Abstract
Infusing drugs directly into the brain is advantageous to oral or intravenous delivery for large molecules or drugs requiring high local concentrations with low off-target exposure. However, surgeons manually planning the cannula position for drug delivery in the brain face a challenging three-dimensional visualization task. This study presents an intuitive inverse-planning technique to identify the optimal placement that maximizes coverage of the target structure while minimizing the potential for leakage outside the target. The technique was retrospectively validated using intraoperative magnetic resonance imaging of infusions into the striatum of non-human primates and into a tumor in a canine model and applied prospectively to upcoming human clinical trials.
Highlights
As image-guided drug delivery into the brain becomes more broadly adopted in the clinic, there is an increasing need for rapid, robust, intuitive inverse-planning algorithms
The quality of infusions is highly variable and the effective coverage observed pre-clinically [1,2] has been poorly reproduced in clinical trials of glial-derived neurotrophic factor (GDNF) for treating Parkinson’s disease [3] neurturin gene for treating Parkinson’s disease [4], the immunotoxin cintredekin besudotox [5,6] for treating brain tumors or the chemotherapeutic paclitaxel [7], for treating brain tumors
The technique is an extension of previous work showing that cannulae placed in the central Green zone of key brain structures including the brainstem [27], thalamus [27], and putamen [28,29] consistently produce spheroid-shaped distributions
Summary
As image-guided drug delivery into the brain becomes more broadly adopted in the clinic, there is an increasing need for rapid, robust, intuitive inverse-planning algorithms. Inverse-planning identifies the optimal inputs, such as the infusion cannula location and infusion volume, to achieve a desired output, such as the drug distribution.
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
