PhD, University of Cincinnati, 2001, Engineering : Nuclear and Radiological Engineering

The Monte Carlo code MCNP4B was used to investigate the radiation dose distribution in several areas of intravascular brachytherapy that would be very difficult or impossible to investigate experimentally or analytically. A model for a liquid-filled balloon catheter was developed and validated by comparing the results of Monte Carlo simulations with experimental measurements made in a tissue equivalent phantom. The dose distribution in the coronary vessel wall from a liquid-filled balloon catheter containing the following radioisotopes was examined: Y-90, Re-188, P-32, Re-186, Sm-153, In-111, and Tc-99m. At 0.5 mm from the vessel surface, the beta emitters deliver a higher dose per unit cumulated activity than the gamma emitters. The gamma emitters, however, deliver a dose that is more uniform throughout the vessel wall. Eight sizes of balloon catheters were modeled and the effect of balloon catheter size on the radiation dose distribution was examined. Effects that perturb the radiation dose distribution for a liquid-filled balloon catheter were investigated. These perturbing effects were: (1) an air bubble within the balloon catheter, (2) contrast media within the balloon catheter, (3) a Palmaz-Schatz stent surrounding the balloon catheter, and (4) the deflation of the balloon catheter. The radiation dose distribution produced from a P-32 coated Palmaz-Schatz stent was investigated by developing a model with P-32 deposited on the stent surface to a depth of one micron, and calculating the dose delivered to the coronary vessel wall. High dose fluctuations were observed near the surface of the stent, but these fluctuations leveled off at depth in the vessel wall. The radiation dose distribution for the case of direct injection of radioisotopes into the coronary vessel wall using the Infiltrator angioplasty balloon catheter (IABC) was also investigated. The source distribution produced by the IABC was modeled for two configurations within the vessel wall: (1) uniform (open full item for complete abstract)

Committee: Dr. Henry Spitz (Advisor) Subjects: Engineering, Nuclear

MS, University of Cincinnati, 2005, Engineering : Mechanical Engineering

A major consequence of stent implantation is restenosis that occurs due to neointimal formation. Recent evidence suggests that there are several factors such as geometry and size of vessel, and stent design that alters hemodynamic parameters, including local wall shear stress distributions, which influence the progression of restenosis. The present three-dimensional analysis of developing pulsatile flow in a deployed coronary stent quantifies hemodynamic parameters and illustrates the changes in local wall shear stress distributions and their impact on restenosis. The present model mimics the worst possible scenario where the stent is placed at the entrance region of a branched coronary artery. The present results indicate that the immediate downstream of strut intersections are areas highly susceptible to restenosis whereas a high shear stress at the strut intersection may cause platelet activation and free emboli formation.

Committee: Dr. Rupak Banerjee (Advisor) Subjects:

Doctor of Philosophy, The Ohio State University, 2008, Biomedical Engineering

A novel synthetic analog of curcumin, the active ingredient in the commonly used spice turmeric, was recently synthesized. The drug shows promise, both as an anti-proliferative agent against restenosis in bare-metal stents and as a cytotoxin against ovarian cancer, following direct administration. However, a major limitation is its insolubility in aqueous media, and limited solubility in most organic solvents. The inability to safely deliver this drug in a soluble form presents a major challenge to further in vivo validation and eventual clinical applicability. Poly(lactic-co-glycolic acid) (PLGA) is a well-known biodegradable polymer that is widely used as a sustained-release vehicle for various drugs. We hypothesized that the controlled release of the drug from a PLGA matrix would provide an alternative route for its administration in vivo. To improve dosage while limiting systemic cytotoxicity, localized release from disease-specific constructs was proposed, in which the mode of delivery is adapted to suit the different pathologies presented by the disease in vivo. Hence, drug-eluting films, PLGA-coated drug-eluting stents and drug-encapsulating nanoparticles were developed for evaluation in proliferative cardiovascular disease and ovarian cancer. Fourier transform infrared spectroscopy and electron paramagnetic resonance spectroscopy were used for physical characterization of the biodegradable constructs. Additionally, dynamic light scattering and transmission electron microscopy were used for size characterization of the drug-encapsulating nanoparticles. Viability assays established the dose- and time-dependent anti-proliferative and cytotoxic effects of the biodegradable constructs. Western blot analysis on drug-eluting PLGA films and PLGA-coated PET matrices validated that the cellular mechanism of the action of the drug was conserved between direct administration and sustained release. TEM studies confirmed the internalization of the nanoparticles in vitro. (open full item for complete abstract)

Committee: Periannan Kuppusamy PhD (Advisor); Mark Ruegsegger PhD (Committee Member); Stephen Lee PhD (Committee Member) Subjects: Biomedical Research

Master of Science, The Ohio State University, 2008, Pathology

Percutaneous transluminal coronary angioplasty (PTCA) has greatly benefited patients with occluded coronary arteries, but its benefits have been undermined by a high incidence of restenosis. The introduction of coronary stents has significantly improved the short and long term outcome but restenosis still occurs in approximately 15-30 % of patients within 6 months. Research efforts are now being directed toward combination stenting and drug delivery. Among the therapeutic targets being pursued are agents which can impede smooth muscle cell (SMC) migration and proliferation as these processes are critical components of restenosis injury. We propose that inhibiting the conversion of ribonucleotides to deoxyribonucleotides will impede cell proliferation and as such limit the degree of restenosis. Therefore, we tested whether the potent Ribonucleotide Reductase (RR) inhibitors, Didox and Imidate, can limit the neointimal proliferation associated with restenosis using rat, rabbit and porcine models of vascular injury. Results demonstrated that systemic administration of the RR inhibitors Didox, Imidate and Hydroxyurea significantly reduced intimal thickening, intima/media ratio and lumen loss. Results from cell proliferation studies suggest that the mechanism of protection is inhibition of SMC proliferation and decreased number of circulating leukocytes. These results suggest that inhibition of Ribonucleotide Reductase may provide a potent strategy to prevent post PTCA restenosis.

Committee: James Waldman Phd (Advisor); Arturo Cardounel Phd (Committee Member); Guanglong He Phd (Committee Member) Subjects: Pathology