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Table of Contents
Vol. 89, No. 3, 2011
Issue release date: June 2011
Section title: Laboratory Investigation
Free Access
Stereotact Funct Neurosurg 2011;89:141–151

Novel Platform for MRI-Guided Convection-Enhanced Delivery of Therapeutics: Preclinical Validation in Nonhuman Primate Brain

Richardson R.M.a · Kells A.P.a · Martin A.J.b · Larson P.S.a · Starr P.A.a · Piferi P.G.c · Bates G.c · Tansey L.c · Rosenbluth K.H.a · Bringas J.R.a · Berger M.S.a · Bankiewicz K.S.a
Departments of aNeurological Surgery and bRadiology, University of California San Francisco, San Francisco, Calif., and cSurgiVision Inc., Irvine, Calif., USA
email Corresponding Author

R. Mark Richardson, MD, PhD

Department of Neurological Surgery

505 Parnassus Avenue, Room M779

San Francisco, CA 94143-0112 (USA)

E-Mail richardsonma@neurosurg.ucsf.edu

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Background/Aims: A skull-mounted aiming device and integrated software platform has been developed for MRI-guided neurological interventions. In anticipation of upcoming gene therapy clinical trials, we adapted this device for real-time convection-enhanced delivery of therapeutics via a custom-designed infusion cannula. The targeting accuracy of this delivery system and the performance of the infusion cannula were validated in nonhuman primates. Methods: Infusions of gadoteridol were delivered to multiple brain targets and the targeting error was determined for each cannula placement. Cannula performance was assessed by analyzing gadoteridol distributions and by histological analysis of tissue damage. Results: The average targeting error for all targets (n = 11) was 0.8 mm (95% CI = 0.14). For clinically relevant volumes, the distribution volume of gadoteridol increased as a linear function (R2 = 0.97) of the infusion volume (average slope = 3.30, 95% CI = 0.2). No infusions in any target produced occlusion, cannula reflux or leakage from adjacent tracts, and no signs of unexpected tissue damage were observed. Conclusions: This integrated delivery platform allows real-time convection-enhanced delivery to be performed with a high level of precision, predictability and safety. This approach may improve the success rate for clinical trials involving intracerebral drug delivery by direct infusion.

© 2011 S. Karger AG, Basel

Article / Publication Details

First-Page Preview
Abstract of Laboratory Investigation

Received: September 18, 2010
Accepted: December 10, 2010
Published online: April 14, 2011
Issue release date: June 2011

Number of Print Pages: 11
Number of Figures: 7
Number of Tables: 1

ISSN: 1011-6125 (Print)
eISSN: 1423-0372 (Online)

For additional information: http://www.karger.com/SFN

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