Richard A. P. Takx

Diagnostic Accuracy of Stress Myocardial Perfusion Imaging Compared to Invasive Coronary Angiography With Fractional Flow Reserve Meta-Analysis

Background—Hemodynamically significant coronary artery disease is an important indication for revascularization. Stress myocardial perfusion imaging is a noninvasive alternative to invasive fractional flow reserve for evaluating hemodynamically significant coronary artery disease. The aim was to determine the diagnostic accuracy of myocardial perfusion imaging by single-photon emission computed tomography, echocardiography, MRI, positron emission tomography, and computed tomography compared with invasive coronary angiography with fractional flow reserve for the diagnosis of hemodynamically significant coronary artery disease. Methods and Results—The meta-analysis adhered to the Preferred Reporting Items for Systematic Reviews and Meta-analyses statement. PubMed, EMBASE, and Web of Science were searched until May 2014. Thirty-seven studies, reporting on 4721 vessels and 2048 patients, were included. Meta-analysis yielded pooled sensitivity, pooled specificity, pooled likelihood ratios (LR), pooled diagnostic odds ratio, and summary area under the receiver operating characteristic curve. The negative LR (NLR) was chosen as the primary outcome. At the vessel level, MRI (pooled NLR, 0.16; 95% confidence interval [CI], 0.13–0.21) was performed similar to computed tomography (pooled NLR, 0.22; 95% CI, 0.12–0.39) and positron emission tomography (pooled NLR, 0.15; 95% CI, 0.05–0.44), and better than single-photon emission computed tomography (pooled NLR, 0.47; 95% CI, 0.37–0.59). At the patient level, MRI (pooled NLR, 0.14; 95% CI, 0.10–0.18) performed similar to computed tomography (pooled NLR, 0.12; 95% CI, 0.04–0.33) and positron emission tomography (pooled NLR, 0.14; 95% CI, 0.02–0.87), and better than single-photon emission computed tomography (pooled NLR, 0.39; 95% CI, 0.27–0.55) and echocardiography (pooled NLR, 0.42; 95% CI, 0.30–0.59). Conclusions—Stress myocardial perfusion imaging with MRI, computed tomography, or positron emission tomography can accurately rule out hemodynamically significant coronary artery disease and can act as a gatekeeper for invasive revascularization. Single-photon emission computed tomography and echocardiography are less suited for this purpose.

Relation between resting amygdalar activity and cardiovascular events: a longitudinal and cohort study

BACKGROUND Emotional stress is associated with increased risk of cardiovascular disease. We imaged the amygdala, a brain region involved in stress, to determine whether its resting metabolic activity predicts risk of subsequent cardiovascular events. METHODS Individuals aged 30 years or older without known cardiovascular disease or active cancer disorders, who underwent 18F-fluorodexoyglucose PET/CT at Massachusetts General Hospital (Boston, MA, USA) between Jan 1, 2005, and Dec 31, 2008, were studied longitudinally. Amygdalar activity, bone-marrow activity, and arterial inflammation were assessed with validated methods. In a separate cross-sectional study we analysed the relation between perceived stress, amygdalar activity, arterial inflammation, and C-reactive protein. Image analyses and cardiovascular disease event adjudication were done by mutually blinded researchers. Relations between amygdalar activity and cardiovascular disease events were assessed with Cox models, log-rank tests, and mediation (path) analyses. FINDINGS 293 patients (median age 55 years [IQR 45·0-65·5]) were included in the longitudinal study, 22 of whom had a cardiovascular disease event during median follow-up of 3·7 years (IQR 2·7-4·8). Amygdalar activity was associated with increased bone-marrow activity (r=0·47; p<0·0001), arterial inflammation (r=0·49; p<0·0001), and risk of cardiovascular disease events (standardised hazard ratio 1·59, 95% CI 1·27-1·98; p<0·0001), a finding that remained significant after multivariate adjustments. The association between amygdalar activity and cardiovascular disease events seemed to be mediated by increased bone-marrow activity and arterial inflammation in series. In the separate cross-sectional study of patients who underwent psychometric analysis (n=13), amygdalar activity was significantly associated with arterial inflammation (r=0·70; p=0·0083). Perceived stress was associated with amygdalar activity (r=0·56; p=0·0485), arterial inflammation (r=0·59; p=0·0345), and C-reactive protein (r=0·83; p=0·0210). INTERPRETATION In this first study to link regional brain activity to subsequent cardiovascular disease, amygdalar activity independently and robustly predicted cardiovascular disease events. Amygdalar activity is involved partly via a path that includes increased bone-marrow activity and arterial inflammation. These findings provide novel insights into the mechanism through which emotional stressors can lead to cardiovascular disease in human beings. FUNDING None.

Quantification of left and right ventricular function and myocardial mass: comparison of low-radiation dose 2nd generation dual-source CT and cardiac MRI.

OBJECTIVE To prospectively evaluate the accuracy of left and right ventricular function and myocardial mass measurements based on a dual-step, low radiation dose protocol with prospectively ECG-triggered 2nd generation dual-source CT (DSCT), using cardiac MRI (cMRI) as the reference standard. MATERIALS AND METHODS Twenty patients underwent 1.5T cMRI and prospectively ECG-triggered dual-step pulsing cardiac DSCT. This image acquisition mode performs low-radiation (20% tube current) imaging over the majority of the cardiac cycle and applies full radiation only during a single adjustable phase. Full-radiation-phase images were used to assess cardiac morphology, while low-radiation-phase images were used to measure left and right ventricular function and mass. Quantitative CT measurements based on contiguous multiphase short-axis reconstructions from the axial CT data were compared with short-axis SSFP cardiac cine MRI. Contours were manually traced around the ventricular borders for calculation of left and right ventricular end-diastolic volume, end-systolic volume, stroke volume, ejection fraction and myocardial mass for both modalities. Statistical methods included independent t-tests, the Mann-Whitney U test, Pearson correlation statistics, and Bland-Altman analysis. RESULTS All CT measurements of left and right ventricular function and mass correlated well with those from cMRI: for left/right end-diastolic volume r=0.885/0.801, left/right end-systolic volume r=0.947/0.879, left/right stroke volume r=0.620/0.697, left/right ejection fraction r=0.869/0.751, and left/right myocardial mass r=0.959/0.702. Mean radiation dose was 6.2±1.8mSv. CONCLUSIONS Prospectively ECG-triggered, dual-step pulsing cardiac DSCT accurately quantifies left and right ventricular function and myocardial mass in comparison with cMRI with substantially lower radiation exposure than reported for traditional retrospective ECG-gating.

Radiation Dose at Coronary CT Angiography: Second-Generation Dual-Source CT Versus Single-Source 64-MDCT and First-Generation Dual-Source CT

OBJECTIVE The purpose of this study was to assess the radiation doses of different coronary CTA (CTA) protocols: second-generation dual-source 128-MDCT, first-generation dual-source 64-MDCT, and single-source 64-MDCT. MATERIALS AND METHODS Thermoluminescent dosimetry was used to determine scanner-specific dose coefficients for standard coronary CTA of an anthropomorphic phantom. These coefficients were used to estimate the effective doses (EDs) of retrospectively gated, prospectively triggered, and prospectively triggered high pitch coronary CTA performed at 100 and 120 kV. The coronary CTA protocols used in imaging of 43 patients undergoing dual-source 128-MDCT were analyzed for ED, image quality, and signal-to-noise ratio. RESULTS Regardless of coronary CTA protocol and CT system, imaging at 100 kV lowered the ED 40-50%. In retrospectively gated 120-kV coronary CTA, the ED ranged from 5.7 to 10.7 mSv and was approximately 50% lower with single-source 64-MDCT than with either DSCT protocol. In prospectively triggered 120-kV coronary CTA, the ED ranged from 3.8 to 4.0 mSv. The lowest ED of all protocols (1.3 mSv) was observed in prospectively triggered high-pitch 100-kV coronary CTA performed with dual-source 128-MDCT. Patient measurements showed similar dose reductions for prospective triggering and low voltage settings without an influence on signal-to-noise ratio or image quality. CONCLUSION A combination of prospective triggering with low voltage settings is an effective measure for reducing the ED of coronary CTA to values of 2-4 mSv independent of scanner system. Further dose reduction to nearly 1 mSv can be achieved with high-pitch prospectively triggered coronary CTA.

Coronary CT angiography: Comparison of a novel iterative reconstruction with filtered back projection for reconstruction of low-dose CT—Initial experience

OBJECTIVE To prospectively compare subjective and objective image quality in 20% tube current coronary CT angiography (cCTA) datasets between an iterative reconstruction algorithm (SAFIRE) and traditional filtered back projection (FBP). MATERIALS AND METHODS Twenty patients underwent a prospectively ECG-triggered dual-step cCTA protocol using 2nd generation dual-source CT (DSCT). CT raw data was reconstructed using standard FBP at full-dose (Group_1a) and 80% tube current reduced low-dose (Group_1b). The low-dose raw data was additionally reconstructed using iterative raw data reconstruction (Group_2). Attenuation and image noise were measured in three regions of interest and signal-to-noise-ratio (SNR) as well as contrast-to-noise-ratio (CNR) was calculated. Subjective diagnostic image quality was evaluated using a 4-point Likert scale. RESULTS Mean image noise of group_2 was lowered by 22% on average when compared to group_1b (p<0.0001-0.0033), while there were no significant differences in mean attenuation within the same anatomical regions. The lower image noise resulted in significantly higher SNR and CNR ratios in group_2 compared to group_1b (p<0.0001-0.0232). Subjective image quality of group_2 (1.88 ± 0.63) was also rated significantly higher when compared to group_1b (1.58 ± 0.63, p=0.004). CONCLUSIONS Image quality of 80% tube current reduced iteratively reconstructed cCTA raw data is significantly improved when compared to standard FBP and consequently may improve the diagnostic accuracy of cCTA.

Coronary Artery Calcification Scoring with State-of-the-Art CT Scanners from Different Vendors Has Substantial Effect on Risk Classification

PURPOSE To determine the intervendor variability of Agatston scoring determined with state-of-the-art computed tomographic (CT) systems from the four major vendors in an ex vivo setup and to simulate the subsequent effects on cardiovascular risk reclassification in a large population-based cohort. MATERIALS AND METHODS Research ethics board approval was not necessary because cadaveric hearts from individuals who donated their bodies to science were used. Agatston scores obtained with CT scanners from four different vendors were compared. Fifteen ex vivo human hearts were placed in a phantom resembling an average human adult. Hearts were scanned at equal radiation dose settings for the systems of all four vendors. Agatston scores were quantified semiautomatically with software used clinically. The ex vivo Agatston scores were used to simulate the effects of different CT scanners on reclassification of 432 individuals aged 55 years or older from a population-based study who were at intermediate cardiovascular risk based on Framingham risk scores. The Friedman test was used to evaluate overall differences, and post hoc analyses were performed by using the Wilcoxon signed-rank test with Bonferroni correction. RESULTS Agatston scores differed substantially when CT scanners from different vendors were used, with median Agatston scores ranging from 332 (interquartile range, 114-1135) to 469 (interquartile range, 183-1381; P < .05). Simulation showed that these differences resulted in a change in cardiovascular risk classification in 0.5%-6.5% of individuals at intermediate risk when a CT scanner from a different vendor was used. CONCLUSION Among individuals at intermediate cardiovascular risk, state-of the-art CT scanners made by different vendors produced substantially different Agatston scores, which can result in reclassification of patients to the high- or low-risk categories in up to 6.5% of cases.

The Effects of Computed Tomography with Iterative Reconstruction on Solid Pulmonary Nodule Volume Quantification

Background The objectives of this study were to evaluate the influence of iterative reconstruction (IR) on pulmonary nodule volumetry with chest computed tomography (CT). Methods Twenty patients (12 women and 8 men, mean age 61.9, range 32–87) underwent evaluation of pulmonary nodules with a 64-slice CT-scanner. Data were reconstructed using filtered back projection (FBP) and IR (Philips Healthcare, iDose4-levels 2, 4 and 6) at similar radiation dose. Volumetric nodule measurements were performed with semi-automatic software on thin slice reconstructions. Only solid pulmonary nodules were measured, no additional selection criteria were used for the nature of nodules. For intra-observer and inter-observer variability, measurements were performed once by one observer and twice by another observer. Algorithms were compared using the concordance correlation-coefficient (pc) and Friedman-test, and post-hoc analysis with the Wilcoxon-signed ranks-test with Bonferroni-correction (significance-level p<0.017). Results Seventy-eight nodules were present including 56 small nodules (volume<200 mm3, diameter<8 mm) and 22 large nodules (volume≥200 mm3, diameter≥8 mm). No significant differences in measured pulmonary nodule volumes between FBP, iDose4-levels 2, 4 and 6 were found in both small nodules and large nodules. FBP and iDose4-levels 2, 4 and 6 were correlated with pc-values of 0.98 or higher for both small and large nodules. Pc-values of intra-observer and inter-observer variability were 0.98 or higher. Conclusions Measurements of solid pulmonary nodule volume measured with standard-FBP were comparable with IR, regardless of the IR-level and no significant differences between measured volumes of both small and large solid nodules were found.

Computed tomography radiation dose reduction: effect of different iterative reconstruction algorithms on image quality.

Objective We evaluated the effects of hybrid and model-based iterative reconstruction (IR) algorithms from different vendors at multiple radiation dose levels on image quality of chest phantom scans. Methods A chest phantom was scanned on state-of-the-art computed tomography scanners from 4 vendors at 4 dose levels (4.1 mGy, 3.0 mGy, 1.9 mGy, and 0.8 mGy). All data were reconstructed with filtered back projection (FBP) and reduced-dose data also with IR (iDose4, Adaptive Iterative Dose Reduction 3D, Adaptive Statistical Iterative Reconstruction, Sinogram-Affirmed Iterative Reconstruction, prototype Iterative Model Reconstruction, and Veo). Computed tomography numbers and noise were measured in the spine and lungs. Signal-to-noise ratios (SNR) and contrast-to-noise ratios (CNR) were calculated and differences were analyzed with the Friedman test. Results For all vendors, radiation dose reduction with FBP resulted in significantly increased noise levels (⩽148%) as well as decreased SNR (⩽57%) and CNR (⩽58%) (P < 0.001). Conversely, IR resulted in decreased noise levels (⩽48%) as well as increased SNR (⩽94%) and CNR (⩽94%). The SNRs and CNRs of the model-based algorithms at 80% reduced dose were similar to reference-dose FBP. Conclusions Hybrid IR algorithms have the potential to reduce radiation dose with 27% to 54% and model-based IR algorithms with up to 80%.

Sublingual Nitroglycerin Administration in Coronary Computed Tomography Angiography: a Systematic Review

ObjectiveTo systematically investigate the literature for the influence of sublingual nitroglycerin administration on coronary diameter, the number of evaluable segments, image quality, heart rate and blood pressure, and diagnostic accuracy of coronary computed tomography (CT) angiography.MethodsA systematic search was performed in PubMed, EMBASE and Web of Science. The studies were evaluated for the effect of sublingual nitroglycerin on coronary artery diameter, evaluable segments, objective and subjective image quality, systemic physiological effects and diagnostic accuracy. Due to the heterogeneous reporting of outcome measures, a narrative synthesis was applied.ResultsOf the 217 studies identified, nine met the inclusion criteria: seven reported on the effect of nitroglycerin on coronary artery diameter, six on evaluable segments, four on image quality, five on systemic physiological effects and two on diagnostic accuracy. Sublingual nitroglycerin administration resulted in an improved evaluation of more coronary segments, in particular, in smaller coronary branches, better image quality and improved diagnostic accuracy. Side effects were mild and were alleviated without medical intervention.ConclusionSublingual nitroglycerin improves the coronary diameter, the number of assessable segments, image quality and diagnostic accuracy of coronary CT angiography without major side effects or systemic physiological changes.Key Points• Sublingual nitroglycerin administration results in significant coronary artery dilatation.• Nitroglycerin increases the number of evaluable coronary branches.• Image quality is improved the most in smaller coronary branches.• Nitroglycerin increases the diagnostic accuracy of coronary CT angiography.• Most side effects are mild and do not require medical intervention.

Automated coronary artery calcification scoring in non-gated chest CT: Agreement and reliability

Objective To determine the agreement and reliability of fully automated coronary artery calcium (CAC) scoring in a lung cancer screening population. Materials and Methods 1793 low-dose chest CT scans were analyzed (non-contrast-enhanced, non-gated). To establish the reference standard for CAC, first automated calcium scoring was performed using a preliminary version of a method employing coronary calcium atlas and machine learning approach. Thereafter, each scan was inspected by one of four trained raters. When needed, the raters corrected initially automaticity-identified results. In addition, an independent observer subsequently inspected manually corrected results and discarded scans with gross segmentation errors. Subsequently, fully automatic coronary calcium scoring was performed. Agatston score, CAC volume and number of calcifications were computed. Agreement was determined by calculating proportion of agreement and examining Bland-Altman plots. Reliability was determined by calculating linearly weighted kappa (κ) for Agatston strata and intraclass correlation coefficient (ICC) for continuous values. Results 44 (2.5%) scans were excluded due to metal artifacts or gross segmentation errors. In the remaining 1749 scans, median Agatston score was 39.6 (P25–P75∶0–345.9), median volume score was 60.4 mm3 (P25–P75∶0–361.4) and median number of calcifications was 2 (P25–P75∶0–4) for the automated scores. The κ demonstrated very good reliability (0.85) for Agatston risk categories between the automated and reference scores. The Bland-Altman plots showed underestimation of calcium score values by automated quantification. Median difference was 2.5 (p25–p75∶0.0–53.2) for Agatston score, 7.6 (p25–p75∶0.0–94.4) for CAC volume and 1 (p25–p75∶0–5) for number of calcifications. The ICC was very good for Agatston score (0.90), very good for calcium volume (0.88) and good for number of calcifications (0.64). Discussion Fully automated coronary calcium scoring in a lung cancer screening setting is feasible with acceptable reliability and agreement despite an underestimation of the amount of calcium when compared to reference scores.