Electrocardiographic alterations by pneumothorax: a case-control study with review of the literature.

BACKGROUND: Numerous ECG alterations due to pneumothorax have been reported. The objective of the study was to establish the presence of ECG changes associated with pneumothorax in the literature, and in a cohort of patients with proven pneumothorax compared with age- and sex-matched healthy controls. METHODS: A systematic review for ECG alterations associated with pneumothorax was performed. We then reviewed our hospital database for patients with pneumothorax and identified all patients with an ECG available at this time. The retrieved ECG alterations in the systematic review were identified in our pneumothorax patients and compared with a healthy sex- and age-matched control group. Accordingly, we calculated sensitivity and specificity for all alterations. RESULTS: Seventeen ECG alterations were found and defined from the systematic review. Our pneumothorax cohort consisted of 82 pneumothorax patients and 82 control patients. Specificity was mostly more than 90%, but sensitivities were low. Phasic R voltage (pneumothorax group 25.6% vs control group 1.2%), T-wave inversion (31.7% vs 2.4%), prolonged QTc (11.0% vs 2.4%), right axis deviation (14.6% vs 3.6%) and QRS voltage ratio in aVF/I >2 (41.5% vs 22.0%) were significantly more frequent in pneumothorax patients compared with controls. CONCLUSION: The sensitivity of published ECG signs in predicting pneumothorax in our cohort was low, which means that ECG findings are an unsuitable tool for pneumothorax screening. However, presence of these ECG signs might raise a suspicion of pneumothorax in patients presenting with dyspnoea, or unclear chest discomfort.

Nano-analytical characterization of endogenous minerals in healthy placental tissue: mineral distribution, composition and ultrastructure.

Despite its crucial role, the placenta is the least understood human organ. Recent clinical studies indicate a direct association between placental calcification and maternal and offspring health. This study reveals distinct characteristics of minerals formed during gestational ageing using cutting-edge nano-analytical characterization and paves the way for investigations focused on the identification of potential markers for disease risks in a clinical setting based on atypical placental mineral fingerprints.

Organ-specific response to nivolumab in patients with non-small cell lung cancer (NSCLC).

BACKGROUND: Response to immune checkpoint inhibitors depends on tumor intrinsic properties and also on host factors in the tumour microenvironment including the presence of immune cells (IC). We hypothesized that nivolumab efficacy varies across different metastatic sites. METHODS: We retrospectively analyzed computed tomography scans of patients with metastatic non-small cell lung carcinoma (NSCLC) receiving nivolumab. RECIST 1.1 criteria were applied to assess the overall response rate (ORR) and organ-specific response rate (OSRR). RESULTS: We analyzed 52 patients including 44% females, 58% adenocarcinoma and 8% never smokers. Involved organs had target-lesions in the lung (42%), liver (25%), lymph nodes (56%) and soft tissue (13%) and non-target lesions in the bones (23%). ORR and disease control rate (DCR) were 20% and 45%, respectively. Median overall survival, progression-free survival and duration of response were 11.9, 2.3 and 10.3 months. OSRR and organ-specific DCR (OSDCR) were 28% and 90% in lymph nodes, 8% and 54 in the liver, and 9% and 55% in lung metastases. Nine out of 12 patients with bone metastases had progressive lesions. The cumulative incidence probability of organ-specific progression at 6 months was 14% in lymph nodes, 42% in the liver, 36% in lung metastases and 26% in the primary tumor, 29% in soft tissue and 33% in adrenal metastases. CONCLUSION: In conclusion, the efficacy of immunotherapy is dependent on the metastatic location. Treatment appears more active in lymph nodes compared to other organ sites such as liver, adrenals and bone. Future strategies may include additional local treatment in case of oligoprogression in these organs in patients with otherwise sustained treatment benefit.

Ultralow dose CT for pulmonary nodule detection with chest x-ray equivalent dose - a prospective intra-individual comparative study.

PURPOSE: To prospectively evaluate the accuracy of ultralow radiation dose CT of the chest with tin filtration at 100 kV for pulmonary nodule detection. MATERIALS AND METHODS: 202 consecutive patients undergoing clinically indicated chest CT (standard dose, 1.8 ± 0.7 mSv) were prospectively included and additionally scanned with an ultralow dose protocol (0.13 ± 0.01 mSv). Standard dose CT was read in consensus by two board-certified radiologists to determine the presence of lung nodules and served as standard of reference (SOR). Two radiologists assessed the presence of lung nodules and their locations on ultralow dose CT. Sensitivity and specificity of the ultralow dose protocol was compared against the SOR, including subgroup analyses of different nodule sizes and types. A mixed effects logistic regression was used to test for independent predictors for sensitivity of pulmonary nodule detection. RESULTS: 425 nodules (mean diameter 3.7 ± 2.9 mm) were found on SOR. Overall sensitivity for nodule detection by ultralow dose CT was 91%. In multivariate analysis, nodule type, size and patients BMI were independent predictors for sensitivity (p < 0.001). CONCLUSIONS: Ultralow dose chest CT at 100 kV with spectral shaping enables a high sensitivity for the detection of pulmonary nodules at exposure levels comparable to plain film chest X-ray. KEYPOINTS: • 91% of all lung nodules were detected with ultralow dose CT • Sensitivity for subsolid nodule detection is lower in ultralow dose CT (77.5%) • The mean effective radiation dose in 202 patients was 0.13 mSv • Ultralow dose CT seems to be feasible for lung cancer screening.

Noise Texture Deviation: A Measure for Quantifying Artifacts in Computed Tomography Images With Iterative Reconstructions.

OBJECTIVES: The aims of this study were to introduce the measure noise texture deviation as quantitative parameter for evaluating iterative reconstruction (IR)-specific artifacts in computed tomography (CT) images and to test whether IR-specific artifacts, quantified through this measure, are reduced in advanced modeled IR (ADMIRE) as compared with sinogram-affirmed IR (SAFIRE) images of the liver ex vivo and in patients with hypodense liver lesions. MATERIALS AND METHODS: In the ex vivo study part, an abdominal phantom was used. In the institutional review board-approved in vivo study part, 40 consecutive patients (mean age, 63 years) with hypodense liver lesions undergoing abdominal CT in the portal-venous phase were included. Images were reconstructed with filtered back projection, with the second-generation IR algorithm SAFIRE and with the third-generation IR algorithm ADMIRE. Noise power spectra and noise texture deviation were calculated in the phantom; image noise was measured in the phantom and in patients. Two blinded readers evaluated all image data regarding IR-specific artifacts (plastic-like, blotchy appearance); patient data were evaluated regarding conspicuity and confidence for detecting hypodense liver lesions. RESULTS: Image noise was significantly reduced at increasing IR levels (P < 0.001) with both algorithms, with no significant differences between corresponding strength levels of SAFIRE and ADMIRE (all, P > 0.05). Noise power spectra were similar at corresponding strength levels of SAFIRE and ADMIRE (all, P > 0.05). Noise texture deviation in ADMIRE was reduced compared with corresponding strength levels of SAFIRE (all, P < 0.001) and strongly correlated with subjective IR-specific artifacts (r = 0.88, P < 0.001). Iterative reconstruction-specific artifacts were significantly reduced in ADMIRE compared with that in SAFIRE images at strength levels 3 or greater, both ex vivo and in vivo (all, P < 0.001). There were no significant differences in the readers' ratings of lesion conspicuity and lesion confidence in detecting hypodense liver lesions between SAFIRE and ADMIRE (P > 0.05). Only lesion conspicuity was superior with SAFIRE and ADMIRE compared with filtered back projection (all, P < 0.001). CONCLUSIONS: Noise texture deviation is a quantitative measure reflecting IR-specific artifacts and is reduced in CT images with ADMIRE compared with SAFIRE.

Impact of Advanced Modeled Iterative Reconstruction on Coronary Artery Calcium Quantification.

RATIONALE AND OBJECTIVES: To evaluate the influence of advanced modeled iterative reconstruction (ADMIRE) on the coronary artery calcium (CAC) scores by computed tomography (CT). MATERIALS AND METHODS: Sixty patients underwent CAC imaging with dual-source 192-slice CT. Agatston, volume and mass score were calculated from filtered back projection (FBP) and iterative reconstructions with different levels of ADMIRE. Friedman test and Wilcoxon rank sum test were used for multiple comparisons of CAC values and the difference ratio among different ADMIRE groups using FBP as reference. RESULTS: The median Agatston score (range) using FBP was 115 (0.1-3047) and significantly decreased with incremental ADMIRE levels 1-5: 96 (0.1-2813), 91 (0-2764), 87 (0-2699), 80 (0-2590), 70 (0-2440); all P < 0.001. In comparison with FBP Agatston, volume and mass scores significantly decreased with increasing ADMIRE levels 1-5 (P < 0.001): from -12% to -39%, from -14% to -41%, and from -13% to -40%, respectively. In four patients with low calcium burden, the use of ADMIRE 2 or higher resulted in the disappearance of calcium that was detectable using FBP or ADMIRE 1. The decrease of CAC in high-level ADMIRE resulted in a reassignment to a lower Agatston risk group in 27%. CONCLUSIONS: ADMIRE causes a substantial reduction of the CAC scores measured by cardiac CT, which leads to an underestimation of cardiovascular risk scores in some patients.

Correlation between Dual-Energy and Perfusion CT in Patients with Hepatocellular Carcinoma.

Purpose To develop a dual-energy contrast media-enhanced computed tomographic (CT) protocol by using time-attenuation curves from previously acquired perfusion CT data and to evaluate prospectively the relationship between iodine enhancement metrics at dual-energy CT and perfusion CT parameters in patients with hepatocellular carcinoma (HCC). Materials and Methods Institutional review board and local ethics committee approval and written informed consent were obtained. The retrospective part of this study included the development of a dual-energy CT contrast-enhanced protocol to evaluate peak arterial enhancement of HCC in the liver on the basis of time-attenuation curves from previously acquired perfusion CT data in 20 patients. The prospective part of the study consisted of an intraindividual comparison of dual-energy CT and perfusion CT data in another 20 consecutive patients with HCC. Iodine density and iodine ratio (iodine attenuation of the lesion divided by iodine attenuation in the aorta) from dual-energy CT and arterial perfusion (AP), portal venous perfusion, and total perfusion (TP) from perfusion CT were compared. Pearson R and linear correlation coefficients were calculated for AP and iodine density, AP and iodine ratio, TP and iodine density, and TP and iodine ratio. Results The dual-energy CT protocol consisted of bolus tracking in the abdominal aorta (threshold, 150 HU; scan delay, 9 seconds). The strongest intraindividual correlations in HCCs were found between iodine density and AP (r = 0.75, P = .0001). Moderate correlations were found between iodine ratio and AP (r = 0.50, P = .023) and between iodine density and TP (r = 0.56, P = .011). No further significant correlations were found. The volume CT dose index (11.4 mGy) and dose-length product (228.0 mGy · cm) of dual-energy CT was lower than those of the arterial phase of perfusion CT (36.1 mGy and 682.3 mGy · cm, respectively). Conclusion A contrast-enhanced dual-energy CT protocol developed by using time-attenuation curves from previously acquired perfusion CT data sets in patients with HCC could show good correlation between iodine density from dual-energy CT with AP from perfusion CT. (©) RSNA, 2016.

Optimizing radiation dose by using advanced modelled iterative reconstruction in high-pitch coronary CT angiography.

PURPOSE: To evaluate the potential of advanced modeled iterative reconstruction (ADMIRE) for optimizing radiation dose of high-pitch coronary CT angiography (CCTA). METHODS: High-pitch 192-slice dual-source CCTA was performed in 25 patients (group 1) according to standard settings (ref. 100 kVp, ref. 270 mAs/rot). Images were reconstructed with filtered back projection (FBP) and ADMIRE (strength levels 1-5). In another 25 patients (group 2), high-pitch CCTA protocol parameters were adapted according to results from group 1 (ref. 160 mAs/rot), and images were reconstructed with ADMIRE level 4. In ten patients of group 1, vessel sharpness using full width at half maximum (FWHM) analysis was determined. Image quality was assessed by two independent, blinded readers. RESULTS: Interobserver agreements for attenuation and noise were excellent (r = 0.88/0.85, p < 0.01). In group 1, ADMIRE level 4 images were most often selected (84%, 21/25) as preferred data set; at this level noise reduction was 40% compared to FBP. Vessel borders showed increasing sharpness (FWHM) at increasing ADMIRE levels (p < 0.05). Image quality in group 2 was similar to that of group 1 at ADMIRE levels 2-3. Radiation dose in group 2 (0.3 ± 0.1 mSv) was significantly lower than in group 1 (0.5 ± 0.3 mSv; p < 0.05). CONCLUSIONS: In a selected population, ADMIRE can be used for optimizing high-pitch CCTA to an effective dose of 0.3 mSv. KEY POINTS: • Advanced modeled IR (ADMIRE) reduces image noise up to 50% as compared to FBP. • Coronary artery vessel borders show an increasing sharpness at higher ADMIRE levels. • High-pitch CCTA with ADMIRE is possible at a radiation dose of 0.3 mSv.

Advanced virtual monoenergetic computed tomography of hyperattenuating and hypoattenuating liver lesions: ex-vivo and patient experience in various body sizes.

OBJECTIVE: To determine the value of advanced virtual monoenergetic images (mono+) from dual-energy computed tomography (CT) of hyperattenuating and hypoattenuating liver lesions in various phantom sizes and patients in comparison with standard monoenergetic images (mono). MATERIALS AND METHODS: Anthropomorphic phantoms simulating 4 patient sizes (S, 300 × 200 mm; M, 350 × 250 mm; L, 400 × 300 mm; and XL, 600 × 450 mm) with a liver insert containing both hyperattenuating and hypoattenuating iodine-containing lesions were imaged with dose-equivalent dual-energy (100/150 Sn kilovolt [peak] [kV{p}]) and single-energy (120 kV[p]) protocols on a 192-slice dual-source CT system. In addition, 4 patients with 3 hypoattenuating and 3 hyperattenuating hepatocellular carcinoma were included and underwent dual-energy CT imaging with the same scanner at similar kV(p) settings (100/150 Sn kV[p]). Images were reconstructed with standard mono and with the mono+ algorithm at 10-kiloelectron volt (keV) intervals from 40 to 190 keV. Attenuation of the liver and lesions were measured, and contrast-to-noise ratios (CNRs) were calculated. Lesion conspicuity was rated by 2 blinded independent readers in all mono and mono+ data sets from 40 to 190 keV using a 5-point Likert scale (1, lowest conspicuity; and 5, highest conspicuity). RESULTS: Attenuation in the liver and in both hyperattenuating and hypoattenuating lesions did not differ between mono and mono+ (P = 0.41-0.49). Noise on mono+ was significantly lower than on mono for all phantom sizes (P < 0.05) and was increasing with phantom size. Hyperattenuating lesion CNR was highest for mono+ images at 40 keV in the S phantom (6.73), with significantly higher CNR for mono+ than for mono and for single energy (120 kV[p]) in all phantom sizes (all P < 0.001) except for the XL phantom. Hypoattenuating lesion CNR was highest for high-keV mono+ being significantly higher than on mono and on single-energy (120 kV[p]) images (all P < 0.001), except for the XL phantom with significantly higher CNR for mono (1.3) compared with mono+ (0.47) and 120 kV(p) (1.26). In patients, CNR curves of hyperattenuating hepatocellular carcinoma were in accordance with the phantom data, whereas hypoattenuating lesions demonstrate varying curves, some being in accordance with findings in phantoms. Interreader agreement for lesion conspicuity was very good (intraclass correlation, 0.95), with higher conspicuity scores for mono+ than for mono and single energy (120 kV[p]) at all phantom sizes (all P < 0.05) and within patients. CONCLUSION: Our ex vivo and patient data demonstrate added value for imaging of both hyperattenuating and hypoattenuating liver lesions with advanced virtual monoenergetic dual-energy CT by decreased noise, increased CNR, and higher lesion conspicuity, although with limitations in XL body sizes.

High-pitch coronary CT angiography with third generation dual-source CT: limits of heart rate.

To determine the average heart rate (HR) and heart rate variability (HRV) required for diagnostic imaging of the coronary arteries in patients undergoing high-pitch CT-angiography (CTA) with third-generation dual-source CT. Fifty consecutive patients underwent CTA of the thoracic (n = 8) and thoracoabdominal (n = 42) aorta with third-generation dual-source 192-slice CT with prospective electrocardiography (ECG)-gating at a pitch of 3.2. No ß-blockers were administered. Motion artifacts of coronary arteries were graded on a 4-point scale. Average HR and HRV were noted. The average HR was 66 ± 11 beats per minute (bpm) (range 45-96 bpm); the HRV was 7.3 ± 4.4 bpm (range 3-20 bpm). Interobserver agreement on grade of image quality for the 642 coronary segments evaluated by both observers was good (κ = 0.71). Diagnostic image quality was found for 608 of the 642 segments (95%) in 43 of 50 patients (86%). In 14% of the patients, image quality was nondiagnostic for at least one segment. HR (p = 0.001) was significantly higher in patients with at least one non-diagnostic segment compared to those without. There was no significant difference (p > 0.05) in HRV between patients with nondiagnostic segments and those with diagnostic images of all segments. All patients with a HR < 70 bpm had diagnostic image quality in all coronary segments. The effective radiation dose and scan time for the heart were 0.4 ± 0.1 mSv and 0.17 ± 0.02 s, respectively. Third-generation dual-source 192-slice CT allows for coronary angiography in the prospectively ECG-gated high-pitch mode with diagnostic image quality at HR up to 70 bpm. HRV is not significantly related to image quality of coronary CTA.

Performance of turbo high-pitch dual-source CT for coronary CT angiography: first ex vivo and patient experience.

OBJECTIVES: To evaluate image quality, maximal heart rate allowing for diagnostic imaging, and radiation dose of turbo high-pitch dual-source coronary computed tomographic angiography (CCTA). METHODS: First, a cardiac motion phantom simulating heart rates (HRs) from 60-90 bpm in 5-bpm steps was examined on a third-generation dual-source 192-slice CT (prospective ECG-triggering, pitch 3.2; rotation time, 250 ms). Subjective image quality regarding the presence of motion artefacts was interpreted by two readers on a four-point scale (1, excellent; 4, non-diagnostic). Objective image quality was assessed by calculating distortion vectors. Thereafter, 20 consecutive patients (median, 50 years) undergoing clinically indicated CCTA were included. RESULTS: In the phantom study, image quality was rated diagnostic up to the HR75 bpm, with object distortion being 1 mm or less. Distortion increased above 1 mm at HR of 80-90 bpm. Patients had a mean HR of 66 bpm (47-78 bpm). Coronary segments were of diagnostic image quality for all patients with HR up to 73 bpm. Average effective radiation dose in patients was 0.6 ± 0.3 mSv. CONCLUSIONS: Our combined phantom and patient study indicates that CCTA with turbo high-pitch third-generation dual-source 192-slice CT can be performed at HR up to 75 bpm while maintaining diagnostic image quality, being associated with an average radiation dose of 0.6 mSv. KEY POINTS: • CCTA is feasible with the turbo high-pitch mode. • Turbo high-pitch CCTA provides diagnostic image quality up to 73 bpm. • The radiation dose of high-pitch CCTA is 0.6 mSv on average.

Systematic analysis on the relationship between luminal enhancement, convolution kernel, plaque density, and luminal diameter of coronary artery stenosis: a CT phantom study.

To systematically investigate into the relationships between luminal enhancement, convolution kernel, plaque density, and stenosis severity in coronary computed tomography (CT) angiography. A coronary phantom including 63 stenoses (stenosis severity, 10-90%; plaque densities, -100 to 1,000 HU) was loaded with increasing solutions of contrast material (luminal enhancement, 0-700 HU) and scanned in an anthropomorphic chest. CT data was acquired with prospective triggering using 64-section dual-source CT; reconstructions were performed with soft-tissue (B26f) and sharp convolution kernels (B46f). Two blinded and independent readers quantitatively assessed luminal diameter and CT number of plaque using electronic calipers. Measurement bias between phantom dimensions and CT measurements were calculated. Multivariate linear regression models identified predictors of bias. Inter- and intra-reader agreements of luminal diameter and CT number measurements were excellent (ICCs > 0.91, p < 0.01, each). Measurement bias of luminal diameter and plaque density was significantly (p < 0.01, each) lower (-12% and 58 HU, respectively) with B46f as opposed to B26f, especially in plaque densities >200 HU. Measurement bias was significantly (p < 0.01, each) correlated (ρ = 0.37-55 and ρ = -0.70-85) with the differences between luminal enhancement and plaque density. In multivariate models, bias of luminal diameter assessment with CT was correlated with plaque density (ß = 0.09, p < 0.05). Convolution kernel (ß = -0.29 and -0.38), stenosis severity (ß = -0.45 and -0.38), and luminal enhancement (ß = -0.11 and -0.29) represented independent (p < 0.05,each) predictors of measurement bias of luminal diameter and plaque number, respectively. Significant independent relationships exist between luminal enhancement, convolution kernel, plaque density, and luminal diameter, which have to be taken into account when performing, evaluating, and interpreting coronary CT angiography.

Stenosis quantification in coronary CT angiography: impact of an integrated circuit detector with iterative reconstruction.

OBJECTIVES: The objective of this study was to assess the value of an integrated circuit (IC) detector, potentially improving spatial resolution by means of reduced cross talk between detector channels, in coronary computed tomographic (CT) angiography regarding image quality and stenosis quantification compared with conventional detector technology. MATERIALS AND METHODS: In the ex vivo part of the study, a coronary phantom including 63 defined stenoses and 7 plaque densities (degree of stenosis, 10%-90%; plaque densities, -100 to 1000 Hounsfield unit [HU]) was loaded with contrast agent diluted to 300 HU and placed in an anthropomorphic chest phantom. The phantom was scanned in 0-, 45-, and 90-degree orientations to the z-axis of the CT scanner table. Images were acquired using 128-section dual-source CT equipped with IC and with conventional detector technology. Data were reconstructed with filtered back projection (FBP) and with sinogram-affirmed iterative reconstruction (IR) at a slice thickness of 0.6 mm (increment, 0.4 mm). Data acquired with the IC detector were additionally reconstructed with a slice thickness of 0.5 mm (increment, 0.3 mm) combined with IR. Two readers rated image quality; image noise and degree of stenosis were assessed. In the in vivo part of the study, phantom observations were validated in 30 consecutive patients (11 women; mean [SD] age, 62 [13] years; mean [SD] heart rate, 81 [17] beats per minute) undergoing coronary CT angiography with IC for clinical indications. Images of the patients were reconstructed with FBP (slice thickness, 0.6 mm) and with IR (slice thickness, 0.5 mm) and were assessed for image quality and degree of stenosis. Interreader agreement for image quality was evaluated using intraclass correlation coefficients. The image quality was compared with the Wilcoxon signed rank test. The image noise and the degree of stenosis were compared with the Student t test for paired samples. RESULTS: The interreader agreement for the assessment of image quality was substantial (intraclass correlation coefficients, 0.79). The image quality was significantly (P < 0.001) higher for the images acquired with the IC detector as compared with the conventional detector. The image noise with IR was significantly (P = 0.020) reduced for the IC detector as compared with the conventional detector. The IC detector yielded significantly more accurate results regarding stenosis grading when compared with the images acquired with the conventional detector regarding both FBP (mean [SD] error FBP, 12.1% [7.6%] vs 13.7% [7.6%]; P = 0.043) and IR (mean [SD] error IR, 10.5% [6.6%] vs 13.0% [6.9%]; P < 0.001). The images with a slice thickness of 0.5 mm reconstructed with IR (mean [SD] error, 8.8% [5.9%]) obtained by the IC detector significantly (P < 0.001) improved measurement accuracy in the phantom as compared with FBP with a slice thickness of 0.6 mm (mean [SD] error, 12.1% [7.6%]). In the patients, we found a significantly (P < 0.001) higher image quality, and stenoses were quantified significantly (P = 0.009) smaller with FBP as compared with IR (mean stenosis, 47.6% vs 42.1%; mean difference, 5.5%). CONCLUSIONS: Our ex vivo and patient study indicates significantly reduced image noise and more accurate stenosis quantification in coronary CT angiography when acquiring data using an IC detector and combining IR with high-resolution images as compared with conventional detector technology and FBP reconstructions.

Prediction model to estimate presence of coronary artery disease: retrospective pooled analysis of existing cohorts.

OBJECTIVES: To develop prediction models that better estimate the pretest probability of coronary artery disease in low prevalence populations. DESIGN: Retrospective pooled analysis of individual patient data. SETTING: 18 hospitals in Europe and the United States. PARTICIPANTS: Patients with stable chest pain without evidence for previous coronary artery disease, if they were referred for computed tomography (CT) based coronary angiography or catheter based coronary angiography (indicated as low and high prevalence settings, respectively). MAIN OUTCOME MEASURES: Obstructive coronary artery disease (≥ 50% diameter stenosis in at least one vessel found on catheter based coronary angiography). Multiple imputation accounted for missing predictors and outcomes, exploiting strong correlation between the two angiography procedures. Predictive models included a basic model (age, sex, symptoms, and setting), clinical model (basic model factors and diabetes, hypertension, dyslipidaemia, and smoking), and extended model (clinical model factors and use of the CT based coronary calcium score). We assessed discrimination (c statistic), calibration, and continuous net reclassification improvement by cross validation for the four largest low prevalence datasets separately and the smaller remaining low prevalence datasets combined. RESULTS: We included 5677 patients (3283 men, 2394 women), of whom 1634 had obstructive coronary artery disease found on catheter based coronary angiography. All potential predictors were significantly associated with the presence of disease in univariable and multivariable analyses. The clinical model improved the prediction, compared with the basic model (cross validated c statistic improvement from 0.77 to 0.79, net reclassification improvement 35%); the coronary calcium score in the extended model was a major predictor (0.79 to 0.88, 102%). Calibration for low prevalence datasets was satisfactory. CONCLUSIONS: Updated prediction models including age, sex, symptoms, and cardiovascular risk factors allow for accurate estimation of the pretest probability of coronary artery disease in low prevalence populations. Addition of coronary calcium scores to the prediction models improves the estimates.

Ventricular short-axis measurements in patients with pulmonary embolism: effect of ECG-gating on variability, accuracy, and risk prediction.

OBJECTIVE: To assess prospectively the intra- and interobserver variability, accuracy, and prognostic value of right and left ventricular short-axis diameter (RVd and LVd) measurements for risk stratification in patients with pulmonary embolism (PE) using ECG-gated compared to non-gated CT. MATERIALS AND METHODS: Sixty consecutive patients (33 women; mean age 58.7±10.3 years) with suspicion of PE underwent both non-gated and ECG-gated chest CT. RVd and LVd on four-chamber views and intra- and interobserver agreements were calculated for both protocols. RVd/LVd ratios were calculated and were related to 30-days adverse clinical events using receiver operating characteristics with area-under-the-curve (AUC) analyses. RESULTS: Both inter- and intraobserver variability showed narrower limits of agreement for all measurements with ECG-gated as compared to non-gated CT. Diameter measurements were significantly lower using non-ECG-gated CT as compared to ECG-gated CT for RVd and LVd (both p<.05). The AUC for the RVd/LVd ratio from ECG-gated CT was significantly larger than that from non-gated CT (0.956, 95% CI: 0.768-0.999 versus 0.675, 95% CI: 0.439-0.860; p=.048). CONCLUSION: RVd and LVd measurements from ECG-gated chest CT show less intra- and interobserver variability and more accurately reflect ventricular function. In our patient cohort ECG-gated chest CT allows better prediction of short-term outcome of patients with acute PE that needs to be validated in a larger outcome study.

Computed high concentrations of low-density lipoprotein correlate with plaque locations in human coronary arteries.

Subendothelial accumulation of low-density lipoprotein (LDL) in arterial walls is an initiator of atherosclerotic plaque formation. We report here on the correlation between healthy state subendothelial LDL concentration distribution and sites of subsequent plaque formation in coronary arteries of patients with coronary artery disease (CAD). We acquired left (LCA) and right coronary artery (RCA) and atherosclerotic plaque geometries of 60 patients with CAD using dual-source computed tomography angiography. After virtually removing all plaques to obtain an approximation of the arteries' healthy state, we calculated LDL concentration in the artery walls as a function of local lumen-side shear stress. We found that maximum subendothelial LDL concentrations at plaque locations were, on average, 45% (RCA) and 187% (LCA) higher than the respective average subendothelial concentration. Our results demonstrate that locally elevated subendothelial LDL concentration correlates with subsequent plaque formation at the same location.

Coronary artery plaques and myocardial ischaemia.

OBJECTIVE: To prospectively examine coronary artery plaques as predictors of myocardial ischaemia using cardiac magnetic resonance (CMR). METHODS: Fifty-two patients (46 men; age 64 ± 10) with suspected coronary artery disease (CAD) referred for catheter coronary angiography (CA) underwent CMR and computed tomography coronary angiography (CTCA). All coronary segments were evaluated for morphological stenosis based on CA. Any plaque according to its composition was assessed based on CTCA. RESULTS: Numbers of total and calcified coronary artery plaques represented the best predictors of myocardial ischaemia (AUC = 0.87; [95%CI: 0.77-0.97] and AUC = 0.87; [95%CI: 0.77-0.96], respectively, p = 0.56) with the total plaque number significantly higher in patients with corresponding ischaemia than those without (p < 0.01, p < 0.05 adjusted for pre-test probability and stenosis). Compared with the AUC of coronary stenosis assessment by CA (AUC = 0.90; [95%CI: 0.80-1.00]), AUCs were equivalent using either the total number or the number of calcified plaques alone (p = 0.73 and p = 0.69). Multivariate logistic regression analyses demonstrated the total plaque number as an independent predictor of ischaemia (odds +20%; [95%CI: 1.096-1.368]), improving a model including clinical probability estimates of CAD (c-statistics, 0.66 to 0.89). CONCLUSION: Coronary artery plaque number according to CTCA is a significant, independent predictor of myocardial ischaemia with similar accuracy to stenosis assessment.

A clinical prediction rule for the diagnosis of coronary artery disease: validation, updating, and extension.

AIMS: The aim was to validate, update, and extend the Diamond-Forrester model for estimating the probability of obstructive coronary artery disease (CAD) in a contemporary cohort. METHODS AND RESULTS: Prospectively collected data from 14 hospitals on patients with chest pain without a history of CAD and referred for conventional coronary angiography (CCA) were used. Primary outcome was obstructive CAD, defined as ≥ 50% stenosis in one or more vessels on CCA. The validity of the Diamond-Forrester model was assessed using calibration plots, calibration-in-the-large, and recalibration in logistic regression. The model was subsequently updated and extended by revising the predictive value of age, sex, and type of chest pain. Diagnostic performance was assessed by calculating the area under the receiver operating characteristic curve (c-statistic) and reclassification was determined. We included 2260 patients, of whom 1319 had obstructive CAD on CCA. Validation demonstrated an overestimation of the CAD probability, especially in women. The updated and extended models demonstrated a c-statistic of 0.79 (95% CI 0.77-0.81) and 0.82 (95% CI 0.80-0.84), respectively. Sixteen per cent of men and 64% of women were correctly reclassified. The predicted probability of obstructive CAD ranged from 10% for 50-year-old females with non-specific chest pain to 91% for 80-year-old males with typical chest pain. Predictions varied across hospitals due to differences in disease prevalence. CONCLUSION: Our results suggest that the Diamond-Forrester model overestimates the probability of CAD especially in women. We updated the predictive effects of age, sex, type of chest pain, and hospital setting which improved model performance and we extended it to include patients of 70 years and older.

Computed tomography of the lung in the high-pitch mode: is breath holding still required?

OBJECTIVES: To prospectively investigate whether the high-pitch mode (HPM) for computed tomography (CT) enables the diagnostic visualization of the lung parenchyma without suspended respiration. MATERIALS AND METHODS: A total of 40 consecutive patients (age, 67 ± 11 years) underwent 128-slice dual-source CT of the chest including nonenhanced, arterial, and venous phase of contrast. CT was performed in the HPM with a pitch of 3.2 during continuous breathing (group A) and during breath-hold (group B), and at standard pitch of 1 during deep-inspiratory breath-hold (group C). The 3 protocols were scanned in a random order in each patient. Two blinded readers independently assessed the image quality of 5 regions in both the lungs using a semiquantitative 3-point score. Image noise was measured as the standard deviation of attenuation. Presence and size of pulmonary nodules were noted and measured on each CT dataset. Lung volume was measured using dedicated semi-automated segmentation software. RESULTS: Interobserver agreement for image quality ratings was excellent (κ = 0.91). There were no significant differences in the number of lung regions having an image quality other than excellent between group A (2.5%) and B (1.5%, P = 0.48), whereas significantly less regions had impaired image quality in group B compared with group C (5.5%, P < 0.01). Image quality impairment in group C was because of breathing in 36% and cardiac pulsation in 64%. Image noise in group C (9 ± 2 HU) was significantly lower than that in group B (30 ± 2 HU, P < 0.001) whereas no significant difference was found between group A and B (P = 0.52). There were no significant differences for the depiction (P = 1.0) and size (P = 0.94) of lung nodules among the 3 modes. Average lung volume in group A was 75% ± 15% of that in deep inspiration (group B/C) being significantly smaller (P < 0.05). Estimated effective radiation doses in group C and group B were 5.8 ± 0.5 mSv and 1.6 ± 0.1 mSv, respectively. CONCLUSIONS: CT of the lung can be accomplished using the HPM at a low radiation dose with a diagnostic image quality even without suspended respiration.

Coronary artery disease: which degree of coronary artery stenosis is indicative of ischemia?

PURPOSE: To prospectively determine the best cut-off value of stenosis degree for low-dose computed tomography coronary angiography (CTCA) to predict the hemodynamic significance of coronary artery stenoses compared to catheter angiography (CA) using a cardiac magnetic resonance based approach as standard of reference. MATERIALS AND METHODS: Fifty-two patients (mean age, 64±10 years) scheduled for CA underwent cardiac magnetic resonance (CMR) at 1.5-T and dual-source CTCA using prospective ECG-triggering the same day. Diagnostic performance of CTCA and CA to detect myocardial ischemia was evaluated with CMR as the standard of reference. The diagnostic performance and best cut-off values to predict the hemodynamic significance of coronary were determined from receiver operating characteristics analysis (ROC). RESULTS: CA revealed >50% stenoses in 131/832 segments (15.7%) in 78/156 (50.0%) coronary arteries in 32/52 (62%) patients. CTCA revealed >50% stenoses in 148/807 (18.3%) segments, corresponding to 83/156 (53.2%) coronary arteries in 34/52 (65.4%) patients. CMR revealed ischemia in 118/832 (14.2%) myocardial segments corresponding to the territories of 60/156 (38.5%) coronary arteries in 29/52 (56%) patients. ROC analysis showed equal diagnostic performance for low-dose CTCA and CA with areas under the curve (AUC) of 0.82 and 0.83 (P=0.64). The optimal cut-off value was determined at stenosis of >60% for the prediction of hemodynamically significant coronary stenosis by CTCA. Using this cut-off value, sensitivity, specificity, NPV and PPV to predict hemodynamic significance by CTCA were 100%, 83%, 100%, and 88% on a per-patient basis and 88%, 73%, 83% and 81% on a per-artery analysis, respectively. CONCLUSION: By considering coronary stenosis >60%, diagnostic performance for predicting the hemodynamic significance of coronary stenosis by CTCA is optimal and equals that of CA.