Parkinson’s disease (PD) is characterized by loss of dopaminergic neurons in the substantia nigra secondary to free iron deposition(1). Iron chelation therapy may be able to reduce excess brain iron levels in PD to reduce the disease burden. A double-blind placebo-controlled six month study of the iron chelator Deferiprone was performed with two MRI-derived measures of iron: T2* mapping and quantitative susceptibility mapping (QSM).25 PD subjects were randomized into placebo (n=8), or 20 (n=7) or 30 (n=7) mg/day Deferiprone, and imaged at baseline, 3 months and 6 months. 12 Control subjects had one imaging visit only. 3 PD subjects were not enrolled into therapy after baseline due to exclusion criteria; 2 withdrew from adverse events; 1 withdrew for compliance. A Siemens 3T Verio with a 32-channel headcoil acquired a 3D (240x256x160mm) T1w SPGR of isotropic 1mm resolution at six TEs from 6 to 49ms. A double-contrast inversion recovery sequence (MP2RAGE(2,3)) at identical resolution and coverage (TI=409ms and 1100ms) gave two co-registered volumes: one with fluid nulled similar to the ADNI MPRAGE and one with white matter nulled for subcortical segmentation. The first echo volume was segmented with FIRST and SIENAX(4), and rigid-body FLIRT(5) was used to co-register to the fluid-nulled MP2RAGE volume from the first imaging visit. This MP2RAGE volume was used for the manual delineation of the pre-specified ROIs of the substantia nigra (SN), red nucleus (RN), and the dentate nucleus (DN) for QSM and T2*. Six more pre-specified ROIs were used for T2* mapping: Whole white matter, whole grey matter, striatum, caudate, and pallidum. The T2* decay across the six echoes was fit to the non-linear signal equation for T2* mapping. For QSM, the co-registered multiecho complex data was converted to a field map(6,7), unwrapped using the Laplacian formulation in k-space(8), background removed via projection onto dipole fields(9) and sphere mean value removal(10) from which the susceptibility map (χ) was generated via weighted kspace derivative(10). Χ values were normalized to the CSF value. All ROIs were then applied to the paired T2* and QSM volumes, which are derived from the same acquisition, on each visit. Baseline group differences were tested with independent samples t-tests, and mixed models were applied to the change from baseline data to explore longitudinal changes - treatment (placebo, Deferiprone 20mg/day, Deferiprone 30mg/day) and months (3, 6) as fixed effects, subject as a random effect - within each ROI. Pairwise comparisons explored treatment-dependent changes at each visit.A treatment-dependent increase in T2* over placebo could be demonstrated in the caudate, striatum, dentate, and global grey and white matter (Figure 1). These regions except the dentate had a significant change from baseline in the treated condition at 6 months (Figure 2). Susceptibility values were similar with previously reported values for age group (66+/-2 years)(11), and as T2* did not differ between PD and controls (Table 1), and remained stable (Figure 3). No changes in T2* nor χ were noted in the substantia nigra, an area of interest in PD.A differential effect of iron chelator therapy on T2* and X values has been demonstrated. PD subjects were early in disease (duration 3.15+/- 0.4yrs), who may not have excessive free iron and neuromelanin remains patent. Many groups have demonstrated increased iron, susceptibility or transverse relaxation rates in later PD stages, but no differences in early PD. Ferritin’s relaxation mechanism is not straightforward outside of T2* (12), and has several susceptibility states, including superparamagnetic. Further exploration of this effect is warranted in PD.