On reduced‑order modeling of drug dispersion in the spinal canal Parras-Martos, Francisco Javier Sanchez, Antonio Luis Sánchez, Antonio Luis Martínez Bazán, Jesús Carlos Coenen, Wilfried Gutiérrez-Montes, Cándido CSF Flow Intrathecal drug delivery Biomedical fluid dynamics Lagrangian motion This work is part of the I+D+i coordinated projects PID2023-151343NB-C31, PID2023-151343NB-C32, PID2023-151343NB-C33, and PID2020-115961RB-C31, PID2020-115961RB-C32, PID2020-115961RA-C33 funded by MICIU/AEI/10.13039/501100011033 and by FEDER, UE. The work has been partly financed by the NIH National Institute of Neurological Disorders and Stroke through award #1R01NS120343-01. W.C. acknowledges the support of a 2023 Leonardo Grant for Scientific Research and Cultural Creation, BBVA Foundation. C.G.M. acknowledges the support of Grant M.1.B.B TA_000779_UJA23, funded by Consejería de Universidad, Investigación e Innovación and by ERDF Andalusia Program 2021-2027. 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: disper‑ sion 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. Approxi‑ mate descriptions assuming convective transport to be governed by the mean Eulerian velocity are found to signifi‑ cantly 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 mod‑ eling efforts. 2025-07-08T09:41:30Z 2025-07-08T09:41:30Z 2025-07-02 journal article Parras-Martos, F.J., Sánchez, A.L., Martínez-Bazán, C. et al. On reduced-order modeling of drug dispersion in the spinal canal. Fluids Barriers CNS 22, 66 (2025). https://doi.org/10.1186/s12987-025-00657-6 https://hdl.handle.net/10481/105115 10.1186/s12987-025-00657-6 eng http://creativecommons.org/licenses/by-nc-nd/4.0/ open access Attribution-NonCommercial-NoDerivatives 4.0 Internacional Springer Nature