Quantitative Susceptibility Mapping for the Evaluation of Subcortical Iron Abnormality in Parkinson’s Disease with Dementia
Darrell Ting Hung Li1, Edward Sai Kam Hui1, Queenie Chan2, Nailin Yao3, Siew-eng Chua4, Grainne M. McAlonan4,5, Shu Leong Ho6, and Henry Ka Fung Mak1

1Department of Diagnostic Radiology, The University of Hong Kong, Hong Kong, Hong Kong, 2Philips Healthcare, Hong Kong, Hong Kong, 3Department of Psychiatry, Yale University, New Haven, CT, United States, 4Department of Psychiatry, The University of Hong Kong, Hong Kong, Hong Kong, 5Department of Forensic and Neurodevelopmental Science, King’s College London, London, United Kingdom, 6Department of Medicine, The University of Hong Kong, Hong Kong, Hong Kong


Parkinson’s disease (PD) patients may develop other non-motor comorbidities when the disease progress. While increased nigral iron was considered as a biomarker of the disease, it was also believed that iron deposition is associated with the development of other non-motor symptoms. In this study, magnetic susceptibility as a surrogate of iron concentration was measured in six major subcortical brain regions on the QSM images. Increased magnetic susceptibilities were observed in hippocampus and amygdala of the PD patients with dementia, suggesting a possible association of iron with the development of dementia symptom in late stage of PD.


Late stage Parkinson’s disease (PD) patients were commonly observed with other non-motor comorbidities such as dementia and psychosis. While abnormal iron level in the substantia nigra was clinically accepted as the biomarker of PD 1-3, it was also suggested that the increased iron deposition could also impair other brain regions and induced non-motor symptoms along with PD. In this study, we aimed to investigate the iron level of different subcortical brain regions of the demented PD patients (PDD) with the aid of the quantitative susceptibility mapping (QSM) technique.


MR susceptibility imaging were performed on 69 subjects, with 11 PDD patients (8 males, mean age ± S.D. = 73 ± 6 years, mean illness duration ± S.D. = 13 ± 8 years), 32 PD patients without other known comorbidities (18 males, mean age ± S.D. = 63 ± 8 years, mean illness duration ± S.D. = 8 ± 5 years) and 26 healthy control (15 males, mean age ± S.D. = 62 ± 7 years). All images were acquired by a Philips 3.0T Achieva TX system. The imaging protocol was as follows: 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. L1-norm QSM images were generated from the unwrapped and background-field-removed phase images with the total variation regularization method 4-5. Same session 3D-MPRAGE images were affine registered to the magnitude of the susceptibility images, which were subsequently passed to FSL-FIRST for automatic subcortical structure segmentation. Six bilateral structures (left and right caudate nucleus, putamen, pallidum, thalamus, hippocampus and amygdala) were segmented on each subject’s native space (fig. 1) and were used as the ROI to analyze both mean estimated volume and the mean magnetic susceptibility of the corresponding structure.


Age and gender were considered as covariates and were adjusted in this study. The mean estimated volume of each structure were compared between the three groups (fig. 2). One-way ANCOVA, after adjusted for age and gender, showed significant differences for volume of left (p = 0.04) and right putamen (p = 0.023) between the groups. Post-hoc test with Bonferroni adjustment suggested that volume of left putamen in the PDD group is smaller than that in the PD group (p = 0.044). Other subcortical brain regions did not show any significant volume reduction in PD or PDD groups. Mean magnetic susceptibility of the structures were then compared with the same approach (fig. 3). The result of one-way ANCOVA showed significant group differences for left (p < 0.001) and right hippocampus (p = 0.004); left (p = 0.007) and right thalamus (p = 0.001) and left amygdala (p = 0.021). Post-hoc test for multiple group comparison suggested higher magnetic susceptibility in the PDD group than the healthy group in the left (p < 0.001) and right hippocampus (p = 0.046), left (p = 0.022) and right thalamus (p = 0.034) and the left amygdala (p = 0.018). PDD group also had higher susceptibility than the PD group in left hippocampus (p = 0.040).


The volumetric analysis suggested no significant brain atrophy in the subcortical structures concerned. The measured magnetic susceptibilities in the bilateral hippocampus, bilateral thalamus and left amygdala were significantly higher in the PDD group when compared to that in the PD and the healthy control groups, suggesting possible increment of iron deposition in these brain regions 6. It was also worth noted that positive susceptibilities were found in the hippocampus and amygdala in the PDD group, as opposed to the negative susceptibilities in the healthy brain. Increasing iron load in human brain is believed to be neurotoxic and contributed to neurodegeneration and neuronal cell death. While hippocampus is associated with memory function in human brain, the major role of amygdala is to process memory and emotion. Damage to the two brain nuclei could impair the memory function and induce dementia-related symptom. This study, by employing the in vivo MRI with QSM method, demonstrated that the impairment of memory function in the PDD group is associated with the increased iron load in hippocampus or amygdala, despite the small sample size of the dementia group recruited in this study. Causal relationship of abnormal iron deposition and development of dementia in late stage PD patients or concomitant Alzheimer type neurodegeneration, however, is yet to be explored.


Abnormal increment of magnetic susceptibility in the hippocampus and amygdala, reflecting increased iron level, is associated with the development of dementia symptom in PD patients.


No acknowledgement found.


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Fig. 1 (Upper row) L1-regularized QSM images of one of the patients in the PDD group. (Lower row) The corresponding affine registered 3D-MPRAGE images with the segmented subcortical structures overlaid (Red: Caudate; Violet: Putamen; Green: Pallidum; Yellow: Thalamus; Blue: Hippocampus; Cyan: Amygdala).

Fig. 2 Comparison of mean estimated volume of the subcortical structures segmented with FSL-FIRST between healthy, PD and PDD groups. Statistical analysis was performed with one-way ANCOVA with Bonferroni post-hoc test was employed. The asterisk corresponds to statistical significance after post-hoc multiple comparison.

Fig. 3 Comparison of mean magnetic susceptibility of the subcortical structures segmented with FSL-FIRST between healthy, PD and PDD groups. Statistical analysis was performed with one-way ANCOVA with Bonferroni post-hoc test was employed. The asterisk corresponds to statistical significance after post-hoc multiple comparison.

Proc. Intl. Soc. Mag. Reson. Med. 24 (2016)