Tracer based MRI perfusion measurements is a clinically useful tool to assess regional distributions of tissue blood flow and volume. The method may be based on any of the three relaxation mechanisms T1, T1 and T2*, the latter denoted DSC-MRI being the most common. The primary aim of this work was to study the feasibility of obtaining quantitative estimates using these methods. 1) Feasibility of DSC-MRI for kidneys using an iron oxide based contrast agent and the influence of secondary relaxation effects on the results, part of a clinical phase II trial: The method proved feasible and the underestimation induced by secondary relaxation can be corrected for by using a double echo sequence. 2) Influence of blood flow rate on risk factors for developing cerebral ischemia during cardio pulmonary bypass, measurements in pig with gadolinium based DSC-MRI: The results indicated an ischemic threshold level at a blood flow rate of approximately 6 ml/kg/min. 3) The ability of gadolinium based DSC-MRI to detect changes in global blood flow, experimental measurements in pig and numerical simulations: The results support that DSC-MRI can discriminate between global flow levels in the same subject given that all other parameters are kept constant. The results also indicate that calculated perfusion values are highly sensitive to the arterial deconvolution procedure. 4) Influence of differences in blood/tissue relaxivity and secondary relaxation for a gadolinium based contrast agent, measurements in pig and numerical simulations: The blood/tissue relaxivity ratio is not unity and the situation is complicated by secondary relaxation effects. Deconvolution regularization appears to partly counteract the overestimation induced by difference in blood/tissue relaxivity for DSC-MRI. In summary, the fundamental assumption of equal blood and tissue relaxivity is experimentally shown to be invalid and the influence of this discrepancy is substantial. Several factors contribute to measurement errors, a combination of these factors can incidentally lead to additive errors or error cancellation based on a variety of experimental and analysis conditions. Given that the differences in blood/tissue relaxivity cannot readily be accounted for in a clinical setting, absolute perfusion quantification by tracer based MRI remains challenging if not impossible.

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Abstract This thesis proposes to scrutinize and analyze the contrasts that abound in Sarah Fielding¡¦s novel, The Adventures of David Simple. Contrasts pervade the novel because they exist in the themes, between the paired protagonists, and between part one and part two. The hero, David Simple, is characterized by his extreme benevolence that rarely exists among us. He seems uncommon by prioritizing friendship over anything else. He is an extremist in point of godliness, innocence, spirituality, sentimentality, and benevolence. With like-minded friends, David sets up a utopian community that grows from four to eleven members, but at last only two female members survive. The annihilation of David¡¦s secluded utopia brings about the enigma that good seems to go unrewarded. This thesis attempts to draw on feudalism and capitalism to explain the decline of David¡¦s utopia by analyzing the patron-client relationship that evolves between David Simple and Mr. Orgueil. Chapter one gives an overview of this novel, mentions the novel¡¦s reception by major critics, and introduces each chapter that follows. Chapter two delineates the thematic structure of the novel. Major themes are Christian spirit, friendship, and envy. Sub-themes are composed of thematic contrasts between innocence and sophistication, spirituality and materialism, sentimentality and rationality, and benevolence and malevolence. Chapter three analyzes parallels in the contrasts between Cynthia and Mrs. Orgueil in order to prove my hypothesis that Cynthia equals Mrs. Orgueil in temperament, in intelligence, and in persistence. Chapter four explores the contrasting notions of happiness between David and Mr. Orgueil. These contrasts are those between godliness and worldliness, innocence and sophistication, spirituality and materialism, sentimentality and rationality, and benevolence and malevolence. This analysis of contrasting notions of happiness will lead me to conclude that both David and Mr. Orgueil attain transient and earthly happiness when they are alive, but only David attains eternal and heavenly happiness at the end of the novel. To sum up, the threshold of heavenly happiness is death. The prerequisite for an approach to that threshold of permanent happiness is benevolence, which avails to transcend sublunary happiness.

Medical ultrasound imaging is ubiquitous in clinics due to its safety, low cost, portability, and imaging depth. The development of technologies to assist ultrasound in the diagnosis of diseases thus have a potentially broad clinical impact. More recently, photoacoustics has emerged as a complementary, high contrast modality for imaging optical absorption. Injectable dyes and nanoparticles locally amplify ultrasound and photoacoustic signal, helping to identify disease markers and track its progression. We have constructed a dual ultrasound and photoacoustic contrast agent that can be activated using an external optical trigger. In response to pulsed laser irradiation, the particle undergoes a liquid to gas phase change, or vaporization, which emits a strong acoustic wave and results in an echogenic microbubble, simultaneously enhancing contrast for both modalities. We designed and developed several iterations of particles, altering parameters to optimize biocompatibility, cost, and image contrast enhancement, and we then characterized key traits of the particles. Next, we imaged the contrast agents in phantom, ex vivo, and in vivo models to validate the image enhancement, developing image process algorithms to maximize image quality. These optically triggered contrast agents are a valuable tool for minimally invasive, highly specific, early identification of cancer. / text

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This thesis presents the development of a novel, targeted, lipid-based, microbubble ultrasound contrast agent (UCA) for assessment of coronary heart disease (CHD) with high frequency intravascular ultrasound (IVUS). The targeting mechanisms assessed for microbubble attachment include a streptavidin-biotin mechanism, electrostatic mechanism and antibody targeting. The microbubble has been optimized for use with 40MHz IVUS through an investigation into the effect of various production methods on the echogenicity of the agent. Echogenicity has been assessed from quantification of the RF data and determination of the mean ultrasound backscatter. Agitation was found to be the optimal method of production resulting in a 3.94(±1.14)dB increase in the mean backscatter. The stability of the agent has also been assessed over time and optimal storage of the agent determined. A novel flow chamber has been developed for assessment of microbubble detachment under very high WSS. The flow chamber has been calibrated to 50Pa wall shear stress (WSS) using laser Doppler anemometry (LDA). Higher WSS was achieved through the use of higher viscosity fluids. The streptavidin-biotin bond has been assessed within the flow chamber and was found to be 75 times stronger than an electrostatic control. Antibody attachment to the microbubbles via a streptavidin-biotin bridge has been optimised with 91.20(±0.02)% of the microbubbles having antibodies attached. A flow system has also been developed for assessment of microbubble attachment to cells under very low WSS. Microbubbles have been successfully targeted to SK-Hep-1 cells using acoustic radiation force. In addition attachment of the microbubbles to SK-Hep-1 cells has been observed under 0.03Pa WSS in the Ibidi μ-slides.

Early visual processing is subject to binocular interactions because cells in striate cortex show binocular responses and ocular dominance (Hubel & Weisel, 1968). The work presented in this thesis suggests that these physiological interactions can be revealed in psychophysical experiments using normal human observers. In the region corresponding to the blind spot, where binocular interactions differ from areas of the visual field which are represented by two eyes, monocular contrast sensitivity is increased. This finding can be partially explained by an absence of normal binocular interactions in this location (Chapter 2). A hemianopic patient was studied in an attempt to discover whether the effect in normal observers was mediated by either a mechanism in striate cortex or via a subcortical pathway. However, the results were unable to distinguish between these two explanations (Chapter 3).In a visual search task, no difference in reaction time was observed for targets presented to the region corresponding to the blind spot compared with targets presented to adjacent binocularly represented areas of the visual field. Since performance was unaffected by the monocularity of the region corresponding to the blind, pop-out for orientation may be mediated beyond striate cortex where cells are binocularly balanced (Chapter 5). Further support for this contention was provided by studies of orientation pop-out in central vision which found that dichoptic presentation of stimuli did not affect the degree of pop-out obtained and that in general, visual search for a target based solely on eye of origin is impossible (Chapter 6). However, a task that measured orientation difference sensitivity more directly than the search experiments, found that thresholds were higher for dichoptically presented stimuli. This suggests the involvement of neurons that receive a weighted input from each eye. A model of orientation difference coding can account for the results by assuming that the range of inhibition across which orientation differences are coded is narrower for dichoptic stimuli leading to a greater resolvable orientation difference (Chapter 7).

Thesis (M.S.)--Virginia Polytechnic Institute and State University, 1992. / Vita. Abstract. Includes bibliographical references (leaves 46-51). Also available via the Internet.

Thesis (doctoral)--University of Lund, 1981. / Includes bibliographical references.

Thesis (Ph. D.)--University of Hong Kong, 2005. / Title proper from title frame. Also available in printed format.