Assessment of the Radiation Effects of Cardiac CT Angiography Using Protein and Genetic Biomarkers.
ABSTRACT: The purpose of this study was to evaluate whether radiation exposure from cardiac computed tomographic angiography (CTA) is associated with deoxyribonucleic acid (DNA) damage and whether damage leads to programmed cell death and activation of genes involved in apoptosis and DNA repair.Exposure to radiation from medical imaging has become a public health concern, but whether it causes significant cell damage remains unclear.We conducted a prospective cohort study in 67 patients undergoing cardiac CTA between January 2012 and December 2013 in 2 U.S. medical centers. Median blood radiation exposure was estimated using phantom dosimetry. Biomarkers of DNA damage and apoptosis were measured by flow cytometry, whole genome sequencing, and single cell polymerase chain reaction.The median dose length product was 1,535.3 mGy·cm (969.7 to 2,674.0 mGy·cm). The median radiation dose to the blood was 29.8 mSv (18.8 to 48.8 mSv). Median DNA damage increased 3.39% (1.29% to 8.04%, p < 0.0001) and median apoptosis increased 3.1-fold (interquartile range [IQR]: 1.4- to 5.1-fold, p < 0.0001) post-radiation. Whole genome sequencing revealed changes in the expression of 39 transcription factors involved in the regulation of apoptosis, cell cycle, and DNA repair. Genes involved in mediating apoptosis and DNA repair were significantly changed post-radiation, including DDB2 (1.9-fold [IQR: 1.5- to 3.0-fold], p < 0.001), XRCC4 (3.0-fold [IQR: 1.1- to 5.4-fold], p = 0.005), and BAX (1.6-fold [IQR: 0.9- to 2.6-fold], p < 0.001). Exposure to radiation was associated with DNA damage (odds ratio [OR]: 1.8 [1.2 to 2.6], p = 0.003). DNA damage was associated with apoptosis (OR: 1.9 [1.2 to 5.1], p < 0.0001) and gene activation (OR: 2.8 [1.2 to 6.2], p = 0.002).Patients exposed to >7.5 mSv of radiation from cardiac CTA had evidence of DNA damage, which was associated with programmed cell death and activation of genes involved in apoptosis and DNA repair.
Project description:BACKGROUND:Coronary computed tomography angiography (CTA) and functional testing strategies for stable chest pain yield similar outcomes; one aspect that may guide test choice is safety. METHODS:We compared test safety (test complications, incidental findings, and effective radiation dose) between CTA and functional testing as-tested in PROMISE (PROspective Multicenter Imaging Study for Evaluation of Chest Pain). In the subgroup whose physicians intended nuclear stress over other functional tests if randomized to the functional arm, we compared radiation dose of CTA versus nuclear stress and identified characteristics associated with dose. RESULTS:Of 9470 patients, none had major and <1% had minor complications (CTA: 0.8% [37/4633] vs. functional: 0.6% [27/4837]). CTA identified more incidental findings (11.6% [539/4633] vs. 0.7% [34/4837], p < 0.001), most commonly pulmonary nodules (9.4%, 437/4633). CTA had similar 90-day cumulative radiation dose to functional testing. However, in the subgroup whose physicians intended nuclear stress (CTA 3147; nuclear 3203), CTA had lower median index test (8.8 vs. 12.6 mSv, p < 0.001) and 90-day cumulative (11.6 vs. 13.1 mSv, p < 0.001) dose, independent of patient characteristics. The lowest nuclear doses employed 1-day Tc-99m protocols (12.2 mSv). The lowest CTA doses were at sites performing ?500 CTAs/year (6.9 mSv) and with advanced (latest available) CT scanners (5.5 mSv). CONCLUSION:Complications were negligibly rare for both CTA and functional testing. CTA detects more incidental findings. Compared to nuclear stress testing, CTA's lower radiation dose, independent of patient characteristics, makes it an attractive test choice. Radiation dose varies with imaging protocol, indicating opportunities to further reduce dose. (ClinicalTrials.gov number, NCT01174550).
Project description:Many patients have symptoms suggestive of coronary artery disease (CAD) and are often evaluated with the use of diagnostic testing, although there are limited data from randomized trials to guide care.We randomly assigned 10,003 symptomatic patients to a strategy of initial anatomical testing with the use of coronary computed tomographic angiography (CTA) or to functional testing (exercise electrocardiography, nuclear stress testing, or stress echocardiography). The composite primary end point was death, myocardial infarction, hospitalization for unstable angina, or major procedural complication. Secondary end points included invasive cardiac catheterization that did not show obstructive CAD and radiation exposure.The mean age of the patients was 60.8±8.3 years, 52.7% were women, and 87.7% had chest pain or dyspnea on exertion. The mean pretest likelihood of obstructive CAD was 53.3±21.4%. Over a median follow-up period of 25 months, a primary end-point event occurred in 164 of 4996 patients in the CTA group (3.3%) and in 151 of 5007 (3.0%) in the functional-testing group (adjusted hazard ratio, 1.04; 95% confidence interval, 0.83 to 1.29; P=0.75). CTA was associated with fewer catheterizations showing no obstructive CAD than was functional testing (3.4% vs. 4.3%, P=0.02), although more patients in the CTA group underwent catheterization within 90 days after randomization (12.2% vs. 8.1%). The median cumulative radiation exposure per patient was lower in the CTA group than in the functional-testing group (10.0 mSv vs. 11.3 mSv), but 32.6% of the patients in the functional-testing group had no exposure, so the overall exposure was higher in the CTA group (mean, 12.0 mSv vs. 10.1 mSv; P<0.001).In symptomatic patients with suspected CAD who required noninvasive testing, a strategy of initial CTA, as compared with functional testing, did not improve clinical outcomes over a median follow-up of 2 years. (Funded by the National Heart, Lung, and Blood Institute; PROMISE ClinicalTrials.gov number, NCT01174550.).
Project description:The primary study objective was to assess radiation doses using a modified form of the Imaging Performance Assessment of Computed Tomography (CT) scanner (ImPACT) patient dosimetry for cardiac applications on an Aquilion ONE ViSION Edition scanner, including the Ca score, target computed tomography angiography (CTA), prospective CTA, continuous CTA/cardiac function analysis (CFA), and CTA/CFA modulation. Accordingly, we clarified the CT dose index (CTDI) to determine the relationship between heart rate (HR) and X-ray exposure. As a secondary objective, we compared radiation doses using modified ImPACT, a whole-body dosimetry phantom study, and the k-factor method to verify the validity of the dose results obtained with modified ImPACT. The effective dose determined for the reference person (4.66 mSv at 60 beats per minute (bpm) and 33.43 mSv at 90bpm) were approximately 10% less than those determined for the phantom study (5.28 mSv and 36.68 mSv). The effective doses according to the k-factor (0.014 mSv•mGy-1•cm-1; 2.57 mSv and 17.10 mSv) were significantly lower than those obtained with the other two methods. In the present study, we have shown that ImPACT, when modified for cardiac applications, can assess both absorbed and effective doses. The results of our dose comparison indicate that modified ImPACT dose assessment is a promising and practical method for evaluating coronary CTA.
Project description:OBJECTIVES:To evaluate the efficiency and safety of emergency department (ED) coronary computed tomography angiography (CTA) during a 3-year clinical experience. METHODS:Single-center registry of coronary CTA in consecutive ED patients with suspicion of acute coronary syndrome (ACS). The primary outcome was efficiency of coronary CTA defined as the length of hospitalization. Secondary endpoints of safety were defined as the rate of downstream testing, normalcy rates of invasive coronary angiography (ICA), absence of missed ACS, and major adverse cardiac events (MACE) during follow-up, and index radiation exposure. RESULTS:One thousand twenty two consecutive patients were referred for clinical coronary CTA with suspicion of ACS. Overall, median time to discharge home was 10.5 (5.7-24.1) hours. Patient disposition was 42.7 % direct discharge from the ED, 43.2 % discharge from emergency unit, and 14.1 % hospital admission. ACS rate during index hospitalization was 9.1 %. One hundred ninety two patients underwent additional diagnostic imaging and 77 underwent ICA. The positive predictive value of CTA compared to ICA was 78.9 % (95 %-CI 68.1-87.5 %). Median CT radiation exposure was 4.0 (2.5-5.8) mSv. No ACS was missed; MACE at follow-up after negative CTA was 0.2 %. CONCLUSIONS:Coronary CTA in an experienced tertiary care setting allows for efficient and safe management of patients with suspicion for ACS. KEY POINTS:• ED Coronary CTA using advanced systems is associated with low radiation exposure. • Negative coronary CTA is associated with low rates of MACE. • CTA in ED patients enables short median time to discharge home. • CTA strategy is characterized by few downstream tests including unnecessary ICA.
Project description:To (a) use a new second-generation wide-volume 320-detector row computed tomographic (CT) scanner to explore optimization of radiation exposure in coronary CT angiography in an unselected and consecutive cohort of patients referred for clinical purposes and (b) compare estimated radiation exposure and image quality with that from a cohort of similar patients who underwent imaging with a previous first-generation CT system.The study was approved by the institutional review board, and all subjects provided written consent. Coronary CT angiography was performed in 107 consecutive patients with a new second-generation 320-detector row unit. Estimated radiation exposure and image quality were compared with those from 100 consecutive patients who underwent imaging with a previous first-generation scanner. Effective radiation dose was estimated by multiplying the dose-length product by an effective dose conversion factor of 0.014 mSv/mGy ? cm and reported with size-specific dose estimates (SSDEs). Image quality was evaluated by two independent readers.The mean age of the 107 patients was 55.4 years ± 12.0 (standard deviation); 57 patients (53.3%) were men. The median body mass index was 27.3 kg/m(2) (range, 18.1-47.2 kg/m(2)); however, 71 patients (66.4%) were overweight, obese, or morbidly obese. A tube potential of 100 kV was used in 97 patients (90.6%), single-volume acquisition was used in 104 (97.2%), and prospective electrocardiographic gating was used in 106 (99.1%). The mean heart rate was 57.1 beats per minute ± 11.2 (range, 34-96 beats per minute), which enabled single-heartbeat scans in 100 patients (93.4%). The median radiation dose was 0.93 mSv (interquartile range [IQR], 0.58-1.74 mSv) with the second-generation unit and 2.67 mSv (IQR, 1.68-4.00 mSv) with the first-generation unit (P < .0001). The median SSDE was 6.0 mGy (IQR, 4.1-10.0 mGy) with the second-generation unit and 13.2 mGy (IQR, 10.2-18.6 mGy) with the first-generation unit (P < .0001). Overall, the radiation dose was less than 0.5 mSv for 23 of the 107 CT angiography examinations (21.5%), less than 1 mSv for 58 (54.2%), and less than 4 mSv for 103 (96.3%). All studies were of diagnostic quality, with most having excellent image quality. Three of four image quality indexes were significantly better with the second-generation unit compared with the first-generation unit.The combination of a gantry rotation time of 275 msec, wide volume coverage, iterative reconstruction, automated exposure control, and larger x-ray power generator of the second-generation CT scanner provides excellent image quality over a wide range of body sizes and heart rates at low radiation doses.http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.13122621/-/DC1.
Project description:BACKGROUND:Inter-patient heterogeneity in radiation-induced DNA damage responses is proposed to reflect intrinsic variations in tumour and normal tissue radiation sensitivity, but the prediction of phenotype by a molecular biomarker is influenced by clinical confounders and assay reproducibility. Here, we characterised the intrapatient and inter-patient heterogeneity in biomarkers of DNA damage and repair and radiation-induced apoptosis. METHODS:We enrolled 85 of 172 patients with locally advanced nasopharynx cancer from a randomised controlled phase II/III trial of induction chemotherapy added to chemo-radiotherapy. G0 blood lymphocytes were harvested from these patients, and irradiated with 1, 4, and 8 Gy ex vivo. DNA damage induction (1 Gy 0.5 h) and repair (4 Gy 24 h) were assessed by duplicate ?H2AX foci assays in 50-100 cells. Duplicate FLICA assays performed at 48 h post-8 Gy were employed as surrogate of radiation-induced apoptosis; %FLICA-positive cells were quantified by flow cytometry. RESULTS:We observed limited intrapatient variation in ?H2AX foci and %FLICA readouts; median difference of duplicate foci scores was -?0.37 (IQR?=?-?1.256-0.800) for 1 Gy 0.5 h and 0.09 (IQR?=?-?0.685-0.792) for 4 Gy 24 h; ICC of ?0.80 was observed for duplicate %FLICA0Gy and %FLICA8Gy assays of CD4+ and CD8+ T lymphocytes. As expected, we observed wide inter-patient heterogeneity in both assays that was independent of intrapatient variation and clinical covariates, with the exception of age, which was inversely correlated with %FLICAbackground-corrected (Spearman R =?-?0.406, P <?0.001 [CD4+]; R =?-?0.220, P =?0.04 [CD8+]). Lastly, an exploratory case-control analysis indicates increased levels of ?H2AX foci at 4 Gy 24 h in patients with severe late radiotherapy-induced xerostomia (P =?0.05). CONCLUSION:Here, we confirmed the technical reproducibility of DNA damage response assays for clinical implementation as biomarkers of clinical radiosensitivity in nasopharynx cancer patients.
Project description:Patients with coronary artery disease can accumulate significant radiation dose through repeated exposures to coronary computed tomographic angiography, myocardial perfusion imaging with single photon emission computed tomography or positron emission tomography, and to invasive coronary angiography. Aim of the study was to audit radiation doses of coronary computed tomographic angiography, single photon emission computed tomography, positron emission tomography and invasive coronary angiography in patients enrolled in the prospective, randomized, multi-centre European study-EVINCI (Evaluation of Integrated Cardiac Imaging for the Detection and Characterization of Ischemic Heart Disease).We reviewed 1070 tests (476 coronary computed tomographic angiographies, 85 positron emission tomographies, 310 single photon emission computed tomographies, 199 invasive coronary angiographies) performed in 476 patients (mean age 60?±?9 years, 60% males) enrolled in 12 centers of the EVINCI. The effective doses were calculated in milli-Sievert (mSv) as median, interquartile range (IQR) and coefficient of variation of the mean.Coronary computed tomographic angiography (476 exams in 12 centers) median effective dose was 9.6 mSv (IQR?=?13.2 mSv); single photon emission computed tomography (310 exams in 9 centers) effective dose was 9.3 (IQR?=?2.8); positron emission tomography (85 in 3 centers) effective dose 1.8 (IQR?=?1.6) and invasive coronary angiography (199 in 9 centers) effective dose 7.4 (IQR?=?7.3). Inter-institutional variability was highest for invasive coronary angiography (100%) and coronary computed tomographic angiography (54%) and lowest for single photon emission computed tomography (20%). Intra-institutional variability was highest for invasive coronary angiography (121%) and coronary computed tomographic angiography (115%) and lowest for single photon emission computed tomography (14%).Coronary computed tomographic angiography and invasive coronary angiography doses vary substantially between and within centers. The variability in nuclear medicine procedures is substantially lower. The findings highlight the need to audit doses, to track cumulative exposures and to standardize doses for imaging techniques.The study protocol is available at https://www.clinicaltrials.gov/ (ClinicalTrials.gov Identifier: NCT00979199 ). Information provided on September 16, 2009.
Project description:Aims:Advances of cardiac computed tomography angiography (CTA) have been developed for dose reduction, but their efficacy in clinical practice is largely unknown. This study was designed to evaluate radiation dose exposure and utilization of dose-saving strategies for contrast-enhanced cardiac CTA in daily practice. Methods and results:Sixty one hospitals from 32 countries prospectively enrolled 4502 patients undergoing cardiac CTA during one calendar month in 2017. Computed tomography angiography scan data and images were analysed in a central core lab and compared with a similar dose survey performed in 2007. Linear regression analysis was performed to identify independent predictors associated with dose. The most frequent indication for cardiac CTA was the evaluation of coronary artery disease in 89% of patients. The median dose-length product (DLP) of coronary CTA was 195?mGy*cm (interquartile range 110-338?mGy*cm). When compared with 2007, the DLP was reduced by 78% (P?<?0.001) without an increase in non-diagnostic coronary CTAs (1.7% in 2007 vs. 1.9% in 2017 surveys, P?=?0.55). A 37-fold variability in median DLP was observed between the hospitals with lowest and highest DLP (range of median DLP 57-2090?mGy*cm). Independent predictors for radiation dose of coronary CTA were: body weight, heart rate, sinus rhythm, tube voltage, iterative image reconstruction, and the selection of scan protocols. Conclusion:This large international radiation dose survey demonstrates considerable reduction of radiation exposure in coronary CTA during the last decade. However, the large inter-site variability in radiation exposure underlines the need for further site-specific training and adaptation of contemporary cardiac scan protocols.
Project description:OBJECTIVE:To assess cumulative radiation doses from computed tomography (CT), patient characteristics, and clinical indications for CT in a population-based sample. PATIENTS AND METHODS:A cohort study using medical records linkage through the Rochester Epidemiology Project was conducted to ascertain all CT examinations in Olmsted County, Minnesota, performed between January 1, 2004, and December 31, 2013, among all adults who were alive for 3 or more years after the end of follow-up (to exclude exposures preceding death). Ten-year cumulative effective ionizing radiation doses were estimated on the basis of typical doses per CT modality. Among patients with high doses (?100 mSv/10 years), CT scans were reviewed for clinical setting, indications, and results. RESULTS:Of 54,447 adults (median age, 44.0 years at inclusion), 26,377 (48.4%) underwent at least one CT. Ten-year radiation doses from CT were 0.1 to 9.9 mSv in 15.8% of the population (8593 patients), 10 to 24.9 mSv in 16.9% (9502), 25 to 99.9 mSv in 13.8% (7492), and 100 mSv or greater in 1.9% (1041). Computed tomography of the abdomen and pelvis accounted for 67.2% of the estimated dose. In multivariable models, doses differed 1.21-fold to 2.16-fold between extreme categories of age, body mass index, education level, smoking status, and by race. Of 600 CTs in 200 patients with high doses, 70.5% were obtained for restaging of solid cancers and lymphoma, abdominal pain, infection, kidney stones, follow-up of nodules or masses, and chest pain/evaluation for pulmonary embolism. CONCLUSION:Exposure to ionizing radiation from CT occurred disproportionally in specific subgroups of the population. A limited number of clinical indications contributed the majority of radiation among adults with high doses.