Zhu Yuran, Zhu Junqing, Ni Chenxin, Chen Anbang, Li Longshun, Gao Yue, Shoffstall Andrew J, Yu Xin
Department of Biomedical Engineering, Case Western Reserve University, Cleveland, Ohio, USA.
Department of Radiology, Case Western Reserve University, Cleveland, Ohio, USA.
bioRxiv. 2025 Jan 24:2025.01.21.634133. doi: 10.1101/2025.01.21.634133.
Tracer imaging has been instrumental in mapping the brain's solute transport pathways facilitated by cerebrospinal fluid (CSF) flow. However, the impact of tracer infusion parameters on CSF flow remains incompletely understood. This study evaluated the influence of infusion location, rate, and anesthetic regimens on tracer transport using dynamic contrast-enhanced MRI with Gd-DTPA as a CSF tracer. Infusion rate effects were assessed by administering Gd-DTPA into the cisterna magna (ICM) at two rates under isoflurane anesthesia. Anesthetic effects were evaluated by comparing transport patterns between isoflurane and ketamine/xylazine (K/X) anesthesia at the slower rate. Gd-DTPA transport was also examined after lateral ventricle (ICV) infusion, the primary site of CSF production. The results demonstrate that, besides anesthesia, both the location and rate of infusion substantially affected solute transport within the brain. ICV infusion led to rapid, extensive transport into deep brain regions, while slower ICM infusion resulted in more pronounced transport to dorsal brain regions. Cross-correlation and hierarchical clustering analyses of region-specific Gd-DTPA signal time courses revealed that ICM infusion facilitated transport along periarterial spaces, while ICV infusion favored transport across the ventricular-parenchymal interface. These findings underscore the importance of experimental conditions in influencing tracer kinetics and spatial distribution in the brain.
示踪成像在绘制由脑脊液（CSF）流动促进的大脑溶质转运途径方面发挥了重要作用。然而，示踪剂注入参数对脑脊液流动的影响仍未完全了解。本研究使用以钆喷酸葡胺（Gd-DTPA）作为脑脊液示踪剂的动态对比增强磁共振成像（MRI），评估了注入位置、速率和麻醉方案对示踪剂转运的影响。通过在异氟烷麻醉下以两种速率将Gd-DTPA注入小脑延髓池（ICM）来评估注入速率的影响。通过比较异氟烷麻醉和氯胺酮/赛拉嗪（K/X）麻醉在较慢速率下的转运模式来评估麻醉效果。在侧脑室（ICV）注入后，也对Gd-DTPA的转运进行了检查，侧脑室是脑脊液产生的主要部位。结果表明，除了麻醉外，注入的位置和速率均对脑内溶质转运有显著影响。ICV注入导致快速、广泛地转运至脑深部区域，而较慢的ICM注入则导致向脑背侧区域的转运更为明显。对特定区域的Gd-DTPA信号时间进程进行互相关和层次聚类分析表明，ICM注入促进沿动脉周围间隙的转运，而ICV注入则有利于跨脑室-实质界面的转运。这些发现强调了实验条件在影响脑内示踪剂动力学和空间分布方面的重要性。
