Thoracic aorta calcium detection and quantification using convolutional neural networks in a large cohort of intermediate-risk patients

Arterial calcification is an independent predictor of cardiovascular disease (CVD) events whereas thoracic aorta calcium (TAC) detection might anticipate extracoronary outcomes. In this work, we trained six convolutional neural networks (CNNs) to detect aortic calcifications and to automate the TAC score assessment in intermediate CVD risk patients. Cardiac computed tomography images from 1415 patients were analyzed together with their aortic geometry previously assessed. Orthogonal patches centered in each aortic candidate lesion were reconstructed and a dataset with 19,790 images (61% positives) was built. Three single-input 2D CNNs were trained using axial, coronal and sagittal patches together with two multi-input 2.5D CNNs combining the orthogonal patches and identifying their best regional combination (BRC) in terms of lesion location. Aortic calcifications were concentrated in the descending (66%) and aortic arch (26%) portions. The BRC of axial patches to detect ascending or aortic arch lesions and sagittal images for the descending portion had the best performance: 0.954 F1-Score, 98.4% sensitivity, 87% of the subjects correctly classified in their TAC category and an average false positive TAC score per patient of 30. A CNN that combined axial and sagittal patches depending on the candidate aortic location ensured an accurate TAC score prediction.Fil: Guilenea, Federico Nicolás. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Medicina Traslacional, Trasplante y Bioingeniería. Fundación Favaloro. Instituto de Medicina Traslacional, Trasplante y Bioingeniería; ArgentinaFil: Casciaro, Mariano Ezequiel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Medicina Traslacional, Trasplante y Bioingeniería. Fundación Favaloro. Instituto de Medicina Traslacional, Trasplante y Bioingeniería; ArgentinaFil: Pascaner, Ariel Fernando. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Medicina Traslacional, Trasplante y Bioingeniería. Fundación Favaloro. Instituto de Medicina Traslacional, Trasplante y Bioingeniería; ArgentinaFil: Soulat, Gilles. Hopital Europeen Georges Pompidou; FranciaFil: Mousseaux, Elie. Hopital Europeen Georges Pompidou; FranciaFil: Craiem, Damian. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Medicina Traslacional, Trasplante y Bioingeniería. Fundación Favaloro. Instituto de Medicina Traslacional, Trasplante y Bioingeniería; Argentin

Vessel tractography using an intensity based tensor model with branch detection

In this paper, we present a tubular structure seg- mentation method that utilizes a second order tensor constructed from directional intensity measurements, which is inspired from diffusion tensor image (DTI) modeling. The constructed anisotropic tensor which is fit inside a vessel drives the segmen- tation analogously to a tractography approach in DTI. Our model is initialized at a single seed point and is capable of capturing whole vessel trees by an automatic branch detection algorithm developed in the same framework. The centerline of the vessel as well as its thickness is extracted. Performance results within the Rotterdam Coronary Artery Algorithm Evaluation framework are provided for comparison with existing techniques. 96.4% average overlap with ground truth delineated by experts is obtained in addition to other measures reported in the paper. Moreover, we demonstrate further quantitative results over synthetic vascular datasets, and we provide quantitative experiments for branch detection on patient Computed Tomography Angiography (CTA) volumes, as well as qualitative evaluations on the same CTA datasets, from visual scores by a cardiologist expert

Quantification of atherosclerotic plaque in the elderly with positron emission tomography/computed tomography

L'athérosclérose est une maladie cardiovasculaire inflammatoire qui est devenue la première cause de morbidité et de mortalité dans les pays développés et parmi les principales causes d’invalidité au monde. Elle se caractérise par l’épaississement de la paroi vasculaire artérielle suite à l'accumulation de lipides et le dépôt d'autres substances au niveau de l’intima (endothélium) pour former la plaque d’athérome. Avec l'âge, cette plaque peut grossir, se calcifier et ainsi rétrécir le calibre de l'artère pour diminuer son débit et à un stade avancé de la maladie, elle peut se rompre et obstruer les petites artères dans n'importe quelle partie du corps causant des complications aigues, y compris la mort soudaine. L'objectif de cette thèse est de pouvoir détecter l'inflammation de la plaque athérosclérotique quantitativement avec la TEP/TDM dans le but de prévenir son détachement. Les mesures avec la TDM et la TEP avec le 18F-FDG ont été acquises chez des sujets humains âgés de 65 à 85 ans. Des analyses quantitatives ont été conduites sur les images de TDM en fonction de l'intensité et des étendues des calcifications, et sur les images de la TEP pour évaluer le métabolisme des plaques. L'effet des traitements par les statines a aussi été étudié. Au-delà la couverture de cette étude de façon détaillée au niveau physiologique en corrélant différents paramètres des plaques, et au niveau méthodologique en utilisant de nouvelles approches pour l'analyse pharmacocinétique, il en ressort principalement la suggestion de la détection de la vulnérabilité de la plaque artérielle par la TDM, plus disponible et moins coûteuse, en remplacement des analyses biochimiques, surtout la protéine C-réactive (CRP) considérée être la méthode standard.Abstract : Atherosclerosis is an inflammatory cardiovascular disease considered the leading cause of morbidity and mortality in developed countries and among the leading causes of disability worldwide. It is characterized by the thickening of the arterial vascular wall due to the accumulation of lipids and the deposition of other substances in the intima (endothelium) to form atheroma plaque. With age, this plaque can grow larger, calcify and thus narrow the size of the artery to decrease blood flow and at an advanced stage of the disease, it can rupture, be transported by blood and block the small arteries in any part of the body causing acute complications, including sudden death. The objective of this thesis was to be able to detect the inflammation of the atherosclerotic plaque quantitatively with PET/CT in order to prevent its detachment. Measurements with CT and PET with 18F-FDG were acquired in human subjects aged 65 to 85 years. Quantitative analyzes were performed on CT images based on the intensity and extent of calcifications, and on PET images to assess plaque metabolism. The effect of statin treatments has also been studied. Beyond the coverage of this study in a detailed manner at the physiological level by correlating different parameters of the plaques, and at the methodological level by using new approaches for pharmacokinetic analysis, it mainly emerges the suggestion for the detection of the vulnerability of the arterial plaque by CT alone, more available and less expensive, replacing biochemical analyzes, especially Creactive protein (CRP) considered to be the standard method

Preoperative Systems for Computer Aided Diagnosis based on Image Registration: Applications to Breast Cancer and Atherosclerosis

Computer Aided Diagnosis (CAD) systems assist clinicians including radiologists and cardiologists to detect abnormalities and highlight conspicuous possible disease. Implementing a pre-operative CAD system contains a framework that accepts related technical as well as clinical parameters as input by analyzing the predefined method and demonstrates the prospective output. In this work we developed the Computer Aided Diagnostic System for biomedical imaging analysis of two applications on Breast Cancer and Atherosclerosis. The aim of the first CAD application is to optimize the registration strategy specifically for Breast Dynamic Infrared Imaging and to make it user-independent. Base on the fact that automated motion reduction in dynamic infrared imaging is on demand in clinical applications, since movement disarranges time-temperature series of each pixel, thus originating thermal artifacts that might bias the clinical decision. All previously proposed registration methods are feature based algorithms requiring manual intervention. We implemented and evaluated 3 different 3D time-series registration methods: 1. Linear affine, 2. Non-linear Bspline, 3. Demons applied to 12 datasets of healthy breast thermal images. The results are evaluated through normalized mutual information with average values of 0.70±0.03, 0.74±0.03 and 0.81±0.09 (out of 1) for Affine, BSpline and Demons registration, respectively, as well as breast boundary overlap and Jacobian determinant of the deformation field. The statistical analysis of the results showed that symmetric diffeomorphic Demons registration method outperforms also with the best breast alignment and non-negative Jacobian values which guarantee image similarity and anatomical consistency of the transformation, due to homologous forces enforcing the pixel geometric disparities to be shortened on all the frames. We propose Demons registration as an effective technique for time-series dynamic infrared registration, to stabilize the local temperature oscillation. The aim of the second implemented CAD application is to assess contribution of calcification in plaque vulnerability and wall rupture and to find its maximum resistance before break in image-based models of carotid artery stenting. The role of calcification inside fibroatheroma during carotid artery stenting operation is controversial in which cardiologists face two major problems during the placement: (i) “plaque protrusion” (i.e. elastic fibrous caps containing early calcifications that penetrate inside the stent); (ii) “plaque vulnerability” (i.e. stiff plaques with advanced calcifications that break the arterial wall or stent). Finite Element Analysis was used to simulate the balloon and stent expansion as a preoperative patient-specific virtual framework. A nonlinear static structural analysis was performed on 20 patients acquired using in vivo MDCT angiography. The Agatston Calcium score was obtained for each patient and subject-specific local Elastic Modulus (EM) was calculated. The in silico results showed that by imposing average ultimate external load of 1.1MPa and 2.3MPa on balloon and stent respectively, average ultimate stress of 55.7±41.2kPa and 171±41.2kPa are obtained on calcifications. The study reveals that a significant positive correlation (R=0.85, p<0.0001) exists on stent expansion between EM of calcification and ultimate stress as well as Plaque Wall Stress (PWS) (R=0.92, p<0.0001), comparing to Ca score that showed insignificant associations with ultimate stress (R=0.44, p=0.057) and PWS (R=0.38, p=0.103), suggesting minor impact of Ca score in plaque rupture. These average data are in good agreement with results obtained by other research groups and we believe this approach enriches the arsenal of tools available for pre-operative prediction of carotid artery stenting procedure in the presence of calcified plaques

The significance of fluoride uptake and inflammation within the atherosclerotic plaque: a PET/CT analysis

Background and aims: Atherosclerosis is a vessel disease, having a relatively early onset and a slow progression, and is currently the first cause for morbidity and mortality worldwide. Patients with atherosclerosis are usually classified according to their cardiovascular risk; however, tools to characterize the atherosclerotic plaque or to predict its progression are presently missing. In this thesis, we present a novel approach to this issue, by applying multimodal (CT- ad PET-based) imaging, in synergy with segmentation analysis, to the atherosclerotic plaques. Materials and Methods: Patients were recruited from three different databases retrospectively and then assigned to three different study populations. Population A consisted of 51 patients (19 females, mean age 69\uf0b19 years, range 49-82), submitted to 18F-NaF-PET/CT (NaF-PET). Each patient underwent at least 2 Naf-PET, spaced on average 14 months apart. In each patient, a VOI was placed on each visible CT plaque, using a CT-iso-contour approach; mean blood-pool normalized SUV (TBR), mean HU and Agaston-like calcification score (CS) were computed. TBR was compared with the mean percent variation of HU and CS, normalized for elapsed time between NaF-PETs (NDHU% and NDCS%, respectively). Whole-aorta TBR was then compared to whole-aorta NDCS%. Population B included 79 patients (51 women, 70.8 \ub18 years) who underwent NaF-PET. Plaque analysis was performed as described above. An in-house software application was used to identify and segment the trabecular bone semi-automatically. TBR and HU of trabecular bone were compared to the ones of arterial plaques. Population C consisted of twenty-seven patients (12 males, mean age 69.4 \ub1 8, range 56-87), who underwent a 18F-FDG and a 68Ga-DOTATOC PET/CT within a two-weeks period Cardiovascular risk score was estimated in all patients; TBRmax and TBRmean was calculated in a large VOI, placed on the aorta, in FDG and DOTATOC scans. Results: In population A, mean HU and CS significantly increased from the first to the second PET/CT (p<0.001). A tight and direct correlation was noted between TBR in the plaques in the baseline PET and both NDHU% (R=0.67, p<0.01) and NDCS% (R=0,7, p<0.001). Whole-aorta TBR correlated with NDCS% in the entire vessel (R=0,85, p<0.001). In the population B, mean plaque density showed an inverse association with vertebral HU density (R=-0.56, p<0.01). Plaque and trabecular bone TBR were directly and closely correlated (R=0.63 and p<0.001). At univariate analysis, mean HU density of aortic plaque was not predicted by any of the cardiovascular risk factor or by age; conversely, it was related to its own TBR (p=<0.001) as well as by trabecular bone TBR. In population C, the mean of TBRmax was significantly higher in 68Ga-DOTATOC PET, when compared to FDG (5,7\ub13,1 Vs. 2\ub11,2, p<0.01). A tight and direct correlation was noted between FDG TBRmean and CV risk score (R=0.82, p<0.001), as well as between 68Ga-DOTATOC TBRmean and CV risk score (R=0.81, p<0.001). Average TBRmax of 68Ga-DOTATOC was slightly higher in DM patients when compared to the non-diabetic ones (6\ub12.1 Vs. 4,9\ub10,9, p<0.05). Conclusions: PET/CT with NaF can predict subsequent plaque evolution: in particular, plaque displaying a higher uptake have a greater progression of calcification at follow-up. Observing the behavior of skeletal bone might represent a new window for assessing the plaques\ub4 characteristics. Inflammation within the plaque can be detected by 18F-FDG and by 68Ga-DOTATOC, the latter tracer might perform better, especially in diabetic patients. Overall PET techniques could display a great relevance in diverse research fields, such as assessment of therapy effectiveness and identification of vulnerable plaques; further study could allow the possibly enabling a patient-centered treatment and improving therapy outcomes as well as quality of life.application of this methods to larger population

Implementation and extended use of computed tomography coronary angiography

Despite ongoing advances in prevention, diagnostic strategies and treatment options, coronary artery disease (CAD) remains a leading cause of death worldwide and has an unfavourable impact on quality of life. The use of upfront computed tomography coronary angiography (CTCA) has shown potential to reduce fatal and nonfatal myocardial infarction in patients with stable CAD. Furthermore, it is a less invasive option compared to standard coronary angiography. In this thesis we examined the impact and challenges of implementing CTCA in the Netherlands and we investigated methods to improve image acquisition. In the third part of this thesis, we evaluated the extended use of CTCA, both for the detection of CAD in the work-up for transcatheter aortic valve implantation (TAVI) and to predict the occurrence of chronic silent brain infarctions following this procedure. Considering implementation, we found that there already is high coverage of CTCA-services in the Netherlands. However, a substantial increase in CTCA capacity is necessary to fully implement CTCA in cardiologic care. Furthermore, we found that implementation of CTCA will result in a substantial reduction in costly and invasive CAG. Considering improved methods of image acquisition, we found that patient tailored contrast delivery protocols for CTCA, adjusting the contrast delivery to body weight and CT-scanner kV settings, improved attenuation values in the coronary arteries and therefore may result in improved diagnostic qualities of CTCA. In the third part of this thesis, we found that CTCA has high diagnostic accuracy to detect CAD in the work-up TAVI and could be used to reduce CAG in these fragile patients by up to 70%. These same pre-TAVI CTCA scans may be used for additional purposes other than the evaluation of CAD. We found that the degree of aortic valve calcifications, measured on these pre-TAVI CTCA scans, was associated with a larger increase in the white matter hyperintensity volume, and therefore shows potential to predict chronic silent brain infarctions

Whole-brain histogram and voxel-based analyses of apparent diffusion coefficient and magnetization transfer ratio in celiac disease, epilepsy, and cerebral calcifications syndrome

BACKGROUND AND PURPOSE: Diffusion and magnetization transfer (MT) techniques have been applied to the investigation with MR of epilepsy and have revealed changes in patients with or without abnormalities on MR imaging. We hypothesized that also in the coeliac disease (CD), epilepsy and cerebral calcifications (CEC) syndrome diffusion and MT techniques could reveal brain abnormalities undetected by MR imaging and tentatively correlated to epilepsy. MATERIALS AND METHODS: Diffusion and MT weighted images were obtained in 10 patients with CEC, 8 patients with CD without epilepsy and 17 healthy volunteers. The whole brain apparent diffusion coefficient (ADC) and MT ratio (MTR) maps were analyzed with histograms and the Statistical Parametric Mapping 2 (SPM2) software. We employed the non-parametric Mann-Whitney U test to assess differences for ADC and MTR histogram metrics. Voxel by voxel comparison of the ADC and MTR maps was performed with 2 tails t-test corrected for multiple comparison. RESULTS: A significantly higher whole brain ADC value as compared to healthy controls was observed in CEC (P = 0.006) and CD (P = 0.01) patients. SPM2 showed bilateral areas of significantly decreased MTR in the parietal and temporal subcortical white matter (WM) in the CEC patients. CONCLUSION: Our study indicates that diffusion and MT techniques are also capable of revealing abnormalities undetected by MR imaging. In particular patients with CEC syndrome show an increase of the whole brain ADC histogram which is more pronounced than in patients with gluten intolerance. IN CEC patients, voxel-based analysis demonstrates a localized decrease of the MTR in the parieto-temporal subcortical WM

Determination of Pericardial Adipose Tissue Increases the Prognostic Accuracy of Coronary Artery Calcification for Future Cardiovascular Events

Objectives: Pericardial adipose tissue (PAT) is associated with coronary artery plaque accumulation and the incidence of coronary heart disease. We evaluated the possible incremental prognostic value of PAT for future cardiovascular events. Methods: 145 patients (94 males, age 60 10 years) with stable coronary artery disease underwent coronary artery calcification (CAC) scanning in a multislice CT scanner, and the volume of pericardial fat was measured. Mean observation time was 5.4 years. Results: 34 patients experienced a severe cardiac event. They had a significantly higher CAC score (1,708 +/- 2,269 vs. 538 +/- 1,150, p 400, 3.5 (1.9-5.4; p = 0.007) for scores > 800 and 5.9 (3.7-7.8; p = 0.005) for scores > 1,600. When additionally a PAT volume > 200 cm(3) was determined, there was a significant increase in the event rate and relative risk. We calculated a relative risk of 2.9 (1.9-4.2; p = 0.01) for scores > 400, 4.0 (2.1-5.0; p = 0.006) for scores > 800 and 7.1 (4.1-10.2; p = 0.005) for scores > 1,600. Conclusions:The additional determination of PAT increases the predictive power of CAC for future cardiovascular events. PAT might therefore be used as a further parameter for risk stratification. Copyright (C) 2012 S. Karger AG, Base