QSM vs dopamine transporter PET: χ+ Mapping Shows Stronger Longitudinal Associations with Nigral Degeneration than Conventional QSM in Parkinson's Disease.

BACKGROUND: Iron accumulation in the substantia nigra (SN) is a hallmark of Parkinson's disease (PD). Quantitative susceptibility mapping (QSM) including source separation can generate maps of total susceptibility χ, paramagnetic or positive susceptibility [Formula: see text] likely dominated by tissue iron, and diamagnetic or negative susceptibility [Formula: see text] reflecting myelin and other sources. PURPOSE: To compare χ, [Formula: see text], and [Formula: see text] for tracking SN longitudinal changes in PD and for correlating with dopaminergic PET measures and cognitive decline. MATERIALS AND METHODS: This longitudinal study included 32 patients with PD (mean age, 65.88 ± 8.47 years) who underwent 3T MRI with 3D multi-echo gradient-echo (mGRE) and dynamic 11C-N-(3-iodoprop-2E-enyl)-2β-carbomethoxy-3β-(4-methylphenyl) nortropane (PE2I) PET between August 2018 and April 2024. χ, [Formula: see text], and [Formula: see text] maps were reconstructed from mGRE data using the MEDI algorithm with susceptibility source separation. Dopamine transporter binding potential (BP) images were estimated from dynamic PET using a deep learning based kinetic model. Paired t tests, linear regression, and Pearson correlation analyses with Bonferroni correction were performed, with P < .05 considered significant. RESULTS: Both χ and [Formula: see text] from QSM revealed significant longitudinal susceptibility increases in the rostral and caudal SN (Bonferroni-corrected P < .05), with [Formula: see text] showing larger effect sizes (t = 9.99 vs 2.65 for the caudal SN). The left putaminal BP from PET significantly decreased at follow-up (P < .05). The longitudinal increase in [Formula: see text] within the rostral SN strongly correlated with the reduction in putaminal BP (r = - 0.60, P = .005, Bonferroni-corrected), whereas χ showed no significant association. Higher baseline [Formula: see text] values in the rostral and caudal SN predicted greater longitudinal cognitive decline (P = .01-.02, Bonferroni-corrected). Subregional analyses confirmed significant [Formula: see text] increases predominantly in the rostral-anterior SN. No significant change or correlation was observed with [Formula: see text] mapping at the SN. CONCLUSION: Positive susceptibility [Formula: see text] mapping showed larger longitudinal effect sizes for SN changes and stronger associations with dopaminergic PET decline and cognitive deterioration than to total susceptibility χ. These findings support [Formula: see text] mapping as a biologically informative MRI measure for the longitudinal assessment of SN changes in PD.