Intrasubject subcortical quantitative referencing to boost MRI sensitivity to Parkinson's disease

Several postmortem studies have shown iron accumulation in the substantia nigra of Parkinson's disease patients. Iron concentration can be estimated via MRI-R₂^∗ mapping. To assess the changes in R₂^∗ occurring in Parkinson's disease patients compared to controls, a multicentre transversal study was carried out on a large cohort of Parkinson's disease patients (n = 163) with matched controls (n = 82). In this study, 44 patients and 11 controls were removed due to motion artefacts, 21 patient and 6 controls to preserve matching. Thus, 98 patients and 65 age and sex-matched healthy subjects were selected with enough image quality. The study was conducted on patients with early to late stage Parkinson's disease. The images were acquired at 3Tesla in 12 clinical centres. R₂^∗ values were measured in subcortical regions of interest (substantia nigra, red nucleus, striatum, globus pallidus externus and globus pallidus internus) contralateral (dominant side) and ipsilateral (non dominant side) to the most clinically affected hemibody. As the observed inter-subject R₂^∗ variability was significantly higher than the disease effect, an original strategy (intrasubject subcortical quantitative referencing, ISQR) was developed using the measurement of R₂^∗ in the red nucleus as an intra-subject reference. R₂^∗ values significantly increased in Parkinson's disease patients when compared with controls; in the substantia nigra (SN) in the dominant side (D) and in the non dominant side (ND), respectively (P_{SN_D} and P_{SN_ND} < 0.0001). After stratification into four subgroups according to the disease duration, no significant R₂^∗ difference was found in all regions of interest when comparing Parkinson's disease subgroups. By applying our ISQR strategy, R_2(ISQR)^∗ values significantly increased in the substantia nigra (P_{SN_D} and P_{SN_ND} < 0.0001) when comparing all Parkinson's disease patients to controls. R_2(ISQR)^∗ values in the substantia nigra significantly increased with the disease duration (P_{SN_D} = 0.01; P_{SN_ND} = 0.03) as well as the severity of the disease (Hoehn & Yahr scale <2 and ≥ 2, P_{SN_D} = 0.02). Additionally, correlations between R_2(ISQR)^∗ and clinical features, mainly related to the severity of the disease, were found. Our results support the use of ISQR to reduce variations not directly related to Parkinson's disease, supporting the concept that ISQR strategy is useful for the evaluation of Parkinson's disease.