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...
Main Authors: | , , , , , , , |
---|---|
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 |
_version_ | 1797338414386774016 |
---|---|
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. |
first_indexed | 2024-03-08T09:30:52Z |
format | Article |
id | doaj.art-58d2238cf65b4837b23deeaace3ff819 |
institution | Directory Open Access Journal |
issn | 2673-8740 |
language | English |
last_indexed | 2024-03-08T09:30:52Z |
publishDate | 2024-01-01 |
publisher | Frontiers Media S.A. |
record_format | Article |
series | Frontiers in Radiology |
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 |
work_keys_str_mv | AT chisomozimphango invitrogadoliniumretromicrodialysisinagarosegelahumanbrainphantomstudy AT mariusomada invitrogadoliniumretromicrodialysisinagarosegelahumanbrainphantomstudy AT mariusomada invitrogadoliniumretromicrodialysisinagarosegelahumanbrainphantomstudy AT stephenjsawiak invitrogadoliniumretromicrodialysisinagarosegelahumanbrainphantomstudy AT stephenjsawiak invitrogadoliniumretromicrodialysisinagarosegelahumanbrainphantomstudy AT susangiorgicoll invitrogadoliniumretromicrodialysisinagarosegelahumanbrainphantomstudy AT tadriancarpenter invitrogadoliniumretromicrodialysisinagarosegelahumanbrainphantomstudy AT peterjhutchinson invitrogadoliniumretromicrodialysisinagarosegelahumanbrainphantomstudy AT peterjhutchinson invitrogadoliniumretromicrodialysisinagarosegelahumanbrainphantomstudy AT kerilhcarpenter invitrogadoliniumretromicrodialysisinagarosegelahumanbrainphantomstudy AT kerilhcarpenter invitrogadoliniumretromicrodialysisinagarosegelahumanbrainphantomstudy AT matthewgstovell invitrogadoliniumretromicrodialysisinagarosegelahumanbrainphantomstudy AT matthewgstovell invitrogadoliniumretromicrodialysisinagarosegelahumanbrainphantomstudy |