Non-invasive MRI quantification of cerebrospinal fluid dynamics in amyotrophic lateral sclerosis patients.
Amyotrophic lateral sclerosis
Cerebrospinal fluid
Intrathecal drug delivery
Magnetic resonance imaging
Spinal cord
Journal
Fluids and barriers of the CNS
ISSN: 2045-8118
Titre abrégé: Fluids Barriers CNS
Pays: England
ID NLM: 101553157
Informations de publication
Date de publication:
21 Jan 2020
21 Jan 2020
Historique:
received:
26
07
2019
accepted:
19
12
2019
entrez:
22
1
2020
pubmed:
22
1
2020
medline:
20
11
2020
Statut:
epublish
Résumé
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. 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. 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. 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.
Sections du résumé
BACKGROUND
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
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
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
CONCLUSIONS
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.
Identifiants
pubmed: 31959193
doi: 10.1186/s12987-019-0164-3
pii: 10.1186/s12987-019-0164-3
pmc: PMC6971921
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
4Subventions
Organisme : NIGMS NIH HHS
ID : P20 GM103408
Pays : United States
Organisme : NIGMS NIH HHS
ID : 4U54GM104944-04TBD
Pays : United States
Organisme : NINDS NIH HHS
ID : 1R01NS111283-01
Pays : United States
Organisme : The National Institutes of Mental Health
ID : 1R44MH112210-01A1
Organisme : NIGMS NIH HHS
ID : P20GM1033408
Pays : United States
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