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- Title
- A KINETIC MODEL TO ESTIMATE VASCULAR PERMEABILITY FROM FLUORESCEIN VIDEOANGIOGRAPHY DATA
- Creator
- Hu, Shaoxian
- Date
- 2017, 2017-05
- Description
-
Diabetic retinopathy (DR) is a disease affecting the tissue of the retina through hemodynamics and vascular damage that is a side effect of...
Show moreDiabetic retinopathy (DR) is a disease affecting the tissue of the retina through hemodynamics and vascular damage that is a side effect of hyperglycemia. As such, markers of hemodynamic and vascular irregularity have been proposed as potential early indicators of the disease. However, conventional approaches to estimate these conditions are not sensitive enough, leading to indications that are too late, appearing only after irreversible vision problems have occurred. Indicator-dye-dilution tracer kinetic modeling is a decades-old methodology that can be used to quantify blood flow and vascular permeability based on the kinetics of a rapidly injected blood pool imaging agent. The methodology is able to track sensitive hemodynamic changes in stroke and heart disease patients, yet it has never been applied to blood flow and vascular permeability mapping of the retina. The purpose of my Master’s thesis was to adapt those tracer kinetic methods to fluorescein retinal videoangiography data collected in human to map both blood flow and vascular permeability so that in future work, changes in these parameters can be quantified at varying stages of the development of DR. Studies were carried out on simulated data, healthy and diabetic rats, and healthy and diabetic humans. While a robust validation of measures of blood flow and vascular permeability are still required, this first-of-its-kind study exposed many unique complications in applying the kinetic models to human fluorescein videoangiography data. Specifically, eye motion must be accounted for, both detector and fluorescein fluorescence quenching signal saturation must be avoided, and standard use of automatic gain control of imaging exposure should not be used (though corrections were developed for this); rather, data should be collected at a stable exposure throughout a measurement. Solutions were developed for all of these complications that were tested in rat models (optimal data collection in humans is ongoing). In rat study, average vascular permeability in the rat measured by the “extraction fraction”, the extraction fraction in control subject (n=3) 9.4e-4±1.3e-3, is lower than STZ-diabetic subjects (n=3) 5.5-2±5.17e-2 and VEGF group (n=3) 7.6e-2±5.1e-2. In healthy human volunteers, retinal extraction fraction was measured to be 5.0e-5 ± 6.1e-5 (n=2), whereas this was found to be elevated to 1.2e-3 ± 1.0e-3 in patients for diagnosed DR (n=3). These early results clearly demonstrated a statistically significant elevation in vascular permeability in all diabetic groups compared to controls (p<0.05). The human study was carried out on advanced cases of patients who were known to have DR as a test case; however, the sensitivity of the approaches is demonstrated by the eatly changes in extraction fraction observed at only 48 h after the onset of hyperglycemia in the rat experiments (well before irreversible damage to the retina had occurred). These results are promising for the adaptation of our modified kinetic modeling approach to measure hemodynamics and vascular permeability changes during the early onset of DR when preventative therapies could be most effective.
M.S. in Biomedical Engineering, May 2017
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- Title
- THERMAL INACTIVATION OF SALMONELLA AGONA IN LOW-MOISTURE FOOD SYSTEMS AS INFLUENCED BY WATER ACTIVITY
- Creator
- Jin, Yuqiao
- Date
- 2016, 2016-07
- Description
-
Salmonella can survive in low-moisture, high-protein and high-fat foods for several years. Despite nationwide recalls for Salmonella in low...
Show moreSalmonella can survive in low-moisture, high-protein and high-fat foods for several years. Despite nationwide recalls for Salmonella in low-moisture products, information on survival of Salmonella during high-protein and high-fat food processing is limited. This project evaluated Salmonella enterica serovar Agona 447967 thermal inactivation kinetics in a high-protein and a high-fat matrix using a defined matrix composition, varying water activities and process conditions. A high-protein matrix, composed of 60:6:25 weight ratio of flour: oil: protein, and a high-fat matrix, composed of 60:25:6 weight ratio of flour: oil: protein was studied. Each matrix was inoculated with Salmonella enterica serovar Agona 447967 at activities of 0.5, and 0.9. Samples were packed in aluminum test cells and heat treated over a range of temperatures and time intervals. Survival of Salmonella Agona was detected on trypticase soy agar with 0.6% yeast extract. The average z-values for the high-protein matrix at the water activity (aw) of 0.5 and 0.9 were 9.01ºC, and 7.51ºC, respectively. The average z-values for the high-fat matrix was 11.91ºC at aw 0.5, and 7.08ºC at aw 0.9. Results showed that the z-value at aw 0.5 was significantly different from the z-value at aw 0.9 (p < 0.05) in both the highprotein and high-fat matrices. Critical process factors associated with pathogen destruction were identified during thermal treatments in this project. Results indicated that a correlation existed between temperature and water activity and must be accounted for when predicating inactivation of Salmonella enterica in these model matrices under dynamic process conditions.
M.S. in Food Process Engineering, July 2016
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