In-vitro gadolinium retro-microdialysis in agarose gel—a human brain phantom study

Rationale and objectivesCerebral microdialysis is a technique that enables monitoring of the neurochemistry of patients with significant acquired brain injury, such as traumatic brain injury (TBI) and subarachnoid haemorrhage (SAH). Cerebral microdialysis can also be used to characterise the neuro-p...

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Main Authors: Chisomo Zimphango, Marius O. Mada, Stephen J. Sawiak, Susan Giorgi-Coll, T. Adrian Carpenter, Peter J. Hutchinson, Keri L. H. Carpenter, Matthew G. Stovell
Format: Article
Language:English
Published: Frontiers Media S.A. 2024-01-01
Series:Frontiers in Radiology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fradi.2024.1085834/full
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author Chisomo Zimphango
Marius O. Mada
Marius O. Mada
Stephen J. Sawiak
Stephen J. Sawiak
Susan Giorgi-Coll
T. Adrian Carpenter
Peter J. Hutchinson
Peter J. Hutchinson
Keri L. H. Carpenter
Keri L. H. Carpenter
Matthew G. Stovell
Matthew G. Stovell
author_facet Chisomo Zimphango
Marius O. Mada
Marius O. Mada
Stephen J. Sawiak
Stephen J. Sawiak
Susan Giorgi-Coll
T. Adrian Carpenter
Peter J. Hutchinson
Peter J. Hutchinson
Keri L. H. Carpenter
Keri L. H. Carpenter
Matthew G. Stovell
Matthew G. Stovell
author_sort Chisomo Zimphango
collection DOAJ
description Rationale and objectivesCerebral microdialysis is a technique that enables monitoring of the neurochemistry of patients with significant acquired brain injury, such as traumatic brain injury (TBI) and subarachnoid haemorrhage (SAH). Cerebral microdialysis can also be used to characterise the neuro-pharmacokinetics of small-molecule study substrates using retrodialysis/retromicrodialysis. However, challenges remain: (i) lack of a simple, stable, and inexpensive brain tissue model for the study of drug neuropharmacology; and (ii) it is unclear how far small study-molecules administered via retrodialysis diffuse within the human brain.Materials and methodsHere, we studied the radial diffusion distance of small-molecule gadolinium-DTPA from microdialysis catheters in a newly developed, simple, stable, inexpensive brain tissue model as a precursor for in-vivo studies. Brain tissue models consisting of 0.65% weight/volume agarose gel in two kinds of buffers were created. The distribution of a paramagnetic contrast agent gadolinium-DTPA (Gd-DTPA) perfusion from microdialysis catheters using magnetic resonance imaging (MRI) was characterized as a surrogate for other small-molecule study substrates.ResultsWe found the mean radial diffusion distance of Gd-DTPA to be 18.5 mm after 24 h (p < 0.0001).ConclusionOur brain tissue model provides avenues for further tests and research into infusion studies using cerebral microdialysis, and consequently effective focal drug delivery for patients with TBI and other brain disorders.
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spelling doaj.art-58d2238cf65b4837b23deeaace3ff8192024-01-31T04:29:23ZengFrontiers Media S.A.Frontiers in Radiology2673-87402024-01-01410.3389/fradi.2024.10858341085834In-vitro gadolinium retro-microdialysis in agarose gel—a human brain phantom studyChisomo Zimphango0Marius O. Mada1Marius O. Mada2Stephen J. Sawiak3Stephen J. Sawiak4Susan Giorgi-Coll5T. Adrian Carpenter6Peter J. Hutchinson7Peter J. Hutchinson8Keri L. H. Carpenter9Keri L. H. Carpenter10Matthew G. Stovell11Matthew G. Stovell12Division of Neurosurgery, Department of Clinical Neurosciences, University of Cambridge, Cambridge, United KingdomWolfson Brain Imaging Centre, Department of Clinical Neurosciences, University of Cambridge, Cambridge, United KingdomMRC Cognition and Brain Sciences Unit, University of Cambridge, Cambridge, United KingdomWolfson Brain Imaging Centre, Department of Clinical Neurosciences, University of Cambridge, Cambridge, United KingdomDepartment of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, United KingdomDivision of Neurosurgery, Department of Clinical Neurosciences, University of Cambridge, Cambridge, United KingdomWolfson Brain Imaging Centre, Department of Clinical Neurosciences, University of Cambridge, Cambridge, United KingdomDivision of Neurosurgery, Department of Clinical Neurosciences, University of Cambridge, Cambridge, United KingdomWolfson Brain Imaging Centre, Department of Clinical Neurosciences, University of Cambridge, Cambridge, United KingdomDivision of Neurosurgery, Department of Clinical Neurosciences, University of Cambridge, Cambridge, United KingdomWolfson Brain Imaging Centre, Department of Clinical Neurosciences, University of Cambridge, Cambridge, United KingdomDivision of Neurosurgery, Department of Clinical Neurosciences, University of Cambridge, Cambridge, United KingdomDepartment of Neurosurgery, The Walton Centre, Liverpool, United KingdomRationale and objectivesCerebral microdialysis is a technique that enables monitoring of the neurochemistry of patients with significant acquired brain injury, such as traumatic brain injury (TBI) and subarachnoid haemorrhage (SAH). Cerebral microdialysis can also be used to characterise the neuro-pharmacokinetics of small-molecule study substrates using retrodialysis/retromicrodialysis. However, challenges remain: (i) lack of a simple, stable, and inexpensive brain tissue model for the study of drug neuropharmacology; and (ii) it is unclear how far small study-molecules administered via retrodialysis diffuse within the human brain.Materials and methodsHere, we studied the radial diffusion distance of small-molecule gadolinium-DTPA from microdialysis catheters in a newly developed, simple, stable, inexpensive brain tissue model as a precursor for in-vivo studies. Brain tissue models consisting of 0.65% weight/volume agarose gel in two kinds of buffers were created. The distribution of a paramagnetic contrast agent gadolinium-DTPA (Gd-DTPA) perfusion from microdialysis catheters using magnetic resonance imaging (MRI) was characterized as a surrogate for other small-molecule study substrates.ResultsWe found the mean radial diffusion distance of Gd-DTPA to be 18.5 mm after 24 h (p < 0.0001).ConclusionOur brain tissue model provides avenues for further tests and research into infusion studies using cerebral microdialysis, and consequently effective focal drug delivery for patients with TBI and other brain disorders.https://www.frontiersin.org/articles/10.3389/fradi.2024.1085834/fullgadoliniumdiffusionMRIbrain phantomagarmicrodialysis
spellingShingle Chisomo Zimphango
Marius O. Mada
Marius O. Mada
Stephen J. Sawiak
Stephen J. Sawiak
Susan Giorgi-Coll
T. Adrian Carpenter
Peter J. Hutchinson
Peter J. Hutchinson
Keri L. H. Carpenter
Keri L. H. Carpenter
Matthew G. Stovell
Matthew G. Stovell
In-vitro gadolinium retro-microdialysis in agarose gel—a human brain phantom study
Frontiers in Radiology
gadolinium
diffusion
MRI
brain phantom
agar
microdialysis
title In-vitro gadolinium retro-microdialysis in agarose gel—a human brain phantom study
title_full In-vitro gadolinium retro-microdialysis in agarose gel—a human brain phantom study
title_fullStr In-vitro gadolinium retro-microdialysis in agarose gel—a human brain phantom study
title_full_unstemmed In-vitro gadolinium retro-microdialysis in agarose gel—a human brain phantom study
title_short In-vitro gadolinium retro-microdialysis in agarose gel—a human brain phantom study
title_sort in vitro gadolinium retro microdialysis in agarose gel a human brain phantom study
topic gadolinium
diffusion
MRI
brain phantom
agar
microdialysis
url https://www.frontiersin.org/articles/10.3389/fradi.2024.1085834/full
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