Uncertainty quantification of parenchymal tracer distribution using random diffusion and convective velocity fields

<br/><strong>Background: </strong>Influx and clearance of substances in the brain parenchyma occur by a combination of diffusion and convection, but the relative importance of these mechanisms is unclear. Accurate modeling of tracer distributions in the brain relies on parameters t...

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Main Authors: Croci, M, Vinje, V, Rognes, M
Format: Journal article
Published: BioMed Central 2019
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author Croci, M
Vinje, V
Rognes, M
author_facet Croci, M
Vinje, V
Rognes, M
author_sort Croci, M
collection OXFORD
description <br/><strong>Background: </strong>Influx and clearance of substances in the brain parenchyma occur by a combination of diffusion and convection, but the relative importance of these mechanisms is unclear. Accurate modeling of tracer distributions in the brain relies on parameters that are partially unknown and with literature values varying by several orders of magnitude. In this work, we rigorously quantified the variability of tracer distribution in the brain resulting from uncertainty in diffusion and convection model parameters.<br/><strong>Methods: </strong>Using the convection–diffusion–reaction equation, we simulated tracer distribution in the brain parenchyma after intrathecal injection. Several models were tested to assess the uncertainty both in type of diffusion and velocity fields and also the importance of their magnitude. Our results were compared with experimental MRI results of tracer enhancement.<br/><strong>Results: </strong>In models of pure diffusion, the expected amount of tracer in the gray matter reached peak value after 15 h, while the white matter did not reach peak within 24 h with high likelihood. Models of the glymphatic system were similar qualitatively to the models of pure diffusion with respect to expected time to peak but displayed less variability. However, the expected time to peak was reduced to 11 h when an additional directionality was prescribed for the glymphatic circulation. In a model including drainage directly from the brain parenchyma, time to peak occured after 6–8 h for the gray matter.<br/><strong>Conclusion: </strong>Even when uncertainties are taken into account, we find that diffusion alone is not sufficient to explain transport of tracer deep into the white matter as seen in experimental data. A glymphatic velocity field may increase transport if a large-scale directional structure is included in the glymphatic circulation.
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spelling oxford-uuid:e57c7041-c2bc-4b6c-9fd2-6144a466b8752022-03-27T10:24:23ZUncertainty quantification of parenchymal tracer distribution using random diffusion and convective velocity fieldsJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:e57c7041-c2bc-4b6c-9fd2-6144a466b875Symplectic Elements at OxfordBioMed Central2019Croci, MVinje, VRognes, M<br/><strong>Background: </strong>Influx and clearance of substances in the brain parenchyma occur by a combination of diffusion and convection, but the relative importance of these mechanisms is unclear. Accurate modeling of tracer distributions in the brain relies on parameters that are partially unknown and with literature values varying by several orders of magnitude. In this work, we rigorously quantified the variability of tracer distribution in the brain resulting from uncertainty in diffusion and convection model parameters.<br/><strong>Methods: </strong>Using the convection–diffusion–reaction equation, we simulated tracer distribution in the brain parenchyma after intrathecal injection. Several models were tested to assess the uncertainty both in type of diffusion and velocity fields and also the importance of their magnitude. Our results were compared with experimental MRI results of tracer enhancement.<br/><strong>Results: </strong>In models of pure diffusion, the expected amount of tracer in the gray matter reached peak value after 15 h, while the white matter did not reach peak within 24 h with high likelihood. Models of the glymphatic system were similar qualitatively to the models of pure diffusion with respect to expected time to peak but displayed less variability. However, the expected time to peak was reduced to 11 h when an additional directionality was prescribed for the glymphatic circulation. In a model including drainage directly from the brain parenchyma, time to peak occured after 6–8 h for the gray matter.<br/><strong>Conclusion: </strong>Even when uncertainties are taken into account, we find that diffusion alone is not sufficient to explain transport of tracer deep into the white matter as seen in experimental data. A glymphatic velocity field may increase transport if a large-scale directional structure is included in the glymphatic circulation.
spellingShingle Croci, M
Vinje, V
Rognes, M
Uncertainty quantification of parenchymal tracer distribution using random diffusion and convective velocity fields
title Uncertainty quantification of parenchymal tracer distribution using random diffusion and convective velocity fields
title_full Uncertainty quantification of parenchymal tracer distribution using random diffusion and convective velocity fields
title_fullStr Uncertainty quantification of parenchymal tracer distribution using random diffusion and convective velocity fields
title_full_unstemmed Uncertainty quantification of parenchymal tracer distribution using random diffusion and convective velocity fields
title_short Uncertainty quantification of parenchymal tracer distribution using random diffusion and convective velocity fields
title_sort uncertainty quantification of parenchymal tracer distribution using random diffusion and convective velocity fields
work_keys_str_mv AT crocim uncertaintyquantificationofparenchymaltracerdistributionusingrandomdiffusionandconvectivevelocityfields
AT vinjev uncertaintyquantificationofparenchymaltracerdistributionusingrandomdiffusionandconvectivevelocityfields
AT rognesm uncertaintyquantificationofparenchymaltracerdistributionusingrandomdiffusionandconvectivevelocityfields