Background Developing novel therapeutic agents to treat amyotrophic lateral sclerosis (ALS) has been difficult due to multifactorial pathophysiologic processes at work. Intrathecal drug administration shows promise due to close proximity of cerebrospinal fluid (CSF) to affected tissues. Development of effective intrathecal pharmaceuticals will rely on accurate models of how drugs are dispersed in the CSF. Therefore, a method to quantify these dynamics and a characterization of differences across disease states is needed. Methods Complete intrathecal 3D CSF geometry and CSF flow velocities at six axial locations in the spinal canal were collected by T2-weighted and phase-contrast MRI, respectively. Scans were completed for eight people with ALS and ten healthy controls. Manual segmentation of the spinal subarachnoid space was performed and coupled with an interpolated model of CSF flow within the spinal canal. Geometric and hydrodynamic parameters were then generated at 1 mm slice intervals along the entire spine. Temporal analysis of the waveform spectral content and feature points was also completed. Results Comparison of ALS and control groups revealed a reduction in CSF flow magnitude and increased flow propagation velocities in the ALS cohort. Other differences in spectral harmonic content and geometric comparisons may support an overall decrease in intrathecal compliance in the ALS group. Notably, there was a high degree of variability between cases, with one ALS patient displaying nearly zero CSF flow along the entire spinal canal. Conclusion While our sample size limits statistical confidence about the differences observed in this study, it was possible to measure and quantify inter-individual and cohort variability in a non-invasive manner. Our study also shows the potential for MRI based measurements of CSF geometry and flow to provide information about the hydrodynamic environment of the spinal subarachnoid space. These dynamics may be studied further to understand the behavior of CSF solute transport in healthy and diseased states.

中文翻译：

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肌萎缩侧索硬化患者脑脊液动力学的无创 MRI 量化

背景 由于起作用的多因素病理生理过程，开发治疗肌萎缩侧索硬化 (ALS) 的新型治疗剂一直很困难。由于脑脊液 (CSF) 与受影响的组织非常接近，鞘内给药显示出前景。有效鞘内药物的开发将依赖于药物如何在脑脊液中分散的准确模型。因此，需要一种量化这些动态和表征不同疾病状态差异的方法。方法 分别通过 T2 加权和相衬 MRI 收集完整的鞘内 3D CSF 几何形状和椎管中六个轴向位置的 CSF 流速。完成了八名 ALS 患者和十名健康对照者的扫描。对脊髓蛛网膜下腔进行手动分割，并结合椎管内脑脊液流动的内插模型。然后沿整个脊柱以 1 毫米的切片间隔生成几何和流体动力学参数。还完成了波形频谱内容和特征点的时间分析。结果 ALS 组和对照组的比较显示 ALS 队列中 CSF 流幅度降低和流传播速度增加。频谱谐波含量和几何比较的其他差异可能支持 ALS 组鞘内顺应性的整体下降。值得注意的是，病例之间存在高度可变性，一名 ALS 患者显示沿整个椎管的 CSF 流量几乎为零。结论 虽然我们的样本量限制了本研究中观察到的差异的统计置信度，但可以以非侵入性方式测量和量化个体间和队列变异。我们的研究还显示了基于 MRI 的 CSF 几何形状和流量测量的潜力，以提供有关脊髓蛛网膜下腔流体动力学环境的信息。可以进一步研究这些动态以了解健康和患病状态下 CSF 溶质运输的行为。