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 ($3-12K for filter retrieval and ~$67K 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 radiopaque absorbable filters that can be routinely imaged to offer a less expensive alternative for 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 (made of gold, bismuth, ytterbium, or tantalum), iodine, and calcium deposits, which could provide better image quality and quantification of the materials present in the filter. Specifically, we propose the following aims:
Aim 1. Determine the radiopacity, mechanical strength, and crystallinity of nanoparticle-infused PPDO sutures and quantify the amount of nanoparticles (composed of gold, bismuth, ytterbium, and tantalum) infused and released within PPDO sutures in human physiological conditions over a period of 10 weeks.
Aim 2. Investigate the ability of DECT to differentiate various radiopaque materials from thrombus and to optimize the parameters for imaging radiopaque PDDO filters using DECT.
Aim 3 : Determine in swine animal model the radiopacity and mechanical strength of nanoparticle-infused PPDO sutures and identify adverse reactions to the sutures after necropsies. 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 nanoparticles 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 this project 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 for 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 in real-time, their deployment and integrity over time.
| 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 |
| 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; Chang, Ashley; Melancon, Marites P (2017) Exploring gold nanoparticle interactions with proteins and the tumor microenvironment in biological systems. Transl Cancer Res 6:S309-S312 |
| Tian, Li; Lee, Patrick; Singhana, Burapol et al. (2017) Radiopaque Resorbable Inferior Vena Cava Filter Infused with Gold Nanoparticles. Sci Rep 7:2147 |
