Billimoria, Kharmen (2022) Quantitative multimodal elemental imaging strategies applied to Alzheimer’s disease : from tissue to cells. PhD thesis, University of Warwick.

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Abstract

Elemental imaging techniques such as laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) and synchrotron x-ray fluorescence (XRF) are used to investigate chemical element distributions in samples. Quantitative imaging remains a challenge for both techniques, limited by a lack of appropriate reference materials, driving dependence on in-house strategies. This work focuses on improving quantitative strategies for tissue and cell samples in ways suitable for general adoption by the research community. These strategies are tested and validated using both LAICP- MS and XRF mapping to overcome technique-specific constraints and to benefit from their complementary strengths.

Gelatin and homogenised tissue matrices were investigated as options for matrixmatched calibration standards for tissue samples and scope to match the chemical form of the spike analyte. For both, optimisation of experimental conditions and the use of signal normalisation were successfully incorporated to reduce matrix effects in the quantitative analysis.

Elemental imaging of cells has greatly benefitted from the introduction of low-volume ablation cells and fast, simultaneous, ICP-Time-of-flight detectors. Signal normalisation for cell imaging cannot be approached as for tissue sections due to differences in sample area scale. Here, calibration performance was improved via an internal standard layer covering the cell samples that used the ratio of two elements to produce a constant signal for normalisation.

Imaging of selenium (Se) at a biologically relevant spatial resolutions via LA-ICP-MS is challenging due to the relatively poor ionisation efficiency of Se and presence of polyatomic inferences. To address this, synchrotron-XRF mapping was used to investigate distributions of Se in Alzheimer’s disease (AD) and healthy control hippocampus, notably finding evidence of co-accumulation with mercury, associated with toxicity, in AD tissue. Extending this observation, synchrotron nano-focus XRF was used to image isolated plaque cores from human AD cases showing, for first time via this method, mercury accumulation in amyloid plaques.

Item Type:	Thesis (PhD)
Subjects:	Q Science > QC Physics Q Science > QD Chemistry Q Science > QP Physiology R Medicine > RC Internal medicine R Medicine > RS Pharmacy and materia medica
Library of Congress Subject Headings (LCSH):	Tissues -- Imaging, Tissues -- Analysis, Speciation (Chemistry), Laser ablation, X-ray spectroscopy, Alzheimer's disease, Selenium
Official Date:	January 2022
Dates:	Date Event January 2022 UNSPECIFIED
Institution:	University of Warwick
Theses Department:	Molecular Analytical Science Centre for Doctoral Training
Thesis Type:	PhD
Publication Status:	Unpublished
Supervisor(s)/Advisor:	Collingwood, Joanna Frances ; Goenaga-Infante, Heidi
Sponsors:	Engineering and Physical Sciences Research Council ; Laboratory of the Government Chemist (Great Britain)
Format of File:	pdf
Extent:	209 leaves : illustrations
Language:	eng

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