Martin J. Willemink

New Applications of Cardiac Computed Tomography: Dual-Energy, Spectral, and Molecular CT Imaging.

Computed tomography (CT) has evolved into a powerful diagnostic tool, and it is impossible to imagine current clinical practice without CT imaging. Because of its widespread availability, ease of clinical application, superb sensitivity for the detection of coronary artery disease, and noninvasive nature, CT has become a valuable tool within the armamentarium of cardiologists. In the past few years, numerous technological advances in CT have occurred, including dual-energy CT, spectral CT, and CT-based molecular imaging. By harnessing the advances in technology, cardiac CT has advanced beyond the mere evaluation of coronary stenosis to an imaging tool that permits accurate plaque characterization, assessment of myocardial perfusion, and even probing of molecular processes that are involved in coronary atherosclerosis. Novel innovations in CT contrast agents and pre-clinical spectral CT devices have paved the way for CT-based molecular imaging.

Systematic Error in Lung Nodule Volumetry: Effect of Iterative Reconstruction Versus Filtered Back Projection at Different CT Parameters

OBJECTIVE Iterative reconstruction potentially can reduce radiation dose compared with filtered back projection (FBP) for chest CT. This is especially important for repeated CT scanning, as is the case in patients with indeterminate lung nodules. It is currently unknown whether absolute nodule volumes measured with iterative reconstruction are comparable to those measured with FBP. We compared nodule volumes measured with iterative reconstruction and FBP at different CT parameters. MATERIALS AND METHODS An anthropomorphic chest phantom was scanned using a 256-MDCT scanner at various tube voltages and tube current-time products. Raw data were reconstructed using FBP or a commercially available iterative reconstruction algorithm. Five inserted nodules with 100 HU radiodensity and different sizes (3, 5, 8, 10, and 12 mm) were measured by two observers using semiautomatic software. Volumetric nodule measurements were performed using thin-slice reconstructions. RESULTS For very small nodules (volume, 14.1 mm(3); diameter, 3 mm), FBP and iterative reconstruction measurements exhibited large errors and overestimated the nodule size by up to 160%. For larger nodules (volume, ≥ 65.4 mm(3); diameter, ≥ 5 mm), CT underestimated the actual size, but errors were small (within 25%) and remained small when the tube voltage and tube current-time product were reduced, even without iterative reconstruction. CONCLUSION In a phantom model, no clinically relevant differences beyond reported interscan variation levels between lung nodule volumes were measured in nodules 5 mm or larger at reduced tube voltage and tube current-time product, with radiation dose reductions up to 90.6% for both FBP and iterative reconstruction, suggesting that it is safe to convert FBP protocols to iterative reconstruction and reduce tube voltage and tube current-time product for lung nodule follow-up. CT appears to slightly underestimate actual nodule volume.

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%.

Achievable dose reduction using iterative reconstruction for chest computed tomography: A systematic review

OBJECTIVES Iterative reconstruction (IR) allows for dose reduction with maintained image quality in CT imaging. In this systematic review the reported effective dose reductions for chest CT and the effects on image quality are investigated. METHODS A systematic search in PubMed and EMBASE was performed. Primary outcome was the reported local reference and reduced effective dose and secondary outcome was the image quality with IR. Both non contrast-enhanced and enhanced studies comparing reference dose with reduced dose were included. RESULTS 24 studies were included. The median number of patients per study was 66 (range 23-200) with in total 1806 patients. The median reported local reference dose of contrast-enhanced chest CT with FBP was 2.6 (range 1.5-21.8) mSv. This decreased to 1.4 (range 0.4-7.3) mSv at reduced dose levels using IR. With non contrast-enhanced chest CT the dose decreased from 3.4 (range 0.7-7.8) mSv to 0.9 (range 0.1-4.5) mSv. Objective mage quality and diagnostic confidence and acceptability remained the same or improved with IR compared to FBP in most studies while data on diagnostic accuracy was limited. CONCLUSION Radiation dose can be reduced to less than 2 mSv for contrast-enhanced chest CT and non contrast-enhanced chest CT is possible at a submillisievert dose using IR algorithms.

New horizons in cardiac CT

Until recently, cardiovascular computed tomography angiography (CCTA) was associated with considerable radiation doses. The introduction of tube current modulation and automatic tube potential selection as well as high-pitch prospective ECG-triggering and iterative reconstruction offer the ability to decrease dose with approximately one order of magnitude, often to sub-millisievert dose levels. In parallel, advancements in computational technology have enabled the measurement of fractional flow reserve (FFR) from CCTA data (FFRCT). This technique shows potential to replace invasively measured FFR to select patients in need of coronary intervention. Furthermore, developments in scanner hardware have led to the introduction of dual-energy and photon-counting CT, which offer the possibility of material decomposition imaging. Dual-energy CT reduces beam hardening, which enables CCTA in patients with a high calcium burden and more robust myocardial CT perfusion imaging. Future-generation CT systems will be capable of counting individual X-ray photons. Photon-counting CT is promising and may result in a substantial further radiation dose reduction, vastly increased spatial resolution, and the introduction of a whole new class of contrast agents.

Computer-Aided Segmentation and Volumetry of Artificial Ground- Glass Nodules at Chest CT

OBJECTIVE The purpose of this study was to investigate a new software program for semiautomatic measurement of the volume and mass of ground-glass nodules (GGNs) in a chest phantom and to investigate the influence of CT scanner, reconstruction filter, tube voltage, and tube current. MATERIALS AND METHODS We used an anthropomorphic chest phantom with eight artificial GGNs with two different CT attenuations and four different volumes. CT scans were obtained with four models of CT scanner at 120 kVp and 25 mAs with a soft and a sharp reconstruction filter. On the 256-MDCT scanner, the tube current-exposure time product and tube voltage settings were varied. GGNs were measured with software that automatically segmented the nodules. Absolute percentage error (APE) was calculated for volume, mass, and density. Wilcoxon signed rank, Mann-Whitney U, and Kruskal-Wallis tests were used for analysis. RESULTS Volume and mass did not differ significantly from the true values. When measurements were expressed as APE, the error range was 2-36% for volume and 5-46% for mass, which was significantly different from no error. We did not find significant differences in APE between CT scanners with filters for lower tube current for volume or lower tube voltage for mass. CONCLUSION Computer-aided segmentation and mass and volume measurements of GGNs with the prototype software had promising results in this study.

Quantification of coronary artery calcium in nongated CT to predict cardiovascular events in male lung cancer screening participants: results of the NELSON study.

OBJECTIVE To evaluate the incremental prognostic value of the number and maximum volume of coronary artery calcifications over modified Agatston score strata, age, pack-years, and smoking status for predicting cardiovascular events. METHODS A total of 3559 male current and former smokers received a CT examination for lung cancer screening. Smoking characteristics, patient demographics, and physician-diagnosed cardiovascular events were collected. Images were acquired without electrocardiography gating on 16-slice CT scanners. The association between the presence of both fatal and nonfatal cardiovascular events and the predictors was quantified using Cox proportional hazard analysis. RESULTS Median follow-up period was 2.9 years. Incident cardiovascular events occurred in 186 participants. Adjusted hazard ratios for modified Agatston score strata of 1 to 10, 11 to 100, 101 to 400, and >400 were 3.39 (95% confidence interval [CI], 1.20-9.59), 6.52 (95% CI, 2.73-15.60), 6.58 (95% CI, 2.75-15.78), and 12.58 (95% CI, 5.42-29.16), respectively. Moreover, comparing the models with and without modified Agatston score strata to the model with age, pack-years, and smoking status yielded a significantly better net reclassification improvement (NRI; 27.3%; P < .0001). Adding the number of calcifications to the model with age, pack-years, smoking status, and modified Agatston score strata resulted in a slightly better NRI (1.68%; P = .0490) with a hazard ratio of 1.13 (95% CI, 1.05-1.21) per 10 calcifications. The incremental prognostic information contained in the volume of the largest calcification was not statistically significant (NRI, 0.14%; P = .3458). CONCLUSION Cardiovascular event rate increased with higher numbers of calcified lesions. The number but not maximum volume of calcifications has independent, although minimal, prognostic value over age, pack-years, smoking status, and modified Agatston score strata in our population.

Dose reduction with iterative reconstruction for coronary CT angiography: A systematic review and meta-analysis

OBJECTIVE To investigate the achievable radiation dose reduction for coronary CT angiography (CCTA) with iterative reconstruction (IR) in adults and the effects on image quality. METHODS PubMed and EMBASE were searched, and original articles concerning IR for CCTA in adults using prospective electrocardiogram triggering were included. Primary outcome was the effective dose using filtered back projection (FBP) and IR. Secondary outcome was the effect of IR on objective and subjective image quality. RESULTS The search yielded 1616 unique articles, of which 10 studies (1042 patients) were included. The pooled routine effective dose with FBP was 4.2 mSv [95% confidence interval (CI) 3.5-5.0]. A dose reduction of 48% to a pooled effective dose of 2.2 mSv (95% CI 1.3-3.1) using IR was reported. Noise, contrast-to-noise ratio and subjective image quality were equal or improved in all but one study, whereas signal-to-noise ratio was decreased in two studies with IR at reduced dose. CONCLUSION IR allows for CCTA acquisition with an effective dose of 2.2 mSv with preserved objective and subjective image quality.