In vivo distribution of cerebrospinal fluid tracer in human upper spinal cord and brain stem
Erik Melin, Are Hugo Pripp, Per Kristian Eide, Geir Ringstad
Erik Melin, Are Hugo Pripp, Per Kristian Eide, Geir Ringstad
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Clinical Research and Public Health Neuroscience

In vivo distribution of cerebrospinal fluid tracer in human upper spinal cord and brain stem

Abstract

BACKGROUND Intrathecal injection is an attractive route through which drugs can be administered and directed to the spinal cord, restricted by the blood-spinal cord barrier. However, in vivo data on the distribution of cerebrospinal fluid (CSF) substances in the human spinal cord are lacking. We conducted this study to assess the enrichment of a CSF tracer in the upper cervical spinal cord and the brain stem.METHODS After lumbar intrathecal injection of a magnetic resonance imaging (MRI) contrast agent, gadobutrol, repeated blood samples and MRI of the upper cervical spinal cord, brain stem, and adjacent subarachnoid spaces (SAS) were obtained through 48 hours. The MRI scans were then analyzed for tracer distribution in the different regions and correlated to age, disease, and amounts of tracer in the blood to determine CSF-to-blood clearance.RESULTS The study included 26 reference individuals and 35 patients with the dementia subtype idiopathic normal pressure hydrocephalus (iNPH). The tracer enriched all analyzed regions. Moreover, tracer enrichment in parenchyma was associated with tracer enrichment in the adjacent SAS and with CSF-to-blood clearance. Clearance from the CSF was delayed in patients with iNPH compared with younger reference patients.CONCLUSION A CSF tracer substance administered to the lumbar thecal sac can access the parenchyma of the upper cervical spinal cord and brain stem. Since CSF-to-blood clearance is highly individual and is associated with tracer level in CSF, clearance assessment may be used to tailor intrathecal treatment regimes.FUNDING South-Eastern Norway Regional Health and Østfold Hospital Trust supported the research and publication of this work.

Authors

Erik Melin, Are Hugo Pripp, Per Kristian Eide, Geir Ringstad

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Figure 1

Tracer distribution over time and regions of interest for one reference patient.

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Tracer distribution over time and regions of interest for one reference ...
(A–E) Images of all time points and anatomical regions: mesencephalon (A), pons (B), medulla oblongata (C), C1 level of the spinal cord (D), and C3-level of the spinal cord (E). The 3D T1 images for all time points were first registered using Philips IntelliSpace, version 12.1. The signal in the T1-weighted images before contrast was then subtracted from the normalized signal for each time point. The tracer moves in a centripetal direction with higher and earlier detected levels of tracer in the superficial regions compared with the deep regions. For each time point, 15 regions of interest (ROIs) were placed on axial T1-weighted images in the hospital’s picture and archiving system (Sectra, version 7). The ROIs for each region are marked with circles in the anatomical images: blue represents ROIs in cerebrospinal fluid, yellow represents ROIs in the superficial parts of the parenchyma, and red represents ROIs in the deep parts of the parenchyma.