http://repub.eur.nl/res/aut/24135/ List of Publications en http://repub.eur.nl/static-eur/img/logo.png http://repub.eur.nl http://repub.eur.nl/res/pub/34299/ 2011-08-01T00:00:00Z 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. http://repub.eur.nl/res/pub/26104/ 2011-06-09T00:00:00Z We propose a minimum cost path approach to track the centerlines of the internal and external carotid arteries in multispectral MR data. User interaction is limited to the annotation of three seed points. The cost image is based on both a measure of vessel medialness and lumen intensity similarity in two MRA image sequences: Black Blood MRA and Phase Contrast MRA. After intensity inhomogeneity correction and noise reduction, the two images are aligned using affine registration. The two parameters that control the contrast of the cost image were determined in an optimization experiment on 40 training datasets. Experiments on the training datasets also showed that a cost image composed of a combination of gradient-based medialness and lumen intensity similarity increases the tracking accuracy compared to using only one of the constituents. Furthermore, centerline tracking using both MRA sequences outperformed tracking using only one of these MRA images. An independent test set of 152 images from 38 patients served to validate the technique. The centerlines of 148 images were successfully extracted using the parameters optimized on the training sets. The average mean distance to the reference standard, manually annotated centerlines, was 0.98 mm, which is comparable to the in-plane resolution. This indicates that the proposed method has a high potential to replace the manual centerline annotation. http://repub.eur.nl/res/pub/22998/ 2011-04-01T00:00:00Z 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. http://repub.eur.nl/res/pub/34231/ 2011-03-15T00:00:00Z Diffusion MRI can be used to study the structural connectivity within the brain. Brain connectivity is often represented by a binary network whose topology can be studied using graph theory. We present a framework for the construction of weighted structural brain networks, containing information about connectivity, which can be effectively analyzed using statistical methods. Network nodes are defined by segmentation of subcortical structures and by cortical parcellation. Connectivity is established using a minimum cost path (mcp) method with an anisotropic local cost function based directly on diffusion weighted images. We refer to this framework as Statistical Analysis of Minimum cost path based Structural Connectivity (SAMSCo) and the weighted structural connectivity networks as mcp-networks. In a proof of principle study we investigated the information contained in mcp-networks by predicting subject age based on the mcp-networks of a group of 974 middle-aged and elderly subjects. Using SAMSCo, age was predicted with an average error of 3.7. years. This was significantly better than predictions based on fractional anisotropy or mean diffusivity averaged over the whole white matter or over the corpus callosum, which showed average prediction errors of at least 4.8. years. Additionally, we classified subjects, based on the mcp-networks, into groups with low and high white matter lesion load, while correcting for age, sex and white matter atrophy. The SAMSCo classification outperformed the classification based on the diffusion measures with a classification accuracy of 76.0% versus 63.2%. We also performed a classification in groups with mild and severe atrophy, correcting for age, sex and white matter lesion load. In this case, mcp-networks and diffusion measures yielded similar classification accuracies of 68.3% and 67.8% respectively. The SAMSCo prediction and classification experiments indicate that the mcp-networks contain information regarding age, white matter lesion load and white matter atrophy, and that in case of age and white matter lesion load the mcp-network based models outperformed the predictions based on diffusion measures. http://repub.eur.nl/res/pub/21853/ 2010-12-15T00:00:00Z Despite advances in diagnosis, treatment and interventions, cardiovascular disease remains a major health problem in the western world. Owing to the ageing society and changing lifestyle, cardiovascular disease affects an increasing number of individuals. Often, there are no symptoms prior to clinical cardiovascular disease related events such as myocardial infarction (heart attack), and irreversible damage or death may occur prior to any medical intervention. Advances in imaging technology have great potential to improve the management of cardiovascular disease through early detection, improved diagnosis and treatment monitoring [30]. This requires not only advanced techniques to image cardiovascular anatomy and function, but also robust methods to extract relevant (quantitative) parameters from these imaging data and novel techniques that effectively visualize diagnostically relevant image information. This thesis describes the development and validation of quantitative image analysis and visualization methods, which are essential steps towards improved imagebased diagnosis and prognosis of cardiovascular disease. In the subsequent sections we will introduce the cardiac anatomy, coronary artery disease, CT angiography (CTA) imaging of the coronary arteries, and methods for quantitative CTA image analysis. Following the introduction, we will provide an outline of this thesis in Section 1.2. http://repub.eur.nl/res/pub/20478/ 2010-12-01T00:00:00Z We propose and validate a semi-automatic method for lumen segmentation of the carotid bifurcation in computed tomography angiography (CTA). First, the central vessel axis is obtained using path tracking between three user-defined points. Second, starting from this path, the segmentation is automatically obtained using a level set. The cost and speed functions for path tracking and segmentation make use of intensity and homogeneity slice-based image features. The method is validated on a large data set of 234 carotid bifurcations of 129 ischemic stroke patients with atherosclerotic disease. The results are compared to manually obtained lumen segmentations. Parameter optimization is carried out on a subset of 30 representative carotid bifurcations. With the optimized parameter settings the method successfully tracked the central vessel paths in 201 of the remaining 204 bifurcations (99%) which were not part of the training set. Comparison with manually drawn segmentations shows that the average overlap between the method and observers is similar (for the inter-observer set the results were 92% vs. 87% and for the intra-observer set 94% vs. 94%). Therefore the method has potential to replace the manual procedure of lumen segmentation of the atherosclerotic bifurcation in CTA. © 2010 Elsevier B.V. http://repub.eur.nl/res/pub/26741/ 2010-12-01T00:00:00Z A method to obtain motion artifact-free reconstructed images of the coronary arteries is proposed and evaluated. The method relies on the integration of coronary motion estimation in an iterative computed tomography reconstruction technique. Coronary motion fields are derived from a set of coronary centerlines extracted at multiple cardiac phases within the R-R interval. Start and end points are provided by the user in one time-frame only. Corresponding centerline positions are used to determine the motion fields from phase to phase. Finally, dense motion fields are achieved by thin-plate-spline interpolation and are used to perform a motion-corrected iterative reconstruction of a selected region of interest, which results in an effective improvement of the reconstructed image quality. http://repub.eur.nl/res/pub/31567/ 2010-12-01T00:00:00Z 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. http://repub.eur.nl/res/pub/27896/ 2010-11-22T00:00:00Z Quantitative information about the geometry of the carotid artery bifurcation may help in predicting the development of atherosclerosis. A geodesic active contours based segmentation method combining both gradient and intensity information was developed for semi-automatic, accurate and robust quantification of the carotid bifurcation angle in Black Blood MRA data. The segmentation method was evaluated by comparing its accuracy to inter and intra observer variability on a large dataset that has been acquired as part of a longitudinal population study which investigates the natural progression of carotid atherosclerosis. Furthermore, the method is shown to be robust to initialization differences. The bifurcation angle obtained from the segmented lumen corresponds well with the angle derived from the manual lumen segmentation, which demonstrates that the method has large potential to replace manual segmentations for extracting the carotid bifurcation angle from Black Blood MRA data. http://repub.eur.nl/res/pub/27967/ 2010-11-22T00:00:00Z We propose a conditional statistical shape model to predict patient specific cardiac motion from the 3D end-diastolic CTA scan. The model is built from 4D CTA sequences by combining atlas based segmentation and 4D registration. Cardiac motion estimation is, for example, relevant in the dynamic alignment of pre-operative CTA data with intra-operative X-ray imaging. Due to a trend towards prospective electrocardiogram gating techniques, 4D imaging data, from which motion information could be extracted, is not commonly available. The prediction of motion from shape information is thus relevant for this purpose. Evaluation of the accuracy of the predicted motion was performed using CTA scans of 50 patients, showing an average accuracy of 1.1 mm. http://repub.eur.nl/res/pub/27998/ 2010-11-22T00:00:00Z We present a framework for statistical analysis in large cohorts of structural brain connectivity, derived from diffusion weighted MRI. A brain network is defined between subcortical gray matter structures and a cortical parcellation obtained with FreeSurfer. Connectivity is established through minimum cost paths with an anisotropic local cost function and is quantified per connection. The connectivity network potentially encodes important information about brain structure, and can be analyzed using multivariate regression methods. The proposed framework can be used to study the relation between connectivity and e.g. brain function or neurodegenerative disease. As a proof of principle, we perform principal component regression in order to predict age and gender, based on the connectivity networks of 979 middle-aged and elderly subjects, in a 10-fold cross-validation. The results are compared to predictions based on fractional anisotropy and mean diffusivity averaged over the white matter and over the corpus callosum. Additionally, the predictions are performed based on the best predicting connection in the network. Principal component regression outperformed all other prediction models, demonstrating the age and gender information encoded in the connectivity network. http://repub.eur.nl/res/pub/28595/ 2010-10-01T00:00:00Z Wall shear stress, the force per area acting on the lumen wall due to the blood flow, is an important biomechanical parameter in the localization and progression of atherosclerosis. To calculate shear stress and relate it to atherosclerosis, a 3D description of the lumen and vessel wall is required. We present a framework to obtain the 3D reconstruction of human coronary arteries by the fusion of intravascular ultrasound (IVUS) and coronary computed tomography angiography (CT). We imaged 23 patients with IVUS and CT. The images from both modalities were registered for 35 arteries, using bifurcations as landmarks. The IVUS images together with IVUS derived lumen and wall contours were positioned on the 3D centerline, which was derived from CT. The resulting 3D lumen and wall contours were transformed to a surface for calculation of shear stress and plaque thickness. We applied variations in selection of landmarks and investigated whether these variations influenced the relation between shear stress and plaque thickness. Fusion was successfully achieved in 31 of the 35 arteries. The average length of the fused segments was 36.4 ± 15.7 mm. The length in IVUS and CT of the fused parts correlated excellently (R2= 0.98). Both for a mildly diseased and a very diseased coronary artery, shear stress was calculated and related to plaque thickness. Variations in the selection of the landmarks for these two arteries did not affect the relationship between shear stress and plaque thickness. This new framework can therefore successfully be applied for shear stress analysis in human coronary arteries. http://repub.eur.nl/res/pub/24468/ 2009-10-01T00:00:00Z Efficiently obtaining a reliable coronary artery centerline from computed tomography angiography data is relevant in clinical practice. Whereas numerous methods have been presented for this purpose, up to now no standardized evaluation methodology has been published to reliably evaluate and compare the performance of the existing or newly developed coronary artery centerline extraction algorithms. This paper describes a standardized evaluation methodology and reference database for the quantitative evaluation of coronary artery centerline extraction algorithms. The contribution of this work is fourfold: (1) a method is described to create a consensus centerline with multiple observers, (2) well-defined measures are presented for the evaluation of coronary artery centerline extraction algorithms, (3) a database containing 32 cardiac CTA datasets with corresponding reference standard is described and made available, and (4) 13 coronary artery centerline extraction algorithms, implemented by different research groups, are quantitatively evaluated and compared. The presented evaluation framework is made available to the medical imaging community for benchmarking existing or newly developed coronary centerline extraction algorithms. http://repub.eur.nl/res/pub/24463/ 2009-03-01T00:00:00Z 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. http://repub.eur.nl/res/pub/24498/ 2009-02-01T00:00:00Z 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. http://repub.eur.nl/res/pub/29698/ 2008-12-15T00:00:00Z The sensitivity of DNA-repair-deficient Rad54/Rad54B mice for clastogens was studied and compared to that of wild-type mice. LacZ mutant frequencies (MF) in Rad54/Rad54B mice, after treatment with mitomycin C (MMC), bleomycin (BLM) and γ-irradiation, were compared to those of the wild-type mice following the same treatments. While none of the clastogens showed an induction of the lacZ MF in the wild-type mice, there was a significant increase of the lacZ MF in the bone marrow of the Rad54/Rad54B mice after treatment with BLM and γ-irradiation and in the spleen after MMC treatment. As expected, the positive control ENU showed a significant increase in the lacZ MF in all tested organs in wild-type mice. Mutant colonies were hybridized with total mouse DNA in order to discriminate between small gene mutations and large DNA rearrangements and translocations (size-change mutations). The hybridization studies showed a significant increase in mouse DNA positive clones 4 days after treatment with MMC and BLM in the bone marrow of the wild-type mice, which is indicative for chromosomal rearrangements and translocations to occur. An even more pronounced increase was seen 28 days after treatment with the same compounds in the Rad54/Rad54B mice. http://repub.eur.nl/res/pub/29571/ 2008-12-01T00:00:00Z Generation of a reference standard from multiple manually annotated datasets is a non-trivial problem. This paper discusses the weighted averaging of 3D open curves, which we used to generate a reference standard for vessel tracking data. We show how weighted averaging can be implemented by applying the Mean Shift algorithm to paths, and discuss the details of our implementation. Our approach can handle cases where the observer centerlines take different branches in a natural way. The method has been evaluated on synthetic data, and has been used to generate reference centerlines for evaluation of vessel tracking algorithms.