Objective: To assess iron levels in dopaminergic midbrain nuclei using quantitative susceptibility mapping for identification of biomarkers of PD.

Background: The midbrain dopaminergic system plays a major role in the pathology of Parkinson’s disease (PD). There is a differential degeneration of dopaminergic neurons in the substantia nigra pars compacta (SNc) and ventral tegmental area (VTA), which could underlie the appearance of different PD symptoms over the disease progression. Excessive iron accumulation in the midbrain is thought to cause this degeneration through mechanisms such as ferroptosis. Magnetic resonance imaging (MRI) can localize and quantify iron in the brain based on its magnetic susceptibility. There are currently no biomarkers of PD that are used in clinical practice. Our understanding of changes in iron deposition in PD  presents the possibility of using neuroimaging of iron as a potential biomarker of PD.

Method: Twenty early-stage PD patients and age-matched healthy controls were scanned once at 3T and 7T. T1-weighted anatomicals were used for segmenting the midbrain nuclei based on the CIT168 probabilistic subcortical atlas [1]. Using quantitative susceptibility mapping (QSM) and R2* images registered to these anatomical scans, we segmented the midbrain structures and analyzed the average iron content in the SNc, VTA, and substantia nigra pars reticulata (SNr).

Results: Repeated measures analysis of variance of average susceptibility values from QSM revealed significantly higher SNc iron content in early-stage PD patients compared to elderly controls at both field strengths. R2* mapping could only detect this difference at 7T suggesting this method is less sensitive than QSM. No significant group differences in iron content were found in the SNr or the VTA. To assess these values as biomarkers, we compared them using receiver operating characteristic curves. Findings from these curves suggest that QSM outperforms R2* at both field strengths when considering hemispheres and the more affected body side.

Conclusion: These findings suggest that increased iron load in the SNc of early-stage PD patients, best detected using QSM, could be function as a diagnostic biomarker of PD that could ultimately be used in clinical practice.

References: [1] Pauli, W. M., Nili, A. N., & Tyszka, J. M. (2018). A high-resolution probabilistic in vivo atlas of human subcortical brain nuclei. Sci Data, 5, 180063. doi:10.1038/sdata.2018.63

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MDS Abstracts - https://www.mdsabstracts.org/abstract/differentiating-the-substantia-nigra-pars-compacta-and-ventral-tegmental-area-in-early-stage-parkinsons-disease-using-quantitative-susceptibility-mapping/