Neuromelanin and T2*-MRI for the assessment of genetically at-risk, prodromal, and symptomatic Parkinson’s disease

Dafna Ben Bashat*, Avner Thaler, Hedva Lerman Shacham, Einat Even-Sapir, Matthew Hutchison, Karleyton C. Evans, Avi Orr-Urterger, Jesse M. Cedarbaum, Amgad Droby, Nir Giladi, Anat Mirelman, Moran Artzi

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

MRI was suggested as a promising method for the diagnosis and assessment of Parkinson’s Disease (PD). We aimed to assess the sensitivity of neuromelanin-MRI and T2* with radiomics analysis for detecting PD, identifying individuals at risk, and evaluating genotype-related differences. Patients with PD and non-manifesting (NM) participants [NM-carriers (NMC) and NM-non-carriers (NMNC)], underwent MRI and DAT-SPECT. Imaging-based metrics included 48 neuromelanin and T2* radiomics features and DAT-SPECT specific-binding-ratios (SBR), were extracted from several brain regions. Imaging values were assessed for their correlations with age, differences between groups, and correlations with the MDS-likelihood-ratio (LR) score. Several machine learning classifiers were evaluated for group classification. A total of 127 participants were included: 46 patients with PD (62.3 ± 10.0 years) [15:LRRK2-PD, 16:GBA-PD, and 15:idiopathic-PD (iPD)], 47 NMC (51.5 ± 8.3 years) [24:LRRK2-NMC and 23:GBA-NMC], and 34 NMNC (53.5 ± 10.6 years). No significant correlations were detected between imaging parameters and age. Thirteen MRI-based parameters and radiomics features demonstrated significant differences between PD and NMNC groups. Support-Vector-Machine (SVM) classifier achieved the highest performance (AUC = 0.77). Significant correlations were detected between LR scores and two radiomic features. The classifier successfully identified two out of three NMC who converted to PD. Genotype-related differences were detected based on radiomic features. SBR values showed high sensitivity in all analyses. In conclusion, neuromelanin and T2* MRI demonstrated differences between groups and can be used for the assessment of individuals at-risk in cases when DAT-SPECT can’t be performed. Combining neuromelanin and T2*-MRI provides insights into the pathophysiology underlying PD, and suggests that iron accumulation precedes neuromelanin depletion during the prodromal phase.

Original languageEnglish
Article number139
Journalnpj Parkinson's Disease
Volume8
Issue number1
DOIs
StatePublished - Dec 2022

Funding

FundersFunder number
LTI
Michael J. Fox Foundation for Parkinson's Research
National Parkinson Foundation
Pfizer
Biogen20416
Seventh Framework Programme
Israel Science Foundation

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