Abstract

Abstract Glioblastoma has a 5 year survival of only 5.5% and a median patient survival of 12 to 15 months even with gold standard treatment. One potential method of improving treatment of glioblastoma is the use of convection-enhanced delivery (CED) which utilizes local delivery of therapeutics to the brain. However, clinical trials have shown an inability of standard catheters to deliver therapeutics to the entire target area. In this study, we explore the potential of controlled catheter movement to increase the volume dispersed (Vd) of indigo carmine dye in agarose gel brain tissue phantoms. We use four catheter control protocols: stationary, continuous retraction, continuous insertion, and intermittent insertion using a single port stepped catheter. The continuous retraction group resulted in consistent catheter clogging caused by the continued insertion of the catheter and therefore was removed from further analysis. Vd and backflow distance was quantified for all other catheter movement protocols using optical images captured throughout the infusion. Catheter retraction resulted in an increase in Vd of 51% while intermittent insertion resulted in a Vd increase of 24% compared to the stationary catheter. Additionally, a 37% reduction in backflow distance was seen with the retracting catheter when compared to the stationary catheter. These results are further supported by a simplified computational model that we have created. The computational model simulates the infusion of indigo carmine dye through an agarose gel brain tissue phantom and shows an increase in Vd of over 100% with catheter retraction. The increased Vd and decreased backflow distance afforded by the retracting catheter, suggests that the use of catheter movement may be a useful technique in increasing drug dispersal in tumorous tissue. Additional work in live and excised tissue should be conducted to confirm these results and an exploration of optimal needle movement protocols is necessary.

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