http://smartech.gatech.edu/handle/1853/7940 Original work done by students in Georgia Tech's Interdisciplinary Bioengineering Graduate Degree Program Search the Channel search http://smartech.gatech.edu/simple-search http://smartech.gatech.edu/handle/1853/24775 Title: Bayesian based risk stratification of atrial fibrillation in coronary artery bypass graft patients <br/> <br/>Authors: Wiggins, Matthew Corbin <br/> <br/>Abstract: Roughly thirty percent of coronary artery bypass graft (CABG) patients develop atrial fibrillation (AF) in the five days following surgery, increasing the risk of stroke, prolonging hospital stay three to four days, and increasing the overall cost of the procedure. Current pharmacologic and nonpharmacologic means of AF prevention are suboptimal, and their side effects, expense, and inconvenience limit their widespread application. An accurate method for identifying patients at high risk for postoperative AF would allow these methods to be focused on the patients on which its utility would be highest. The main objective of this research was to develop a Bayesian network (BN) which could model/predict/assign risk of the occurrence of atrial fibrillation in CABG patients using retrospective data. A secondary objective was to develop an integrated framework for more advanced methods of feature selection and fusion for medical classification/prediction. We determined that the naïve Bayesian network classifier used with features selected by a genetic algorithm is a better classifier to use, given our cohort. The naïve BN allows for reasonable prediction despite being presented with patients with missing data points as might occur in the hospital. This classifier achieves a sensitivity of 0.63 and a specificity of 0.73 with an AUC of 0.74. Furthermore, this system is based on probabilities that are well understood and easily incorporated into a clinical environment. These probabilities can be altered based on the cardiologists prior knowledge through Bayesian statistics, allowing for online sensitivity analysis by doctors, to perceive the best treatment options. Contributions of this research include: - An accurate, physician-friendly, postoperative AF risk stratification system that performs even under missing data conditions, while outperforming the state of the art system, - A thorough analysis of previously examined and novel pre- and postoperative clinical and ECG features for postoperative AF risk stratification, - A new methodology for genetic algorithm-built traditional Bayesian network classifiers allowing dynamic structure through novel chromosome, operator, and fitness definitions, and - An integrated methodology for inclusion of doctor s expert knowledge into a probabilistic diagnosis support system. http://smartech.gatech.edu/handle/1853/24711 Title: Coated Microneedles and Microdermabrasion for Transdermal Delivery <br/> <br/>Authors: Gill, Harvinder Singh <br/> <br/>Abstract: The major hurdle in the development of transdermal route as a versatile drug delivery method is the formidable transport barrier provided by the stratum corneum. Despite decades of research to overcome the stratum corneum barrier, limited success has been achieved. The objectives of this research were to develop and characterize two different strategies to overcome the stratum corneum barrier for transdermal delivery of biopharmaceuticals and vaccines. In the first strategy, coated microneedles (sharp-tipped, micron-sized structures) were developed to enable delivery of drugs directly into the skin by bypassing the stratum corneum barrier. In the second strategy, instead of bypassing the barrier, microdermabrasion was used to selectively abrade stratum corneum with sharp microparticles for topical drug application. Coated microneedles For developing painless microneedles, the first detailed study was performed to characterize the effect of microneedle geometry on pain caused by microneedle insertions in human volunteers. This study demonstrated that microneedles are significantly less painful than a 26-gage hypodermic needle and that decreasing microneedle length and numbers reduces pain. Next, the first in-depth study of microneedle coating methods and formulations was performed to (i) develop a novel micron-scale dip-coating process, (ii) test the breadth of compounds that can be coated onto microneedles, and (iii) develop a rational basis to design novel coating formulations based on the physics of dip-coating. Finally, a plasmid DNA-vaccine was coated onto microneedles to immunize mice, to provide the first evidence that microneedle-based skin immunization can generate a robust in vivo antigen-specific cytotoxic-T-lymphocyte response using similar, or lower, DNA doses on microneedles as when using the gene gun or intramuscular injection. Microdermabrasion We demonstrated for the first time that microdermabrasion in monkeys and humans can selectively, yet completely remove the stratum corneum layer. Using a mobile mode of microdermabrasion, an increase in the number of treatment passes led to greater tissue removal. Furthermore, topical application of Modified Vaccinia Ankara virus after microdermabrasion induced virus-specific antibodies in monkeys. In conclusion, both coated microneedles and microdermabrasion were developed to enable delivery of biomolecules into the skin, indicating their potential for transdermal delivery of a wide range of biopharmaceuticals and vaccines. http://smartech.gatech.edu/handle/1853/24684 Title: Microstimulation and Multicellular Analysis: A Neural Interfacing System for Spatiotemporal Stimulation <br/> <br/>Authors: Ross, James David <br/> <br/>Abstract: Willfully controlling the focus of an extracellular stimulus remains a significant challenge in the development of neural prosthetics and therapeutic devices. In part, this challenge is due to the vast set of complex interactions between the electric fields induced by the microelectrodes and the complex morphologies and dynamics of the neural tissue. Overcoming such issues to produce methodologies for targeted neural stimulation requires a system that is capable of (1) delivering precise, localized stimuli a function of the stimulating electrodes and (2) recording the locations and magnitudes of the resulting evoked responses a function of the cell geometry and membrane dynamics. In order to improve stimulus delivery, we developed microfabrication technologies that could specify the electrode geometry and electrical properties. Specifically, we developed a closed-loop electroplating strategy to monitor and control the morphology of surface coatings during deposition, and we implemented pulse-plating techniques as a means to produce robust, resilient microelectrodes that could withstand rigorous handling and harsh environments. In order to evaluate the responses evoked by these stimulating electrodes, we developed microscopy techniques and signal processing algorithms that could automatically identify and evaluate the electrical response of each individual neuron. Finally, by applying this simultaneous stimulation and optical recording system to the study of dissociated cortical cultures in multielectode arrays, we could evaluate the efficacy of excitatory and inhibitory waveforms. Although we found that the proximity of the electrode is a poor predictor of individual neural excitation thresholds, we have shown that it is possible to use inhibitory waveforms to globally reduce excitability in the vicinity of the electrode. Thus, the developed system was able to provide very high resolution insight into the complex set of interactions between the stimulating electrodes and populations of individual neurons. http://smartech.gatech.edu/handle/1853/22702 Title: Thick brain slice cultures and a custom-fabricated multiphoton imaging system: progress towards development of a 3D hybrot model <br/> <br/>Authors: Rambani, Komal <br/> <br/>Abstract: Development of a three dimensional (3D) HYBROT model with targeted in vivo like intact cellular circuitry in thick brain slices for multi-site stimulation and recording will provide a useful in vitro model to study neuronal dynamics at network level. In order to make this in vitro model feasible, we need to develop several associated technologies. These technologies include development of a thick organotypic brain slice culturing method, a three dimensional (3D) micro-fluidic multielectrode Neural Interface system (µNIS) and the associated electronic interfaces for stimulation and recording of/from tissue, development of targeted stimulation patterns for closed-loop interaction with a robotic body, and a deep-tissue non-invasive imaging system. To make progress towards this goal, I undertook two projects: (i) to develop a method to culture thick organotypic brain slices, and (ii) construct a multiphoton imaging system that allows long-term and deep-tissue imaging of two dimensional and three dimensional cultures. Organotypic brain slices preserve cytoarchitecture of the brain. Therefore, they make more a realistic reduced model for various network level investigations. However, current culturing methods are not successful for culturing thick brain slices due to limited supply of nutrients and oxygen to inner layers of the culture. We developed a forced-convection based perfusion method to culture viable 700µm thick brain slices. Multiphoton microscopy is ideal for imaging living 2D or 3D cultures at submicron resolution. We successfully fabricated a custom-designed high efficiency multiphoton microscope that has the desired flexibility to perform experiments using multiple technologies simultaneously. This microscope was used successfully for 3D and time-lapse imaging. Together these projects have contributed towards the progress of development of a 3D HYBROT. ----- 3D Hybrot: A hybrid system of a brain slice culture embodied with a robotic body.