Visual hallucinations is one of the major non-motor comorbidities exists in some of the Parkinson’s disease (PD) patients ¹. However, the underlying pathophysiology is yet to be understood. Nigral iron deposition was postulated to be the cause of neurodegeneration of the substantia nigra, and increased iron concentration was commonly observed in substantia nigra of the PD patients ^2-4. The aim of this study was to examine the association between subcortical iron deposition in PD and the development of visual hallucinations in the PD patients (PDVH).77 subjects were recruited in this study, with 19 PDVH patients (15 males, mean age ± S.D. = 71 ± 8 years, mean illness duration ± S.D. = 10 ± 4 years), 32 PD patients without visual hallucinations (18 males, mean age ± S.D. = 63 ± 8 years, mean illness duration ± S.D. = 8 ± 5 years) and 26 healthy control subjects (15 males, mean age ± S.D. = 62 ± 7 years). Susceptibility imaging were performed on all subjects with the 3.0T Philips scanner with the following parameters: 3D-T1FFE sequence, TR/TE = 28/23 ms, flip angle = 15°, NEX = 1, FOV = 230 x 230 x 180 mm³, reconstructed resolution = 0.45 x 0.45 x 1 mm³. The raw phase images were unwrapped with Laplacian-based algorithm and processed with ReSHARP to removal the background field. The phase images were subsequently processed with the total-variation-regularization algorithm to obtain the L1-norm regularized QSM images ^{5, 6}. Same session 3D-T1MPRAGE images, affine registered to the subject’s native space, were processed with FSL-FIRST to segment the subcortical structures. The six subcortical structures (bilateral caudate nucleus, putamen, pallidum, thalamus, hippocampus and amygdala) segmented (fig. 1) were used as the ROI to analyze both mean estimated volume and the mean magnetic susceptibility of the corresponding structure. All values were normalized to the averaged susceptibility values of the bilateral frontal white matter regions.One-way ANOVA of group mean age showed significant differences between group (p = 0.001). Post-hoc test with Bonferroni correction suggested that mean age of the PDVH group is significantly higher than that of the healthy (p = 0.001) and PD groups (p = 0.002). Age and gender were then included as covariates in further analyses for adjustment. One-way ANCOVA of the average estimated subcortical volume did not show any significant difference when comparing the PDVH group with the other two groups (fig. 2). One-way ANCOVA adjusting age and gender was also employed to examine the difference in mean magnetic susceptibility of the subcortical structures between groups. Significance was observed between groups in bilateral hippocampus and thalamus (p < 0.005, for all). Post-hoc multiple comparison with Bonferroni adjustment suggested that higher susceptibility values observed in the PDVH groups when compared with the healthy control in bilateral hippocampus (p < 0.001, both) and bilateral thalamus (left: p = 0.002, right: p < 0.001); and compared with the PD group in the right hippocampus (p = 0.028) (fig. 3).Preliminary study of subcortical volume suggested no brain atrophy in the examined regions. In measuring magnetic susceptibility of each subcortical nucleus, right hippocampus was found to have significantly higher magnetic susceptibility in the PDVH group compared to both PD and healthy group, suggesting possible iron accumulation in this brain region. Abnormal iron accumulation in the brain is postulated to be the cause of neuronal cell death by the mechanism of increased oxidative stress to the cell ². Hippocampus, which has a specialized role in the consolidation of memories, is also associated with the function of spatial navigation. In a recent study to examine the disease with both DTI and resting-state fMRI, the hippocampal functional connectivity was reported to be altered in the PDVH patients, postulated that the symptom of visual hallucinations was due to the impairment of the visuospatial memory pathway of the hippocampus¹. This study supported the previous study that hippocampus abnormality could be involved in the onset of visual hallucinations in PD patients. On the other hand, hippocampal magnetic susceptibility as a biomarker of the development of visual hallucination in PD patients is worth further exploration.PD patients with visual hallucinations were found to have higher magnetic susceptibility, possibly due to iron deposition, in hippocampus compared to healthy and the other PD patients. High hippocampal magnetic susceptibility could be a biomarker to examine the development of non-motor impairment, e.g. visual hallucination, in PD patients. This study also supported the hypothesis that hippocampus abnormality may induce visuospatial memory impairment which ultimately cause visual hallucination in PD patients.