Quantitative Susceptibility Mapping in Parkinson's Disease.

Christian Langkammer,Karoline Wenzel,Franz Fazekas,Andreas Deistung,Tamara Pendl,Nina Homayoon,Ferdinand Schweser,Stephan Seiler,Stefan Ropele,Eva Maria Stoegerer,Jürgen Rainer Reichenbach,Reinhold Schmidt,Mariella Koegl-Wallner,Lukas Pirpamer,Petra Katschnig-Winter,Sebastian Franthal,Petra Schwingenschuh,Jan Kassubek

doi:10.1371/journal.pone.0162460

Abstract

BackgroundQuantitative susceptibility mapping (QSM) and R2* relaxation rate mapping have demonstrated increased iron deposition in the substantia nigra of patients with idiopathic Parkinson’s disease (PD). However, the findings in other subcortical deep gray matter nuclei are converse and the sensitivity of QSM and R2* for morphological changes and their relation to clinical measures of disease severity has so far been investigated only sparsely.MethodsThe local ethics committee approved this study and all subjects gave written informed consent. 66 patients with idiopathic Parkinson’s disease and 58 control subjects underwent quantitative MRI at 3T. Susceptibility and R2* maps were reconstructed from a spoiled multi-echo 3D gradient echo sequence. Mean susceptibilities and R2* rates were measured in subcortical deep gray matter nuclei and compared between patients with PD and controls as well as related to clinical variables.ResultsCompared to control subjects, patients with PD had increased R2* values in the substantia nigra. QSM also showed higher susceptibilities in patients with PD in substantia nigra, in the nucleus ruber, thalamus, and globus pallidus. Magnetic susceptibility of several of these structures was correlated with the levodopa-equivalent daily dose (LEDD) and clinical markers of motor and non-motor disease severity (total MDS-UPDRS, MDS-UPDRS-I and II). Disease severity as assessed by the Hoehn & Yahr scale was correlated with magnetic susceptibility in the substantia nigra.ConclusionThe established finding of higher R2* rates in the substantia nigra was extended by QSM showing superior sensitivity for PD-related tissue changes in nigrostriatal dopaminergic pathways. QSM additionally reflected the levodopa-dosage and disease severity. These results suggest a more widespread pathologic involvement and QSM as a novel means for its investigation, more sensitive than current MRI techniques.

Highlights

Magnetic susceptibility of several of these structures was correlated with the levodopa-equivalent daily dose (LEDD) and clinical markers of motor and non-motor disease severity
The established finding of higher R2* rates in the substantia nigra was extended by quantitative susceptibility mapping (QSM) showing superior sensitivity for Parkinson’s disease (PD)-related tissue changes in nigrostriatal dopaminergic pathways
QSM reflected the levodopa-dosage and disease severity. These results suggest a more widespread pathologic involvement and QSM as a novel means for its investigation, more sensitive than current MRI techniques

Summary

Introduction

The loss of dopaminergic neurons in the pars compacta of the substantia nigra is a patho-histological hallmark of Parkinson’s disease (PD), which is paralleled by increased iron deposition [1,2]. Iron is paramagnetic and it is increasing the relaxivity as reflected in R2 and R2Ã, and shifting the magnetic susceptibility of brain tissue toward more positive values [9]. This has led to the development of a novel MR technique for the assessment of brain iron in vivo which is quantitative susceptibility mapping (QSM) [10]. Quantitative susceptibility mapping (QSM) and R2* relaxation rate mapping have demonstrated increased iron deposition in the substantia nigra of patients with idiopathic Parkinson’s disease (PD). The findings in other subcortical deep gray matter nuclei are converse and the sensitivity of QSM and R2* for morphological changes and their relation to clinical measures of disease severity has so far been investigated only sparsely

Methods

Results

Conclusion