Hybrid PET-MRI for early detection of dopaminergic dysfunction and microstructural degradation involved in Parkinson\u2019s disease

Song’An Shang,Xindao Yin,Youyong Tian,Yingdong Zhang,Liyun Zheng,Yu-Chen Chen,Rushuai Li,Daixin Li,Hongdong Zhao

doi:10.1038/s42003-021-02705-x

Abstract

Dopamine depletion and microstructural degradation underlie the neurodegenerative processes in Parkinson’s disease (PD). To explore early alterations and underlying associations of dopamine and microstructure in PD patients utilizing the hybrid positron emission tomography (PET)-magnetic resonance imaging (MRI). Twenty-five PD patients in early stages and twenty-four matched healthy controls underwent hybrid 18F-fluorodopa (DOPA) PET-diffusion tensor imaging (DTI) scanning. The striatal standardized uptake value ratio (SUVR), DTI maps (fractional anisotropy, FA; mean diffusivity, MD) in subcortical grey matter, and deterministic tractography of the nigrostriatal pathway were processed. Values in more affected (MA) side, less affected (LA) side and mean were analysed. Correlations and mediations among PET, DTI and clinical characteristics were further analysed. PD groups exhibited asymmetric pattern of dopaminergic dysfunction in putamen, impaired integrity in the microstructures (nigral FA, putaminal MD, and FA of nigrostriatal projection). On MA side, significant associations between DTI metrics (nigral FA, putaminal MD, and FA of nigrostriatal projection) and motor performance were significantly mediated by putaminal SUVR, respectively. Early asymmetric disruptions in putaminal dopamine concentrations and nigrostriatal pathway microstructure were detected using hybrid PET-MRI. The findings further implied that molecular degeneration mediates the modulation of microstructural disorganization on motor dysfunction in the early stages of PD.

Highlights

Dopamine depletion and microstructural degradation underlie the neurodegenerative processes in Parkinson’s disease (PD)
We implemented hybrid positron emission tomography (PET)-magnetic resonance imaging (MRI), which is superior for the synchronous detection of different aspects of brain alterations, and systemically investigated the early molecular changes and microstructural degradation within the dopaminergic system in PD patients and obtained several principal findings
In comparison to healthy controls (HC) subjects, PD patients demonstrated early dopamine depletion in putamen and microstructural damage in the substantia nigra (SN), striatum, and nigrostriatal fibre tracts, which were significantly correlated with clinical motor deficits

Summary

Introduction

Dopamine depletion and microstructural degradation underlie the neurodegenerative processes in Parkinson’s disease (PD). Asymmetric disruptions in putaminal dopamine concentrations and nigrostriatal pathway microstructure were detected using hybrid PET-MRI. Asymmetrical loss of dopaminergic neurons in the substantia nigra (SN) is the core pathological feature of Parkinson’s disease (PD), resulting in concomitantly decreased dopamine concentrations in the striatum[1] This dopaminergic denervation is presumed to cause dysfunction in the nigrostriatal pathway and impairments in the basal ganglia circuitry, which would lead to characteristic motor symptoms (bradykinesia, resting tremor, rigidity) with unilateral onset and persistent asymmetry. We conducted a hybrid PET-MRI study with a cohort of de novo, drug-naïve, and non-demented PD patients in the early stages and comprehensively investigated the early disruptions in dopamine concentrations, integrity in subcortical regions (including the SN, components of the basal ganglia), and microstructure of nigrostriatal pathways (fibre tracts from the SN to the striatum). Mediation analysis was performed to examine whether dopaminergic dysfunction mediate the influence of microstructural nigrostriatal damage on movement disorders in the early stages

Methods

Results

Conclusion