archives@tulane.edu / Hepatocellular carcinoma is an intractable cancer with a high mortality rate. Transarterial chemoembolization, a non-curative method, is the first line therapy for intermediate stage patients. This effectively extends patient survival but requires a complicated intraarterial catheterization procedure and is poorly suited to repeated administration. Gas embolization has been proposed as a fast, easily administered, more spatially selective, and less invasive alternative. This process involves generating emboli in situ using acoustic droplet vaporization, the noninvasive focused ultrasound-mediated conversion of intravenously administered perfluorocarbon microdroplets into microbubbles. The work presented in this dissertation provides the first evidence of the feasibility and efficacy of gas embolization in vivo. Following confirmation of the cessation of tumor growth after treatment in a preliminary study, two additional preclinical studies were conducted. Varying treatment parameters and the use of systemic chemotherapy alongside gas embolization resulted in consistent, substantial tumor regression and a suppression of tumor recurrence following the cessation of treatment. Subsequent steps toward optimizing the treatment method, primarily intended to mitigate off-target tissue damage and to maximize the uniformity of treatment coverage across a lesion, involved the implementation of two specialized imaging modes for tumor detection and treatment planning and the development of an ultrasound-guided treatment method. Finally, retention of the lipid droplet shell upon vaporization was investigated in the context of selective targeting for localized drug delivery. The dissertation closes with a discussion of the implications of the presented work and proposed future studies. / 1 / Jonah Harmon

An intracranial aneurysm can be a serious, life-threatening condition which may go undetected until the aneurysm ruptures causing hemorrhaging within the brain. The typical treatment method for large aneurysms is by embolization using platinum coils. However, in about 15% of the cases treated by platinum coils, the aneurysm eventually re-opens. The solution to the problem of aneurysm recurrence may be to develop more bio-active materials, including certain polymers, to use as coil implants. In this research, a shape memory polymer (SMP) was investigated as a potential candidate for aneurysm coils. The benefit of a shape memory polymer is that a small diameter fiber can be fed through a micro-catheter and then change its shape into a three-dimensional configuration when heated to body temperature. The SMP was tested to determine its thermo-mechanical properties and the strength of the shape recovery force. In addition, composite specimens containing tantalum filler were produced and tested to determine the mechanical effect of adding this radio-opaque metal. Thermo-mechanical testing showed that the material exhibited a shape recovery force a few degrees above Tg. The effects of the metal filler were small and included depression of Tg and recovery force. SMP coils deployed inside a simulated aneurysm model demonstrated that typical hemodynamic forces would not hinder the shape recovery process. The x-ray absorption capability the tantalum-filled material was characterized using x-ray diffractometry and clinical fluoroscopy. Diffractometry revealed that x-ray absorption increased with tantalum concentration, however, not as the rule of mixtures would predict. Fluoroscopic imaging of the composite coils in a clinical setting verified the radio-opacity of the material.