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Abstract: Objective: A powerful combination of high-field high-resolution magnetic resonance imaging (MRI) and X-ray absorption spectroscopy (XAS) is used to identify the distribution and nature of iron accumulation in the Substantia Nigra zona compacta (SNzc) in Parkinson’s disease (PD) and normal elderly individuals. Background: Regional accumulation of brain iron occurs in many neurodegenerative disorders, and provides a degree of natural contrast in MRI. Previous studies have shown statistically significant differences in relaxation parameters in the SN for PD versus controls, with differences attributed to altered iron concentrations. A combination of high-field high-resolution MRI and XAS is used to investigate the contribution of specific iron compounds to magnetic relaxation in unfixed post-mortem tissue. Cellular-level XAS will contribute to our understanding of iron mediated neurotoxicity, and correlation with MRI will allow the contribution of iron to magnetic relaxation to be determined, supporting non-invasive diagnosis and monitoring techniques. Methods: Relaxation parameters T1, T2 and T2* are determined in unfixed tissue at a resolution of 60 lm 3 60 lm 3 80 lm in a Bruker 600 MHz instrument. Tissue is cryosectioned and analysed at 10 lm in-plane resolution using microfocus XAS to determine iron distribution and state. Results: PD and control SN tissue was imaged at near-cellular resolution, with scan sequences optimised to permit calculation of the relaxation parameters within each slice. An example of an MGE sequence to obtain T2* is shown in Figure 1, with three different echo times (TE). X-ray mapping and spectroscopy analysis of cryosectioned tissue was performed at subcellular resolution, revealing local iron concentrations (Figure 2) and details of the associated iron compounds. Conclusions: We have succeeded in obtaining high-resolution MRI and synchrotron analyses of unfixed tissues, which is necessary to avoid fixation-induced iron redistribution and phase alteration. Our approach has potential for application in a broad range of neurodegenerative disorders. The findings contribute to our understanding of altered iron storage in the PD SNzc, and to the interpretation of magnetic relaxation parameters in the SNzc of PD patients and agematched controls (Figs. 1 and 2).