Development and Validation of the Automated Imaging Differentiation in Parkinsonism (AID-P): A Multi-Site Machine Learning Study.

Background: There is a critical need to develop valid, non-invasive biomarkers for Parkinsonian syndromes. The current 17-site, international study assesses whether non-invasive diffusion MRI (dMRI) can distinguish between Parkinsonian syndromes.

Methods: We used dMRI from 1002 subjects, along with the Movement Disorders Society Unified Parkinson's Disease Rating Scale part III (MDS-UPDRS III), to develop and validate disease-specific machine learning comparisons using 60 template regions and tracts of interest in Montreal Neurological Institute (MNI) space between Parkinson's disease (PD) and Atypical Parkinsonism (multiple system atrophy - MSA, progressive supranuclear palsy - PSP), as well as between MSA and PSP. For each comparison, models were developed on a training/validation cohort and evaluated in a test cohort by quantifying the area under the curve (AUC) of receiving operating characteristic (ROC) curves.

Findings: In the test cohort for both disease-specific comparisons, AUCs were high in the dMRI + MDS-UPDRS (PD vs. Atypical Parkinsonism: 0·962; MSA vs. PSP: 0·897) and dMRI Only (PD vs. Atypical Parkinsonism: 0·955; MSA vs. PSP: 0·926) models, whereas the MDS-UPDRS III Only models had significantly lower AUCs (PD vs. Atypical Parkinsonism: 0·775; MSA vs. PSP: 0·582).

Interpretations: This study provides an objective, validated, and generalizable imaging approach to distinguish different forms of Parkinsonian syndromes using multi-site dMRI cohorts. The dMRI method does not involve radioactive tracers, is completely automated, and can be collected in less than 12 minutes across 3T scanners worldwide. The use of this test could thus positively impact the clinical care of patients with Parkinson's disease and Parkinsonism as well as reduce the number of misdiagnosed cases in clinical trials.