Venous thromboembolism (VTE) is the third most common cardiovascular illness after acute coronary syndrome and stroke. The first line of therapy for VTE is blood thinners; however, these agents are temporarily contraindicated for many at-risk VTE patients, such as those with major trauma and those who undergo complex surgeries, for whom bleeding is a concern. Inferior vena cava (IVC) filters are indicated in this population. Most IVC filters (70%) are intended to be retrieved after their indicated use; however, only 19%- 30% are removed. Unfortunately, complications mount when IVC filters are not removed, which can be very costly ($3,000-$12,000 for filter retrieval and ~$67,000 for treatment of complications). Therefore, resorbable IVC filters were developed, which provide critical protection during their required duration and then simply vanish from the body, thereby alleviating costly removal procedures and downstream complications. However, an important limitation of a resorbable IVC filter system is significant clot burden. Monitoring the absorption time and any significant clot burden with use of imaging techniques would greatly improve the efficacy of deep vein thrombosis treatment. In this study, we will develop of radiopaque absorbable filters that can be routinely imaged to offer a less expensive alternative to assessing filter integrity. Moreover, visualization of the filter under dual-energy computed tomography (DECT) would facilitate discrimination between two or more materials, such as nanoparticles (NPs), iodine, and calcium deposits, which could provide better image quality and quantification of the materials present in the filter. Specifically, we propose to incorporate NPs (made up of gold, bismuth, ytterbium, tantalum, tungsten, barium, and zirconium), into clinically available resorbable polydioxanone (PPDO) suture, investigate the effect of NP infusion within PPDO sutures in terms of mechanical strength, toxicity, and physico-chemical properties over a period of 10 weeks when subjected to human physiological conditions, and perform large animal imaging study using optimized DECT parameters to determine radiopacity, toxicity, and mechanical strength, as well as adverse reactions of image-enhanced suture during necropsies. We will also develop a mathematical algorithm for DECT for the quantification of the different high atomic (Z) number contrast materials infused within the PPDO. Our long-term goal is to develop a totally absorbable IVC filter, inexpensively deployed and monitored by conventional imaging methods that prevents pulmonary embolism for the recommended prophylactic period and then simply vanishes without intervention. The experiments outlined here will be critical to demonstrating the feasibility of using NPs as radiopaque material for DECT imaging embedded within this medical device. Successful development of imaging enhancers for IVC filters may also lead to widespread use of absorbable devices in other cardiovascular and orthopedic applications in which fixtures (such as plates, screws, nails, and rods) are needed only on a temporary basis.
The proposed research is relevant to public health because it is aimed at developing the first totally absorbable, radiopaque inferior vena cava filter inserted via catheter to capture blood clots and prevent their passage to the lungs for a prophylactic period of 5 weeks in at-risk patients for whom anticoagulants are temporarily contraindicated. The use of absorbable filters would obviate the time, money, and effort required for filter removal and reduces the problems associated with chronic filter use. Also, by making these filters radiopaque, we will be able to routinely monitor their deployment and integrity over time.
| Melancon, Marites P; Appleton Figueira, Tomas; Fuentes, David T et al. (2018) Development of an Electroporation and Nanoparticle-based Therapeutic Platform for Bone Metastases. Radiology 286:149-157 |
| Tian, Li; Qiao, Yang; Lee, Patrick et al. (2018) Antitumor efficacy of liposome-encapsulated NVP-BEZ 235 in combination with irreversible electroporation. Drug Deliv 25:668-678 |
| Tian, Li; Lu, Linfeng; Feng, James et al. (2018) Radiopaque nano and polymeric materials for atherosclerosis imaging, embolization and other catheterization procedures. Acta Pharm Sin B 8:360-370 |
