| Cannula placement for effective convection-enhanced delivery in the nonhuman primate thalamus and brainstem: implications for clinical delivery of therapeutics. | |
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MedLine Citation:
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PMID: 20367078 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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OBJECT: The purpose of this study was to optimize stereotactic coordinates for delivery of therapeutic agents into the thalamus and brainstem, using convection-enhanced delivery (CED) to avoid leakage into surrounding anatomical structures while maximizing CED of therapeutics within the target volume. METHODS: The authors recently published targeting data for the nonhuman primate putamen in which they defined infusion parameters, referred to as "red," "blue," and "green" zones, that describe cannula placements resulting in poor, suboptimal, and optimal volumes of distribution, respectively. In the present study, the authors retrospectively analyzed 22 MR images with gadoteridol as a contrast reagent, which were obtained during CED infusions into the thalamus (14 cases) and brainstem (8 cases) of nonhuman primates. RESULTS: Excellent distribution of gadoteridol within the thalamus was obtained in 8 cases and these were used to define an optimal target locus (or green zone). Good distribution in the thalamus, with variable leakage into adjacent anatomical structures, was noted in 6 cases, defining a blue zone. Quantitative containment (99.7 +/- 0.2%) of gadoteridol within the thalamus was obtained when the cannula was placed in the green zone, and less containment (85.4 +/- 3.8%) was achieved with cannula placement in the blue zone. Similarly, a green zone was also defined in the brainstem, and quantitative containment of infused gadoteridol within the brainstem was 99.4 +/- 0.6% when the cannula was placed in the green zone. These results were used to determine a set of 3D stereotactic coordinates that define an optimal site for infusions intended to cover the thalamus and brainstem of nonhuman primates. CONCLUSIONS: The present study provides quantitative analysis of cannula placement and infusate distribution using real-time MR imaging and defines an optimal zone for infusion in the nonhuman primate thalamus and brainstem. Cannula placement recommendations developed from such translational nonhuman primate studies have significant implications for the design of anticipated clinical trials featuring CED therapy into the thalamus and brainstem for CNS diseases. |
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Authors:
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Dali Yin; R Mark Richardson; Massimo S Fiandaca; John Bringas; John Forsayeth; Mitchel S Berger; Krystof S Bankiewicz |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Journal of neurosurgery Volume: 113 ISSN: 1933-0693 ISO Abbreviation: J. Neurosurg. Publication Date: 2010 Aug |
Date Detail:
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Created Date: 2010-08-02 Completed Date: 2010-08-23 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0253357 Medline TA: J Neurosurg Country: United States |
Other Details:
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Languages: eng Pagination: 240-8 Citation Subset: AIM; IM |
Affiliation:
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Department of Neurosurgery, University of California, San Francisco, California 94103, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Brain Stem* Catheterization / methods* Contrast Media / pharmacokinetics Drug Delivery Systems / instrumentation, methods* Female Heterocyclic Compounds / pharmacokinetics Imaging, Three-Dimensional Macaca fascicularis Macaca mulatta Magnetic Resonance Imaging Male Models, Animal Organometallic Compounds / pharmacokinetics Stereotaxic Techniques* Thalamus* |
| Grant Support | |
ID/Acronym/Agency:
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P50 CA097257/CA/NCI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Contrast Media; 0/Heterocyclic Compounds; 0/Organometallic Compounds; 112188-16-6/gadoteridol |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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