Preclinical validation of the advection diffusion flow estimation method using computational patient specific coronary tree phantoms.

Coronary computed tomography angiography (CCTA) does not allow the quantification of reduced blood flow due to coronary artery disease (CAD). In response, numerical methods based on the CCTA image have been developed to compute coronary blood flow and assess the impact of disease. However to compute blood flow in the coronary arteries, numerical methods require specification of boundary conditions that are difficult to estimate accurately in a patient-specific manner. We describe herein a new noninvasive flow estimation method, called Advection Diffusion Flow Estimation (ADFE), to compute coronary artery flow from CCTA to use as boundary conditions for numerical models of coronary blood flow. ADFE uses image contrast variation along the tree-like structure to estimate flow in each vessel. For validating this method we used patient specific software phantoms on which the transport of contrast was simulated. This controlled validation setting enables a direct comparison between estimated flow and actual flow and a detailed investigation of factors affecting accuracy. A total of 10 CCTA image data sets were processed to extract all necessary information for simulating contrast transport. A spectral element method solver was used for computing the ground truth simulations with high accuracy. On this data set, the ADFE method showed a high correlation coefficient of 0.998 between estimated flow and the ground truth flow together with an average relative error of only 1 % . Comparing the ADFE method with the best method currently available (TAFE) for image-based blood flow estimation, which showed a correlation coefficient of 0.752 and average error of 20 % , it can be concluded that the ADFE method has the potential to significantly improve the quantification of coronary artery blood flow derived from contrast gradients in CCTA images.

Image-based automated Psoriasis Area Severity Index scoring by Convolutional Neural Networks.

BACKGROUND: The Psoriasis Area and Severity Index (PASI) score is commonly used in clinical practice and research to monitor disease severity and determine treatment efficacy. Automating the PASI score with deep learning algorithms, like Convolutional Neural Networks (CNNs), could enable objective and efficient PASI scoring. OBJECTIVES: To assess the performance of image-based automated PASI scoring in anatomical regions by CNNs and compare the performance of CNNs to image-based scoring by physicians. METHODS: Imaging series were matched to PASI subscores determined in real life by the treating physician. CNNs were trained using standardized imaging series of 576 trunk, 614 arm and 541 leg regions. CNNs were separately trained for each PASI subscore (erythema, desquamation, induration and area) in each anatomical region (trunk, arms and legs). The head region was excluded for anonymity. Additionally, PASI-trained physicians retrospectively determined image-based subscores on the test set images of the trunk. Agreement with the real-life scores was determined with the intraclass correlation coefficient (ICC) and compared between the CNNs and physicians. RESULTS: Intraclass correlation coefficients between the CNN and real-life scores of the trunk region were 0.616, 0.580, 0.580 and 0.793 for erythema, desquamation, induration and area, respectively, with similar results for the arms and legs region. PASI-trained physicians (N = 5) were in moderate-good agreement (ICCs 0.706-0.793) with each other for image-based PASI scoring of the trunk region. ICCs between the CNN and real-life scores were slightly higher for erythema (0.616 vs. 0.558), induration (0.580 vs. 0.573) and area scoring (0.793 vs. 0.694) than image-based scoring by physicians. Physicians slightly outperformed the CNN on desquamation scoring (0.580 vs. 0.589). CONCLUSIONS: Convolutional Neural Networks have the potential to automatically and objectively perform image-based PASI scoring at an anatomical region level. For erythema, desquamation and induration scoring, CNNs performed similar to physicians, while for area scoring CNNs outperformed physicians on image-based PASI scoring.

Oxygen supplementation before induction of general anaesthesia in horses.

REASONS FOR PERFORMING STUDY: Hypoventilation or apnoea, caused by the induction of general anaesthesia, may cause hypoxaemia. Preoxygenation may lengthen the period before this happens. No scientific studies are published on preoxygenation in equine anaesthesia. OBJECTIVES: To determine whether supplementation of oxygen at a flow rate of 15 l/min for 3 min via a nasal cannula before induction of general anaesthesia is effective in elevating the arterial partial pressure of oxygen (PaO2 ) directly after induction. STUDY DESIGN: Randomised, prospective clinical trial. METHODS: A total of 18 American Society of Anesthesiologists physical status 1 or 2 adult horses undergoing elective anaesthesia were randomly allocated to one of 2 groups. The first group (control) received no oxygen supplementation before induction of general anaesthesia, whereas the second group (oxygen) did. All horses were anaesthetised with intravenous detomidine, butorphanol, ketamine, midazolam and isoflurane. Directly after induction (T = 0) and 30 min later (T = 30) an arterial blood sample was taken for blood gas analysis. At T = 30 an estimate of intrapulmonary shunt fraction (Qs/Qt) was calculated. RESULTS: At T = 0 arterial partial pressure of oxygen (PaO2 ) was significantly higher in the oxygen group compared with the control group (11.0 ± 2.6 kPa vs. 7.4 ± 1.6 kPa; mean ± s.d., P = 0.005) and at T = 30 differences were not statistically significant. Partial pressure of carbon dioxide (PaCO2 ) and Qs/Qt did not differ between groups. CONCLUSIONS: Supplementing oxygen by a nasal cannula before induction of general anaesthesia in horses is feasible and does effectively elevate the PaO2 immediately after induction. Future research is needed to determine whether supplementation of oxygen before induction of general anaesthesia in horses will affect outcomes.

Detection of the mechanism of immunotoxicity of cyclosporine A in murine in vitro and in vivo models.

Transcriptomics in combination with in vitro cell systems is a powerful approach to unravel modes of action of toxicants. An important question is to which extent the modes of action as revealed by transcriptomics depend on cell type, species and study type (in vitro or in vivo). To acquire more insight into this, we assessed the transcriptomic effects of the immunosuppressive drug cyclosporine A (CsA) upon 6 h of exposure of the mouse cytotoxic T cell line CTLL-2, the thymoma EL-4 and primary splenocytes and compared these to the effects in spleens of mice orally treated with CsA for 7 days. EL-4 and CTLL-2 cells showed the highest similarities in response. CsA affected many genes in primary splenocytes that were not affected in EL-4 or CTLL-2. Pathway analysis demonstrated that CsA upregulated the unfolded protein response, endoplasmic reticulum stress and NRF2 activation in EL-4 cells, CTLL-2 cells and primary mouse splenocytes but not in mouse spleen in vivo. As expected, CsA downregulated cell cycle and immune response in splenocytes in vitro, spleens in vivo as well as CTLL-2 in vitro. Genes up- and downregulated in human Jurkat, HepG2 and renal proximal tubular cells were similarly affected in CTLL-2, EL-4 and primary splenocytes in vitro. In conclusion, of the models tested in this study, the known mechanism of immunotoxicity of CsA is best represented in the mouse cytotoxic T cell line CTLL-2. This is likely due to the fact that this cell line is cultured in the presence of a T cell activation stimulant (IL-2) making it more suitable to detect inhibitory effects on T cell activation.

Creatine kinase inhibits ADP-induced platelet aggregation.

Bleeding risk with antiplatelet therapy is an increasing clinical challenge. However, the inter-individual variation in this risk is poorly understood. We assessed whether the level of plasma creatine kinase, the enzyme that utilizes ADP and phosphocreatine to rapidly regenerate ATP, may modulate bleeding risk through a dose-dependent inhibition of ADP-induced platelet activation. Exogenous creatine kinase (500 to 4000 IU/L, phosphocreatine 5 mM) added to human plasma induced a dose-dependent reduction to complete inhibition of ADP-induced platelet aggregation. Accordingly, endogenous plasma creatine kinase, studied in 9 healthy men (mean age 27.9 y, SE 3.3; creatine kinase 115 to 859 IU/L, median 358), was associated with reduced ADP-induced platelet aggregation (Spearman's rank correlation coefficient, -0.6; p < 0.05). After exercise, at an endogenous creatine kinase level of 4664, ADP-induced platelet aggregation was undetectable, normalizing after rest, with a concomitant reduction of creatine kinase to normal values. Thus, creatine kinase reduces ADP-induced platelet activation. This may promote bleeding, in particular when patients use platelet P2Y12 ADP receptor inhibitors.

Standardized evaluation framework for evaluating coronary artery stenosis detection, stenosis quantification and lumen segmentation algorithms in computed tomography angiography.

Though conventional coronary angiography (CCA) has been the standard of reference for diagnosing coronary artery disease in the past decades, computed tomography angiography (CTA) has rapidly emerged, and is nowadays widely used in clinical practice. Here, we introduce a standardized evaluation framework to reliably evaluate and compare the performance of the algorithms devised to detect and quantify the coronary artery stenoses, and to segment the coronary artery lumen in CTA data. The objective of this evaluation framework is to demonstrate the feasibility of dedicated algorithms to: (1) (semi-)automatically detect and quantify stenosis on CTA, in comparison with quantitative coronary angiography (QCA) and CTA consensus reading, and (2) (semi-)automatically segment the coronary lumen on CTA, in comparison with expert's manual annotation. A database consisting of 48 multicenter multivendor cardiac CTA datasets with corresponding reference standards are described and made available. The algorithms from 11 research groups were quantitatively evaluated and compared. The results show that (1) some of the current stenosis detection/quantification algorithms may be used for triage or as a second-reader in clinical practice, and that (2) automatic lumen segmentation is possible with a precision similar to that obtained by experts. The framework is open for new submissions through the website, at http://coronary.bigr.nl/stenoses/.

Benzo[a]pyrene-induced transcriptomic responses in primary hepatocytes and in vivo liver: toxicokinetics is essential for in vivo-in vitro comparisons.

The traditional 2-year cancer bioassay needs replacement by more cost-effective and predictive tests. The use of toxicogenomics in an in vitro system may provide a more high-throughput method to investigate early alterations induced by carcinogens. Recently, the differential gene expression response in wild-type and cancer-prone Xpa (-/-) p53 (+/-) primary mouse hepatocytes after exposure to benzo[a]pyrene (B[a]P) revealed downregulation of cancer-related pathways in Xpa (-/-) p53 (+/-) hepatocytes only. Here, we investigated pathway regulation upon in vivo B[a]P exposure of wild-type and Xpa (-/-) p53 (+/-) mice. In vivo transcriptomics analysis revealed a limited gene expression response in mouse livers, but with a significant induction of DNA replication and apoptotic/anti-apoptotic cellular responses in Xpa (-/-) p53 (+/-) livers only. In order to be able to make a meaningful in vivo-in vitro comparison we estimated internal in vivo B[a]P concentrations using DNA adduct levels and physiologically based kinetic modeling. Based on these results, the in vitro concentration that corresponded best with the internal in vivo dose was chosen. Comparison of in vivo and in vitro data demonstrated similarities in transcriptomics response: xenobiotic metabolism, lipid metabolism and oxidative stress. However, we were unable to detect cancer-related pathways in either wild-type or Xpa (-/-) p53 (+/-) exposed livers, which were previously found to be induced by B[a]P in Xpa (-/-) p53 (+/-) primary hepatocytes. In conclusion, we showed parallels in gene expression responses between livers and primary hepatocytes upon exposure to equivalent concentrations of B[a]P. Furthermore, we recommend considering toxicokinetics when modeling a complex in vivo endpoint with in vitro models.

Statistical shape model-based femur kinematics from biplane fluoroscopy.

Studying joint kinematics is of interest to improve prosthesis design and to characterize postoperative motion. State of the art techniques register bones segmented from prior computed tomography or magnetic resonance scans with X-ray fluoroscopic sequences. Elimination of the prior 3D acquisition could potentially lower costs and radiation dose. Therefore, we propose to substitute the segmented bone surface with a statistical shape model based estimate. A dedicated dynamic reconstruction and tracking algorithm was developed estimating the shape based on all frames, and pose per frame. The algorithm minimizes the difference between the projected bone contour and image edges. To increase robustness, we employ a dynamic prior, image features, and prior knowledge about bone edge appearances. This enables tracking and reconstruction from a single initial pose per sequence. We evaluated our method on the distal femur using eight biplane fluoroscopic drop-landing sequences. The proposed dynamic prior and features increased the convergence rate of the reconstruction from 71% to 91%, using a convergence limit of 3 mm. The achieved root mean square point-to-surface accuracy at the converged frames was 1.48 ± 0.41 mm. The resulting tracking precision was 1-1.5 mm, with the largest errors occurring in the rotation around the femoral shaft (about 2.5° precision).

Cardiac motion-corrected iterative cone-beam CT reconstruction using a semi-automatic minimum cost path-based coronary centerline extraction.

In this paper a method which combines iterative computed tomography reconstruction and coronary centerline extraction technique to obtain motion artifact-free reconstructed images of the coronary arteries are proposed and evaluated. The method relies on motion-vector fields derived from a set of coronary centerlines extracted at multiple cardiac phases within the R-R interval. Hereto, start and end points are provided by the user in one time-frame only. Using an elastic image registration, these points are propagated to all the remaining cardiac phases. Consequently, a multi-phase three-dimensional coronary centerline is determined by applying a semi-automatic minimum cost path based extraction method. Corresponding centerline positions are used to determine the relative motion-vector fields from phase to phase. Finally, dense motion-vector fields are achieved by thin-plate-spline interpolation and used to perform a motion-corrected iterative reconstruction of a selected region of interest. The performance of the method is validated on five patients, showing the improved sharpness of cardiac motion-corrected gated iterative reconstructions compared to the results achieved by a classical gated iterative method. The results are also compared to known manual and fully automatic coronary artery motion estimation methods.

Impact of forest fires on particulate matter and ozone levels during the 2003, 2004 and 2005 fire seasons in Portugal.

The main purpose of this work is to estimate the impact of forest fires on air pollution applying the LOTOS-EUROS air quality modeling system in Portugal for three consecutive years, 2003-2005. Forest fire emissions have been included in the modeling system through the development of a numerical module, which takes into account the most suitable parameters for Portuguese forest fire characteristics and the burnt area by large forest fires. To better evaluate the influence of forest fires on air quality the LOTOS-EUROS system has been applied with and without forest fire emissions. Hourly concentration results have been compared to measure data at several monitoring locations with better modeling quality parameters when forest fire emissions were considered. Moreover, hourly estimates, with and without fire emissions, can reach differences in the order of 20%, showing the importance and the influence of this type of emissions on air quality.

Comprehensive visualization of multimodal cardiac imaging data for assessment of coronary artery disease: first clinical results of the SMARTVis tool.

PURPOSE: In clinical practice, both coronary anatomy and myocardial perfusion information are needed to assess coronary artery disease (CAD). The extent and severity of coronary stenoses can be determined using computed tomography coronary angiography (CTCA); the presence and amount of ischemia can be identified using myocardial perfusion imaging, such as perfusion magnetic resonance imaging (PMR). To determine which specific stenosis is associated with which ischemic region, experts use assumptions on coronary perfusion territories. Due to the high variability between patient's coronary artery anatomies, as well as the uncertain relation between perfusion territories and supplying coronary arteries, patient-specific systems are needed. MATERIAL AND METHODS: We present a patient-specific visualization system, called Synchronized Multimodal heART Visualization (SMARTVis), for relating coronary stenoses and perfusion deficits derived from CTCA and PMR, respectively. The system consists of the following comprehensive components: (1) two or three-dimensional fusion of anatomical and functional information, (2) automatic detection and ranking of coronary stenoses, (3) estimation of patient-specific coronary perfusion territories. RESULTS: The potential benefits of the SMARTVis tool in assessing CAD were investigated through a case-study evaluation (conventional vs. SMARTVis tool): two experts analyzed four cases of patients with suspected multivessel coronary artery disease. When using the SMARTVis tool, a more reliable estimation of the relation between perfusion deficits and stenoses led to a more accurate diagnosis, as well as a better interobserver diagnosis agreement. CONCLUSION: The SMARTVis comprehensive visualization system can be effectively used to assess disease status in multivessel CAD patients, offering valuable new options for the diagnosis and management of these patients.

Effect of roasting on the allergenicity of major peanut allergens Ara h 1 and Ara h 2/6: the necessity of degranulation assays.

BACKGROUND: Peanuts are often consumed after roasting, a process that alters the three-dimensional structure of allergens and leads to Maillard modification. Such changes are likely to affect their allergenicity. OBJECTIVE: We aimed to establish the effect of thermal treatment mimicking the roasting process on the allergenicity of Ara h 1 and a mix of 2S albumins from peanut (Ara h 2/6). METHODS: Ara h 1 and Ara h 2/6 were purified from raw peanuts and heated in a dry form for 20 min at 145°C in the presence (R+g) or absence (R-g) of glucose, and soluble proteins were then extracted. Sera obtained from 12 well-characterized peanut-allergic patients were used to assess the IgE binding and degranulation capacities of the allergens. RESULTS: Extensive heating at low moisture resulted in the hydrolysis of both Ara h 1 and Ara h 2/6. However, in contrast to Ara h 2/6, soluble R+g Ara h 1 formed large aggregates. Although the IgE-binding capacity of R+g and R-g Ara h 1 was decreased 9000- and 3.6-fold, respectively, compared with native Ara h 1, their capacity to elicit mediator release was increased. Conversely, both the IgE-binding capacity and the degranulation capacity of R-g Ara h 2/6 were 600-700-fold lower compared with the native form, although the presence of glucose during heating significantly moderated these losses. CONCLUSIONS AND CLINICAL RELEVANCE: Extensive heating reduced the degranulation capacity of Ara h 2/6 but significantly increased the degranulation capacity of Ara h 1. This observation can have important ramifications for component-resolved approaches for diagnosis and demonstrates the importance of investigating the degranulation capacity in addition to IgE reactivity when assessing the effects of food processing on the allergenicity of proteins.

Evaluation framework for carotid bifurcation lumen segmentation and stenosis grading.

This paper describes an evaluation framework that allows a standardized and objective quantitative comparison of carotid artery lumen segmentation and stenosis grading algorithms. We describe the data repository comprising 56 multi-center, multi-vendor CTA datasets, their acquisition, the creation of the reference standard and the evaluation measures. This framework has been introduced at the MICCAI 2009 workshop 3D Segmentation in the Clinic: A Grand Challenge III, and we compare the results of eight teams that participated. These results show that automated segmentation of the vessel lumen is possible with a precision that is comparable to manual annotation. The framework is open for new submissions through the website http://cls2009.bigr.nl.

Complement activation on the surface of cell-derived microparticles during cardiac surgery with cardiopulmonary bypass - is retransfusion of pericardial blood harmful?

OBJECTIVES: To investigate whether cell-derived microparticles play a role in complement activation in pericardial blood of patients undergoing cardiac surgery with cardiopulmonary bypass (CPB) and whether microparticles in pericardial blood contribute to systemic complement activation upon retransfusion. METHODS: Pericardial blood of 13 patients was retransfused in 9 and discarded in 4 cases. Microparticles were isolated from systemic blood collected before anesthesia (T1) and at the end of CPB (T2), and from pericardial blood. The microparticles were analyzed by flow cytometry for bound complement components C1q, C4 and C3, and bound complement activator molecules C-reactive protein (CRP), serum amyloid P-component (SAP), immunoglobulin (Ig)M and IgG. Fluid-phase complement activation products (C4b/c, C3b/c) and activator molecules were determined by ELISA. RESULTS: Compared with systemic T1 blood, pericardial blood contained increased C4b/c and C3b/c, and increased levels of microparticles with bound complement components. In systemic T1 samples, microparticle-bound CRP, whereas in pericardial blood, microparticle-bound SAP and IgM were associated with complement activation. At the end of CPB, increased C3b/c (but not C4b/c) was present in systemic T2 blood compared with T1, while concentrations of microparticles binding complement components and of those binding complement activator molecules were similar. Concentrations of fluid-phase complement activation products and microparticles were similar in patients whether or not retransfused with pericardial blood. CONCLUSIONS: In pericardial blood of patients undergoing cardiac surgery with CPB, microparticles contribute to activation of the complement system via bound SAP and IgM. Retransfusion of pericardial blood, however, does not contribute to systemic complement activation.

Nonrigid registration of dynamic medical imaging data using nD + t B-splines and a groupwise optimization approach.

A registration method for motion estimation in dynamic medical imaging data is proposed. Registration is performed directly on the dynamic image, thus avoiding a bias towards a specifically chosen reference time point. Both spatial and temporal smoothness of the transformations are taken into account. Optionally, cyclic motion can be imposed, which can be useful for visualization (viewing the segmentation sequentially) or model building purposes. The method is based on a 3D (2D+time) or 4D (3D+time) free-form B-spline deformation model, a similarity metric that minimizes the intensity variances over time and constrained optimization using a stochastic gradient descent method with adaptive step size estimation. The method was quantitatively compared with existing registration techniques on synthetic data and 3D+t computed tomography data of the lungs. This showed subvoxel accuracy while delivering smooth transformations, and high consistency of the registration results. Furthermore, the accuracy of semi-automatic derivation of left ventricular volume curves from 3D+t computed tomography angiography data of the heart was evaluated. On average, the deviation from the curves derived from the manual annotations was approximately 3%. The potential of the method for other imaging modalities was shown on 2D+t ultrasound and 2D+t magnetic resonance images. The software is publicly available as an extension to the registration package elastix.

Evaluation of a multi-atlas based method for segmentation of cardiac CTA data: a large-scale, multicenter, and multivendor study.

PURPOSE: Computed tomography angiography (CTA) is increasingly used for the diagnosis of coronary artery disease (CAD). However, CTA is not commonly used for the assessment of ventricular and atrial function, although functional information extracted from CTA data is expected to improve the diagnostic value of the examination. In clinical practice, the extraction of ventricular and atrial functional information, such as stroke volume and ejection fraction, requires accurate delineation of cardiac chambers. In this paper, we investigated the accuracy and robustness of cardiac chamber delineation using a multiatlas based segmentation method on multicenter and multivendor CTA data. METHODS: A fully automatic multiatlas based method for segmenting the whole heart (i.e., the outer surface of the pericardium) and cardiac chambers from CTA data is presented and evaluated. In the segmentation approach, eight atlas images are registered to a new patient's CTA scan. The eight corresponding manually labeled images are then propagated and combined using a per voxel majority voting procedure, to obtain a cardiac segmentation. RESULTS: The method was evaluated on a multicenter/multivendor database, consisting of (1) a set of 1380 Siemens scans from 795 patients and (2) a set of 60 multivendor scans (Siemens, Philips, and GE) from different patients, acquired in six different institutions worldwide. A leave-one-out 3D quantitative validation was carried out on the eight atlas images; we obtained a mean surface-to-surface error of 0.94 +/- 1.12 mm and an average Dice coefficient of 0.93 was achieved. A 2D quantitative evaluation was performed on the 60 multivendor data sets. Here, we observed a mean surface-to-surface error of 1.26 +/- 1.25 mm and an average Dice coefficient of 0.91 was achieved. In addition to this quantitative evaluation, a large-scale 2D and 3D qualitative evaluation was performed on 1380 and 140 images, respectively. Experts evaluated that 49% of the 1380 images were very accurately segmented (below 1 mm error) and that 29% were accurately segmented (error between 1 and 3 mm), which demonstrates the robustness of the presented method. CONCLUSIONS: A fully automatic method for whole heart and cardiac chamber segmentation was presented and evaluated using multicenter/multivendor CTA data. The accuracy and robustness of the method were demonstrated by successfully applying the method to 1420 multicenter/ multivendor data sets.

Monitoring of socio-economic inequalities in smoking: learning from the experiences of recent scientific studies.

OBJECTIVES: To support policies to tackle socio-economic inequalities in smoking, monitoring systems should include information on smoking according to socio-economic position (SEP). This paper aims to review the methods applied in recent scientific studies on inequalities in smoking, with the aim of drawing lessons for the monitoring of smoking inequalities. STUDY DESIGN: Literature review. METHODS: Seventy studies on socio-economic inequalities in smoking, published since 1990, were selected and reviewed, with particular focus on study design, indicators of SEP and smoking outcomes. RESULTS: Most studies had a cross-sectional design and measured smoking prevalence rates among adults in relation to educational level. In addition to educational level, measures of household wealth and occupational class had strong associations with smoking outcomes. In addition to smoking prevalence, other outcome measures such as initiation rates, cessation rates and consumption level are needed to provide in-depth knowledge of the effect of SEP on smoking, especially from a life-course perspective. CONCLUSIONS: It is recommended that, as well as educational level, other socio-economic indicators should be used to identify socio-economic groups where smoking rates are highest. Estimates of inequalities in initiation and cessation rates are needed to identify the most important age groups and entry points for policies to tackle inequalities in smoking.

Coronary centerline extraction from CT coronary angiography images using a minimum cost path approach.

PURPOSE: The application and large-scale evaluation of minimum cost path approaches for coronary centerline extraction from computed tomography coronary angiography (CTCA) data and the development and evaluation of a novel method to reduce the user-interaction time. METHODS: A semiautomatic method based on a minimum cost path approach is evaluated for two different cost functions. The first cost function is based on a frequently used vesselness measure and intensity information, and the second is a recently proposed cost function based on region statistics. User interaction is minimized to one or two mouse clicks distally in the coronary artery. The starting point for the minimum cost path search is automatically determined using a newly developed method that finds a point in the center of the aorta in one of the axial slices. This step ensures that all computationally expensive parts of the algorithm can be precomputed. RESULTS: The performance of the aorta localization procedure was demonstrated by a success rate of 100% in 75 images. The success rate and accuracy of centerline extraction was quantitatively evaluated on 48 coronary arteries in 12 images by comparing extracted centerlines with a manually annotated reference standard. The method was able to extract 88% and 47% of the vessel center-lines correctly using the vesselness/intensity and region statistics cost function, respectively. For only the proximal part of the vessels these values were 97% and 86%, respectively. Accuracy of centerline extraction, defined as the average distance from correctly automatically extracted parts of the centerline to the reference standard, was 0.64 mm for the vesselness/intensity and 0.51 mm for the region statistics cost function. The interobserver variability was 99% for the success rate measure and 0.42 mm for the accuracy measure. Qualitative evaluation using the best performing cost function resulted in successful centerline extraction for 233 out of the 252 coronaries (92%) in 63 additional CTCA images. CONCLUSIONS: The presented results, in combination with minimal user interaction and low computation time, show that minimum cost path approaches can effectively be applied as a preprocessing step for subsequent analysis in clinical practice and biomedical research.

Socioeconomic inequalities in lung cancer mortality in 16 European populations.

OBJECTIVES: This paper aims to describe socioeconomic inequalities in lung cancer mortality in Europe and to get further insight into socioeconomic inequalities in lung cancer mortality in different European populations by relating these to socioeconomic inequalities in overall mortality and smoking within the same or reference populations. Particular attention is paid to inequalities in Eastern European and Baltic countries. METHODS: Data were obtained from mortality registers, population censuses and health interview surveys in 16 European populations. Educational inequalities in lung cancer and total mortality were assessed by direct standardization and calculation of two indices of inequality: the Relative Index of Inequality (RII) and the Slope Index of Inequality (SII). SIIs were used to calculate the contribution of inequalities in lung cancer mortality to inequalities in total mortality. Indices of inequality in lung cancer mortality in the age group 40-59 years were compared with indices of inequalities in smoking taking into account a time lag of 20 years. RESULTS: The pattern of inequalities in Eastern European and Baltic countries is more or less similar as the one observed in the Northern countries. Among men educational inequalities are largest in the Eastern European and Baltic countries. Among women they are largest in Northern European countries. Whereas among Southern European women lung cancer mortality rates are still higher among the high educated, we observe a negative association between smoking and education among young female adults. The contribution of lung cancer mortality inequalities to total mortality inequalities is in most male populations more than 10%. Important smoking inequalities are observed among young adults in all populations. In Sweden, Hungary and the Czech Republic smoking inequalities among young adult women are larger than lung cancer mortality inequalities among women aged 20 years older. CONCLUSIONS: Important socioeconomic inequalities exist in lung cancer mortality in Europe. They are consistent with the geographical spread of the smoking epidemic. In the next decades socioeconomic inequalities in lung cancer mortality are likely to persist and even increase among women. In Southern European countries we may expect a reversal from a positive to a negative association between socioeconomic status and lung cancer mortality. Continuous efforts are necessary to tackle socioeconomic inequalities in lung cancer mortality in all European countries.