Three-Dimensional Iron Oxide Nanoparticle-Based Contrast-Enhanced Magnetic Resonance Imaging for Characterization of Cerebral Arteriogenesis in the Mouse Neocortex

Purpose: Subsurface blood vessels in the cerebral cortex have been identified as a bottleneck in cerebral perfusion with the potential for collateral remodeling. However, valid techniques for non-invasive, longitudinal characterization of neocortical microvessels are still lacking. In this study, we...

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Autores principales: Till de Bortoli, Philipp Boehm-Sturm, Stefan P. Koch, Melina Nieminen-Kelhä, Lars Wessels, Susanne Mueller, Giovanna D. Ielacqua, Jan Klohs, Peter Vajkoczy, Nils Hecht
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Publicado: Frontiers Media S.A. 2021
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spelling oai:doaj.org-article:11bcb034aa864a1d82d3645863352de82021-12-01T08:23:08ZThree-Dimensional Iron Oxide Nanoparticle-Based Contrast-Enhanced Magnetic Resonance Imaging for Characterization of Cerebral Arteriogenesis in the Mouse Neocortex1662-453X10.3389/fnins.2021.756577https://doaj.org/article/11bcb034aa864a1d82d3645863352de82021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fnins.2021.756577/fullhttps://doaj.org/toc/1662-453XPurpose: Subsurface blood vessels in the cerebral cortex have been identified as a bottleneck in cerebral perfusion with the potential for collateral remodeling. However, valid techniques for non-invasive, longitudinal characterization of neocortical microvessels are still lacking. In this study, we validated contrast-enhanced magnetic resonance imaging (CE-MRI) for in vivo characterization of vascular changes in a model of spontaneous collateral outgrowth following chronic cerebral hypoperfusion.Methods: C57BL/6J mice were randomly assigned to unilateral internal carotid artery occlusion or sham surgery and after 21 days, CE-MRI based on T2*-weighted imaging was performed using ultra-small superparamagnetic iron oxide nanoparticles to obtain subtraction angiographies and steady-state cerebral blood volume (ss-CBV) maps. First pass dynamic susceptibility contrast MRI (DSC-MRI) was performed for internal validation of ss-CBV. Further validation at the histological level was provided by ex vivo serial two-photon tomography (STP).Results: Qualitatively, an increase in vessel density was observed on CE-MRI subtraction angiographies following occlusion; however, a quantitative vessel tracing analysis was prone to errors in our model. Measurements of ss-CBV reliably identified an increase in cortical vasculature, validated by DSC-MRI and STP.Conclusion: Iron oxide nanoparticle-based ss-CBV serves as a robust, non-invasive imaging surrogate marker for neocortical vessels, with the potential to reduce and refine preclinical models targeting the development and outgrowth of cerebral collateralization.Till de BortoliTill de BortoliPhilipp Boehm-SturmPhilipp Boehm-SturmPhilipp Boehm-SturmStefan P. KochStefan P. KochStefan P. KochMelina Nieminen-KelhäMelina Nieminen-KelhäLars WesselsLars WesselsSusanne MuellerSusanne MuellerSusanne MuellerGiovanna D. IelacquaJan KlohsPeter VajkoczyPeter VajkoczyNils HechtNils HechtFrontiers Media S.A.articlecontrast-enhanced MRIcerebral blood volumeiron oxide nanoparticlesstrokecerebrovascular diseasevessel imagingNeurosciences. Biological psychiatry. NeuropsychiatryRC321-571ENFrontiers in Neuroscience, Vol 15 (2021)
institution DOAJ
collection DOAJ
language EN
topic contrast-enhanced MRI
cerebral blood volume
iron oxide nanoparticles
stroke
cerebrovascular disease
vessel imaging
Neurosciences. Biological psychiatry. Neuropsychiatry
RC321-571
spellingShingle contrast-enhanced MRI
cerebral blood volume
iron oxide nanoparticles
stroke
cerebrovascular disease
vessel imaging
Neurosciences. Biological psychiatry. Neuropsychiatry
RC321-571
Till de Bortoli
Till de Bortoli
Philipp Boehm-Sturm
Philipp Boehm-Sturm
Philipp Boehm-Sturm
Stefan P. Koch
Stefan P. Koch
Stefan P. Koch
Melina Nieminen-Kelhä
Melina Nieminen-Kelhä
Lars Wessels
Lars Wessels
Susanne Mueller
Susanne Mueller
Susanne Mueller
Giovanna D. Ielacqua
Jan Klohs
Peter Vajkoczy
Peter Vajkoczy
Nils Hecht
Nils Hecht
Three-Dimensional Iron Oxide Nanoparticle-Based Contrast-Enhanced Magnetic Resonance Imaging for Characterization of Cerebral Arteriogenesis in the Mouse Neocortex
description Purpose: Subsurface blood vessels in the cerebral cortex have been identified as a bottleneck in cerebral perfusion with the potential for collateral remodeling. However, valid techniques for non-invasive, longitudinal characterization of neocortical microvessels are still lacking. In this study, we validated contrast-enhanced magnetic resonance imaging (CE-MRI) for in vivo characterization of vascular changes in a model of spontaneous collateral outgrowth following chronic cerebral hypoperfusion.Methods: C57BL/6J mice were randomly assigned to unilateral internal carotid artery occlusion or sham surgery and after 21 days, CE-MRI based on T2*-weighted imaging was performed using ultra-small superparamagnetic iron oxide nanoparticles to obtain subtraction angiographies and steady-state cerebral blood volume (ss-CBV) maps. First pass dynamic susceptibility contrast MRI (DSC-MRI) was performed for internal validation of ss-CBV. Further validation at the histological level was provided by ex vivo serial two-photon tomography (STP).Results: Qualitatively, an increase in vessel density was observed on CE-MRI subtraction angiographies following occlusion; however, a quantitative vessel tracing analysis was prone to errors in our model. Measurements of ss-CBV reliably identified an increase in cortical vasculature, validated by DSC-MRI and STP.Conclusion: Iron oxide nanoparticle-based ss-CBV serves as a robust, non-invasive imaging surrogate marker for neocortical vessels, with the potential to reduce and refine preclinical models targeting the development and outgrowth of cerebral collateralization.
format article
author Till de Bortoli
Till de Bortoli
Philipp Boehm-Sturm
Philipp Boehm-Sturm
Philipp Boehm-Sturm
Stefan P. Koch
Stefan P. Koch
Stefan P. Koch
Melina Nieminen-Kelhä
Melina Nieminen-Kelhä
Lars Wessels
Lars Wessels
Susanne Mueller
Susanne Mueller
Susanne Mueller
Giovanna D. Ielacqua
Jan Klohs
Peter Vajkoczy
Peter Vajkoczy
Nils Hecht
Nils Hecht
author_facet Till de Bortoli
Till de Bortoli
Philipp Boehm-Sturm
Philipp Boehm-Sturm
Philipp Boehm-Sturm
Stefan P. Koch
Stefan P. Koch
Stefan P. Koch
Melina Nieminen-Kelhä
Melina Nieminen-Kelhä
Lars Wessels
Lars Wessels
Susanne Mueller
Susanne Mueller
Susanne Mueller
Giovanna D. Ielacqua
Jan Klohs
Peter Vajkoczy
Peter Vajkoczy
Nils Hecht
Nils Hecht
author_sort Till de Bortoli
title Three-Dimensional Iron Oxide Nanoparticle-Based Contrast-Enhanced Magnetic Resonance Imaging for Characterization of Cerebral Arteriogenesis in the Mouse Neocortex
title_short Three-Dimensional Iron Oxide Nanoparticle-Based Contrast-Enhanced Magnetic Resonance Imaging for Characterization of Cerebral Arteriogenesis in the Mouse Neocortex
title_full Three-Dimensional Iron Oxide Nanoparticle-Based Contrast-Enhanced Magnetic Resonance Imaging for Characterization of Cerebral Arteriogenesis in the Mouse Neocortex
title_fullStr Three-Dimensional Iron Oxide Nanoparticle-Based Contrast-Enhanced Magnetic Resonance Imaging for Characterization of Cerebral Arteriogenesis in the Mouse Neocortex
title_full_unstemmed Three-Dimensional Iron Oxide Nanoparticle-Based Contrast-Enhanced Magnetic Resonance Imaging for Characterization of Cerebral Arteriogenesis in the Mouse Neocortex
title_sort three-dimensional iron oxide nanoparticle-based contrast-enhanced magnetic resonance imaging for characterization of cerebral arteriogenesis in the mouse neocortex
publisher Frontiers Media S.A.
publishDate 2021
url https://doaj.org/article/11bcb034aa864a1d82d3645863352de8
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