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Doctoral Thesis
DOI
https://doi.org/10.11606/T.59.2023.tde-10112023-150646
Document
Author
Full name
Fábio Seiji Otsuka
E-mail
Institute/School/College
Knowledge Area
Date of Defense
Published
Ribeirão Preto, 2023
Supervisor
Committee
Salmon, Carlos Ernesto Garrido (President)
Fittipaldi, Maria
Langkammer, Christian
Liu, Chunlei
Title in English
Quantification of paramagnetic ions in human brain tissue: correlation to quantitative magnetic resonance imaging
Keywords in English
EPR
Magnetic susceptibility
Paramagnetic ions
QSM
R2*
Abstract in English
Quantitative Magnetic Resonance Imaging (qMRI) is emerging as a promising tool to quantify iron in vivo through R2* and Quantitative Susceptibility Mapping (QSM) techniques, however their relationship to iron and its molecular forms is still unknown. Therefore, this study aims to evaluate the relationship between R2* and QSM's contrast and different metals concentrations assessed by Inductive Coupled-Plasm Mass Spectrometry and Electron Paramagnetic Resonance (EPR). A total of 15 postmortem subjects were recruited with death by non-neurological factors. Postmortem images were processed for R2* and QSM maps, and nine relevant gray matter regions were manually segmented and assessed. Absolute metal concentration was quantified by means of ICP-MS and the paramagnetic ion content by EPR. This study corroborated that iron is the main source of contrast in the imaging techniques R2 and QSM, with a stronger relationship in the structures of the basal ganglia. However, the contrast seems to be locally dependent, and in this study four classes or groups of anatomical regions were identified. The first group consisted of regions that strongly correlated to both total iron and the paramagnetic ion attributed to the ferritin protein. The second group consisted of regions which showed only partial correlation and therefore, may not be totally related to iron and should be carefully evaluated when interpreting their contrast. Substantia Nigra is in the third class, which showed good correlation to total iron, however not to the ferritin protein, indicating a different main contrast mechanism for this structure. Lastly, the fourth group didn't correlate to iron and ferritin. This study indicates a heterogeneous participation of iron in the contrast of R2* and QSM across different gray matter regions, indicating that regions with low iron concentrations are influenced by other factor that were not investigated in this study. Furthermore, among the iron-rich structures that were correlated iron, there seems to be different molecular iron forms associated to their contrast. Specifically, the Substantia Nigra showed poor correlation to the ferritin signal, suggesting other contrast mechanism.
Title in Portuguese
Quantificação de íons paramagnéticos em tecido cerebral humano: correlação com imagens quantitativas de ressonância magnética
Keywords in Portuguese
Íons paramagnéticos
QSM
R2*
RPE
Susceptibilidade magnética
Abstract in Portuguese
Imagens Quantitativas por Ressonância Magnética (IRMq) é uma ferramenta promissora na quantificação de ferro na condição in vivo por meio das R2* e Mapeamento Quantitativo de Susceptibilidade Magnética (QSM), contudo a relação desses mapas com o ferro e suas formas moleculares ainda é incerto. Portanto, este estudo busca avaliar a relação entre mapas de R2* e QSM com a concentração de metais medidos por Espectrometria de Massa (ICP-MS) e íons paramagnéticos medidos por Ressonância Paramagnética Eletrônica (RPE). Um total de 15 indivíduos postmortem foram recrutados com mortes por causas não-neurológicas. Imagens postmortem foram processadas em mapas de R2* e QSM, e nove regiões cerebrais relevantes da substância cinzenta foram manualmente segmentadas. Concentrações absolutas de metais e concentrações relativas de íons paramagnéticos foram medidas em cada região. Este estudo corrobora com os achados da literatura, indicando que o ferro é a principal fonte de contraste em regiões dos Núcleos da Base (NB). Contudo, a relação do ferro aparenta ter dependência local, sendo que neste estudo quatro classes de regiões foram identificadas. A primeira classe consiste de regiões com forte correlação com ferro e ferritina. A Segunda classe consiste em regiões parcialmente correlacionados com ferro e ferritina. A Substância Negra compõe a Terceira classe, que mostrou boa correlação com o ferro, porém não com a ferritina. Finalmente, a quarta classe consistiu de estruturas não correlacionadas com o ferro e ferritina. Este estudo indica uma participação heterogênea do ferro no contraste de R2* e QSM entre as diferentes estruturas da substância cinzenta, indicando que regiões com baixa concentração de ferro são influenciadas por outros fatores, além dos investigados neste estudo. Adicionalmente, dentre as estruturas ricas em ferro, diferentes formas moleculares do ferro parecem influenciar o contraste. Especificamente, a Substância Negra mostrou baixa correlação com a ferririna, sugerindo outra forma molecular de ferro responsável pelo contraste.
 
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Publishing Date
2023-12-20
 
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