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Transport Pathways and Kinetics of Cerebrospinal Fluid Tracers in Mouse Brain Observed by Dynamic Contrast-Enhanced MRI

BACKGROUND: Recent studies have suggested the glymphatic system as a solute transport pathway and waste removal mechanism in the brain. Imaging intracisternally administered tracers provides the opportunity of assessing various aspects of the glymphatic function. Dynamic contrast-enhanced magnetic r...

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Autores principales: Zhu, Yuran, Wang, Guanhua, Kolluru, Chaitanya, Gu, Yuning, Gao, Huiyun, Zhang, Jing, Wang, Yunmei, Wilson, David L., Zhu, Xiaofeng, Flask, Chris A., Yu, Xin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Journal Experts 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9934740/
https://www.ncbi.nlm.nih.gov/pubmed/36798228
http://dx.doi.org/10.21203/rs.3.rs-2544475/v1
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author Zhu, Yuran
Wang, Guanhua
Kolluru, Chaitanya
Gu, Yuning
Gao, Huiyun
Zhang, Jing
Wang, Yunmei
Wilson, David L.
Zhu, Xiaofeng
Flask, Chris A.
Yu, Xin
author_facet Zhu, Yuran
Wang, Guanhua
Kolluru, Chaitanya
Gu, Yuning
Gao, Huiyun
Zhang, Jing
Wang, Yunmei
Wilson, David L.
Zhu, Xiaofeng
Flask, Chris A.
Yu, Xin
author_sort Zhu, Yuran
collection PubMed
description BACKGROUND: Recent studies have suggested the glymphatic system as a solute transport pathway and waste removal mechanism in the brain. Imaging intracisternally administered tracers provides the opportunity of assessing various aspects of the glymphatic function. Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) allows the evaluation of both the kinetics and spatial distribution of tracer transport in the whole brain. However, assessing mouse glymphatic function by DCE-MRI has been challenged by the small size of a mouse brain and the limited volume of fluids that can be delivered intracisternally without significantly altering the intracranial pressure. Further, previous studies in rats suggest that assessment of glymphatic function by DCE-MRI is dependent on the molecular size of the contrast agents. METHODS: We established and validated an intracisternal infusion protocol in mice that allowed the measurements of the entire time course of contrast agent transport for 2 hours. The transport kinetics and distribution of three MRI contrast agents with drastically different molecular weights (MWs): Gd-DTPA (MW=661.8 Da, n=7), GadoSpin-P (MW=200 kDa, n=6), and oxygen-17 enriched water (H(2)(17)O, MW=19 Da, n=7), were investigated. RESULTS: The transport of H(2)(17)O was significantly faster and more extensive than the two gadolinium-based contrast agents. Time-lagged correlation analysis and clustering analysis comparing the kinetics of Gd-DTPA and H(2)(17)O transport also showed different cluster patterns and lag time between different regions of the brain, suggesting different transport pathways for H(2)(17)O because of its direct access to parenchymal tissues via the aquaporin-4 water channels. Further, there were also significant differences in the transport kinetics of the three tracers to the lateral ventricles, which reflects the differences in forces that drive tracer transport in the brain. CONCLUSIONS: Comparison of the transport kinetics and distribution of three MRI contrast agents with different molecular sizes showed drastically different transport profiles and clustering patterns, suggesting that the transport pathways and kinetics in the glymphatic system are size-dependent.
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spelling pubmed-99347402023-02-17 Transport Pathways and Kinetics of Cerebrospinal Fluid Tracers in Mouse Brain Observed by Dynamic Contrast-Enhanced MRI Zhu, Yuran Wang, Guanhua Kolluru, Chaitanya Gu, Yuning Gao, Huiyun Zhang, Jing Wang, Yunmei Wilson, David L. Zhu, Xiaofeng Flask, Chris A. Yu, Xin Res Sq Article BACKGROUND: Recent studies have suggested the glymphatic system as a solute transport pathway and waste removal mechanism in the brain. Imaging intracisternally administered tracers provides the opportunity of assessing various aspects of the glymphatic function. Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) allows the evaluation of both the kinetics and spatial distribution of tracer transport in the whole brain. However, assessing mouse glymphatic function by DCE-MRI has been challenged by the small size of a mouse brain and the limited volume of fluids that can be delivered intracisternally without significantly altering the intracranial pressure. Further, previous studies in rats suggest that assessment of glymphatic function by DCE-MRI is dependent on the molecular size of the contrast agents. METHODS: We established and validated an intracisternal infusion protocol in mice that allowed the measurements of the entire time course of contrast agent transport for 2 hours. The transport kinetics and distribution of three MRI contrast agents with drastically different molecular weights (MWs): Gd-DTPA (MW=661.8 Da, n=7), GadoSpin-P (MW=200 kDa, n=6), and oxygen-17 enriched water (H(2)(17)O, MW=19 Da, n=7), were investigated. RESULTS: The transport of H(2)(17)O was significantly faster and more extensive than the two gadolinium-based contrast agents. Time-lagged correlation analysis and clustering analysis comparing the kinetics of Gd-DTPA and H(2)(17)O transport also showed different cluster patterns and lag time between different regions of the brain, suggesting different transport pathways for H(2)(17)O because of its direct access to parenchymal tissues via the aquaporin-4 water channels. Further, there were also significant differences in the transport kinetics of the three tracers to the lateral ventricles, which reflects the differences in forces that drive tracer transport in the brain. CONCLUSIONS: Comparison of the transport kinetics and distribution of three MRI contrast agents with different molecular sizes showed drastically different transport profiles and clustering patterns, suggesting that the transport pathways and kinetics in the glymphatic system are size-dependent. American Journal Experts 2023-02-07 /pmc/articles/PMC9934740/ /pubmed/36798228 http://dx.doi.org/10.21203/rs.3.rs-2544475/v1 Text en https://creativecommons.org/licenses/by/4.0/This work is licensed under a Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/) , which allows reusers to distribute, remix, adapt, and build upon the material in any medium or format, so long as attribution is given to the creator. The license allows for commercial use. https://creativecommons.org/licenses/by/4.0/License: This work is licensed under a Creative Commons Attribution 4.0 International License. Read Full License (https://creativecommons.org/licenses/by/4.0/)
spellingShingle Article
Zhu, Yuran
Wang, Guanhua
Kolluru, Chaitanya
Gu, Yuning
Gao, Huiyun
Zhang, Jing
Wang, Yunmei
Wilson, David L.
Zhu, Xiaofeng
Flask, Chris A.
Yu, Xin
Transport Pathways and Kinetics of Cerebrospinal Fluid Tracers in Mouse Brain Observed by Dynamic Contrast-Enhanced MRI
title Transport Pathways and Kinetics of Cerebrospinal Fluid Tracers in Mouse Brain Observed by Dynamic Contrast-Enhanced MRI
title_full Transport Pathways and Kinetics of Cerebrospinal Fluid Tracers in Mouse Brain Observed by Dynamic Contrast-Enhanced MRI
title_fullStr Transport Pathways and Kinetics of Cerebrospinal Fluid Tracers in Mouse Brain Observed by Dynamic Contrast-Enhanced MRI
title_full_unstemmed Transport Pathways and Kinetics of Cerebrospinal Fluid Tracers in Mouse Brain Observed by Dynamic Contrast-Enhanced MRI
title_short Transport Pathways and Kinetics of Cerebrospinal Fluid Tracers in Mouse Brain Observed by Dynamic Contrast-Enhanced MRI
title_sort transport pathways and kinetics of cerebrospinal fluid tracers in mouse brain observed by dynamic contrast-enhanced mri
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9934740/
https://www.ncbi.nlm.nih.gov/pubmed/36798228
http://dx.doi.org/10.21203/rs.3.rs-2544475/v1
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