Local drug delivery methods, such as convection-enhanced delivery (CED), are being used to circumvent the blood-brain-barrier and to distribute blood-brain-barrier-impermeable therapeutic agents over large selected volumes within the CNS. In this study, our goal is to provide fundamental understanding of CED transport of compounds into the hippocampus for the treatment of temporal lobe epilepsy (TLE). We will use a coupled modeling-and-experimental CED approach to selectively target a large volume of the hippocampus. Studies will concentrate on quantifying extracellular flows and macromolecular tracer distributions under both normal and pathological conditions. Varying delivery sites, infusion rates, and control conditions will be tested. For computations, tissues will be modeled as porous media and will account for realistic anatomical boundaries, fluid-tissue interactions, and anisotropic transport using high resolution and diffusion tensor magnetic resonance imaging technologies. Extracellular transport properties will be measured using pressure sensor systems and microindentation testing. Corresponding in vivo magnetic resonance imaging studies will quantify spatial concentrations following CED in rodent and primate brains (primate studies will be done in collaboration with researchers at the NIH). Such a comprehensive study, to quantify CED transport within the TLE hippocampal system, has not been previously conducted. This study will also provide fundamental tools and techniques to quantify bio- transport and measure in vivo transport by CED. The study will clarify the roles of extracellular flow, tissue anisotropy, pathological changes, tissue swelling, and backflow. MR-based bio-transport tools provide an important step towards patient-specific treatment since they account for anatomical and structural changes with disease.
In this study, our goal is to provide a fundamental understanding of convection enhanced delivery (CED) of compounds into the hippocampus for the treatment of temporal lobe epilepsy. High-resolution magnetic resonance and diffusion tensor imaging measurements in vivo will guide the development of a three- dimensional computational model that will be used to determine the effects of anatomical boundaries, fluid- tissue interactions, and tissue structure on extracellular CED transport.
|Dai, Wei; Astary, Garrett W; Kasinadhuni, Aditya K et al. (2016) Voxelized Model of Brain Infusion That Accounts for Small Feature Fissures: Comparison With Magnetic Resonance Tracer Studies. J Biomech Eng 138:051007|
|Colon-Perez, Luis M; Couret, Michelle; Triplett, William et al. (2016) Small Worldness in Dense and Weighted Connectomes. Front Phys 4:|
|Colon-Perez, Luis M; Spindler, Caitlin; Goicochea, Shelby et al. (2015) Dimensionless, Scale Invariant, Edge Weight Metric for the Study of Complex Structural Networks. PLoS One 10:e0131493|
|Ã–zarslan, Evren; Westin, Carl-Fredrik; Mareci, Thomas H (2015) Characterizing magnetic resonance signal decay due to Gaussian diffusion: the path integral approach and a convenient computational method. Concepts Magn Reson Part A Bridg Educ Res 44:203-213|
|Colon-Perez, Luis M; King, Michael; Parekh, Mansi et al. (2015) High-field magnetic resonance imaging of the human temporal lobe. Neuroimage Clin 9:58-68|
|Magdoom, Kulam Najmudeen; Pishko, Gregory L; Rice, Lori et al. (2014) MRI-based computational model of heterogeneous tracer transport following local infusion into a mouse hind limb tumor. PLoS One 9:e89594|
|Peprah, Marcus K; Astary, Garrett W; Mareci, Thomas H et al. (2014) Absolute magnetic susceptibility of rat brain tissue. Magn Reson Med 72:876-9|
|Lee, S J; King, M A; Sun, J et al. (2014) Measurement of viscoelastic properties in multiple anatomical regions of acute rat brain tissue slices. J Mech Behav Biomed Mater 29:213-24|
|Casanova, Fernando; Carney, Paul R; Sarntinoranont, Malisa (2014) Effect of needle insertion speed on tissue injury, stress, and backflow distribution for convection-enhanced delivery in the rat brain. PLoS One 9:e94919|
|Casanova, Fernando; Carney, Paul R; Sarntinoranont, Malisa (2014) In vivo evaluation of needle force and friction stress during insertion at varying insertion speed into the brain. J Neurosci Methods 237:79-89|
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