Frameless multimodal image guidance of localized convection-enhanced delivery of therapeutics in the brain
- Imramsjah M J van der Bom1,
- Richard P Moser2,
- Guanping Gao3,
- Miguel Sena-Esteves3,
- Neil Aronin4,
- Matthew J Gounis1
- 1Department of Radiology, University of Massachusetts, Worcester, Massachusetts, USA
- 2Department of Neurosurgery, University of Massachusetts, Worcester, Massachusetts, USA
- 3Department of Microbiology and Physiological Systems, Gene Therapy Center, University of Massachusetts, Worcester, Massachusetts, USA
- 4Department of Medicine, Cell Biology, University of Massachusetts, Worcester, Massachusetts, USA
- Correspondence to Dr Matthew Gounis, Department of Radiology, University of Massachusetts, 55 Lake Ave N, SA-107R, Worcester, MA 01655, USA;
Contributors IMJvdB: study design, data collection, data analysis, manuscript preparation. RPM: study design, operating neurosurgeon, manuscript editing. GG: study design, material production, manuscript editing. MS-E: study design, manuscript editing. NA: PI. MG: study design, data analysis, manuscript preparation.
- Received 21 October 2011
- Accepted 22 November 2011
- Published Online First 22 December 2011
Introduction Convection-enhanced delivery (CED) has been shown to be an effective method of administering macromolecular compounds into the brain that are unable to cross the blood-brain barrier. Because the administration is highly localized, accurate cannula placement by minimally invasive surgery is an important requisite. This paper reports on the use of an angiographic c-arm system which enables truly frameless multimodal image guidance during CED surgery.
Methods A microcannula was placed into the striatum of five sheep under real-time fluoroscopic guidance using imaging data previously acquired by cone beam computed tomography (CBCT) and MRI, enabling three-dimensional navigation. After introduction of the cannula, high resolution CBCT was performed and registered with MRI to confirm the position of the cannula tip and to make adjustments as necessary. Adeno-associated viral vector-10, designed to deliver small-hairpin micro RNA (shRNAmir), was mixed with 2.0 mM gadolinium (Gd) and infused at a rate of 3 μl/min for a total of 100 μl. Upon completion, the animals were transferred to an MR scanner to assess the approximate distribution by measuring the volume of spread of Gd.
Results The cannula was successfully introduced under multimodal image guidance. High resolution CBCT enabled validation of the cannula position and Gd-enhanced MRI after CED confirmed localized administration of the therapy.
Conclusion A microcannula for CED was introduced into the striatum of five sheep under multimodal image guidance. The non-alloy 300 μm diameter cannula tip was well visualized using CBCT, enabling confirmation of the position of the end of the tip in the area of interest.
Funding This research was funded by a grant from Lundbeck Inc.
Competing interests NA is a member of the NIH sponsored DERC (DK 032520).
Provenance and peer review Not commissioned; externally peer reviewed.
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