Modulography: elasticity imaging of atherosclerotic plaques

Modulography is an experimental elasticity imaging method. It has potential to become an all-in-one in vivo tool (a) for detecting vulnerable atherosclerotic coronary plaques, (b) for assessing information related to their rupture-proneness and (c) for imaging their elastic material composition. Modulography determines a cross-sectional image of the elasticity distribution (=Young's modulus) from deformation (=strain) that is processed from intravascular ultrasound (IVUS) measurements. By looking at this image, cardiologists and other researchers can directly identify and characterize soft and stiff plaque-components of thin-cap fibroatheromas and of heterogeneous plaques. As a diagnostic and pharm

Experimental study and computational modelling of the biomechanical properties of arteries

Biomechanics of artery has been shown to play an important role in the progression of cardiovascular diseases. Thus studies of arterial biomechanics are essential to find the causes and preventions of these diseases. The thesis first introduces work demonstrating the use of the optical flow estimation technique to track the deformation of biological tissue in biomechanical experiments. The study shows that the optical flow technique provides a good estimation of the strains for the constructed deformation images by comparing the results with those of the finite element (FE) models. The optical flow technique was then used on the analysis of the images obtained from the experiments of human coronary arteries with atherosclerosis. Atherosclerosis is a cardiovascular disease in which the rupture of atherosclerotic plaque leads to stroke or myocardial infarction, where the risk of the rupture has been associated with mechanical factors. An approach was developed combining the tensile ring tests, optical flow analysis, and FE modelling to obtain the heterogeneous mechanical properties of atherosclerotic arteries. This approach provides a sensible estimation of the hyperelastic properties of atherosclerotic plaques by matching the forces and strains of the experiments and FE models using an error minimisation approach. The study on the biomechanics of atherosclerotic arteries was then extended to the muscle active properties of the diseased vessels. Previous drug response experiments have shown that human atherosclerotic arteries maintained active forces of more than 70% of those in healthy arteries in response to endothelin-1 (ET-1) despite an extensive thinning of the media smooth muscle layer. FE analyses have been performed to model the passive tensile ring tests and active ET-1 response tests, which demonstrate the potential elevated contractile strains of diseased smooth muscle cells in response to ET-1. The results suggest that adaptation mechanisms occur with atherosclerosis to maintain the distensibility of the diseased artery in physiological condition with the presence of cell activation agents. In addition, a project investigating the role of hyaluronan in systemic inflammation-induced aortic stiffening has been carried out. Systemic inflammation occurs in several diseases such as rheumatoid arthritis which increases aortic stiffness and causes altered distribution and function of arterial hyaluronan. Tensile ring tests were performed on rat aortas that have hyaluronan digested by hyaluronidase and control samples. The results show no significant difference between the elastic modulus of the two groups despite successful digestion of the hyaluronan content in the treated samples in biochemistry assays. A potential mechanism of this contradiction is that the hyaluronan accumulation-induced aortic stiffening is a long term effect in patients and cannot be shown with the methodology of this study. In order to solve the non-physiological loading limitation of the tensile ring tests in the studies above, an inflation test system has been designed for future experiments. This system inflates an artery ring with a balloon tube with the cross-sectional deformation captured using a camera in an inverted position. The system has been tested with a pig aortic ring with the deformation analysed using the optical flow technique. The estimated elastic modulus of the artery was compared to that obtained from a tensile ring test, which shows a good matching between the two values. Overall, the thesis demonstrates experimental and computational approaches to study the biomechanical properties of arteries. The results also provide information on the hyperelastic and active properties of atherosclerotic arteries as well as the effects of hyaluronan digestion on the stiffness of rat aortas

Palpography

Intravascular ultrasound palpography is a new imaging technique that allows visualization of the deformation of atherosclerotic plaques. The technique is based on principle of elastography that the strain as response of tissue to a mechanical force is dependent on its mechanical properties. Several techniques had been investigated (van der Steen 1998) to strain the vessel wall. Leaving the mechanical deformation to the intravascular pressure, which is reproducible, is occurring about sixty times per minute and is for free, seemed to be a reasonable idea

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

Biomechanical Modeling of Atherosclerotic Plaques for Risk Assessment

A healthy arterial wall comprises three layers: the adventitia, the media and the intima (Figure 1.1, left side). The adventitia is the outermost layer, mainly composed of collagen. The media underlies the adventitia and is the middle layer in the arterial wall. It is made up of concentrically arranged smooth muscle cells and collagen fibers. The intima is the innermost layer. It is a thin sheet of endothelial cells attached to a basal membrane. Atherosclerosis is a systemic, inflammatory disease of the arterial system characterized by local thickening of vessel walls. Thickened arterial segments are called atherosclerotic plaques (Figure 1.1, right side). During atherogenesis - progression of an atherosclerotic plaque- the major changes take place in the intima due to infiltration of lipids and inflammatory cells from the luminal side, smooth muscle cell migration and proliferation, extracellular matrix deposition, and intraplaque hemorrhage. From a thin cell layer, the intima transforms into a thick layer (Figure 1.1) with the possible structural components being smooth muscle cells, collagen and elastin fibers, and lipids. Besides changes in the intima, atherosclerosis causes differentiation in the media and adventitia layers. Fibrosis, atrophy and inflammation may take place in the media and adventitia during atherogenesis

Stress-strain Analysis of Carotid Arteries with Atheroma

Kardiovaskulární příhody byly a jsou rozšířenou příčinou úmrtí ve většině zemí. Ateroskleróza karotických tepen mnohdy vedoucí k mrtvici je jejich nedílnou součástí. Včasná a vhodně mířená diagnostika rizikových lézí může vést ke snížení kritických příhod, a tím potenciálně snížit počet úmrtí. Porušení nestabilního aterosklerotického plátu je ovlivněno působením sil od proudící krve. V biomechanice měkkých tkání je využíváno výpočtového modelování jakožto potenciálního ukazatele, díky němuž by bylo možné odhalit nestabilitu plátu u pacientů podstupujících pravidelná kontrolní měření. Mechanické veličiny bývají spojovány s klinicky dostupnými ukazateli jako jsou například podstatné rozměry léze nebo přítomnost rizikových komponent. Komplexita a malé rozměry tkáně ovšem stále omezují možnosti tvorby výpočtových modelů a existuje tedy spousta faktorů, které je před možnou implementací do klinických postupů potřeba řádně vyšetřit. Tato práce je členěna do kapitol shrnujících aktuální stav řešené problematiky. Kapitoly jsou doplněny o komentář autorova příspěvku k dané problematice a odkaz na originální práci. Studium problematiky naznačilo velké množství potenciálních směrů výzkumu, což by ovšem nebylo možné zahrnout do jediné práce. Řešená témata se dají rozdělit na: (i) ověření možnosti tvorby 3D výpočtového modelu ze snímků aterosklerotického plátu s následným rozšířením na výpočtovou studii zahrnující řadu faktorů pro ověření vlivu na napjatost, (ii) studium mechanických vlastností aterosklerotických plátů odebíraných z endarterektomie během celé doby řešení, (iii) možnosti analýzy deformačního pole u experimentů zahrnujících měkké tkáně a (iv) experimentální a výpočtovou studii zbytkové deformace, potažmo napětí v souvislosti s karotickými tepnami. Výsledky jednotlivých částí jednoznačně poukázaly na problémy spojené s výpočtovým modelováním jako například časté opomíjení přítomnosti komponent stěny tepny při modelování aterosklerotického plátu, nutnost správného pochopení mechanického chování, ale také na způsob vyhodnocení experimentů s vyšším počtem vzorků. V neposlední řadě bylo ukázáno, že zbytkové napětí nemusí být podstatným faktorem u aterosklerotických plátů karotických tepen.Health risks associated with cardiovascular diseases are apparent in many countries' high mortality rates. Atherosclerosis in carotid arteries can cause a stroke and contributes thus in a large extent. Early detection of risky lesions is substantial to prevent an incident. The forces from the blood flow influence a rupture of a vulnerable plaque. The biomechanics of soft tissue is often incorporated with computational modelling as a potential tool to predict the plaque vulnerability for patients who underwent screening. Mechanical characteristics can then be correlated with clinical biomarkers such as crucial plaque dimensions or the presence of some risky component. However, the plaque complexity, together with a small size, influences a proper model creation leading to simplifications with an unknown effect on the mechanical characteristics. To incorporate computational modelling as a potential diagnostic tool, this is to be solved. The thesis is structured into chapters describing state of the art in computational modelling of atherosclerotic tissue. Relevant chapters are completed with a description of the author's contribution with references to the original works. Many possible directions were discovered during the literature review, although their inclusion was possible only partly as it would require more than one thesis. The main topics of interest were: (i) creation of 3D models from imaging and their subsequent use in computational study augmented by other factors, (ii) study of mechanical properties of endarterectomy samples during the study period, (iii) study of full-field strain detection methods for soft biological tissue and (iv) experimental and computational study of residual deformations and stresses of carotid arteries. The results of each part indicated problems related to computational modelling of atherosclerotic tissue, like omission of the arterial wall when the plaque stress-strain analysis is performed, the necessity of a proper understanding of mechanical responses, and its evaluation for more samples. Last but not least a negligible influence of layer-specific residual stresses for carotid plaques.