Age-related variations in trunk composition and patterns of regional bone and soft tissue changes in adult Caucasian women by DXA.

We explored the regional variations in body composition with advancing age in healthy Caucasian females living in the Mediterranean area. The objectives of this study were to establish body composition values for the trunk in healthy women of a Greek origin and to evaluate the effects of aging on the distribution of truncal bone mass, fat mass (FM) and lean mass (LM). Body composition of the trunk and detailed analysis of its anatomical components-the ribs, the thoracic spine, the lumbar spine and the pelvis, and FM and LM ratios--were calculated in 330 women aged 20-85 years, using DXA. Peak bone mineral density (BMD) of the trunk was attained between ages 30 and 33. The overall truncal BMD reduction with age was 20.7% (p < 0.001). Peak %LM of the trunk was achieved at age 20. The overall reduction of %LM with age for the trunk was 9.8% (p < 0.001). Peak %FM of the trunk was attained between ages 68 and 73, and the overall %FM reduction with age was 2.8% (p > 0.05). Multiple comparative analyses showed that the 51-60 years age group was the landmark age for significant changes of truncal bone mass measures across all age groups (p = 0). For truncal LM and FM metrics, multigroup comparative analysis showed the turning point of significant changes in soft tissue was the 41-50 age bracket (p = 0 and p = 0, respectively). In Greek women, truncal %LM exceeded by far %FM across all ages (p = 0). Our results suggest that aging affects body composition of the trunk in ambulatory healthy women of a Greek origin differently, leading to menopausal loss of bone mass, senior adulthood loss of lean mass, and middle-age storage of fat mass. In adult women, these age-related associations between bone and soft tissue metrics on DXA exams carry implications for the attainment of optimal peak values and shifts in body composition overtime, impacting lifelong skeletal health.

Graph-guided Gaussian Process-based Diagnosis of CVD Severity with Uncertainty Measures.

The severity of coronary artery disease can be assessed invasively using the Fractional Flow Reserve (FFR) index which is a useful diagnostic tool for the clinicians to select the treatment approach. The present work capitalizes a Gaussian process (GP) framework over graphs for the prediction of FFR index using only non-invasive imaging and clinical features. More specifically, taking the per-node one-hop connectivity vector as input, we employed a regression-based task by applying an ensemble of graph-adapted Gaussian process experts, with a data-adaptive fashion via online training. The main novelty of the work lies in the fact that for the first time in a medical field the inference model considers only the similarity condition of the patients, instead of their features. Our results demonstrate the impressive merits of the proposed medical EGP (MedEGP) method, in comparison to the single GP, and Linear Regression (LR) models to predict the FFR index, with well-calibrated uncertainty.Clinical Relevance- This paper establishes an accurate non-invasive approach to predict the FFR for the diagnosis of coronary artery disease.

TAXINOMISIS: A cloud - based platform for risk profiling and patient specific management of the carotid artery disease.

Carotid Artery Disease is a complex multi-disciplinary medical condition causing strokes and several other disfunctions to individuals. Within this work, a cloud - based platform is proposed for clinicians and medical doctors that provides a comprehensive risk assessment tool for carotid artery disease. It includes three modeling levels: baseline data-driven risk assessment, blood flow simulations and plaque progression modeling. The proposed models, which have been validated through a wide set of studies within the TAXINOMISIS project, are delivered to the end users through an easy-to-use cloud platform. The architecture and the deployment of this platform includes interfaces for handling the electronic patient record, the 3D arterial reconstruction, blood flow simulations and risk assessment reporting. TAXINOMISIS, compared with both similar software approaches and with the current clinical workflow, assists clinicians to treat patients more effectively and more accurately by providing innovative and validated tools.Clinical Relevance - Asymptomatic carotid artery disease is a prevalent condition that affects a significant portion of the population, leading to an increased risk of stroke and other cardiovascular events. Early detection and appropriate treatment of this condition can significantly reduce the risk of adverse outcomes and improve patient outcomes. The development of a software tool to assist clinicians in the assessment and management of asymptomatic patients with carotid artery disease is therefore of great clinical relevance. By providing a comprehensive and reliable assessment of the disease and its risk factors, this tool will enable clinicians to make informed decisions regarding patient management and treatment. The impact of this tool on patient outcomes and the reduction of healthcare costs will be of great importance to both patients and the healthcare system.

An All-in-One Tool for 2D Atherosclerotic Disease Assessment and 3D Coronary Artery Reconstruction.

Diagnosis of coronary artery disease is mainly based on invasive imaging modalities such as X-ray angiography, intravascular ultrasound (IVUS) and optical coherence tomography (OCT). Computed tomography coronary angiography (CTCA) is also used as a non-invasive imaging alternative. In this work, we present a novel and unique tool for 3D coronary artery reconstruction and plaque characterization using the abovementioned imaging modalities or their combination. In particular, image processing and deep learning algorithms were employed and validated for the lumen and adventitia borders and plaque characterization at the IVUS and OCT frames. Strut detection is also achieved from the OCT images. Quantitative analysis of the X-ray angiography enables the 3D reconstruction of the lumen geometry and arterial centerline extraction. The fusion of the generated centerline with the results of the OCT or IVUS analysis enables hybrid coronary artery 3D reconstruction, including the plaques and the stent geometry. CTCA image processing using a 3D level set approach allows the reconstruction of the coronary arterial tree, the calcified and non-calcified plaques as well as the detection of the stent location. The modules of the tool were evaluated for efficiency with over 90% agreement of the 3D models with the manual annotations, while a usability assessment using external evaluators demonstrated high usability resulting in a mean System Usability Scale (SUS) score equal to 0.89, classifying the tool as "excellent".

Detection of Asymptomatic Carotid Artery Stenosis through Machine Learning.

Carotid artery disease, the pathological condition of carotid arteries, is considered as the most significant cause of cerebral events and stroke. Carotid artery disease is considered as an inflammatory process, which involves the deposition and accumulation of atherosclerotic plaque inside the carotid intima, resulting in the narrowing of the arteries. Carotid artery stenosis (CAS) is either symptomatic or asymptomatic and its presence and location is determined by different imaging modalities, such as the carotid duplex ultrasound, the computed tomography angiography, the magnetic resonance angiography (MRA) and the cerebral angiography. The aim of this study is to present a machine learning model for the diagnosis and identification of individuals of asymptomatic carotid artery stenosis, using as input typical health data. More specifically, the overall model is trained with typical demographics, clinical data, risk factors and medical treatment data and is able to classify the individuals into high risk (Class 1-CAS group) and low risk (Class 0-non CAS group) individuals. In the presented study, we implemented a statistical analysis to check the data quality and the distribution into the two classes. Different feature selection techniques, in combination with classification schemes were applied for the development of our machine learning model. The overall methodology has been trained and tested using 881 cases (443 subjects in low risk class and 438 in high risk class). The highest accuracy 0.82 and an area under curve 0.9 were achieved using the relief feature selection technique and the random forest classification scheme.

Machine Learning Coronary Artery Disease Prediction Based on Imaging and Non-Imaging Data.

The prediction of obstructive atherosclerotic disease has significant clinical meaning for the decision making. In this study, a machine learning predictive model based on gradient boosting classifier is presented, aiming to identify the patients of high CAD risk and those of low CAD risk. The machine learning methodology includes five steps: the preprocessing of the input data, the class imbalance handling applying the Easy Ensemble algorithm, the recursive feature elimination technique implementation, the implementation of gradient boosting classifier, and finally the model evaluation, while the fine tuning of the presented model was implemented through a randomized search optimization of the model's hyper-parameters over an internal 3-fold cross-validation. In total, 187 participants with suspicion of CAD previously underwent CTCA during EVINCI and ARTreat clinical studies and were prospectively included to undergo follow-up CTCA. The predictive model was trained using imaging data (geometrical and blood flow based) and non-imaging data. The overall predictive accuracy of the model was 0.81, using both imaging and non-imaging data. The innovative aspect of the proposed study is the combination of imaging-based data with the typical CAD risk factors to provide an integrated CAD risk-predictive model.

Prophylaxis for Venous Thromboembolic Events in Elective Total Hip and Total Knee Arthroplasty.

Venous thromboembolism (VTE) is a serious complication after major orthopaedic operations, such as a total hip (THA) and knee (TKA) arthroplasty. Therefore, perioperative VTE prophylaxis is recommended; a multitude of modern options are available, including both pharmacologic (aspirin, unfractionated and lowmolecular- weight heparin, vitamin K antagonists, and novel oral anticoagulants) and/or mechanical interventions (early mobilization, graduated compression stockings, intermittent pneumatic compression devices, and venous foot pumps). However, because of the abundance of these possibilities, it is crucial to understand the benefits and drawbacks of each VTE prophylaxis option to ensure that the optimal treatment plan is developed for each patient. The American College of Chest Physicians (AACP) and the American Academy of Orthopaedic Surgeons (AAOS) have both published individual guidelines on VTE prophylaxis regimens, alongside numerous studies evaluating the efficacy and outcomes of the different prophylaxis modalities. The purpose of this review is to provide a summary of the evidence on VTE prophylaxis after elective total hip and knee arthroplasty based on current guidelines and highlight the major concerns and potential complications.

A Machine Learning Model for the Identification of High risk Carotid Atherosclerotic Plaques.

Carotid artery disease is an inflammatory condition involving the deposition and accumulation of lipid species and leucocytes from blood into the arterial wall, which causes the narrowing of the carotid arteries on either side of the neck. Different imaging modalities can by implemented to determine the presence and the location of carotid artery stenosis, such as carotid ultrasound, computed tomography angiography (CTA), magnetic resonance angiography (MRA), or cerebral angiography. However, except of the presence and the degree of stenosis of the carotid arteries, the vulnerability of the carotid atherosclerotic plaques constitutes a significant factor for the progression of the disease and the presence of disease symptoms. In this study, our aim is to develop and present a machine learning model for the identification of high risk plaques using non imaging based features and non-invasive imaging based features. Firstly, we implemented statistical analysis to identify the most statistical significant features according to the defined output, and subsequently, we implemented different feature selection techniques and classification schemes for the development of our machine learning model. The overall methodology has been trained and tested using 208 cases of 107 cases of low risk plaques and 101 cases of high risk plaques. The highest accuracy of 0.76 was achieved using the relief feature selection technique and the support vector machine classification scheme. The innovative aspect of the proposed machine learning model is both the different categories of the utilized input features and the definition of the problem to be solved.

A proof-of-concept study for the prediction of the de-novo atherosclerotic plaque development using finite elements.

The type of the atherosclerotic plaque has significant clinical meaning since plaque vulnerability depends on its type. In this work, we present a computational approach which predicts the development of new plaques in coronary arteries. More specifically, we employ a multi-level model which simulates the blood fluid dynamics, the lipoprotein transport and their accumulation in the arterial wall and the triggering of inflammation using convection-diffusion-reaction equations and in the final level, we estimate the plaque volume which causes the arterial wall thickening. The novelty of this work relies on the conceptual approach that using the information from 94 patients with computed tomography coronary angiography (CTCA) imaging at two time points we identify the correlation of the computational results with the real plaque components detected in CTCA. In the next step, we use these correlations to generate two types of de-novo plaques: calcified and non-calcified. Evaluation of the model's performance is achieved using eleven patients, who present de-novo plaques at the follow-up imaging. The results demonstrate that the computationally generated plaques are associated significantly with the real plaques indicating that the proposed approach could be used for the prediction of specific plaque type formation.

Error Propagation in the Simulation of Atherosclerotic Plaque Growth and the Prediction of Atherosclerotic Disease Progression.

Assessments of coronary artery disease can be achieved using non-invasive computed tomography coronary angiography (CTCA). CTCA can be further used for the 3D reconstruction of the coronary arteries and the development of computational models. However, image acquisition and arterial reconstruction introduce an error which can be propagated, affecting the computational results and the accuracy of diagnostic and prognostic models. In this work, we investigate the effect of an imaging error, propagated to a diagnostic index calculated using computational modelling of blood flow and then to prognostic models based on plaque growth modelling or binary logistic predictive modelling. The analysis was performed utilizing data from 20 patients collected at two time points with interscan period of six years. The collected data includes clinical and risk factors, biological and biohumoral data, and CTCA imaging. The results demonstrated that the error propagated and may have significantly affected some of the final outcomes. The calculated propagated error seemed to be minor for shear stress, but was major for some variables of the plaque growth model. In parallel, in the current analysis SmartFFR was not considerably affected, with the limitation of only one case located into the gray zone.

Serum Biomarkers in Carotid Artery Disease.

Carotid artery disease is considered a major cause of strokes and there is a need for early disease detection and management. Although imaging techniques have been developed for the diagnosis of carotid artery disease and different imaging-based markers have been proposed for the characterization of atherosclerotic plaques, there is still need for a definition of high-risk plaques in asymptomatic patients who may benefit from surgical intervention. Measurement of circulating biomarkers is a promising method to assist in patient-specific disease management, but the lack of robust clinical evidence limits their use as a standard of care. The purpose of this review paper is to present circulating biomarkers related to carotid artery diagnosis and prognosis, which are mainly provided by statistical-based clinical studies. The result of our investigation showed that typical well-established inflammatory biomarkers and biomarkers related to patient lipid profiles are associated with carotid artery disease. In addition to this, more specialized types of biomarkers, such as endothelial and cell adhesion, matrix degrading, and metabolic biomarkers seem to be associated with different carotid artery disease outputs, assisting vascular specialists in selecting patients at high risk for stroke and in need of intervention.

A Novel Approach to Generate a Virtual Population of Human Coronary Arteries for In Silico Clinical Trials of Stent Design.

Goal: To develop a cardiovascular virtual population using statistical modeling and computational biomechanics. Methods: A clinical data augmentation algorithm is implemented to efficiently generate virtual clinical data using a real clinical dataset. An atherosclerotic plaque growth model is employed to 3D reconstructed coronary arterial segments to generate virtual coronary arterial geometries (geometrical data). Last, the combination of the virtual clinical and geometrical data is achieved using a methodology that allows for the generation of a realistic virtual population which can be used in in silico clinical trials. Results: The results show good agreement between real and virtual clinical data presenting a mean gof 0.1 ± 0.08. 400 virtual coronary arteries were generated, while the final virtual population includes 10,000 patients. Conclusions: The virtual arterial geometries are efficiently matched to the generated clinical data, both increasing and complementing the variability of the virtual population.

Validation study of a novel method for the 3D reconstruction of coronary bifurcations.

Quantitative Coronary Angiography (QCA) is an important tool in the study of coronary artery disease. Validation of this technique is crucial for their ongoing development and refinement although it is difficult due to several factors such as potential sources of error. The present work aims to a further validation of a new semi-automated method for three-dimensional (3D) reconstruction of coronary bifurcations arteries based on X-Ray Coronary Angiographies (CA). In a dataset of 40 patients (79 angiographic views), we used the aforementioned method to reconstruct them in 3D space. The validation was based on the comparison of these 3D models with the true silhouette of 2D models annotated by an expert using specific metrics. The obtained results indicate a good accuracy for the most parameters (≥ 90 %). Comparison with similar works shows that our new method is a promising tool for the 3D reconstruction of coronary bifurcations and for application in everyday clinical use.

A deep learning oriented method for automated 3D reconstruction of carotid arterial trees from MR imaging.

The scope of this paper is to present a new carotid vessel segmentation algorithm implementing the U-net based convolutional neural network architecture. With carotid atherosclerosis being the major cause of stroke in Europe, new methods that can provide more accurate image segmentation of the carotid arterial tree and plaque tissue can help improve early diagnosis, prevention and treatment of carotid disease. Herein, we present a novel methodology combining the U-net model and morphological active contours in an iterative framework that accurately segments the carotid lumen and outer wall. The method automatically produces a 3D meshed model of the carotid bifurcation and smaller branches, using multispectral MR image series obtained from two clinical centres of the TAXINOMISIS study. As indicated by a validation study, the algorithm succeeds high accuracy (99.1% for lumen area and 92.6% for the perimeter) for lumen segmentation. The proposed algorithm will be used in the TAXINOMISIS study to obtain more accurate 3D vessel models for improved computational fluid dynamics simulations and the development of models of atherosclerotic plaque progression.

Site specific prediction of PCI stenting based on imaging and biomechanics data using gradient boosting tree ensembles.

Cardiovascular diseases are nowadays considered as the main cause of morbidity and mortality worldwide. Coronary Artery Disease (CAD), the most typical form of cardiovascular disease is diagnosed by a variety of imaging modalities, both invasive and non-invasive, which involve either risk implications or high cost. Therefore, several attempts have been undertaken to early diagnose and predict either the high CAD risk patients or the cardiovascular events, implementing machine learning techniques. The purpose of this study is to present a classification scheme for the prediction of Percutaneous Coronary Intervention (PCI) stenting placement, using image-based data. The proposed classification model is a gradient boosting classifier, incorporated into a class imbalance handling technique, the Easy ensemble scheme and aims to classify coronary segments into high CAD risk and low CAD risk, based on their PCI placement. Through this study, we investigate the importance of image based features, concluding that the combination of the coronary degree of stenosis and the fractional flow reserve achieves accuracy 78%.

Simulation of atherosclerotic plaque growth using computational biomechanics and patient-specific data.

Atherosclerosis is the one of the major causes of mortality worldwide, urging the need for prevention strategies. In this work, a novel computational model is developed, which is used for simulation of plaque growth to 94 realistic 3D reconstructed coronary arteries. This model considers several factors of the atherosclerotic process even mechanical factors such as the effect of endothelial shear stress, responsible for the initiation of atherosclerosis, and biological factors such as the accumulation of low and high density lipoproteins (LDL and HDL), monocytes, macrophages, cytokines, nitric oxide and formation of foams cells or proliferation of contractile and synthetic smooth muscle cells (SMCs). The model is validated using the serial imaging of CTCA comparing the simulated geometries with the real follow-up arteries. Additionally, we examine the predictive capability of the model to identify regions prone of disease progression. The results presented good correlation between the simulated lumen area (P < 0.0001), plaque area (P < 0.0001) and plaque burden (P < 0.0001) with the realistic ones. Finally, disease progression is achieved with 80% accuracy with many of the computational results being independent predictors.

A three-dimensional quantification of calcified and non-calcified plaques in coronary arteries based on computed tomography coronary angiography images: Comparison with expert's annotations and virtual histology intravascular ultrasound.

The detection, quantification and characterization of coronary atherosclerotic plaques has a major effect on the diagnosis and treatment of coronary artery disease (CAD). Different studies have reported and evaluated the noninvasive ability of Computed Tomography Coronary Angiography (CTCA) to identify coronary plaque features. The identification of calcified plaques (CP) and non-calcified plaques (NCP) using CTCA has been extensively studied in cardiovascular research. However, NCP detection remains a challenging problem in CTCA imaging, due to the similar intensity values of NCP compared to the perivascular tissue, which surrounds the vasculature. In this work, we present a novel methodology for the identification of the plaque burden of the coronary artery and the volumetric quantification of CP and NCP utilizing CTCA images and we compare the findings with virtual histology intravascular ultrasound (VH-IVUS) and manual expert's annotations. Bland-Altman analyses were employed to assess the agreement between the presented methodology and VH-IVUS. The assessment of the plaque volume, the lesion length and the plaque area in 18 coronary lesions indicated excellent correlation with VH-IVUS. More specifically, for the CP lesions the correlation of plaque volume, lesion length and plaque area was 0.93, 0.84 and 0.85, respectively, whereas the correlation of plaque volume, lesion length and plaque area for the NCP lesions was 0.92, 0.95 and 0.81, respectively. In addition to this, the segmentation of the lumen, CP and NCP in 1350 CTCA slices indicated that the mean value of DICE coefficient is 0.72, 0.7 and 0.62, whereas the mean HD value is 1.95, 1.74 and 1.95, for the lumen, CP and NCP, respectively.

A computational multi-level atherosclerotic plaque growth model for coronary arteries.

In this work, we present a novel computational approach for the prediction of atherosclerotic plaque growth. In particular, patient-specific coronary computed tomography angiography (CCTA) data were collected from 60 patients at two time points. Additionally, blood samples were collected for biochemical analysis. The CCTA data were used for 3D reconstruction of the coronary arteries, which were then used for computational modeling of plaque growth. The model of plaque growth is based on a multi-level approach: i) the blood flow is modeled in the lumen and the arterial wall, ii) the low and high density lipoprotein and monocytes transport is included, and iii) the major atherosclerotic processes are modeled including the foam cells formation, the proliferation of smooth muscle cells and the formation of atherosclerotic plaque. Validation of the model was performed using the follow-up CCTA. The results show a correlation of the simulated follow-up arterial wall area to be correlated with the corresponding realistic follow-up with r2=0.49, P<; 0.0001.

A new method for the 3D reconstruction of coronary bifurcations pre and post the angioplasty procedure using the QCA.

The aim of this study is to propose a new semi-automated method for three-dimensional (3D) reconstruction of coronary bifurcations arteries using X-ray Coronary Angiographies (CA). Considering two monoplane angiographic views as the input data, the method is based on a four-step approach. In the first step, the image pre-processing and the vessel segmentation is performed. In the second step the 3D centerline is reconstructed by implementing the back-projection algorithm. In the third step, the lumen borders are reconstructed around the centerline to result to the fourth step, during which the 3D point cloud of the side branch is adjusted to the main branch, to produce the final 3D model of the coronary bifurcation artery. Imaging data from seven patients (pre and post-stenting) were reconstructed in the 3D space. The validation of the proposed methodology was based on the comparison of the 3D model with the 2D CA. Blood flow simulations were performed both for the vessels before and after the angioplasty procedure. Decreased Endothelial Shear Stress (ESS) values were observed for the vessels after the Percutaneous Transluminal Coronary Intervention (PTCI).

A comparison of three multimodality coronary 3D reconstruction methods.

The assessment of the severity of arterial stenoses is of utmost importance in clinical practice. Several image modalities invasive and non-invasive are nowadays available and can be utilized for the 3-dimensional (3D) reconstruction of the arterial geometry. Following our previous study, the present study was conducted to further strengthen the evaluation of three reconstruction methodologies, namely: (i) the Quantitative Coronary Analysis (QCA), (ii) the Virtual Histology Intravascular Ultrasound VH-IVUS-Angiography hybrid method and (iii) the Coronary Computed Tomography Angiography (CCTA). Data from 13 patients were employed to perform a quantitative analysis using specific metrics, such as, the Mean Wall Shear Stress (mWSS), the Minimum Lumen diameter (MLD), the Reference Vessel Diameter (RVD), the Degree of stenosis (DS%), and the Lesion length (LL). A high correlation was observed for the mWSS metric between the three reconstruction methods, especially between the QCA and CCTA (r=0.974, P<; 0.001).