Objective: Here, we investigated whether the functional PDRP topography is reproducible across different PD populations studied in different scanners and whether fPDRP expression values is elevated in PD patients compared to healthy control (HC) subjects and correlated with disease severity.

Background: A robust PET-derived imaging biomarker for Parkinson’s disease (pPDRP) has been described and extensively validated [1]. Resting-state functional MRI (rs-fMRI) techniques offer a non-invasive approach to identifying and measuring the activity of disease-related networks. A rs-fMRI-based version of PDRP (fPDRP) has been identified by use of independent component analysis and bootstrap resampling [2]. This novel approach discriminated normal controls from PD patients based on their pattern expression and was associated with the severity of clinical measures.

Method: We studied 57 off-medication PD patients and 25 age‐matched HC subjects scanned in Cologne, Germany with rs-fMRI [Table 1]. We used our recently-defined ICA approach to derive a PD-related pattern. Validation was performed using an independent North Shore cohort. We correlated pattern expression scores in PD patients with motor symptom severity scores (UPDRS-III). The topography of the rs-fMRI-derived PD pattern was compared to both the fPDRP identified in the North Shore cohort (NS-fPDRP) and the PET-derived PDRP (pPDRP).

Results: A significant fPDRP was identified which discriminated PD patients from healthy control (HC) subjects in both the Cologne and NS datasets. Expression values (subject scores) were significantly elevated in PD relative to HC [Fig. 1] in both Cologne cohorts (training: p <0.0001; testing: p<0.005) and in the NS validation cohort (p<0.05). Expression values for fPDRP topographies correlated with off-state UPDRS III ratings from each cohort (Cologne-fPDRP: Cologne p<0.005; NS p<0.05. NS-fPDRP: Cologne p>0.05; NS p<0.005) [Fig. 2]. The Cologne-fPDRP was topographically similar to both NS-fPDRP and pPDRP [Fig. 3]. Notably, the Cologne-fPDRP included underactive pPDRP regions that were not included in the original NS-fPDRP.

Conclusion: These findings suggest that fPDRP represents a stable disease related network topography across independent PD patient populations. fPDRP represents a potential non-invasive imaging biomarker in PD patients, but needs further validation in longitudinal cohorts.

References: 1. Schindlbeck KA, Eidelberg D (2018): Network imaging biomarkers: insights and clinical applications in Parkinson’s disease. The Lancet Neurology 17(7). 2. Vo A, Sako W, Fujita K et al (2017): Parkinson’s disease-related network topographies characterized with resting state functional MRI. Hum Brain Mapp 38:617-630.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/parkinsons-disease-related-pattern-using-resting-state-functional-mri-validation-and-refinement/