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Microdistribution of Magnetic Resonance Imaging Contrast Agents in Atherosclerotic Plaques Determined by LA-ICP-MS and SR-μXRF Imaging

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Title: Microdistribution of Magnetic Resonance Imaging Contrast Agents in Atherosclerotic Plaques Determined by LA-ICP-MS and SR-μXRF Imaging
Authors: Yavuz Oguz Uca, David Hallmann, Bernhard Hesse, Christian Seim, Nicola Stolzenburg, Hubertus Pietsch, Jörg Schnorr, Matthias Taupitz
Source: Mol Imaging Biol
'Molecular Imaging and Biology ', vol: 23, pages: 382-393 (2021)
Publisher Information: Springer Science and Business Media LLC, 2020.
Publication Year: 2020
Subject Terms: Male, 0301 basic medicine, Iron, extracellular matrix, Contrast Media, Metal Nanoparticles, Gadolinium, Ferric Compounds, Mass Spectrometry, Arterial calcification, Iron oxide nanoparticles, 03 medical and health sciences, 0302 clinical medicine, X-Ray Diffraction, Animals, SXRFS, Magnetite Nanoparticles, LA-ICP-MS, elemental microscopy, Macrophages, 500 Naturwissenschaften und Mathematik::530 Physik::530 Physik, arterial calcification, Angiography, iron oxide nanoparticles, Extracellular matrix, Atherosclerosis, Magnetic Resonance Imaging, Plaque, Atherosclerotic, Extracellular Matrix, Macrophages/pathology [MeSH], Extracellular Matrix/metabolism [MeSH], MRI, Iron/chemistry [MeSH], Angiography [MeSH], Plaque, Atherosclerotic/diagnostic imaging [MeSH], Male [MeSH], Atherosclerosis/diagnostic imaging [MeSH], X-Ray Diffraction/methods [MeSH], Rabbits [MeSH], Research Article, Synchrotrons [MeSH], Gadolinium/chemistry [MeSH], Animals [MeSH], Magnetite Nanoparticles/chemistry [MeSH], Metal Nanoparticles/chemistry [MeSH], Elemental microscopy, Magnetic Resonance Imaging/methods [MeSH], Mass Spectrometry/methods [MeSH], Contrast Media/chemistry [MeSH], Ferric Compounds/chemistry [MeSH], Rabbits, atherosclerosis, Synchrotrons, 600 Technik, Medizin, angewandte Wissenschaften::610 Medizin und Gesundheit::610 Medizin und Gesundheit
Description: Purpose Contrast-enhanced magnetic resonance imaging (MRI) has the potential to replace angiographic evaluation of atherosclerosis. While studies have investigated contrast agent (CA) uptake in atherosclerotic plaques, exact CA spatial distribution on a microscale is elusive. The purpose of this study was to investigate the microdistribution of gadolinium (Gd)- and iron (Fe) oxide-based CA in atherosclerotic plaques of New Zealand White rabbits. Procedures The study was performed as a post hoc analysis of archived tissue specimens obtained in a previous in vivo MRI study conducted to investigate signal changes induced by very small superparamagnetic iron oxide nanoparticles (VSOP) and Gd-BOPTA. For analytical discrimination from endogenous Fe, VSOP were doped with europium (Eu) resulting in Eu-VSOP. Formalin-fixed arterial specimens were cut into 5-μm serial sections and analyzed by immunohistochemistry (IHC: Movat’s pentachrome, von Kossa, and Alcian blue (pH 1.0) staining, anti-smooth muscle cell actin (anti-SMA), and anti-rabbit macrophage (anti-RAM-11) immunostaining) and elemental microscopy with laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) and synchrotron radiation μX-ray fluorescence (SR-μXRF) spectroscopy. Elemental distribution maps of Fe, Eu, Gd, sulfur (S), phosphorus (P), and calcium (Ca) were investigated. Results IHC characterized atherosclerotic plaque pathomorphology. Elemental microscopy showed S distribution to match the anatomy of arterial vessel wall layers, while P distribution corresponded well with cellular areas. LA-ICP-MS revealed Gd and Fe with a limit of detection of ~ 0.1 nmol/g and ~ 100 nmol/g, respectively. Eu-positive signal identified VSOP presence in the vessel wall and allowed the comparison of Eu-VSOP and endogenous Fe distribution in tissue sections. Extracellular matrix material correlated with Eu signal intensity, Fe concentration, and maximum Gd concentration. Eu-VSOP were confined to endothelium in early lesions but accumulated in cellular areas in advanced plaques. Gd distribution was homogeneous in healthy arteries but inhomogeneous in early and advanced plaques. SR-μXRF scans at 0.5 μm resolution revealed Gd hotspots with increased P and Ca concentrations at the intimomedial interface, and a size distribution ranging from a few micrometers to submicrometers. Conclusions Eu-VSOP and Gd have distinct spatial distributions in atherosclerotic plaques. While Eu-VSOP distribution is more cell-associated and might be used to monitor atherosclerotic plaque progression, Gd distribution indicates arterial calcification and might help in characterizing plaque vulnerability.
Document Type: Article
Other literature type
File Description: application/pdf
Language: English
ISSN: 1860-2002
1536-1632
DOI: 10.1007/s11307-020-01563-z
DOI: 10.17169/refubium-36034
DOI: 10.14279/depositonce-18072
Access URL: https://link.springer.com/content/pdf/10.1007/s11307-020-01563-z.pdf
https://pubmed.ncbi.nlm.nih.gov/33289060
https://epn-library.esrf.fr/flora/jsp/index_view_direct_anonymous.jsp?record=doc:PUB_ESRF:56751
https://pubmed.ncbi.nlm.nih.gov/33289060/
https://link.springer.com/article/10.1007/s11307-020-01563-z
https://www.ncbi.nlm.nih.gov/pubmed/33289060
https://link.springer.com/content/pdf/10.1007/s11307-020-01563-z.pdf
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8099766
https://europepmc.org/articles/PMC8099766/
https://repository.publisso.de/resource/frl:6468664
https://refubium.fu-berlin.de/handle/fub188/36318
https://doi.org/10.17169/refubium-36034
https://doi.org/10.1007/s11307-020-01563-z
Rights: CC BY
Accession Number: edsair.doi.dedup.....19c5dbee46bae6a0593768f2ae1552ee
Database: OpenAIRE
Description
Abstract:Purpose Contrast-enhanced magnetic resonance imaging (MRI) has the potential to replace angiographic evaluation of atherosclerosis. While studies have investigated contrast agent (CA) uptake in atherosclerotic plaques, exact CA spatial distribution on a microscale is elusive. The purpose of this study was to investigate the microdistribution of gadolinium (Gd)- and iron (Fe) oxide-based CA in atherosclerotic plaques of New Zealand White rabbits. Procedures The study was performed as a post hoc analysis of archived tissue specimens obtained in a previous in vivo MRI study conducted to investigate signal changes induced by very small superparamagnetic iron oxide nanoparticles (VSOP) and Gd-BOPTA. For analytical discrimination from endogenous Fe, VSOP were doped with europium (Eu) resulting in Eu-VSOP. Formalin-fixed arterial specimens were cut into 5-μm serial sections and analyzed by immunohistochemistry (IHC: Movat’s pentachrome, von Kossa, and Alcian blue (pH 1.0) staining, anti-smooth muscle cell actin (anti-SMA), and anti-rabbit macrophage (anti-RAM-11) immunostaining) and elemental microscopy with laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) and synchrotron radiation μX-ray fluorescence (SR-μXRF) spectroscopy. Elemental distribution maps of Fe, Eu, Gd, sulfur (S), phosphorus (P), and calcium (Ca) were investigated. Results IHC characterized atherosclerotic plaque pathomorphology. Elemental microscopy showed S distribution to match the anatomy of arterial vessel wall layers, while P distribution corresponded well with cellular areas. LA-ICP-MS revealed Gd and Fe with a limit of detection of ~ 0.1 nmol/g and ~ 100 nmol/g, respectively. Eu-positive signal identified VSOP presence in the vessel wall and allowed the comparison of Eu-VSOP and endogenous Fe distribution in tissue sections. Extracellular matrix material correlated with Eu signal intensity, Fe concentration, and maximum Gd concentration. Eu-VSOP were confined to endothelium in early lesions but accumulated in cellular areas in advanced plaques. Gd distribution was homogeneous in healthy arteries but inhomogeneous in early and advanced plaques. SR-μXRF scans at 0.5 μm resolution revealed Gd hotspots with increased P and Ca concentrations at the intimomedial interface, and a size distribution ranging from a few micrometers to submicrometers. Conclusions Eu-VSOP and Gd have distinct spatial distributions in atherosclerotic plaques. While Eu-VSOP distribution is more cell-associated and might be used to monitor atherosclerotic plaque progression, Gd distribution indicates arterial calcification and might help in characterizing plaque vulnerability.
ISSN:18602002
15361632
DOI:10.1007/s11307-020-01563-z