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
- Convection-enhanced delivery
- Interventional MRI
- Gene therapy
- Drug delivery
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R. Mark Richardson, MD, PhD
Department of Neurological Surgery
505 Parnassus Avenue, Room M779
San Francisco, CA 94143-0112 (USA)
Received: September 18, 2010
Accepted after revision: December 10, 2010
Published online: April 14, 2011
Number of Print Pages : 11
Number of Figures : 7, Number of Tables : 1, Number of References : 39
Stereotactic and Functional Neurosurgery
Vol. 89, No. 3, Year 2011 (Cover Date: June 2011)
Journal Editor: Roberts D.W. (Lebanon, N.H.)
ISSN: 1011-6125 (Print), eISSN: 1423-0372 (Online)
For additional information: http://www.karger.com/SFN
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