The storage of iron in the brain is disrupted in Alzheimer’s Disease (AD) where deposition occurs in excess of the global increases associated with healthy ageing[1]. Quantitative susceptibility mapping (QSM) is an emerging MRI technique sensitive to iron concentration in tissue, that has recently displayed comparable sensitivity to that of structural MRI as a biomarker of AD[2]. The ability to spatially map iron stores in-vivo in mouse models of AD may provide a method by which to interrogate their relationship with specific pathological traits. Despite evidence linking iron with tau aggregation and neurofibrillary tangles, studies using MRI as a method of in-vivo iron estimation have focussed on mouse models of AD that develop beta-amyloid pathology[3]. In this work, a QSM protocol was used to probe tissue iron content in the rTg4510, a transgenic mouse model that exhibits selective tau pathology. High resolution ex-vivo data was acquired in the same cohort to support in-vivo findings. Additionally, T2* mapping was performed to compare QSM measurements with this more established MRI method of in-vivo iron mapping[4]. rTg4510 (TR) and wildtype (WT) mice were imaged in-vivo (WT=10, TR=10) and ex-vivo (WT=8, TR=8) at 7.5 months. Mice were secured in a cradle under anaesthesia with 1-2% isoflurane in 100% oxygen for in-vivo imaging which was followed by perfuse fixation (0.9% saline (15–20mL) followed by 50mL 10% buffered formalin). Brains were removed and stored in-skull at 4^oC in buffered formalin. Prior to ex-vivo imaging, each brain was rehydrated in PBS (3 weeks) and transferred to a 20mL syringe filled with a fomblin perfluoropolyether (Solvay Solexis SpA., Italy). Data were acquired at 9.4T using a 72mm birdcage coil for transmission. Signal was detected using a two-channel array head coil (in-vivo) and a 26mm birdcage coil (ex-vivo) (RAPID, Germany). Pulse sequence parameters are listed in Figure 1. Phase images were unwrapped using laplacian (in-vivo) and path-based (ex-vivo) methods, and background contributions were removed using VSHARP[5] (minimum kernel width = 0.6mm). QSMs were generated by TKD (t=5) corrected for underestimation[6]. A fully automated software pipeline was used to register magnitude data and generate brain masks. ROIs were manually drawn on the atlas image (Fig.2) and back propagated onto individual QSM/T2*maps to calculate mean parameter values. Group comparisons were made using two-tailed t-tests (p<0.05).Differences in magnetic susceptibility and T2* in rTg4510s relative to WT controls were most significant in the striatum which appears hyperintense in the mean QSMs (Fig.3a,b). In both the in-vivo, and ex-vivo datasets, an increased paramagnetic susceptibility and reduced T2* was calculated for the rTg4510 (Fig.3c,d). In the hippocampus, a significant increase in magnetic susceptibility was also observed in both in-vivo and ex-vivo data (Fig.4a), with no differences in T2*. A shortening of T2* in the cortex was observed in the in-vivo data only. The ex-vivo measurements of susceptibility were elevated in the rTg4510 thalamus with a reduced T2*, findings that were not replicated in-vivo where magnetic susceptibility was found to be decreased with no change in T2*. An increased magnetic susceptibility (with no difference in T2*) was detected the corpus callosum of the rTg4510 mice in both in-vivo and ex-vivo datasets (Fig.4b). In mean parameter maps, a loss in white-grey matter contrast in the rostral corpus callosum of the rTg4510 is evident in the QSM data only (Fig.5).The basal ganglia contains structures that are known to be iron rich relative to the rest of the brain and are particularly vulnerable to pathological iron accumulation in AD[1]. The striatum, a constituent part of this system, was found to have increased magnetic susceptibility in the rTg4510. Reductions in T2*, a more established method of in-vivo iron mapping[4], supported this finding. These T2* and QSM results are in good agreement with clinical studies of AD[2] and suggest that iron deposition in the striatum may be related to tangle pathology. QSM values in the hippocampus, a region previously shown to exhibit iron accumulation in AD[7], were also more paramagnetic in the rTg4510 relative to controls. Iron has previously been detected in oligodendrocytes and dystrophic myelinated axons in AD[7] and may be responsible for the magnetic susceptibility increases in the corpus callosum of the rTg4510 mice. However, abnormalities in the myelination have been observed in AD[2], and these susceptibility changes may also be caused by reduced myelin content, known to be diamagnetic. Work is ongoing to verify the source of the observed magnetic susceptibility differences through histopathological analysis of the ex-vivo tissue.