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• W1580455465 abstract "It has been proposed that increased tissue iron concentration, which has been observed incertain regions of the brain in individuals with Alzheimer’s Disease (AD), could provide amarker for diagnosis through detection with MRI. This is investigated in this thesis using highfield MRI to examine post mortem human brain tissue. It is shown here that by using data frommultiple brain regions discriminant analysis can successfully differentiate between AD andcontrol samples, even when no statistically significant differences are observed in individualbrain regions.A unique set of complementary techniques was used to investigate iron content, R2 and R2* oftissue samples from the caudate nucleus, putamen, globus pallidus substantia nigra, amygdalaand pons, from a set of three control and AD cases. The particulate iron content of the sampleswas investigated by SQUID magnetometry and was followed by iron quantification. A trend ofincreased particulate and total iron concentration was observed in the AD tissue compared tocontrol, however this did not reach statistical significance in any brain region. High resolutionMRI relaxometry at 9.4 T was carried out on tissue from the caudate nucleus, putamen, globuspallidus and substantia nigra using a custom design Bruker micro-imaging MicWB40 probe. Aspart of the work towards this PhD the probe was tested, and MRI relaxometry protocolsoptimised for high resolution (86 x 86 μm in plane, 150 μm slice thickness) mapping of tissuesamples with high iron concentration. Again, no statistically significant differences wereobserved between AD and control tissue.However, discriminant analysis of these data (particulate or total iron or R2 or R2*) frommultiple brain regions achieved differentiation between control and AD cases with 100%sensitivity and specificity for this small sample set. This demonstrates the potential clinicalusefulness of MRI of measurements of non-haem brain iron to aid in disease diagnosis.Synchrotron X-ray fluorescence (SXRF) mapping of 30 μm thick sections, cut from the MRIsamples, showed the relative concentration distribution of iron, copper and zinc in one AD andcontrol sample from each brain region. Each metal was shown to have a distinct distribution.In particular, the inhomogeneity of iron concentration within individual brain regions, such asthe putamen, was demonstrated. This may explain the wide variation in iron concentrationreported in the literature for the same brain regions, and highlights the importance of closeanatomical matching of samples when making comparisons. The ability of high resolution SXRFmapping to investigate the metal content within individual cells was demonstrated and used toshow an increase in iron in individual AD neurons, in addition to the surrounding grey andwhite matter tissue.Spatially matched SXRF and MRI maps were used to demonstrate a strong, statisticallysignificant linear relationship between tissue iron concentration and R2, R2* and R2’ at 9.4 T.The gradient of the linear relationship between iron and R2, agrees extremely well with thepredicted gradient at this field, where the prediction was made by Vymazal et al. (1996) usingMRI relaxometry at 0.05 to 1.5 T. To the best of my knowledge, this is the first time that thisrelationship has been quantified at 9.4 T, or at any field above 7 T.MRI at 14.1 T was carried out on low iron concentration regions (the pons and amygdala).Matched SXRF and R2* maps did not show a strong linear relationship between iron and R2*.The iron concentration in these regions is less than 50 μg/g and it was concluded that in tissuewith low iron content, other tissue properties - such as water content - are dominating thevalue of R2*. This result was replicated with data measured at 9.4 T, when only tissue with aniron concentration of less than 50 μg/g was considered." @default.
• W1580455465 created "2016-06-24" @default.
• W1580455465 creator A5030561197 @default.
• W1580455465 date "2013-11-01" @default.
• W1580455465 modified "2023-09-28" @default.
• W1580455465 title "Investigation of the relationship between iron and high field MRI in healthy and Alzheimer's disease tissue" @default.
• W1580455465 hasPublicationYear "2013" @default.
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