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A voxelized model of direct infusion into the corpus callosum and hippocampus of the rat brain: model development and parameter analysis

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Abstract

Recent experimental studies have shown convective-enhanced delivery (CED) to be useful for transporting macromolecular therapeutic agents over large tissue volumes in the central nervous system (CNS). There are limited tools currently available for predicting tissue distributions in the brain. We have developed a voxelized modeling methodology in which CNS tissues are modeled as porous media, and transport properties and anatomical boundaries are determined semi-automatically on a voxel-by-voxel basis using diffusion tensor imaging (DTI). By using this methodology, 3D extracellular transport models of the rat brain were developed. Macromolecular tracer distributions following CED in two different infusion sites (corpus callosum and hippocampus) were predicted. Sensitivity of models to changes in infusion parameters, transport properties, and modeling parameters was determined. Predicted tracer distributions were most sensitive to changes in segmentation threshold, DTI resolution, tissue porosity, and infusion site. This DTI-based voxelized modeling methodology provides a potentially rapid means of estimating CED transport.

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Acknowledgments

We would like to thank Dr. Paul Carney for providing the fixed, excised rat brain sample and providing helpful comments and recommendations. We also thank Garrett Astary, Hector Sepulveda, Svetlana Kantorovich and Mansi Parekh for helpful conversations and technical advice. The MRI data was obtained at the Advanced Magnetic Resonance Imaging and Spectroscopy Facility in the McKnight Brain Institute and National High Magnetic Field Laboratory of UF. This work was supported in part by the National Institutes of Health under grants R01 EB004752 (THM) and R01 EB007082 (THM) and R01 NS063360 (MS).

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Authors and Affiliations

  1. Department of Mechanical and Aerospace Engineering, University of Florida, 212 MAE-A, 116250, Gainesville, FL, 32611-6250, USA

    Jung Hwan Kim & Malisa Sarntinoranont

  2. Department of Biochemistry and Molecular Biology, University of Florida, Gainesville, FL, 32611, USA

    Thomas H. Mareci

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  1. Jung Hwan Kim
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Correspondence to Malisa Sarntinoranont.

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Kim, J.H., Mareci, T.H. & Sarntinoranont, M. A voxelized model of direct infusion into the corpus callosum and hippocampus of the rat brain: model development and parameter analysis. Med Biol Eng Comput 48, 203–214 (2010). https://doi.org/10.1007/s11517-009-0564-7

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  • DOI: https://doi.org/10.1007/s11517-009-0564-7

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