Recent advancements in techniques of Cardiac Magnetic Resonance Imaging provide extended quantitative measurements of myocardial T1. Important tissue characteristics can be tracked noninvasively to allow practitioners to quantify important properties of regional and global myocardium function. Quantification of these T1 measures involves the compilation of multiple images to create a T1 recovery curve, providing a map that estimates the T1 value as an encoded pixel value. After contrast injection, the data is compared with native (no applied contrast agent) T1 to examine myocardial disease involving the interstitium as well as the extracellular volume fraction. Myocardial T1 mapping is an emerging biomarker for quantification of myocardial disease (since an important indicator of heart disease is the expansion of myocardial interstitial space, as is fibrosis). This paper explores the detection and quantification of cardiac involvement using delayed gadolinium enhancement combined with T1 mapping and myocardial extracellular volume fraction. It extends the research being conducted on Cardiac sarcoidosis, an important cardiomyopathy. Cardiac sarcoidosis is a multisystem granulomatous disease of unknown etiology. Cardiac MR is able to detect the active, inflammatory phase of the disease as well as the chronic phase where scarring and fibrosis are dominant. The use of gadolinium-based contrast agents improves the ability to discriminate ischemic from nonischemic etiologies, owing to different patterns among the various nonischemic cardiomyopathies. Since gadolinium shortens T1 relaxation time, the result is a brighter signal intensity in areas with increased interstitial space on inversion recovery T1-weighted sequences. The 1.5 Tesla Philips Achieva XR Scanner was used to collect the pre- and post- contrast images from five anonymous patients (subjects), following the MOLLI protocol. These images were stacked and run through MRMap, which creates parametric image maps of the MOLLI data. Data was graphed employing the Gado Partition Coefficient.

In the field of medical imaging, one of the most important concepts consists of the creation of the image from an obtained signal. The creation of the image is broken down into a subset of tasks. The first is the basic concept of isolating the element crucial to creating an image. One example is the isolation of different atoms in different modalities, for example PET or SPECT. Second, is using the intrinsic properties of these atoms to create a signal that can be recorded, this is done by magnets, gradients, coils, and other technological advances specific to other imaging modalities. Third, is the method used to record the signal. This can be done in many different ways, including but not limited to, radon space and k-space. Last but not least is the transform of the data in their respective spaces into images that are read by technologists. What is described here is, a very simple explanation for the process that different modalities go through in order to create an image. This review paper will be focused mainly on k-space acquisition and the different ways that the acquisition of k-space and image creation can be accelerated to improve patient time spent in the machine.

Alzheimer’s disease (AD) has emerged as one of the most widespread and devastating forms of dementia. Over the past few decades, AD has consistently increased in prevalence worldwide due to the rising proportion of elderly individuals and lack of effective screening and treatment modalities. To date, few economically viable and widely applicable tools exist to make definitive, early diagnoses of the disease. Therefore, there is a clear need for interventions that facilitate accurate diagnoses, monitoring, and therapeutic treatment of AD. In the course of AD, cognitive impairment is preceded by physiological changes to the central nervous system (CNS). This includes neuronal atrophy, synaptic dysfunction, and the abnormal post-translational modification of the proteins tau and beta-amyloid (A), which contributes to the deposition of intracellular neurofibrillary tangles (NFTs) and extracellular neuritic plaques (NPs). The pathological cellular changes in AD occur long before the clinical course of the disease, and biomarkers for these changes can be detected prior to measurable cognitive decline. Because the biochemical changes associated with AD are irreversible, effective tools for diagnosis must detect the presence and severity of molecular pathology during the preliminary stages of the disease’s insidious onset. Biomarkers of AD can be detected by neuroimaging technologies, including magnetic resonance imaging (MRI), positron emission tomography (PET), and blood or cerebrospinal fluid (CSF) analyses. However, these methods are not currently suited to diagnose and monitor the unique pathogenesis of AD prior to cognitive decline. An ideal instrument for widespread AD screening, diagnosis, and monitoring must be noninvasive, inexpensive, portable, and accommodating to the cognitive sensitivities of patients on a spectrum from mild cognitive impairment (MCI) to full-blown dementia. Recently, several spectroscopic methods of assessing AD pathology have met these criteria and may be better suited for widespread clinical application. The objective of this thesis is to evaluate the use of near-infrared optical spectroscopy (NIRS) to detect pathological severity in human AD. Near-infrared (NIR) light is poorly absorbed by biological tissue, and can safely penetrate bone, skin, vasculature, and neuronal tissue. NIRS has traditionally been used in biomedical contexts to evaluate cerebral oxygenation changes, however the dense protein aggregates NFTs and NPs in AD tissue have recently been shown to characteristically affect several optical parameters of a NIR signal, including fluorescence and particle path (scattering). To date, applications of NIRS have been used to differentiate AD brains from non-AD controls in vitro, and further identify MCI patients in vivo, suggesting the NIR signal can identify molecular changes in AD. Severe AD cases are characterized by increased involvement of NFTs and NPs in the cerebral cortex, which would be expected to further affect the extent of NIR scatter. The current study aims to quantify AD-related pathology for investigation into whether the extent of optical scattering is correlated with the severity of amyloid plaque load and NFT density in the temporal cortex. Quantification of these lesions was accomplished using immunohistochemistry (IHC) and stereological analyses. Preliminary results show that the severity of AD pathology detected via IHC can be correlated with measured parameters of an in vitro near-infrared signal. Future studies aim to further characterize the relationship between scattering intensity and pathological severity, as well as evaluate the in vivo potential of this technology in predicting the clinical outcome and cognitive status of individuals in different stages of AD.

Arterial LDL deposition is a key step in initiating atherosclerosis. Saturated fat (SAT)-enriched diets increase arterial LDL deposition, total and selective LDL-cholesterol uptakes, and arterial lipoprotein lipase (LpL). Because consumption of n-3 fatty acids (FA), such as EPA and DHA, potentially reduces the risk for cardiovascular disease (CVD), we investigated the mechanisms whereby dietary FA, metabolic syndrome and LpL interact to influence arterial lipid uptake in atherosclerosis. We hypothesized that specific FA, SAT versus n-3, alter the recruitment of different cell populations to the arterial wall and modulate arterial LpL levels and distribution, which in turn affects the development of atherosclerosis. To test these hypotheses, we carried out a series of dietary feeding studies in different mouse models to determine the effects of saturated versus n-3 FA on LDL-cholesterol delivery and arterial LpL levels. The data presented in this thesis demonstrate that high levels of saturated FA and insulin resistance contribute to accumulation of macrophages that secrete LpL and thus favor the development of atherosclerosis. Furthermore, deficiency of LpL in the arterial wall reduced aortic macrophage populations and macrophage infiltration. The reconstitution of macrophage expressing LpL in LpL knockout models led to increases in macrophage populations in the arterial wall. Macrophage-associated LpL may increase "anchoring" of LDL and macrophages. n-3 FA decrease the presence of inflammatory macrophages and LpL; hence are associated with less arterial cholesterol delivery, inflammation and atherosclerosis. In an atherosclerosis-prone mouse model (LDLR-/-), gradual replacements of SAT with n-3 ameliorates abnormal lipid profiles and atherosclerosis. Thus, n-3 FA decrease risk for CVD in part by decreasing arterial macrophage-associated LpL. Interacting factors, such as PPARβ/δ, likely play an important role in regulation of arterial-wall LpL levels in response to FA. Increased arterial Foxo1 expression can contribute to decreased PPARα levels in the group fed n-3 FA. The levels of GPIHBP1 in the arterial wall correlate with arterial macrophage number. This indicates the existence of other pathways important in mediating changes in LpL levels and arterial lipid deposition. These studies as described here defined 'novel' mechanisms underlying the potential of n-3 FA to decrease risk for CVD.

Obesity is on the rise, and its associated comorbidities and health care costs are tremendous. A contributing factor to chronic obesity is binge eating disorder (BED), which is prevalent in 20 to 30 percent of the morbidly obese population, but the distinction between obesity versus obesity with BED is still unclear. The present dissertation project investigated forty two adult men and women, thirteen obese + BED and twenty nine obese controls for multiple psycho-behavioral constructs (rigid dietary restraint, disinhibition, anxiety, and behavioral activation/behavioral inhibition). On a different day, following a 12-hour fast, the participants consumed a fixed liquid meal, and their brain function examined while images of high energy food (e.g. pizza and cakes), low energy food (e.g. cucumber and tomato) and control items (i.e. office supplies) presented to them on a screen. Using a whole brain analysis approach, functional brain activity in response to: 1/food versus nonfood, and 2/high energy food versus low energy food revealed eight brain areas significantly different between the groups: for 'food versus nonfood', activated were seven areas functionally involved in the integration of somatosensory experience with internal state, processing of sensations, cognitions, thoughts, and emotions, integration of sensory functions and memory, visual object recognition and motion, visual - somatosensory functions and associations, integration of emotional value with a sensory stimulus, mediation of motivation and expectancy for outcomes, and the integration of diverse sensory information and visuo-spatial cognition. . One area significantly differed between the groups in response to the comparison of 'high energy food versus low energy food'. This area is functionally involved in thought, cognition, movement, planning, and motor behaviors in response to emotions and drives Thus, in response to cues representing binge-triggers, obese + BED showed greater visual attention, emotional, motivational and reward processing, as well as motor planning of future actions and heightened somatosensory experience, compared with the obese group. Scores on the 'disinhibition' scale were significantly higher in the obese + BED group compared with the obese. Correlation between 'disinhibition' scores and brain activation results in each group showed significant differences between the groups in two brain areas: right anterior cingulate gyrus-Brodmann area #32, and the left postcentral gyrus. Scores on the Behavioral Activation Scale (reward drive) were significantly lower in the obese + BED group, but the correlations between brain activation and scores on this scale did not differ between the groups. To sum the results altogether, the obese + BED may be marked by hyperactive visual-attentional-emotional- and cognitive processing of cues representing binge-triggers, with heightened somatosensory response. The psycho-behavioral construct of 'disinhibition' highly characterizes BED, and its neurobiological substrates may include the right anterior cingulate cortex-Brodmann area #32 and left postcentral gyrus. Reduced reward responsiveness in obese + BED may reflect weak 'liking' response to food, but this behavioral construct and its' relationship to BED are still inconclusive. Future studies may use the results of this dissertation project to further investigate frequent binge eating in the absence of compensatory behaviors in the obese population.

Legionella pneumophila was first recognized as a cause of human pneumonia in 1976 . Since then, much has been learned about the microbiology, pathophysiology and epidemiology of this organism. The features which permit one strain but not another to invade human lung tissue and produce disease remain incompletely understood. This study e valuated several attributes of a virulent and an avirulent strain of L. pneumophila in an attempt to identify characteristics which would distinguish the two. Evaluation of a new medium, buffered egg yolk agar, showed that virulence was maintained after 26 passages, which was the same as the buffered charcoal yeast extract agar used for comparison. However, growth appeared earlier and was heavier on the charcoalcontaining medium. Morphologically, the avirulent strain produced greater numbers of filamentous forms and was found to be encapsulated more frequently. Treatment with polymixin B produced morphologic changes similar to those previously reported but failed to alter the virulence of either strain. No plasmids were found in either strain nor were consistent differences in protein content demonstrated using sodium dodecylsulfate polyacrylamide gel electrophoresis. Both strains reacted less intensely as cultures aged with a monoclonal but not a polyclonal antibody in a direct fluorescent antibody assay . This change was more pronounced when the virulent organism was tested. Chemotactic assays showed similar tendencies when human or guinea pig mononuclear cells were compared to two estuarine species (hogchoker and spot) and one freshwater species (golden shiner minnow) of fish. In vivo results were also similar when two of the three species of fish were tested, suggesting that either the spot or the minnow may be used in evaluation of certain characteristics of L. pneumophila. Organisms were isolated from apparently healthy fish up to 15 days after inoculation in some instances. This suggests that fish may be a possible additional environmental reservoir for Legionella pneumophila.

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Breast cancer is a leading cause of cancer death and in 2009, the American Cancer Society estimates that over 192,000 new cases of breast cancer will be diagnosed, and over 40,000 women will die from breast cancer. Estrogen (E2) is required for normal female development and reproduction, but long-term exposure is carcinogenic and considered a risk factor for breast cancer. Membrane ion channels are essential for cell proliferation and are suggested to have a role in cancer, especially potassium channels. In the present study, we investigate the effects of estrogen and the estrogen antagonist ICI182780 on G-protein inwardly rectifying potassium channels (GIRK) in estrogen responsive MCF-7 breast cancer cells. GIRK1 and GIRK2 specific channels are thought to play a major role in rapid channel activation. We found increases in GIRK1 and GIRK2 membrane protein levels in response to estrogen treatment, as well as increases in intracellular potassium concentrations and cellular proliferation. ICI182780 treatment increased GIRK1, GIRK2 and GIRK4 membrane protein levels but resulted in an initial decrease in intracellular potassium concentration and decreased cell proliferation. GIRK1 RNAi knockdown decreased estrogen receptor alpha protein levels and activation. In addition, estrogen treatment resulted in increased phosphorylation of specific members of GPCR and MAPK signaling pathways that have been shown to be responsive to GIRK1 knockdown. Using microarray analysis of nontreated and E2 treated MCF7 cells, we observed 489 differentially expressed genes (283 upregulated and 206 downregulated) that were comprised largely of transcription and cell cycle associated genes. This study identified several human cell cycle associated genes that are both responsive to E2 treatment and are functionally correlated with GIRKs. Five genes were selected for further analysis by real time PCR. Our data suggests that specific GIRK channel composition at the cell membrane may be stimulated by estrogen exposure or downstream targets of estrogen signaling and may contribute to increased cell proliferation in MCF-7 breast cancer cells. Taken together, these data add further support of GIRK involvement in cancer progression and identify some potential biological roles of GIRKs in cancer biology beyond the initilal findings of GIRK1 assciation in metastatic breast cancer.