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Voxelized Computational Model for Convection-Enhanced Delivery in the Rat Ventral Hippocampus: Comparison with In Vivo MR Experimental Studies

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Abstract

Convection-enhanced delivery (CED) is a promising local delivery technique for overcoming the blood–brain barrier (BBB) and treating diseases of the central nervous system (CNS). For CED, therapeutics are infused directly into brain tissue and the drug agent is spread through the extracellular space, considered to be highly tortuous porous media. In this study, 3D computational models developed using magnetic resonance (MR) diffusion tensor imaging data sets were used to predict CED transport in the rat ventral hippocampus using a voxelized modeling previously developed by our group. Predicted albumin tracer distributions were compared with MR-measured distributions from in vivo CED in the ventral hippocampus up to 10 μL of Gd-DTPA albumin tracer infusion. Predicted and measured tissue distribution volumes and distribution patterns after 5 and 10 μL infusions were found to be comparable. Tracers were found to occupy the underlying landmark structures with preferential transport found in regions with less fluid resistance such as the molecular layer of the dentate gyrus. Also, tracer spread was bounded by high fluid resistance layers such as the granular cell layer and pyramidal cell layer of dentate gyrus. Leakage of tracers into adjacent CSF spaces was observed towards the end of infusions.

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Acknowledgments

We would like to thank Drs. Mansi Parekh and Rabia Zafar for providing valuable scientific discussions. We would also like to thank Wei Dai for help with the manuscript. The project described was supported by award number R01NS063360 from the National Institute of Neurological Disorders and Strokes. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute Neurological Disorders and Strokes or the National Institutes of Health. The MRI data were obtained at the Advanced Magnetic Resonance Imaging and Spectroscopy (AMRIS) facility in the McKnight Brain Institute at the University of Florida.

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Authors and Affiliations

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

    Jung Hwan Kim & Malisa Sarntinoranont

  2. J. Crayton Pruitt Family Department of Biomedical Engineering, University of Florida, Gainesville, FL, 32611, USA

    Garrett W. Astary & Paul R. Carney

  3. Department of Neuroscience, University of Florida, Gainesville, FL, 32611, USA

    Svetlana Kantorovich & Paul R. Carney

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

    Thomas H. Mareci

  5. Division of Pediatric Neurology, University of Florida, Gainesville, FL, 32611, USA

    Paul R. Carney

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  1. Jung Hwan Kim
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Correspondence to Malisa Sarntinoranont.

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Associate Editor K. A. Athanasiou oversaw the review of this article.

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Kim, J.H., Astary, G.W., Kantorovich, S. et al. Voxelized Computational Model for Convection-Enhanced Delivery in the Rat Ventral Hippocampus: Comparison with In Vivo MR Experimental Studies. Ann Biomed Eng 40, 2043–2058 (2012). https://doi.org/10.1007/s10439-012-0566-8

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