Strategies for the Delivery of Multiple Collinear Infusion Clouds in Convection-Enhanced Delivery in the Treatment of Parkinson's Disease

Abstract

Background: Delivery of multiple collinear payloads utilizing convection-enhanced delivery (CED) has historically been performed by retraction of a needle or catheter from the most distal delivery site. Few studies have addressed end-infusion morphology and associated payload reflux in stacked and collinear infusions, and studies comparing the advancement with the retraction mode are lacking. Objective: To compare advancement versus retraction mode infusion results. Methods: Infusion cloud pairs were created with the advancement and retraction technique in agarose gel using both open end-port SmartFlow™ (SF) and valve tip (VT) catheter infusion systems. Backflow, radius of infusion, and morphology were assessed. Results: Infusions with the SF catheter, in contrast to the VT catheter, exhibited significantly more backflow in retraction mode at the shallow infusion site. Infusion morphology differed with the second infusion after retraction: the infusate at the proximal site first filling the channel left by the retraction and then being convected into gel in a pronouncedly non-spherical shape during the second infusion. Conclusions: Significant differences in cloud morphology were noted with respect to external catheter geometry with retraction versus penetration between infusions in an agarose gel model of the brain. Further study is warranted to determine optimal protocols for human clinical trials employing CED with multiple collinear payloads.