Parras-Martos F J, Sánchez A L, Martínez-Bazán C, Coenen W, Gutiérrez-Montes C
Área de Mecánica de Fluidos, Departamento de Ingeniería Mecánica y Minera, Universidad de Jaén, Jaén, 23071, Spain.
Andalusian Institute for Earth System Research, Universidad de Jaén, Campus Las Lagunillas s/n, Jaén, 23071, Spain.
Fluids Barriers CNS. 2025 Jul 2;22(1):66. doi: 10.1186/s12987-025-00657-6.
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.
鞘内给药程序的优化需要对椎管内的流动和传输有更深入的了解。由于时间尺度的差异，药物扩散的数值模拟具有挑战性：扩散发生在1小时内，而由心脏运动驱动的脑脊液脉动发生在1秒的时间尺度上。临床环境中针对特定患者的预测需要简化描述，重点关注药物扩散时间，绕过由周期性运动引起的快速浓度振荡。在此，通过与具有神经根和齿状韧带的颈段椎管模型中药物扩散的MRI信息直接数值模拟（DNS）进行比较，测试了一个先前推导的涉及由平均拉格朗日漂移驱动的对流传输的降阶模型。比较结果表明，简化模型能够精确描述药物传输，能够以DNS计算成本的一小部分进行药物扩散预测。发现假设对流传输由平均欧拉速度控制的近似描述会显著低估药物扩散，突出了平均拉格朗日运动的关键作用。我们的结果还证实了微观解剖特征对药物扩散的重大影响，这与早期分析一致。DNS的一个关键额外发现是分子扩散对药物扩散的影响可以忽略不计，流体颗粒的平均漂移主要决定了药物分布的演变——这一见解对未来的建模工作很有价值。
