Objective: To identify an imaging diagnostic biomarker of PD for use in clinics by applying structural magnetic resonance imaging (MRI) techniques.

Background: The midbrain dopaminergic system plays a major role in the pathophysiology of Parkinson’s disease (PD). Excessive iron accumulation in the substantia nigra pars compacta (SNc) is thought to cause degeneration in the nigrostriatal pathway leading to motor symptoms. MRI can localize and quantify iron in the brain based on its magnetic susceptibility, using measures such as quantitative susceptibility mapping (QSM). Currently, there are no validated imaging diagnostic biomarkers of PD, but MRI has great potential.

Method: Early-stage PD patients and age-matched healthy controls were scanned using 3T MRI. T1-weighted anatomicals coupled with diffusion weighted imaging were used for segmenting the midbrain nuclei and striatum subregions based on the CIT168 probabilistic subcortical atlas (2018). Probabilistic tractography was conducted to parcellate the striatum into seven subregions using the segmentation proposed by Tziortzi and colleagues (2014). Subsequently, we measured average susceptibility in each hemisphere using QSM in midbrain nuclei and striatum subregions.

Results: Repeated measures analysis of variance of average susceptibility values from QSM revealed significantly higher SNc values in early-stage PD patients compared to healthy controls, indicating higher iron content. No significant group differences in average susceptibility were found in the SNr, VTA, or total striatum measures (i.e., caudate, putamen, nucleus accumbens).
We found significant group differences in the caudal motor subregion of the striatum. SNc and caudal motor striatum average susceptibility were combined using a binary logistic regression model. Receiver operating characteristic curve analysis with repeated 5-fold cross validation of this model revealed an excellent diagnostic accuracy of 0.90.

Conclusion: These findings suggest that QSM in the SNc combined with the caudal motor subregion can function as a diagnostic biomarker of PD, following validation, given its excellent diagnostic accuracy at the single-subject level.

References: 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
Tziortzi, A.C., Haber, S.N., Searle, G.E., Tsoumpas, C., Long, C.J., Shotbolt, P., et al. (2014). Connectivity-based functional analysis of dopamine release in the striatum using diffusion-weighted MRI and positron emission tomography. Cereb Cortex, 24: 1165–77.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/using-quantitative-susceptibility-mapping-and-diffusion-magnetic-resonance-imaging-to-identify-structural-features-of-early-stage-parkinsons-disease/