On reduced-order modeling of drug dispersion in the spinal canal
Abstract The optimization of intrathecal drug delivery procedures requires a deeper understanding of flow and transport in the spinal canal. Numerical modeling of drug dispersion is challenging due to the disparity in time scales: dispersion occurs over 1 hour, while cerebrospinal fluid pulsations d...
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| Format: | Article |
| Language: | English |
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BMC
2025-07-01
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| Series: | Fluids and Barriers of the CNS |
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| Online Access: | https://doi.org/10.1186/s12987-025-00657-6 |
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| author | F. J. Parras-Martos A. L. Sánchez C. Martínez-Bazán W. Coenen C. Gutiérrez-Montes |
| author_facet | F. J. Parras-Martos A. L. Sánchez C. Martínez-Bazán W. Coenen C. Gutiérrez-Montes |
| author_sort | F. J. Parras-Martos |
| collection | DOAJ |
| description | Abstract The optimization of intrathecal drug delivery procedures requires a deeper understanding of flow and transport in the spinal canal. Numerical modeling of drug dispersion is challenging due to the disparity in time scales: dispersion occurs over 1 hour, while cerebrospinal fluid pulsations driven by cardiac motion occur on a 1-second scale. Patient-specific predictions in clinical settings demand simplified descriptions that focus on drug-dispersion times, bypassing the rapid concentration oscillations caused by cyclic motion. A previously derived reduced-order model involving convective transport driven by mean Lagrangian drift is tested here through comparisons with MRI-informed direct numerical simulations (DNS) of drug dispersion in a cervical-canal model featuring nerve rootlets and denticulate ligaments. The comparisons demonstrate that the reduced model is able to describe precisely drug transport, enabling drug-dispersion predictions at a fraction of the computational cost involved in the DNS. Approximate descriptions assuming convective transport to be governed by the mean Eulerian velocity are found to significantly underpredict drug dispersion, highlighting the critical role of mean Lagrangian motion. Our results also confirm the substantial influence of microanatomical features on drug dispersion, consistent with earlier analyses. A key additional finding from the DNS is that molecular diffusion has a negligible impact on drug dispersion, with the mean drift of fluid particles primarily dictating the evolution of the drug distribution—an insight valuable for future modeling efforts. |
| format | Article |
| id | doaj-art-9225bfbb4b17440ea11748223cee01bb |
| institution | DOAJ |
| issn | 2045-8118 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | BMC |
| record_format | Article |
| series | Fluids and Barriers of the CNS |
| spelling | doaj-art-9225bfbb4b17440ea11748223cee01bb2025-08-20T03:03:38ZengBMCFluids and Barriers of the CNS2045-81182025-07-0122112210.1186/s12987-025-00657-6On reduced-order modeling of drug dispersion in the spinal canalF. J. Parras-Martos0A. L. Sánchez1C. Martínez-Bazán2W. Coenen3C. Gutiérrez-Montes4Área de Mecánica de Fluidos, Departamento de Ingeniería Mecánica y Minera, Universidad de JaénDepartment of Mechanical and Aerospace Engineering, University of California San DiegoÁrea de Mecánica de Fluidos, Departamento de Mecánica de Estructuras e Ingeniería Hidráulica, Universidad de GranadaGrupo de Mecánica de Fluidos, Departamento de Ingeniería Térmica y de Fluidos, Universidad Carlos III de MadridÁrea de Mecánica de Fluidos, Departamento de Ingeniería Mecánica y Minera, Universidad de JaénAbstract The optimization of intrathecal drug delivery procedures requires a deeper understanding of flow and transport in the spinal canal. Numerical modeling of drug dispersion is challenging due to the disparity in time scales: dispersion occurs over 1 hour, while cerebrospinal fluid pulsations driven by cardiac motion occur on a 1-second scale. Patient-specific predictions in clinical settings demand simplified descriptions that focus on drug-dispersion times, bypassing the rapid concentration oscillations caused by cyclic motion. A previously derived reduced-order model involving convective transport driven by mean Lagrangian drift is tested here through comparisons with MRI-informed direct numerical simulations (DNS) of drug dispersion in a cervical-canal model featuring nerve rootlets and denticulate ligaments. The comparisons demonstrate that the reduced model is able to describe precisely drug transport, enabling drug-dispersion predictions at a fraction of the computational cost involved in the DNS. Approximate descriptions assuming convective transport to be governed by the mean Eulerian velocity are found to significantly underpredict drug dispersion, highlighting the critical role of mean Lagrangian motion. Our results also confirm the substantial influence of microanatomical features on drug dispersion, consistent with earlier analyses. A key additional finding from the DNS is that molecular diffusion has a negligible impact on drug dispersion, with the mean drift of fluid particles primarily dictating the evolution of the drug distribution—an insight valuable for future modeling efforts.https://doi.org/10.1186/s12987-025-00657-6Biomedical fluid dynamicsCerebrospinal fluid flowIntrathecal drug deliveryLagrangian motion |
| spellingShingle | F. J. Parras-Martos A. L. Sánchez C. Martínez-Bazán W. Coenen C. Gutiérrez-Montes On reduced-order modeling of drug dispersion in the spinal canal Fluids and Barriers of the CNS Biomedical fluid dynamics Cerebrospinal fluid flow Intrathecal drug delivery Lagrangian motion |
| title | On reduced-order modeling of drug dispersion in the spinal canal |
| title_full | On reduced-order modeling of drug dispersion in the spinal canal |
| title_fullStr | On reduced-order modeling of drug dispersion in the spinal canal |
| title_full_unstemmed | On reduced-order modeling of drug dispersion in the spinal canal |
| title_short | On reduced-order modeling of drug dispersion in the spinal canal |
| title_sort | on reduced order modeling of drug dispersion in the spinal canal |
| topic | Biomedical fluid dynamics Cerebrospinal fluid flow Intrathecal drug delivery Lagrangian motion |
| url | https://doi.org/10.1186/s12987-025-00657-6 |
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