Seminars at CBA

Parkinson's disease (PD) is characterized by the progressive loss of dopaminergic neurons in the substantia nigra (SN) pars compacta (SNc), which contains neuromelanin pigment, resulting in high T1-weighted signal on MRI. This loss is also associated with an increase in iron deposition in the entire SN including the SNc and the SN pars reticulata in PD. Idiopathic rapid eye movement sleep behavior disorder (iRBD) is considered to be a prodromal stage of Parkinsonism. Moreover, neuromelanin signal diminishes early in the SNc of PD. Thus, neuromelanin-sensitive MRI could be used to monitor disease progression and response to therapies, which requires characterizing the neuromelanin signal variations by investigating the SNc. Furthermore, the iron overload in the SN can be evaluated using quantitative susceptibility mapping (QSM) or the apparent transverse relaxation rate (R2*). We scanned the subjects using a 3T whole body PRISMA scanner (Siemens, Erlangen, Germany) and assessed neuromelanin SNc damage using deep neural network and iron accumulation using Advanced Normalization Tools (ANTs) in iRBD and early PD patients compared to their respective age-matched healthy volunteers (HV). For neuromelanin, SNc Volume, corrected volume using total intracranial volume, signal to noise ratio and contrast to noise ratio were computed. For QSM and R2* maps, quantitative mean susceptibility values and R2* values were computed. One-way general linear model – ANOVA was conducted while adjusting for age and sex. For neuromelanin, iRBD and PD patients demonstrated a significant reduction for all SNc measurements compared to HV whereas for QSM and R2* maps, iRBD and PD patients showed an increase in SNc iron accumulation compared to HV. The proposed automatic method for quantifying SN variations showed comparable diagnostic performance with manual method which can possibly help us better understand the abnormalities in SN and could be useful for the diagnosis of PD. Such imaging techniques might allow a direct non rater-dependent noninvasive evaluation of progression of SN cellular loss in PD and potential target for disease modification biomarker in drug trials.