This prospective 3T MR-STAT relaxometry study found highly repeatable T1 changes in thalamus, globus pallidus, and putaminal subregions that significantly distinguish neurodegenerative from non-neurodegenerative parkinsonism in clinically uncertain patients, while T2 differences were…

Provides a noninvasive, repeatable MRI biomarker that could improve diagnostic stratification of clinically uncertain parkinsonian patients and help select/enrich cohorts for therapeutic trials, though it does not address molecular disease mechanisms or treatment targets.

BACKGROUND: MR Spin TomogrAphy in Time-domain (MR-STAT) enables accelerated multiparametric relaxometry (T1/T2). Previous relaxometry studies predominantly compared Parkinson's disease patients with healthy controls (HC). The potential of relaxometry to distinguish neurodegenerative from non-neurodegenerative parkinsonism in clinically uncertain parkinsonian syndrome (CUPS) patients is unclear. PURPOSE: To investigate T1-/T2-differences between neurodegenerative and non-neurodegenerative parkinsonism in CUPS patients. STUDY TYPE: Prospective cross-sectional study. POPULATION: 52 patients with neurodegenerative and 57 patients with non-neurodegenerative parkinsonism, diagnosed via dopamine transporter single photon emission computed tomography (DAT SPECT) and neurologist review, and 10 HC. FIELDSTRENGTH/SEQUENCE: MP-RAGE (magnetization-prepared rapid acquisition with gradient-echoes) and MR-STAT, a 2D Cartesian-encoded gradient-spoiled gradient-echo sequence with time-varying flip-angle preceded by a non-selective inversion pulse, at 3T. ASSESSMENT: Repeatability of T1-/T2-values was evaluated for cortical gray matter/cerebral white matter/thalamus/putamen/caudate nucleus/globus pallidus (GP) in HC. T1-/T2-values of the parkinsonism groups were compared in the same regions per most/less affected hemisphere (MAH/LAH), determined by the putaminal uptake ratio on DAT SPECT. STATISTICAL TESTS: Regional coefficients of variation (CoV) were computed to assess the repeatability of T1-/T2-values in HC. T-tests (α = 0.05) were used to compare T1-/T2-values between parkinsonism groups, and Cohen's D values were computed with bootstrapping to measure effect sizes with 95% confidence intervals (95% CI). RESULTS: CoVs ranged from 0.5% to 1.7% (T1) to 1.5% to 2.7% (T2). In the MAH, significant T1-differences were found in the thalamus (Cohen's D = 0.635, 95% CI = [0.251, 1.016]); GP (Cohen's D = 0.508, 95% CI = [0.129, 0.887]); internal GP (Cohen's D = 0.603, 95% CI = [0.220, 0.983]); external GP (Cohen's D = 0.411, 95% CI = [0.033, 0.787]); and centromedial putamen (Cohen's D = 0.447, 95% CI = [0.069, 0.824]). In the LAH, significant T1-differences were found in the thalamus (Cohen's D = 0.476, 95% CI = [0.097, 0.853]); GP (Cohen's D = 0.415, 95% CI = [0.037, 0.791]); anteromedial putamen (Cohen's D = 0.388, 95% CI = [0.011, 0.764]); and external GP (Cohen's D = 0.416, 95% CI = [0.038, 0.792]). T2-differences were non-significant. DATA CONCLUSION: MR-STAT showed high repeatability and showed potential to differentiate neurodegenerative from non-neurodegenerative parkinsonism in CUPS patients. EVIDENCE LEVEL: 1. TECHNICAL EFFICACY: 1.