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Proceedings Paper

Image-guided intracranial cannula placement for awake in vivo microdialysis in nonhuman primates
Author(s): Antong Chen; Ashleigh Bone; Catherine D. G. Hines; Belma Dogdas; Tamara O. Montgomery; Maria Michener; Christopher T. Winkelmann; Soheil Ghafurian; Laura S. Lubbers; John Renger; Ansuman Bagchi; Jason M. Uslaner; Colena Johnson; Hatim A. Zariwala
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Paper Abstract

Intracranial microdialysis is used for sampling neurochemicals and large peptides along with their metabolites from the interstitial fluid (ISF) of the brain. The ability to perform this in nonhuman primates (NHP) e.g., rhesus could improve the prediction of pharmacokinetic (PK) and pharmacodynamics (PD) action of drugs in human. However, microdialysis in rhesus brains is not as routinely performed as in rodents. One challenge is that the precise intracranial probe placement in NHP brains is difficult due to the richness of the anatomical structure and the variability of the size and shape of brains across animals. Also, a repeatable and reproducible ISF sampling from the same animal is highly desirable when combined with cognitive behaviors or other longitudinal study end points. Toward that end, we have developed a semi-automatic flexible neurosurgical method employing MR and CT imaging to (a) derive coordinates for permanent guide cannula placement in mid-brain structures and (b) fabricate a customized recording chamber to implant above the skull for enclosing and safeguarding access to the cannula for repeated experiments. In order to place the intracranial guide cannula in each subject, the entry points in the skull and the depth in the brain were derived using co-registered images acquired from MR and CT scans. The anterior/posterior (A/P) and medial-lateral (M/L) rotation in the pose of the animal was corrected in the 3D image to appropriately represent the pose used in the stereotactic frame. An array of implanted fiducial markers was used to transform stereotactic coordinates to the images. The recording chamber was custom fabricated using computer-aided design (CAD), such that it would fit the contours of the individual skull with minimum error. The chamber also helped in guiding the cannula through the entry points down a trajectory into the depth of the brain. We have validated our method in four animals and our results indicate average placement error of cannula to be 1.20 ± 0.68 mm of the targeted positions. The approach employed here for derivation of the coordinates, surgical implantation and post implant validation is built using traditional access to surgical and imaging methods without the necessity of intra-operative imaging. The validation of our method lends support to its wider application in most nonhuman primate laboratories with onsite MR and CT imaging capabilities.

Paper Details

Date Published: 18 March 2016
PDF: 6 pages
Proc. SPIE 9786, Medical Imaging 2016: Image-Guided Procedures, Robotic Interventions, and Modeling, 978620 (18 March 2016); doi: 10.1117/12.2217539
Show Author Affiliations
Antong Chen, Merck Research Labs. (United States)
Ashleigh Bone, Merck Research Labs. (United States)
Catherine D. G. Hines, Merck Research Labs. (United States)
Belma Dogdas, Merck Research Labs. (United States)
Tamara O. Montgomery, Merck Research Labs. (United States)
Maria Michener, Merck Research Labs. (United States)
Christopher T. Winkelmann, Pfizer (United States)
Soheil Ghafurian, Merck Research Labs. (United States)
Rutgers Univ. (United States)
Laura S. Lubbers, Merck Research Labs. (United States)
John Renger, Merck Research Labs. (United States)
Ansuman Bagchi, Merck Research Labs. (United States)
Jason M. Uslaner, Merck Research Labs. (United States)
Colena Johnson, Merck Research Labs. (United States)
Hatim A. Zariwala, Merck Research Labs. (United States)


Published in SPIE Proceedings Vol. 9786:
Medical Imaging 2016: Image-Guided Procedures, Robotic Interventions, and Modeling
Robert J. Webster; Ziv R. Yaniv, Editor(s)

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