자료유형  

 학위논문

Control Number  

0017164311

International Standard Book Number  

9798342144513

Dewey Decimal Classification Number  

615

Main Entry-Personal Name  

Nossa, Gianna.

Publication, Distribution, etc. (Imprint  

[S.l.] : Purdue University., 2024

Publication, Distribution, etc. (Imprint  

Ann Arbor : ProQuest Dissertations & Theses, 2024

Physical Description  

129 p.

General Note  

Source: Dissertations Abstracts International, Volume: 86-04, Section: B.

General Note  

Advisor: Dydak, Ulrike;Rispoli, Joseph;Bowman, Aaron;Shi, Riyi.

Dissertation Note  

Thesis (Ph.D.)--Purdue University, 2024.

Summary, Etc.  

요약High exposure to manganese (Mn) through the inhalation of welding fumes has been shown to have a toxic effect to the human brain, leading to parkinsonian-like symptoms such as changes in mood, cognition, and motor function. Oxidative stress and GABAergic dysfunction, two proposed mechanisms implicated in Mn neurotoxicity, can be measured by edited MR spectroscopy (MRS). Previous animal studies have found depleted levels of glutathione, the brain's antioxidant, and GABA in response to exposure to Mn. Past welder studies have shown altered GABA levels in highly exposed welders. However, GSH has not yet been measured in welders. Recent advances in edited MRS allow for the simultaneous measurement of GABA and GSH, however, one sequence does not 'fit all'. Thus, there is a need to ensure accurate and reproducible measurements of these metabolites in the study of neurological disorders, such as Mn neurotoxicity.The overall goal of this dissertation is to establish a reproducible edited MRS protocol and ensure accurate measurement of metabolites in the context of Mn neurotoxicity. This work has been accomplished in three steps. First, we developed an optimized and reproducible HERMES sequence that allows for the consistently reliable measurement of GABA and GSH at 3T. Second, we investigated whether toenail concentrations of manganese (Mn) and iron (Fe) serve as biomarkers for levels of GABA, GSH, and Glx in the brains of welders exposed to these metals. This aim explores the potential for toenails to be used as a risk assessment tool by evaluating correlations between toenail metal levels and brain metals and metabolites. Lastly, we examined whether excessive accumulation of metals in the brain has an impact on the relaxation times of metabolites. Due to its paramagnetic properties, brain accumulation of two major components of welding fumes, Mn and iron (Fe), may be measured noninvasively through increased magnetic resonance imaging (MRI) relaxation rates, R1 and R2*, respectively. This aim delves into the potential effects of metal exposure on the physical properties of brain metabolites, which could shed light on the accuracy of quantification.Overall, the dissertation is a successful step towards establishing reproducible edited MRS acquisitions, and the accurate quantification in the application of Mn neurotoxicity. This work focused on developing methodologies and assessing physical properties for accurate GABA and GSH measurements and investigating risk-assessment methods for metal-induced neurotoxicity.

Subject Added Entry-Topical Term  

Brain.

Subject Added Entry-Topical Term  

Toxicity.

Subject Added Entry-Topical Term  

Spectrum analysis.

Subject Added Entry-Topical Term  

Metabolites.

Subject Added Entry-Topical Term  

Magnetic resonance imaging.

Subject Added Entry-Topical Term  

Analytical chemistry.

Subject Added Entry-Topical Term  

Medical imaging.

Subject Added Entry-Topical Term  

Optics.

Subject Added Entry-Topical Term  

Toxicology.

Added Entry-Corporate Name  

Purdue University.

Host Item Entry  

Dissertations Abstracts International. 86-04B.

Electronic Location and Access  

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Control Number  

joongbu:657643