Effective R2 relaxation rate, derived from dual-contrast fast-spin-echo MRI, enables detection of hemisphere differences in iron level and dopamine function in Parkinson's disease and healthy individuals

Abstract

Background: Clinical estimates of brain iron concentration are achievable with quantitative transverse relaxation rate R₂, via time-consuming multiple spin-echo (SE) sequences. The objective of this study was to investigate whether quantitative iron-sensitive information may be derived from 3.0 T dual-contrast fast-spin-echo (FSE) sequences (typically employed in anatomical non-quantitative evaluations), as a routinely-collected alternative to evaluate iron levels in healthy (HC) and Parkinson's disease (PD) brains.

New method: MRI 3.0 T FSE data from the Parkinson's Progression Markers Initiative (PPMI) (12 PD, 12 age- and gender-matched HC subjects) were cross-sectionally and longitudinally evaluated. A new measure, 'effective R₂', was calculated for bilateral subcortical grey matter (caudate nucleus, putamen, globus pallidus, red nucleus, substantia nigra). Linear regression analysis was performed to correlate 'effective R₂' with models of age-dependent brain iron concentration and striatal dopamine transporter (DaT) receptor binding ratio.

Results: Effective R₂ was strongly correlated with estimated brain iron concentration. In PD, putaminal effective R₂ difference was observed between the hemispheres contra-/ipsi-lateral to the predominantly symptomatic side at onset. This hemispheric difference was correlated with the putaminal DaT binding ratios in PD.

Comparison with existing method(s): Effective R₂, derived from rapid dual-contrast FSE sequences, showed viability as an alternative to R₂ from SE sequences. Linear correlation of effective R₂ with estimated iron concentration was comparable to documented iron-dependent R₂. The effective R₂ correlation coefficient was consistent with theoretical R₂ iron-dependence at 3.0 T.

Conclusions: Effective R₂ has clinical potential as a fast quantitative method, as an alternative to R₂, to aid evaluation of brain iron levels and DaT function.

Keywords: Asymmetry; Brain iron; Dopamine transporter-specific binding ratio (SBR); Magnetic resonance imaging (MRI); Parkinson’s disease; Transverse relaxation.