Framework for Detection and Localization of Coronary Non-Calcified Plaques in Cardiac CTA using Mean Radial Profiles

Background and Objective: The high mortality rate associated with coronary heart disease (CHD) has driven intensive research in cardiac imaging and image analysis. The advent of computed tomography angiography (CTA) has turned non-invasive diagnosis of cardiovascular anomalies into reality as calcified coronary plaques can be easily identified due to their high intensity values. However, the detection of non-calcified plaques in CTA is still a challenging problem because of lower intensity values, which are often similar to the nearby blood and muscle tissues. In this work, we propose the use of mean radial profiles for the detection of non-calcified plaques in CTA imagery. Methods: Accordingly, we computed radial profiles by averaging the image intensity in concentric rings around the vessel centreline in a first stage. In the subsequent stage, an SVM classifier is applied to identify the abnormal coronary segments. For occluded segments, we further propose a derivative-based method to localize the position and length of the plaque inside the segment. Results: A total of 32 CTA volumes were analysed and a detection accuracy of 88.4% with respect to the manual expert was achieved. The plaque localization accuracy was computed using the Dice similarity coefficient and a mean of 83.2% was achieved. Conclusion: The consistent performance for multi-vendor, multi-institution data demonstrates the reproducibility of our method across different CTA datasets with a good agreement with manual expert annotations

Framework for Detection and Localization of Coronary Non-Calcified Plaques in Cardiac CTA using Mean Radial Profiles

Background and Objective: The high mortality rate associated with coronary heart disease (CHD) has driven intensive research in cardiac imaging and image analysis. The advent of computed tomography angiography (CTA) has turned non-invasive diagnosis of cardiovascular anomalies into reality as calcified coronary plaques can be easily identified due to their high intensity values. However, the detection of non-calcified plaques in CTA is still a challenging problem because of lower intensity values, which are often similar to the nearby blood and muscle tissues. In this work, we propose the use of mean radial profiles for the detection of non-calcified plaques in CTA imagery. Methods: Accordingly, we computed radial profiles by averaging the image intensity in concentric rings around the vessel centreline in a first stage. In the subsequent stage, an SVM classifier is applied to identify the abnormal coronary segments. For occluded segments, we further propose a derivative-based method to localize the position and length of the plaque inside the segment. Results: A total of 32 CTA volumes were analysed and a detection accuracy of 88.4% with respect to the manual expert was achieved. The plaque localization accuracy was computed using the Dice similarity coefficient and a mean of 83.2% was achieved. Conclusion: The consistent performance for multi-vendor, multi-institution data demonstrates the reproducibility of our method across different CTA datasets with a good agreement with manual expert annotations

Automated detection of calcified plaque using higher-order spectra cumulant technique in computer tomography angiography images

Cardiovascular disease continues to be the leading cause of death globally. Often, it stems from atherosclerosis, which can trigger substantial variations in the coronary arteries, possibly causing coronary artery disease (CAD). Coronary artery calcification is known to be a strong and independent forecaster of CAD. Hence, coronary computer tomography angiography (CTA) has become a fundamental noninvasive imaging tool to characterize coronary artery plaques. In this article, an automated algorithm is presented to uncover the presence of a calcified plaque, using 2060 CTA images acquired from 60 patients. Higher-order spectra cumulants were extracted from each image, thereby providing 2448 descriptive features per image. The features were then reduced using numerous well-established techniques, and ranked according to t value. Subsequently, the reduced features were input to several classifiers to achieve the best diagnostic accuracy with a minimum number of features. Optimal results were obtained using the support vector machine with a radial basis function, having 22 features obtained with the multiple factor analysis feature reduction algorithm. The accuracy, positive predictive value, sensitivity, and specificity obtained were 95.83%, 97.05%, 94.54%, and 97.13%, respectively. Based on these results, the technique could be useful to automatically and accurately identify calcified plaque evident in CTA images, and may therefore become an important tool to help reduce procedural costs and patient radiation dose

Quantifying Atherosclerosis: IVUS Imaging For Lumen Border Detection And Plaque Characterization

The importance of atherosclerotic disease in coronary artery has been a subject of study for many researchers in the past decade. In brief, the aim is to understand progression of such a disease, detect plaques at risks (vulnerable plaques), and treat them selectively to prevent mortality and immobility. Consequently, several imaging modalities have been developed and among them intravascular ultrasound (IVUS) has been of particular interest since it provides useful information about tissues microstructures and images with sufficient penetration as well as resolution. In general, the ultimate goal is to provide interventional cardiologists with reliable clinical tools so they can identify vulnerable plaques, make decisions confidently, choose the most appropriate drugs or implant devices (i.e. stent), and stabilize them during catheterization procedures with minimal risk. In this work, we review existing atherosclerotic tissue characterization algorithms including the state-of-the-art virtual histology (VH) framework, which has been implemented in the Volcano (Rancho Cordova, CA) IVUS clinical scanners using 64-elements 20 MHz phased-array transducer. Initially, we intended to extend this technique for data acquired with 40 MHz single-element transducers. For this reason, we started acquiring in vitro IVUS data and studied involved challenges from specimen preparation toward classification. We observed inconsistency among extracted features along with transducer's spectral parameters (i.e. bandwidth, center frequency). This, in addition to infeasibility of construction of reliable training dataset due to heterogeneity of atherosclerotic tissues motivated us to develop an unsupervised texture-based atherosclerotic tissue characterization algorithm. We proposed a two-dimensional multiscale wavelet-based algorithm to expand IVUS backscattered signals and/or grayscale images onto orthogonal symmetric quadrature mirror filters (QMF) such as Lemarie-Battle. At the bottom of decomposition tree, we employed ISODATA to cluster enveloped detected features in an unsupervised fashion and classify atherosclerotic plaque constitutes into fibrotic, lipidic, calcified, and no tissues. For the first time, we studied numbers of factors that were necessary for extension of in vitro derived classifier for in vivo applications such as reliability of classified tissues behind arc of calcified plaques and effects of pressure changes as well as flowing blood on constructed tissue color maps, called prognosis histology (PH) images. The second half of this dissertation is devoted to automatic detection of lumen borders in IVUS grayscale images acquired with high frequency (40 MHz up) transducers where more scattering exhibited within lumen area that makes the problem of interest more challenging. We established our framework on three-dimensional expansion of IVUS sub-volumes onto orthonormal brushlet basis function. The rational behind our framework was presence of incoherent (i.e. blood) versus coherent (i.e. plaque, surrounding fat) textural patterns along pullback direction, which was motivated by what an interventional cardiologist does to locate the lumen border visually by going back and forth among IVUS frames. We studied the feasibility of brushlet analysis through filtering blood speckles and supervised classification of blood versus non-blood regions. Our preliminary study confirmed that the most informative features reside in the innermost cubes, representing low-frequency components in transformed domain. Finally, we explored that tissue responses to IVUS signals are proportionally preserved in brushlet coefficients and it enabled us to classify blood regions in complex brushlet space. Subsequently, we employed surface function actives (SFA) to estimate the lumen borders after regularization. In a comparison study, we quantified our results with two of existing algorithms, employing IVUS grayscale images acquired with 40 MHz and 45 MHz single-element transducers. Overall, our proposed algorithm outperformed and the resulting automated detected borders showed good correlation with manually traced borders by an expert

Design and Performance of a Localized Fiber Optic, Near-Infrared Spectroscopic Prototype Device for the Detection of the Metabolic Status of Vulnerable Plaque : in-vitro Investigation of Human Carotid Plaque

INTRODUCTION: The“vulnerable plaque is defined as the“precursor lesion that ultimately ends in acute coronary thrombi (clots) that create a heart attack. Macrophages and inflammatory cells, found preferentially in vulnerable plaque, sustain their activity in the plaque through anaerobic metabolism and lactate production. The ultimate goal is to assess anaerobic metabolism in-vivo by measuring tissue pH and lactate concentration in atherosclerotic plaques using optical spectroscopy. The proposed in-vitro optical probe design, experimental method, and spectroscopic data analysis methodology are established in this research. METHODS: A fiber optic probe was designed and built based on both Monte Carlo simulations and bench testing with the goal to collect light from a small volume of tissue. A simulation of the depth penetration of the proposed probe was performed on normal and atherosclerotic aortic tissue, and the final probe was bench tested using normal aorta. A method was developed to preserve plaque metabolic status of tissue harvested from patients. Human atherosclerotic tissue obtained immediately after carotid endarterectomy was placed in Minimum Essential Medium (MEM) with non-essential amino acids supplement, bubbled with 75%O2/20%N2/5%CO2 at 37°C. Tissue pH, pCO2, pO2 and temperature with (n=7) and without (n=2) the media preparation over time were reviewed to assess plaque viability and maintenance of physiological conditions. Additional plaques placed in media were used for development of chemometric methods to measure pH and lactate. Areas of each plaque were randomly chosen for analysis. Reflectance spectra were collected with a dispersive spectrometer (400-1100 nm) and a Fourier-transform near-infrared spectrometer (1100-2400 nm) using the fiber optic probe. Reference measurements for tissue pH and lactate were made with glass microelectrodes and micro-enzymatic assay, respectively. Partial least-squares (PLS) data analysis was used to develop multivariate calibration models on an initial set of 5-6 plaques relating the optical spectra to the reference tissue pH (n=20) or the lactate concentration (n=21) to assess data quality. The coefficient of multiple determination (R2), the standard error of cross-validation (SECV), and the number of factors were used to assess the model performance. Additional points were collected from ~14 plaques and added to preliminary data. Pre-processing techniques were then used to see if preliminary data results could be improved by reducing different sources of variability with the introduction of more points. RESULTS: Monte Carlo simulations and depth penetration tests with the final probe design showed light is collected from ~1 mm3 volume of tissue using a 50 micron source-receiver separation. Tissue pH, pCO2, pO2 and temperature values demonstrated that the plaques were viable and stable in the media preparation for a maximum of 4 hours. Data from the first six plaques collected for lactate analysis showed that for seventeen points, a six-factor model produced adequate results (R2=0.83 SECV=1.4 micromoles lactate/gram tissue). Data from the first five plaques collected for tissue pH analysis, showed for seventeen different points, a three-factor model produced adequate results (R2=0.75 SECV=0.09 pH units). When additional points were added to either data set, model results were degraded. CONCLUSIONS: The in-vitro optical probe design and experimental procedures was established and the feasibility of the optical method demonstrated with preliminary data. However, with the addition of more data points, different sources of tissue and spectral variability were observed to affect calibration. The gross pathology type and mismatched optical volume to reference measurement volume limited the tissue pH determination. The reference measurement precision, the spatial resolution of the reference lactate measurement, and unmodeled tissue variability (water and proteins) limited the lactate determination. Large variability in all optical measurements was observed. Additional in-vitro data collection would be required such that the variability due to the tissue is reduced and any spectrometer variability adequately compensated to be able to use the optical calibration in-vivo

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

Shedding light on living cells and mineralised tissues using Raman spectroscopy

Raman micro-spectroscopy presents a highly sensitive, non-invasive, and rapid way to collect biochemical information from cells and tissues. The resulting Raman spectrum is a chemical ‘fingerprint’ containing a wealth of molecular level information which has been used to characterize, monitor, compare and confirm biological processes from the cellular to tissue levels. The work presented in this thesis utilizes Raman spectroscopy to test live in vitro cellular models, classify human tissues of interest, and determine the biomolecular differences in tissue samples which are diseased or undergoing therapeutic treatment. Additionally new ways of visualizing and interpreting multivariate analytical results are proposed and demonstrated to ease the determination of the biomolecular features which are most important when comparing sample groups. A persistent challenge in the interpretation of information rich biological Raman spectra includes the multitude of signals from lipids, proteins, carbohydrates, nucleic acids, and minerals found in a limited spectral range and in some instances overlapping significantly. Partial Least Squares – Discriminant Analysis (PLS-DA) Variable Importance Projection (VIP) scores were presented as heat maps overlaying difference spectra to ease the visualization of significant biochemical bond changes between sample groups and their trends. The advantages of applying PLS-DA VIP scores in this way are demonstrated in well studied and known system including a cultured cellular model incorporating fixation methods and a human tissue comparison between healthy and osteoporotic bone. PLS-DA VIP score plots were additionally utilized to characterize and compare the biolomecular environments surrounding the recently described microscopic mineral inclusions in human aortic valves and aortae. The PLS-DA VIP score plots exposed the chemical differences in these systems through highlighting the corresponding spectral bands in an easy to read and interpret way. Raman micro-spectroscopy was also applied to investigate an in vitro ‘calcified’ porcine aortic valvular interstitial cell model. This model system was probed for the first time using the combination of Raman micro-spectroscopy and complimentary gold standard biological techniques to determine the protein and potential mineral content within these nodular, cellular systems. The ‘calcified’ porcine aortic valvular cell nodules showed no evidence of mineral inclusion. These nodules did exhibit a heavy extracellular matrix production including the production of collagen I. The porcine aortic valvular cell nodules acting as a model system for diseased aortic valve tissue requires not only the characterization of the cell nodule in vitro but also the characterization of the human disease spectrum which the model is suggested to replicate. The discovery and characterisation of microscopic mineral spherical inclusions (50nm-200µm) located in both valvular and vascular tissues leads to an interesting question on the introduction and role of microscopic mineral deposits in cardiovascular disease. Here Raman micro-spectroscopy was utilized to investigate the organic matrix surrounding these microscopic mineral deposits to determine if any colocalised protein changes exist. Protein and specifically collagen changes are demonstrated between tissues with and without the spherical mineral deposits despite being macroscopically indistinguishable. Raman spectroscopy was also utilized to provide direct insights into tissue constituent and structural changes on the molecular level in heat-induced tissue fusion via radio-frequency (RF) energy. This type of tissue fusion has gained wide acceptance clinically and is presented here as the first optical-Raman-spectroscopy study on tissue fusion samples in vitro. This study exposed spectroscopic evidence for the loss of distinct collagen fibres rich tissue layers as well as the denaturing and restructuring of collagen crosslinks post RF fusion. Raman spectroscopy is a demonstrated, powerful, biomolecular imaging technique which benefits from advancements in mathematical analytical techniques as well as its own application in biological investigations. This thesis explores the application of Raman spectroscopy in combination with powerful analytical techniques to further characterize and compare biological systems of interest.Open Acces