PROJECT SUMMARY Minimally invasive transcatheter embolization is a common nonsurgical procedure in interventional radiology used for the deliberate occlusion of blood vessels for the treatment of diseased or injured vasculature. One of the most commonly used embolic agents for clinical practice are microspheres. They come with different materials (i.e., PVA and trisacryl gelatin) in a variety of sizes (50 - 1200 µm), which can be strategically selected to treat various conditions ranging from arteriovenous malformations to hypervascular tumors, Accurate particle size is crucial for localized targeted embolization since the delivery of microspheres is driven by blood flow and their movement and accumulation in vivo is size-dependent. Limitations of marketed microspheres include danger of being washed away, no intrinsic radiopacity for visualization on X-ray, and lack of therapeutics. Despite the similar morphologies microspherical embolic agents, their physical and mechanical properties vary due to differences in their chemical composition and manufacturing processes, which in turn influence microsphere and tissue interactions and clinical outcomes. No systemic platform has been developed to investigate the correlation between these properties and embolic outcomes. More importantly, clinicians have no technology for estimating the trajectory of emboli and as such significant uncertainty exists in embolization treatment. Microsphere transportation to undesired vessels will cause off-target embolization and damage to healthy tissue. The precise prediction of particle-flow behavior and the particle-vessel distribution is difficult even for experienced physicians because this is essentially a fluid-driven transport problem that has not been systemically investigated and validated. In this proposal, we will develop, for the first time, a two-way interactive biomaterial-computational platform that will 1) offer rational design of multifunctional microspheres, 2) accurately guide the transcatheter location for microsphere deployment, and 3) predict microsphere in vivo trajectory and their aggregation in the vasculature to maximize embolic success for personalized therapies. In Aim 1, we will develop microspheres with controllable sizes and tunable properties for effective embolization. In Aim 2, we will develop computational fluid dynamics (CFD) models integrated with biomaterial design to maximize emboli transport to desired locations. Lastly in Aim 3, we will demonstrate predictive capability using in-vitro vasculature and adaptive framework using patient specific physical models. Successful completion of this study shows that the versatile biomaterial-computational platform can maximize the delivery of embolic microspheres under random injection of emboli within the luminal cross-section (current practice) or complete delivery under informed injection with tracking the catheter. This pilot study will set the stage for further guided in vivo testing in large animal studies using clinically relevant models (porcine liver models). We envision that this innovative technology can be applied to liquid embolic agents, and also be widely disseminated to the treatment of diverse vascular conditions, such as prostate hyperplasia, liver tumor, and fibroids, for translation to patient-specific therapy.

PROJECT NARRATIVE Transcatheter arterial embolization using calibrated microsphere technology represents a remarkably successful chapter in minimally invasive interventions to treat various conditions ranging from arteriovenous malformations to hypervascular tumors. Although several types of embolic microspheres have been FDA authorized, clinicians have no technology for estimating the trajectory of emboli and as such significant uncertainty exists in embolization. To address the aforementioned issues, we propose to develop a two-way interactive biomaterial- computational platform to generate effective injection map, while also providing physicians insight into success rate for both informed and randomized injection in different vasculature for personalized embolization.