care markets. MAIN OUTCOME MEASURES Number and type of diagnostic imaging procedures using ionizing radiation in children. RESULTS A total of 355 088 children were identified; 436 711 imaging procedures using ionizing radiation were performed in 150 930 patients (42.5%). The highest rates of use were in children older than 10 years, with frequent use in infants younger than 2 years as well. Plain radiography accounted for 84.7% of imaging procedures performed. Computed tomographic scans-associated with substantially higher doses of radiation-were commonly used, accounting for 11.9% of all procedures during the study period. Overall, 7.9% of children received at least 1 computed tomographic scan and 3.5% received 2 or more, with computed tomographic scans of the head being the most frequent. CONCLUSIONS Exposure to ionizing radiation from medical diagnostic imaging procedures may occur frequently among children. Efforts to optimize and ensure appropriate use of these procedures in the pediatric population should be encouraged.

Patient-Centered Imaging: Shared Decision Making for Cardiac Imaging Procedures With Exposure to Ionizing Radiation

The current paper details the recommendations arising from an NIH-NHLBI/NCI-sponsored symposium held in November 2012, aiming to identify key components of a radiation accountability framework fostering patient-centered imaging and shared decision-making in cardiac imaging. Symposium participants, working in 3 tracks, identified key components of a framework to target critical radiation safety issues for the patient, the laboratory, and the larger population of patients with known or suspected cardiovascular disease. The use of ionizing radiation during an imaging procedure should be disclosed to all patients by the ordering provider at the time of ordering, and reinforced by the performing provider team. An imaging protocol with effective dose ≤3 mSv is considered very low risk, not warranting extensive discussion or written informed consent. However, a protocol effective dose >20 mSv was proposed as a level requiring particular attention in terms of shared decision-making and either formal discussion or written informed consent. Laboratory reporting of radiation dosimetry is a critical component of creating a quality laboratory fostering a patient-centered environment with transparent procedural methodology. Efforts should be directed to avoiding testing involving radiation, in patients with inappropriate indications. Standardized reporting and diagnostic reference levels for computed tomography and nuclear cardiology are important for the goal of public reporting of laboratory radiation dose levels in conjunction with diagnostic performance. The development of cardiac imaging technologies revolutionized cardiology practice by allowing routine, noninvasive assessment of myocardial perfusion and anatomy. It is now incumbent upon the imaging community to create an accountability framework to safely drive appropriate imaging utilization.

Influence of Sex on Risk Stratification With Stress Myocardial Perfusion Rb-82 Positron Emission Tomography: Results From the PET (Positron Emission Tomography) Prognosis Multicenter Registry

OBJECTIVES The aim of the current analysis was to compare sex differences in the prognostic accuracy of stress myocardial perfusion rubidum-82 (Rb-82) positron emission tomography (PET). BACKGROUND The diagnostic evaluation of women presenting with suspected cardiac symptoms is challenging with reported reduced accuracy, attenuation artifact, and more recent concerns regarding radiation safety. Stress myocardial perfusion Rb-82 PET is a diagnostic alternative with improved image quality and radiation dosimetry. Currently, the prognostic accuracy of stress Rb-82 PET in women has not been established. METHODS A total of 6,037 women and men were enrolled in the PET Prognosis Multicenter Registry. Patients were followed for the occurrence of coronary artery disease (CAD) mortality, with a median follow-up of 2.2 years. Cox proportional hazards modeling was used to estimate CAD mortality. The net re-classification improvement index (NRI) was calculated. RESULTS The 5-year CAD mortality was 3.7% for women and 6.0% for men (p < 0.0001). Unadjusted CAD mortality ranged from 0.9% to 12.9% for women (p < 0.0001) and from 1.5% to 17.4% for men (p < 0.0001) for 0% to ≥15% abnormal myocardium at stress. In multivariable models, the percentage of abnormal stress myocardium was independently predictive of CAD mortality in women and men. An interaction term of sex by the percentage of abnormal stress myocardium was nonsignificant (p = 0.39). The categorical NRI when Rb-82 PET data was added to a clinical risk model was 0.12 for women and 0.17 for men. Only 2 cardiac deaths were reported in women <55 years of age; accordingly the percentage of abnormal myocardium at stress was of borderline significance (p = 0.063), but it was highly significant for women ≥55 years of age (p < 0.0001), with an increased NRI of 0.21 (95% confidence interval: 0.09 to 0.34), including 17% of CAD deaths and 3.9% of CAD survivors that were correctly re-classified in this older female subset. CONCLUSIONS Stress Rb-82 PET provides significant and clinically meaningful effective risk stratification of women and men, supporting this modality as an alternative to comparative imaging modalities. Rb-82 PET findings were particularly helpful at identifying high-risk, older women.

Radiation Dose and Cancer Risk Estimates in 16-Slice Computed Tomography Coronary Angiography

BackgroundRecent advances have led to a rapid increase in the number of computed tomography coronary angiography (CTCA) studies performed. Whereas several studies have reported the effective dose, there are no data available on cancer risk for current CTCA protocols.Methods and ResultsEffective and organ doses were estimated, by use of scanner-derived parameters and Monte Carlo methods, for 50 patients having 16-slice CTCA performed for clinical indications. Lifetime attributable risks were estimated with models developed in the National Academies’ Biological Effects of Ionizing Radiation VII report. The effective dose of a complete CTCA averaged 9.5 mSv, whereas that of a complete study, including calcium scoring when indicated, averaged 11.7 mSv. Calcium scoring increased effective dose by 25%, whereas tube current modulation reduced it by 34% and was more effective at lower heart rates. Organ doses to the lungs and female breast were highest. The lifetime attributable risk of cancer incidence from CTCA averaged approximately 1 in 1,600 but varied widely among patients, being highest in younger women. For all patients, the greatest risk was from lung cancer.ConclusionsCTCA is associated with non-negligible risk of malignancy. Doses can be reduced by careful attention to scanning protocol.

Radiation Protection of Patients Undergoing Cardiac Computed Tomographic Angiography

INTEREST IN THE USE OF COMPUTED TOMOGRAPHY (CT) for cardiac evaluation has increased rapidly since the introduction of 64-slice scanners. Reflecting this, the installation base of CT scanners in US cardiology practices has tripled in the past 2 years. Reports of the high diagnostic performance of coronary CT angiography (CTA), and especially its high negative predictive value in populations with low-to-intermediate prevalence of coronary disease, have been tempered by a concern about its high radiation dose to patients and the attendant risk of cancer. Despite a number of single-center studies that have reported a wide range of effective doses for coronary CTA, the existing literature does not adequately answer the questions of what radiation doses patients actually receive in clinical practice, and what factors are associated with higher radiation dose. Such information should help practitioners develop protocols that are in accordance with the goal of maintaining radiation exposure to patients as low as reasonably achievable (the ALARA principle). The Prospective Multicenter Study On Radiation Dose Estimates Of Cardiac CT Angiography In Daily Practice I (PROTECTION I), an observational study of worldwide cardiac CTA practice in 2007 reported by Hausleiter and colleagues in this issue of JAMA, represents an effort to fill this gap. The primary outcome measure used to quantify radiation dose in PROTECTION I is the dose-length product (DLP), a CT-specific term unfamiliar to many physicians. The DLP is a reflection of the total amount of radiation deposited over the entire set of images comprising a patient’s CT series, reported in mGy cm. Better known is the effective dose, a measure applicable beyond the confines of CT and reported in millisieverts (mSv). Effective dose weights the concentrations of energy deposited in each organ from a radiation exposure using factors reflecting the type of radiation and the relative detriment to each organ of potential radiation-associated mutagenic changes. Although effective dose can be compared between different types of exposures, the factors used in its determination to weight each organ are approximate population averages, and therefore it is imprecise to report the effective dose of an individual patient’s study. Thus, in characterizing the amount of radiation from a single CTA study, DLP is a more objective physical metric than effective dose, and the reason PROTECTION I is replete with DLP data. However, effective dose is appropriate to refer to in a population of patients and is especially useful for comparing between different types of exposures in populations with similar age and sex distributions. As in numerous previous studies, effective dose of CTA is estimated in PROTECTION I by multiplying a median DLP by a conversion factor suggested by the European Commission. Hausleiter et al present a number of interesting and surprising findings about radiation dose from cardiac CTA. The estimated overall median effective dose for CTA, excluding calcium scoring when performed as part of the same study, was 12 mSv, somewhat less than the value reported in several earlier studies using 64-slice scanners. A few factors may account for this. Although the conversion factor used in PROTECTION I to estimate effective dose from DLP was derived using single-slice scanners and chest rather than cardiac scan sequences, this factor is the most current available. The value is approximately 20% lower than that used in previous studies, and thus would be expected to result in effective doses that are correspondingly lower. Additionally, as pointed out by Hausleiter et al, invitation of study sites on the basis of previous publications may have introduced a bias favoring more expert centers, which would be expected to be more proficient in managing radiation dose. Indeed, dosereduction techniques were used in at least 80% of patients undergoing 64-slice CTA for coronary assessment. Consistent with the suggestion of lower dose in centers with greater expertise, Raff et al recently reported a reduction in median effective dose of CTA from 25 mSv in the initial month to 13 mSv in the ninth month of a statewide quality improvement program in Michigan, with no change in image quality. This program used a collaborative

Development of Receptor for Advanced Glycation End Products-Directed Imaging of Atherosclerotic Plaque in a Murine Model of Spontaneous Atherosclerosis

Background—The receptor for advanced glycation end products (RAGE) is implicated in the development and progression of atherosclerosis. We tested the hypothesis that 99mTc-labeled anti-RAGE F(ab′)2 can be used as a noninvasive tool to image atherosclerotic lesions in apolipoprotein E–deficient (apoE−/−) mice. Methods and Results—A sequence in the V-type Ig extracellular domain of RAGE was used to develop a peptide injected into rabbits; serum was retrieved, IgG prepared and affinity-purified, and pepsin-digested into F(ab′)2. Thirteen 6-week apoE−/− mice were fed a Western diet. At 20 weeks, 6 were injected with 15.2±1.9 MBq (350 to 411 &mgr;Ci) 99mTc-labeled anti-RAGE F(ab′)2, 6 were injected with 99mTc-labeled control nonspecific IgG F(ab′)2, and 1 was injected with dual-labeled 99mTc and rhodamine anti-RAGE F(ab′)2. Four 20-week C57BL/6 mice were injected with 99mTc-labeled anti-RAGE F(ab′)2. All mice were imaged on a high resolution mini-&ggr; camera 4 hours after injection and euthanized. The aortic tree was dissected and photographed, and the proximal aorta was sectioned for staining after &ggr; scintillation counting. All 6 apoE−/− mice injected with 99mTc-labeled anti-RAGE F(ab′)2 fragments showed focal tracer uptake in the proximal aorta (mean %ID/g, 1.98%). Disease and antibody controls showed no focal tracer uptake in the thorax (%ID/g, <1.0%). Histological sections of the proximal aorta showed American Heart Association class III lesions with lipid laden macrophages, smooth muscle cells, and positive staining for RAGE. On immunofluorescence, RAGE colocalized with macrophages. Conclusion—These data show the feasibility of noninvasively imaging RAGE in atherosclerotic lesions in a murine model and confirm levels of RAGE expression sufficient to allow detection on in vivo imaging.