Browsing by Subject "Cardiovascular Disease"
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Item A Model for the Estimation of Residual Stresses in Soft Tissues(2012-10-19) Joshi, SunnieThis dissertation focuses on a novel approach for characterizing the mechanical behavior of an elastic body. In particular, we develop a mathematical tool for the estimation of residual stress field in an elastic body that has mechanical properties similar to that of the arterial wall, by making use of intravascular ultrasound (IVUS) imaging techniques. This study is a preliminary step towards understanding the progression of a cardiovascular disease called atherosclerosis using ultrasound technology. It is known that residual stresses play a significant role in determining the overall stress distribution in soft tissues. The main part of this work deals with developing a nonlinear inverse spectral technique that allows one to accurately compute the residual stresses in soft tissues. Unlike most conventional experimental, both in vivo and in vitro, and theoretical techniques to characterize residual stresses in soft tissues, the proposed method makes fundamental use of the finite strain non- linear response of the material to a quasi-static harmonic loading. The arterial wall is modeled as a nonlinear, isotropic, slightly compressible elastic body. A boundary value problem is formulated for the residually stressed arterial wall, the boundary of which is subjected to a constant blood pressure, and then an idealized model for the IVUS interrogation is constructed by superimposing small amplitude time harmonic infinitesimal vibrations on large deformations via an asymptotic construction of its solution. We then use a semi-inverse approach to study the model for a specific class of deformations. The analysis leads us to a system of second order differential equations with homogeneous boundary conditions of Sturm-Liouville type. By making use of the classical theory of inverse Sturm-Liouville problems, and root finding and optimization techniques, we then develop several inverse spectral algorithms to approximate the residual stress distribution in the arterial wall, given the first few eigenfrequencies of several induced blood pressures.Item Depressive Symptoms and Subclinical Vascular Disease: a Cross-Cultural Comparison(2013-07-25) Moore, Patricia Sinclair; Cullum, C. Munro; Weiner, Myron F; Hynan, Linda; King, Kevin S; Rossetti, Heidi; Deschner, MartinWhile rates of depression are similar across ethnic groups, severity of symptoms and disability related to depression are greater in African Americans when compared with other groups (Breslau, Kendler, Su, Gaxiola-Aguilar, & Kessler, 2005). Markers of subclinical cardiovascular disease have been associated with depression, and rates of most cardiovascular risk factors are higher in African Americans than Caucasians (Shaya, Gu, & Saunders, 2007). Whereas rates of atherosclerosis are similar across these groups (Jain et al., 2004), atherosclerosis has been shown to be associated with depression in mostly Caucasian samples (Bus et al., 2011; Gebara & Santos, 2010). A more direct marker of subclinical cerebrovascular impact is cerebral white matter hyperintensity volume (WMHv). Differences in WMHv have been reported across ethnic groups, and WMHv is more closely associated with the cardiovascular risk factors that are higher in African Americans. White matter hyperintensities (WMH) have been independently associated with increased depressive symptoms in late-life depression (Pompili et al., 2007; 2008; Sneed et al., 2011; Tham, Woon, Sum, Lee, & Sim, 2011), although the relationship between vascular disease and depression is poorly understood. This study aimed to examine the relationship between atherosclerosis, WMHv, and depressive symptoms in Caucasians and African Americans over age 50 to determine the association between subclinical vascular disease and depressive symptoms across ethnic groups. To this end, specific measures of subclinical vascular diseases (measures of atherosclerosis, WMHv) were compared to identify the best predictors of depressive symptoms within ethnic groups.Item Evaluation of Acute and Chronic Lesions in Percutaneous Coronary Intervention(2012-10-19) Roberts, AaronMetallic implants called stents are an important part of the treatment of coronary heart disease. While clinical trials are excellent indicators of outcomes, microscopic evaluation of the host tissue response to the implant is required to assess their safety and efficacy. However, the evaluation of human autopsy tissue containing metal implants presents unique challenges in order to obtain the best results. We used integrated microscopy techniques incorporating microCT and novel plastic histology techniques to demonstrate its effectiveness on human stented vessels obtained at autopsy. A total of seven cases are demonstrated where our analysis techniques were able to elucidate the pathogenesis of the host response and identify the specific cause of the complications with the stented vessel seen clinically. These techniques are more cost effective and efficient than other techniques currently in use, which could enable them to be used as part of routine autopsy evaluation. The expansion of the pool of stented vessels able to be analyzed to include the often overlooked large population of autopsy cases could provide an enormous amount of data to guide future clinical trials and improve patient care.Item High Performance Lipoprotein Profiling for Cardiovascular Risk Assessment(2012-10-19) Larner, CraigWith the severity of cardiovascular disease (CVD) and the related mortality rate to this disease, new methods are necessary for risk assessment and treatment prior to the onset of the disease. The current paradigm in CVD risk assessment has shifted towards the multivariate approach over the individual use of traditional risk factors or lipid measurements. Through a combination of analytical techniques and multivariate statistical analysis, a novel method of cardiovascular risk assessment was developed. The analytical techniques employed include density gradient ultracentrifugation (DGU) and matrix assisted laser desorption ionization mass spectrometry (MALDI-MS) applied to human serum. These techniques provided detailed information about the characterization of the lipoproteins and their structural components, specifically the apolipoproteins belonging to high density lipoproteins (HDL). This information when combined with multivariate statistical analysis provided a method that accurately identified the presence of CVD in clinical studies between cohorts of subjects that had been previously diagnosed with CVD and cohorts of subjects that had been identified as healthy controls (CTRL) based on a clear angiography. The lipoprotein density profiles were divided into subclasses based on their density and measured using a fluorescent probe to tag the lipoprotein particles. Use of multiple ethylenediaminetetraacetic acid (EDTA) based solutes allowed for the manipulation of the density gradient formation in order to separate the lipoproteins by specific density ranges in order to achieve better baseline separation of the profiles. Application of the integrated fluorescence intensities for each subclass of lipoprotein to linear discriminant analysis/sliced inverse regression (LDA/SIR) and quadratic discriminant analysis (QDA) yielded an advanced and accurate form of risk assessment for CVD. This method was found to be highly accurate as well as identify potential atherogenic lipoprotein subclasses through studying the LDA/SIR prediction equation generated. It was also shown that the LDA/SIR equation could be used to monitor medical treatment and lifestyle change for their effects on the risk assessment model. Further study into the atherogenicity of HDL through analysis of the apolipoproteins using MALDI-MS led to identification of potential risk factors that could be added to the statistical analyses. These risk factors included mass differences in the Apolipoprotein A-I (Apo A-I) and Apolipoprotein C-I (Apo C-I) between CVD and CTRL samples as well as the presence of specific mass peaks related to Apolipoprotein A-II (Apo A-II) that were primarily found in the CVD samples. These differences, in addition to the lipoprotein density profile data, were found to increase the potential accuracy of CVD risk assessment. The combination of these methods has shown great potential in the assessment of CVD risk as well as the ability to increase researchers' understanding of the nature of VD and how to treat it.Item Lipoprotein subclass analysis by immunospecific density(2009-05-15) Lester, Sandy MarieApolipoprotein C-1 (apo C-1) enriched HDL has been described as an atherogenic form of HDL associated with an increased risk for cardiovascular disease (CVD). The objective of the present study was to develop a rapid method for the separation, purification, and characterization of Apo C-1 from serum. We isolated and characterize HDL subclasses from individuals with and without angiographically-proven CVD who have elevated and normal-to-low HDL-C levels. Ultracentrifugation was linked with immunoaffinity separations for the specific separation of Apo C-1 enriched HDL from other lipoproteins. A 50 ?L sample of serum is diluted in TRIS HCl buffer (pH 7.5) and incubated with CNBr-activated Sepharose (Amersham) containing antibodies to apo C-1 (Academy Bio-medical Company). The apo C-1-depleted serum is removed by centrifugation and all apo C-1-containing lipoproteins are released from the Sepharose beads at pH 2. The apo C-1-depleted sample and the apo C-1-containing sample were ultracentrifuged to obtain a lipoprotein density profile in the absence and presence of apo C-1. Density Lipoprotein Profiling (DLP) gives relevant information of lipoproteins, such as density and subclass characterization, and is a novel approach to purify apo C-1-enriched HDL. An additional advantage of this approach is that lipoprotein-a (Lp(a)), which is often an interfering component in the HDL density region, is eliminated. Results show feasibility that these methods could be used in a clinical setting, was achieved. This measurement may yield a precise and quantitative profile of the distribution of apo C-1 for all lipoprotein particles including HDL.