Browsing by Subject "Atherosclerosis"
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Item Algorithms for Fluorescence Lifetime Microscopy and Optical Coherence Tomography Data Analysis: Applications for Diagnosis of Atherosclerosis and Oral Cancer(2014-05-16) Pande, ParitoshWith significant progress made in the design and instrumentation of optical imaging systems, it is now possible to perform high-resolution tissue imaging in near real-time. The prohibitively large amount of data obtained from such high-speed imaging systems precludes the possibility of manual data analysis by an expert. The paucity of algorithms for automated data analysis has been a major roadblock in both evaluating and harnessing the full potential of optical imaging modalities for diagnostic applications. This consideration forms the central theme of the research presented in this dissertation. Specifically, we investigate the potential of automated analysis of data acquired from a multimodal imaging system that combines fluorescence lifetime imaging (FLIM) with optical coherence tomography (OCT), for the diagnosis of atherosclerosis and oral cancer. FLIM is a fluorescence imaging technique that is capable of providing information about auto fluorescent tissue biomolecules. OCT on the other hand, is a structural imaging modality that exploits the intrinsic reflectivity of tissue samples to provide high resolution 3-D tomographic images. Since FLIM and OCT provide complimentary information about tissue biochemistry and structure, respectively, we hypothesize that the combined information from the multimodal system would increase the sensitivity and specificity for the diagnosis of atherosclerosis and oral cancer. The research presented in this dissertation can be divided into two main parts. The first part concerns the development and applications of algorithms for providing quantitative description of FLIM and OCT images. The quantitative FLIM and OCT features obtained in the first part of the research, are subsequently used to perform automated tissue diagnosis based on statistical classification models. The results of the research presented in this dissertation show the feasibility of using automated algorithms for FLIM and OCT data analysis for performing tissue diagnosis.Item Characterization of atherosclerotic plaques using ultrasound guided intravascular photoacoustic imaging(2011-05) Wang, Bo, 1981-; Emelianov, Stanislav Y.; Sokolov, Konstantin; Smalling, Richard; Litovsky, Silvio; Dunn, Andrew; Aglyamov, SalavatRupture of atherosclerotic plaque is closely related to plaque composition. Currently, plaque composition cannot be clinically characterized by any imaging modality. The objective of this dissertation is to use a recently developed imaging modality – ultrasound-guided intravascular photoacoustic (IVPA) imaging – to detect the distribution of two critical components in atherosclerotic plaques: lipid and phagocytically active macrophages. Under the guidance of intravascular ultrasound imaging, spectroscopic IVPA imaging is capable of detecting the spatially resolving optical absorption property inside a vessel wall. In this study, contrast in spectroscopic IVPA imaging was provided by either the endogenous optical property of lipid or optically absorbing contrast agent such as gold nanoparticles (Au NPs). Using a rabbit model of atherosclerosis, this dissertation demonstrated that ultrasound guided spectroscopic IVPA imaging could simultaneously image lipid deposits as well as macrophages labeled in vivo with Au NPs. Information of macrophage activity around lipid rich plaques may help to identify rupture-prone or vulnerable plaques. The results show that ultrasound guided IVPA imaging is promising for detecting plaque composition in vivo. Clinical use of ultrasound guided IVPA imaging may significantly improve the accuracy of diagnosis and lead to more effective treatments of atherosclerosis.Item Detection of Atherosclerotic Coronary Plaques by Fluorescence Lifetime Imaging Angioscopy(2010-10-12) Thomas, Patrick A.Vulnerable plaque is a clinically silent condition of atherosclerotic plaque that leaves a large number of patients at risk of a coronary event. A method to detect vulnerable atherosclerotic plaque would greatly enhance the ability of clinicians to diagnose and treat patients at risk. Fluorescence lifetime imaging microscopy (FLIM) offers a way to extract both spatial and biochemical information from plaque by taking several wide-field images over time. The goal of this study was to determine the potential of a FLIM angioscopy system to detect and differentiate coronary atherosclerotic plaques ex-vivo into several groups including thin, fibrotic, lipid-laden, thick-cap fibroatheroma (FA), and fibrocalcified. Samples were extracted post-mortem weekly and sliced open to have their lumens imaged. For each sample, 51 time resolved wide-field images were taken over 10 nanoseconds at 390 (?40) nm, 450 (?40) nm, and 550 (?88) nm wavelengths. To analyze the samples, the intensity map and lifetime map were created at each wavelength. The intensity map was simply the wide-field images summed in time and normalized. In order to calculate lifetime at each point, a fast, model-free Laguerre deconvolution algorithm was recently developed for FLIM data analysis and was used. This allowed for fast, efficient estimations of the fluorescence decay curves at each pixel of the FLIM images and facilitated the computation of quantitative parameters describing the fluorescence emission of the tissue, specifically, the relative fluorescence intensity and lifetime at defined emission bands. Statistical analysis on these FLIM derived parameters indicated that the autofluorescence emission of the plaques allows for distinguishing relative plaque thickness: thin plaque, whose signal is dominated by elastin fluorophores, shows a marked difference between thicker plaques, such as fibrotic, fibrocalcified and thick-cap FA (who are dominated primarily by collagen). However, the ability of the current FLIM system to differentiate vulnerable plaque remains in question due to the absence of thin-cap FA samples. Further work has also been proposed; of primary concern is gathering thin-cap FA plaque samples needed to validate the system?s ability to differentiate vulnerable plaques from other common groupings.Item Effect of vitamin E supplementation on plasma lipids and oxidized low-density lipoprotein in hypercholesterolemic rats(Texas Tech University, 1997-08) Shankar, PadminiCoronary artery disease is the leading cause of death in the United States. A major risk factor for atherosclerosis is elevated levels of semm cholesterol, particularly lowdensity lipoprotein (LDL) cholesterol in the blood. It has become increasingly evident that LDL must undergo oxidative modification before giving rise to foam cells, one of the earliest stages in the development of atherosclerosis. Micronutrient antioxidants can protect LDL from oxidation and can thus delay or prevent the development of fatty streaks in the arterial wall. The purpose of the present study was to determine the effect of graded doses of vitamin E and selenium on plasma total cholesterol, high-density lipoprotein (HDL) cholesterol, triglycerides and oxidized LDL cholesterol in rats fed control and cholesterol/cholic acid (l%)/0.3%)) enriched diets for five months. Eighty-two female Fischer rats were randomly assigned to seven treatment groups and fed experimental diets containing vitamin E supplementation ranging from 60 mg/kg basal diet (adequate level) to 2400 mg (high level). Six groups of rats were given adequate levels of selenium (0.2 mg/kg diet) and one group was given excess (4,0 mg/kg) selenium. At the end of the study period there was progressive weight gain in all the animals, but the vitamin E deficient group and the selenium excess group consistently showed lower weight gain compared to other treatment groups. Plasma lipids were elevated in all the treatment groups fed cholesterol. A positive association between HDL levels and increasing levels of vitamin E supplementation was noted. The liver weights of animals fed cholesterol were higher than that of the control group. Determination of total plasma oxidation based on malondialdehyde (MDA) formation showed that there was decreased formation of MDA at high levels of vitamin E supplementation. There was a positive association between increasing amoimts of dietary vitamin E supplementation and plasma a-tocopherol levels with the highest concentration found in the treatment group fed the highest amount of vitamin E. The oxidation kinetics of LDL based on the thiobarbituric acid reacting substances assay and conjugated diene assay revealed that the treatment group fed high levels of vitamin E had prolonged lag phase of oxidation compared to the other treatment groups. High levels of vitamin E supplementation did not produce any adverse effects in the rats.Item The effects of prolonged sitting and acute exercise on postprandial plasma triglyceride concentration(2011-12) Kim, Il-Young, 1973-; Coyle, Edward F., 1952-; Ivy, John L.; Tanaka, Hirofumi; Hamilton, Marc T.; Brothers, Robert M.These studies investigated the effect of physical inactivity (prolonged sitting) and physical activity (walking, standing, and moderate intensity exercise) on postprandial plasma triglyceride concentration (PPTG). In the first study, we evaluated the effect of low intensity intermittent walking at ~25% VO₂max (WALK) and energy-matched moderate intensity running at ~65% VO₂max (RUN) on PPTG, compared to a sitting control (SIT). RUN reduced incremental area under the curves for plasma triglyceride concentration (TG AUC[subscript I]), compared to WALK by 17.3% (p = 0.04) and SIT by 27% (p [less than] 0.001). The reduced TG AUC[subscript I] in RUN was accompanied by enhanced whole body insulin sensitivity, compared to WALK and SIT (for both, p [less than] 0.05). Whole body postprandial fat oxidation at rest following a high fat test meal intake was enhanced in RUN by 31% (P [less than] 0.001) and to a lesser extent in WALK by 8.4% (p [less than] 0.005), compared to SIT. In the second study, we evaluated 1) the effect of 2 days of prolonged sitting on PPTG, and 2) the effect of 4 days of SIT on the ability of an acute bout of exercise to reduce PPTG, compared to the same days of active walking and standing with calorically balanced diet (WALK+B). To distinguish the effect of prolonged sitting from the excess calorie effect, we had a sitting condition with calorically balanced diet (SIT+B) in addition to a sitting condition with hypercaloric diet (SIT+H). Following 2 days of respective food and activity control, WALK+B was lower in TG AUC[subscript T] by 21.3% and AUC[subscript I] by 17.4%, compared to SIT+H (for both, p [less than] 0.005). WALK+B was lower than SIT+B for TG AUC[subscript T] by 17.7% (p = 0.165) and AUC[subscript I] by 23.5% (p = 0.145) although statistical significance was not achieved. Remarkably, an acute exercise following 4 days of either SIT+H or SIT+B failed to reduce both TG AUC[subscript T] and AUC[subscript I], compared to SIT+B in HFTT1. The same exercise following 4 days of WALK+B, however, reduced both TG AUC[subscript T] by 29% and TG AUC[subscript I] by 32% in HFTT2, compared to SIT+B in HFTT1 (for both, p [less than] 0.02). Further, both SIT conditions reduced relative whole body fat oxidation in favor of increases in carbohydrate oxidation, compared to WALK+B by more than 40% in both HFTT1 and HFTT2. Taken together, our data suggest that 1) exercise intensity plays an independent role with higher intensity being more effective than lower intensity exercise in reducing PPTG, and 2) prolonged sitting with excess energy intake amplifies PPTG and prolonged sitting impairs the ability of an acute bout of moderate intensity exercise to reduce PPTG. This emphasizes the importance of regular participation in moderate-to-vigorous intensity exercise and reducing sitting time by increasing non-exercise physical activities (i.e., walking and standing) for the favorable postprandial metabolic health from the individual and public health perspectives.Item Intravascular photoacoustics as a theranostic platform for atherosclerosis(2014-08) Yeager, Douglas Edward; Emelianov, Stanislav Y.; Baker, Aaron; Sessler, Jonathan; Smalling, Richard; Sokolov, KonstantinThe persistence of high global mortality rates directly attributable to cardiovascular disease drives ongoing research into novel approaches for improved diagnosis and treatment of its primary underlying cause, atherosclerosis. Combined intravascular ultrasound and photoacoustic (IVUS/IVPA) imaging is one such modality, actively being developed as a tool for improved characterization of high-risk atherosclerotic plaques. The pathophysiology associated with progression and destabilization of atherosclerotic plaques leads to characteristic changes in arterial morphology and composition. IVUS/IVPA imaging seeks to expand upon the ability of clinically utilized intravascular ultrasound (IVUS) imaging to assess vessel anatomy by adding improved sensitivity to image the underlying cellular and molecular composition through intravascular photoacoustic (IVPA) imaging of either endogenous chromophores (e.g. lipid) or exogenously delivered contrast agents. This dissertation focuses on the expansion of IVUS/IVPA imaging using exogenous contrast agents to enable the detection and subsequent optically-triggered therapy of atherosclerotic plaques. The passive extravasation and aggregation of systemically injected plasmonic gold nanorods absorbing within the near infrared tissue optical window within plaques of atherosclerotic rabbit models is first demonstrated, along with the ability to localize the contrast agents using ex vivo IVUS/IVPA imaging. The motivation for nanoparticle labeling of atherosclerosis is then expanded from that of purely image contrast agents to vehicles for image-guided, dual-modality phototherapy. The integrated IVUS/IVPA imaging catheter is utilized for photothermal delivery with simultaneous IVPA temperature monitoring using the high optical absorption of gold nanorod contrast agents to enable localized heating. Subsequently, the potential role for IVUS/IVPA-guided phototherapy is further expanded through the characterization and in vitro assessment of novel multifunctional theranostic nanoparticles comprised of a gold nanorod core with a degradable, photosensitizer-doped silica shell. Together, the results presented within this dissertation provide a framework for ongoing research into the expansion of IVUS/IVPA imaging as a platform for complimentary diagnosis and local treatment of atherosclerotic plaques using multifunctional theranostic nanoparticle contrast agents.Item Magnetic Resonance Imaging of the Heart and Vasculature at 3 Tesla: Novel Strategies for the Diagnosis and Risk Stratification of Cardiovascular Disease(2011-10-03T14:15:07Z) Maroules, Christopher D.; Peshock, Ronald M.Purpose: (1) To study the effects of field strength and parallel imaging on image contrast and the interstudy reproducibility of right and left ventricular (RV and LV) measurements using steady-state free precession (SSFP) cardiac magnetic resonance; (2) to explore the impact of 3T parallel imaging techniques on the assessment and reproducibility of black-blood aortic atherosclerosis imaging; and (3) to evaluate the feasibility of coronary sinus flow imaging by 3T spiral velocity-encoded cine (VEC) MR imaging in overweight women with risk factors for cardiovascular disease Materials and Methods: To evaluate cardiac measurements and aortic atherosclerosis by cardiac magnetic resonance, thirty-two subjects (20 normal, 12 cardiac patients) underwent SSFP cine short-axis imaging and black-blood abdominal aortic imaging: two studies at 1.5T, one study at 3T, and another study at 3T with parallel imaging (SENSE). Contrast-to-noise ratios (CNR) were compared between techniques. To evaluate the feasibility of coronary sinus flow MR imaging, ten women (age 38 years ± 10) with a mean BMI of 33 kg/m2 ± 8 were studied. Coronary sinus flow was measured at baseline and in response to cold pressor stress. Changes in right coronary artery flow were also measured before and after stress using VEC MRI. Results: Cardiac MRI: 3T SENSE imaging reduced cardiac imaging time from 8 ± 2 min to 3 ± 1 min (P<0.001). A significant gain in LV CNR was detected between 1.5T and 3T with SENSE (43.8 ± 6.5 vs 48.4 ± 7.4, P=0.01), but no significant gain was detected in RV CNR. The reproducibility of LV and RV measurements between two 1.5T studies was not significantly different from the reproducibility between a 1.5T study and a 3T study with SENSE. Aortic MRI: Image quality scores were comparable between 1.5-T and 3-T with SENSE (4.0 ± 0.6 vs 4.2 ± 0.6, P = 0.21). Bland-Altman reproducibility for MWT was -0.03 mm ± 0.15 (1.5-T vs 1.5-T) and -0.01 mm ± 0.18 (1.5-T vs 3-T with SENSE), P = 0.83. Detection of the presence of absence of plaque was comparable. Coronary Sinus Flow Imaging: A significant 24% increase in coronary sinus volume flow was observed from baseline to peak cold pressor stress (141 ± 34 ml/min vs. 184 ± 42 ml/min, p = 0.02). Similar increases in RCA flow velocity were observed (15.3 ± 5 cm/sec vs. 23.2 ± 7 cm/sec, P < 0.01). Conclusions: (1) SSFP cardiac MR imaging and black-blood aortic MR imaging are reproducible techniques. (2) Parallel imaging at 3T permits shorter scan time compared to conventional 1.5-T imaging with comparable measurements of cardiac structure and function, as well as aortic atherosclerosis. (3) Coronary sinus spiral velocity-encoded MRI at 3T is a feasible technique for measuring changes in coronary flow in asymptomatic overweight and obese women with risk factors for cardiovascular disease. [Keywords: MRI; 3 Tesla; cardiovascular; imaging; basic stratification]Item Photoacoustic image guidance and tissue characterization in cardiovascular applications(2016-12) Dana, Nicholas Pacheco; Suggs, Laura J.; Emelianov, Stanislav Y.; Dunn, Andrew; Tunnell, James; Bouchard, RichardCollectively, cardiovascular diseases continue to be the leading cause of death, across nations and across decades. Improved diagnostic imaging methods offer promise to alleviate the morbidity associated with these diseases. Photoacoustic (PA) imaging is one such method, poised to make a significant impact on cardiovascular imaging, both as a research tool, as well as a clinical imaging modality. Offering the potential of molecular imaging in real-time, PA methods have been demonstrated in proof-of-concept studies tracking myocyte calcium dynamics. These results open the door to non-invasive longitudinal assessment of cardiac electrophysiological function, with implications for drug and contrast agent development. PA image guidance has also been extended to the characterization of cardiac radiofrequency ablation lesions. This method has been demonstrated to utilize endogenous chromophore changes resulting from ablation for the generation of depth-resolved tissue characterization maps, capable of assessing lesion extent. The technique has been subsequently validated by assessing high-intensity focused ultrasound ablation lesions in myocardium, with the hope for offering thermographic capabilities as well. While PA imaging offers such promise in cardiac ablation procedures, it is also in the process of clinical translation for image guidance and characterization in coronary artery disease applications. Research has shown, using Monte Carlo optical modeling, that using a simple dual-wavelength PA imaging technique has great potential for successful visualization of atherosclerotic plaques across multiple tissue types and at clinically relevant multiple millimeters of depth. Collectively these results offer a suite of PA imaging tools with the potential for molecular and thermographic imaging across a broad range of cardiovascular applications.Item Textured thin metal shells on metal oxide nanoparticles with strong NIR absorbance and high magnetization for imaging and therapy(2010-12) Ma, Li, doctor of chemical engineering; Feldman, Marc David; Johnston, Keith P., 1955-; Milner, Thomas E.; Sokolov, Konstantin V.; Mullins, C. B.; Hwang, Gyeong S.The ability of sub 100 nm nanoparticles to target and modulate the biology of cells will enable major advancements in cellular imaging and therapy in cancer and atherosclerosis. A key challenge is to load an extremely high degree of targeting, imaging, and therapeutic functionality into small, yet stable particles. A general mechanism is presented for thin autocatalytic growth on nanoparticle substrates (TAGS), as demonstrated for a homologous series of < 5 nm textured Au coatings on < 42 nm iron oxide cluster cores. Very low Au supersaturation levels are utilized to prevent commonly encountered excessive autocatalytic growth that otherwise produce thick shells. The degree of separation of nucleation to form the seeds from growth is utilized to control the morphology and uniformity of the thin Au coatings. The thin and asymmetric Au shells produce strong near infrared (NIR) absorbance with a cross section of ~10⁻¹⁴ m², whereas the high magnetic content per particles provides strong r2 spin-spin magnetic relaxivity of 200 mM⁻¹s⁻¹. TAGS may be generalized to a wide variety of substrates and high energy coatings to form core-shell nanoparticles of interest in a variety of applications as diverse as catalysis and bionanotechnology. High uptake of the nanoclusters by macrophages is facilitated by the dextran coating, producing intense NIR contrast both in cell culture and an in vivo rabbit model of atherosclerosis. A novel conjugation technique further allows covalent binding of anti-epidermal growth factor receptor (EGFR) monoclonal antibody (Ab) to the nanoclusters for highly selective targeting to EGFR over expressing cancer cells. AlexaFluor 488 tagged Ab nanocluster conjugates were prepared to correlate the number of conjugated Abs with the hydrodynamic diameter. The high targeting efficacy was evaluated by dark field reflectance imaging and atomic absorbance spectrometry (AAS). Colocalization of the nanoparticles by dual mode in-vitro imaging with dark field and fluorescence microscopy demonstrates the Abs remained attached to the Au surfaces. The extremely high curvature of the Au shells with features below 5 nm influence the spacing and orientations of the Abs on the surface, which has the potential to have a marked effect on biological pathways within cells. These targeted small multifunctional nanoclusters may solve some key molecular imaging challenges for cancer and atherosclerosis.