This work reports an investigation in which localization-receiver-operating-characteristics (LROC) studies employing hybrid images were used. Hybrid images are normal Ga-67 scans modified by the addition of Monte Carlo simulated lesions. After determining a target image contrast using human observers, we conduct pilot LROC studies to determine the optimal parameters for the reconstruction methods. Then we perform a human observer LROC comparison study using the optimal parameters obtained in the pilot studies to determine the relative impact on detection accuracy of the various corrections introduced. We study the effectiveness of attenuation compensation, scatter compensation, and detector resolution compensation strategies used with the RBI reconstruction method and compare it to FBP reconstruction. The relative ranking of the test strategies agreed in most cases with those of previous studies that employed simulated projections of digital anthropomorphic phantoms, thus confirming the findings of those studies. In this work, we specifically focus on the lesion-detection performance of two channelized models, the channelized non-prewhitening observer and the channelized Hotelling observer. They are used in the context of generating performance curves for parameter optimization tasks. We chose channelized models, as they are based on the phenomenon of frequency-selective-contrast-sensitivity exhibited by the human visual system and demonstrated by various psycho-physical studies. Working with these models, however, requires various amounts of knowledge regarding the lesion-free background data, which in the context of hybrid data, is either not known, or difficult to estimate. Various methods are explored that approximate this background data in a manner that is useful for the model observers. We specifically explore boot-strap methods, K-neighbor methods and the wavelets linear enhancement method to generate this approximation. Of the various methods studied, the wavelet method was found to produce the best results. We perform statistical tests to assess the significance of the performance curves obtained. Wavelets can also be used for feature-selective non-linear contrast enhancement of images. This may be especially useful for lesion-detection tasks. The image sets used in our studies are filtered on reconstruction using a 3-D Gaussian filter. This reduces reconstruction noise and enhances lesion definition by bringing in counts from neighboring planes into the plane of interest. 3-D low-pass filtering, however, can introduce considerable masking of the lesion due to blurring of neighboring anatomical structures. Non-linear enhancement using wavelets can undo this blurring effect. This is possible since wavelets employ a multi-scale decomposition scheme. Using this methodology, it is possible to enhance the features of interest while de-emphasizing others. We explore the possibility of lesion contrast enhancement using wavelet filters and conduct human observer LROC studies to assess its impact on detection accuracy. We then propose an internal noise mechanism for the model observer and study its impact using the CNPW model observer. Within the framework of model observers, an internal noise mechanism has been suggested to match the models performance to that of human performance. This is because, model observers typically out-perform humans in detection tasks, as, humans face uncertainty due to choice in the detection process which is absent in a noiseless model. A noise model can simulate this choice and in this work we implement it by chaining a probability prior, that encapsulates the models degree of uncertainty, to a Bernoulli random event generator, that implements the models choice. To achieve this, we define a data-dependent test-statistic/representative variable which is then used to sample the prior. Various methods of defining the parameters of the prior are explored and importantly, methods that use the test variable’s estimated distribution. We see that this leads to different shades of noise-models, beginning from the passive model, that merely degrades the performance curves leaving the dynamics intact, to more active ones, that modify the dynamics as well. A theoretical expression is also derived for the average amount of noise that the mechanism introduces in the observer. Finally, we show that the inclusion of a noise mechanism can yield mean performance curves with greater statistical significance provided we simulate multiple noise instances. (Abstract shortened by UMI.)

Absorption spectra of molecules encode structural details of the local electrostatic environment via coupling of the local electric field with charge redistribution through the molecule upon optical excitation. Electroabsorption spectroscopy, also known as Stark spectroscopy, provides a simple method for determining dependence of electronic transition energies on the local field by measuring and interpreting perturbations to the absorption spectrum due to a well-characterized external electric field. In this dissertation, electroabsorption spectroscopy has been utilized, first, to estimate the second-harmonic generation cross section of the intracellular signaling metabolite lumichrome, second, to measure optical band gap tuning of the molecular electronic component perylene diimide by an external electric field, and, third, to exploit optical transition energies of the ubiquitous enzyme cofactor flavin to measure flavoenzyme active site electric fields. Experimental measurements are complemented by time-dependent density functional theory calculations to interpret experimental results and localize charge redistribution within the molecular frame.Lumichrome is a photodegradation product and catabolite of flavin cofactors that additionally serves as a signaling molecule for plants and bacteria. As a mediator of bacterial quorum sensing, lumichrome is transported across bacterial membranes. While transiting bacterial membranes, the average orientation of the trafficked lumichrome may be sufficiently anisotropic to allow detection by second-harmonic generation spectroscopy, the magnitude of which is a function of charge redistribution upon optical excitation and may be estimated by Stark spectroscopy. Using Stark spectroscopy we have estimated lumichrome’s second harmonic generation cross-section to be approximately 80% that of flavin adenine dinucleotide, which has previously successfully been used as a second-harmonic generation probe. Perylene diimide is an n-type organic semiconductor that is widely used in organic photovoltaics, light emitting diodes, and other molecular opto-electronics. Electric fields within electronic devices utilizing monomeric and / or aggregated perylene diimide alter the band structure of the chromophore, possibly providing a tunable parameter for the improvement of these devices. Stark spectroscopy has been used to measure tuning of the optical bandgap of monomeric perylene diimide by an external electric field. The centrosymmetry of the molecule causes the first optical excitation's difference permanent dipole moment to approach zero. The change in polarizability following excitation is also modest, with the trace of the difference polarizability equal to 42 cubic angstroms and the component of the difference polarizability along the transition dipole moment equal to 29 cubic angstroms. Electric fields within molecular electronics are on the order of 1 MV/cm. Such an electric field would redshift the first optical excitation energy of monomeric perylene diimide by 16.25 wavenumbers, which is less than 0.1% of the transition energy (18500 wavenumbers). Flavin adenine dinucleotide and flavin mononucleotide are ubiquitous enzymatic cofactors mediating catalytic transfer of one or two electrons. Flavin cofactors are ubiquitous because of their versatile and tunable reactivity. For example, the two-electron reduction potential of flavin can be continuously tuned through a range of over 400 mV by differing interactions with flavoenzyme active site residues. We have utilized Stark spectroscopy to measure charge redistribution upon optical excitation for the first two excited states of oxidized flavin in the aprotic, non-polar solvent toluene, with and without a tridentate hydrogen-bonding ligand. In comparing this data with previously reported measurements, we conclude that charge redistribution is independent of solvent polarity. As such, flavin’s optical transition energies may be used to indirectly measure flavoenzyme active site electric fields directly from the perspective of the electrostatically-tuned flavin cofactor, enhancing our understanding of flavin-dependent biochemistry. / Chemistry

OBJECTIVE: Pro-resolving mediators (SPM) are the oxidative products of omega-3 fatty acids which help maintain and control the balance of inflammation and its resolution in the body. Extensive research has shown SPMs can act both chronically and acutely to decrease excessive inflammation and protect against excessive inflammation in cardiovascular disease (atherosclerosis, myocardial infarction, and heart failure). Their powerful effects to resolve inflammation suggest that they will be natural therapeutics for Coronavirus infections and ischemic brain injuries. To optimize mixtures and doses for the fastest and most effective acute delivery of the water-insoluble acylglycerol omega-3 fatty acid (DHA and EPA), we studied fluidity and structural organization in phospholipid membranes by 13C NMR Spectroscopy. METHODS: As models for delivery to cells, acylglycerol omega-3 fatty acids were mixed in increasing proportions with phospholipids and sonicated to make small unilamellar vesicles (SUV) for NMR Spectroscopy. RESULTS: Spectral analysis showed that low proportions (< 5-10 mol %) of omega-3 diglycerides incorporated into the bilayer structure of the phospholipid vesicles without disruption of the bilayer or phase separation. With increases (up to 40mol%) the spectra exhibited separation of the carbonyl peaks and line broadening. With omega-3 triglycerides the narrow aliphatic, glycerol, and carbonyl regions did not exhibit line broadening and were very similar for both omega-3 fatty (DHA or EPA). The olefinic region has the distinct peaks that differentiates one omega-3 fatty acid from the other. Triglyceride mole percentages less than 20mol% that are incorporated into PC emulsions with omega-3 fatty acids do not give detectable signals but at 40mol% we see line broadening of the PC carbonyls. CONCLUSION: At low concentrations of diglycerides with omega-3 fatty acids the vesicle carbonyls were essentially unaffected but at relatively high concentrations they incorporated into the phospholipid vesicles and changed the structural organization at the aqueous interface. In triglycerides with omega-3 fatty acids there was a complete assignment of numerous olefinic peaks, which remained very narrow at all proportions. Comparison of EPA and DHA distinguished the two FA, which will make it possible to quantify whether EPA enters cells more readily, as has been argued because they appear to have better cardiovascular therapeutic effects than DHA in some clinical studies. Acute delivery is feasible with SUVs, but future studies should focus on emulsions with a large triglycerides omega-3 fatty acid core with a greater abundance of triglycerides relative to phospholipid to deliver much larger doses of DHA and EPA.

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