163 Noninvasive Nanoparticle - Based Patency Assessment and Clearance of Ventriculoperitoneal Shunts

INTRODUCTION: Ventriculoperitoneal (VP) shunting continues to be the predominant treatment for both pediatric and adult hydrocephalus. While new techniques for assessing VP shunt patency (and flow) have recently been developed, an improved method for diagnosing VP shunt obstruction and clearing it noninvasively, would be welcomed. Obstruction of properly-positioned shunts can occur for reasons including bleeding, tissue ingrowth, elevated CSF protein, and/or accumulation of cells and debris. METHODS: Iron oxide-based nanoparticles were created in the lab, or purchased commercially. Magnetized nanoparticle clusters were used alone, or in combination with bound/unbound therapeutic agents (such as t-PA or etoposide), and guided at a distance using a rotating permanent magnet or electromagnetic coils. Nanoparticles were conveyed through shunt tubes of different lengths/compositions. Shunt obstructions were created using elevated protein levels, blood, fibroblasts, and tumor cells. Assessment methods included the use of microscopy, video recordings, MRI, and/or ultrasound. A shunt reservoir was devised to harbor nanoparticles until needed for diagnostic or therapeutic use. RESULTS: Magnetic nanoparticle clusters could be propelled through shunt tubing despite elevated protein content, or blood. Nanoparticle velocity in artificial CSF was typically 1 cm/sec depending on positioning of the magnet. An air bubble would obstruct nanoparticle movement. Nanoparticles adhered to cells, and therefore could deliver cytotoxic agents. Over short working distances, nanoparticles could be moved using magnetic attraction alone. Over greater distances (20 cm), the clusters would counter-rotate in response to the rotating magnetic field, and walk along the surface of the tubing. MRI was most sensitive for imaging the particles. The mechanism of action for clearing obstruction was mainly mechanical. CONCLUSIONS: Magnetic nanoparticles hold promise for the noninvasive assessment of VP shunt patency, and shunt clearance.