Fabrication and Characterization of Highly Radiopaque Microspheres for Embolic Applications

Purpose: The purpose of this study was to develop and characterize embolic microspheres that are highly radiopaque, such that they could be used for prostate cancer chemo-embolization. The goals are that the spheres can be visualized during injection on fluoroscopic imaging without additional contrast media (with reasonable injection force), and that they can be imaged (with C-arm CT or MSCT) within the prostate and other non-target organs, both during and after the procedure. Finally, these spheres should be loadable with long-release chemotherapeutic agents.

Materials and Methods: A process was developed to manufacture polyethylene glycol (PEG) microspheres where one of two radiopaque agents were added during the manufacturing process. The process was based on droplet generation microfluidics using an olive oil base. The first type had 1 um barium sulfate particles added at 40% wbv. The second type had 100 nm zirconium oxide particles added at 50% wbv.  After curing, particles were washed to remove the olive oil. Sphere diameter was measured using light microscopy. The spheres' radiopacity were evaluated individually using microCT, and in aggregate, within a 3D printed vascular phantom, using MSCT. Injection force from a syringe was measured. Finally, the spheres were imaged with x-ray fluoroscopy during injection, using a body-sized, water-filled, vascular phantom.

Results: The barium and zirconium spheres measured 111 ± 14 um and 73 ± 18 um respectively. MicroCT measurements of individual sphere radiopacity were 6772 ± 501 HU and 13,486 ± 638 HU. MSCT radiopacity values in a 0.5 mm vessel were 264 HU and 226 HU. The measured injection force from a 3cc syringe was 20 N, compared to 25 N for commercial microspheres with 50% contrast agent. The detectability on the microspheres on fluoroscopy was very similar to that of commercial microspheres with 50% contrast agent, approximately a 30 pixel-value enhancement over the background value.

Conclusion: This project demonstrated the ability to produce highly radiopaque microspheres that have reasonable injection force and are visible both during injection using fluoroscopy, without additional contrast agent, and using MSCT. The HU values in MSCT are lower that microCT due to the lower tube voltage in microCT and also due to the limited spatial resolution (partial volume effect) of MSCT, but these small vessels are nevertheless visible within a 0-100 HU prostate gland. Further work is underway to evaluate drug elution characteristics.