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

• Published in: NeuroImage clinical Vol. 36; p. 103231
• Main Authors: Khedher, Laila, Bonny, Jean-Marie, Marques, Ana, Durand, Elodie, Pereira, Bruno, Chupin, Marie, Vidal, Tiphaine, Chassain, Carine, Defebvre, Luc, Carriere, Nicolas, Fraix, Valerie, Moro, Elena, Thobois, Stéphane, Metereau, Elise, Mangone, Graziella, Vidailhet, Marie, Corvol, Jean-Christophe, Lehéricy, Stéphane, Menjot de Champfleur, Nicolas, Geny, Christian, Spampinato, Umberto, Meissner, Wassilios, Frismand, Solène, Schmitt, Emmanuelle, Doé de Maindreville, Anne, Portefaix, Christophe, Remy, Philippe, Fénelon, Gilles, Luc Houeto, Jean, Colin, Olivier, Rascol, Olivier, Peran, Patrice, Durif, Franck
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Inc 01-01-2022; Elsevier
• Subjects: Humans; Iron; Life Sciences; Magnetic resonance imaging; Magnetic Resonance Imaging - methods; Parkinson Disease - diagnostic imaging; Parkinson’s disease; Red Nucleus; Regular; Substantia Nigra - diagnostic imaging; Variability; MoCA; SN_D; Variability; Iron; PD patients; STR_ND; SPM; LARS; MNI space; LEDD; GPe; FOG-Q; DARTEL; RN_D; ISQR; GPi_D; SN_ND; STR_D; RN_ND; S&E; Magnetic resonance imaging; GPi_ND; H&Y; NMSS; HAM-A; MDS-UPDRS; HAM-D; ASBPD; Parkinson’s disease; Parkinson's disease; variability
• ISSN: 2213-1582; 2213-1582
• DOI: 10.1016/j.nicl.2022.103231

•In the presented work, the changes in R2∗ relaxation rate, which reflects the iron concentration, was studied as a function of the duration and severity of Parkinson’s disease. We have first averaged R2∗ within several basal ganglia regions. In order to take into account the large inter-subject variability of the R2∗ parameter, we have developed an original ISQR approach using an internal referencing in order to highlight the variation in R2∗ linked to Parkinson's disease compared to other sources of R2∗ variance. Our results support the use of ISQR to reduce variations not directly related to Parkinson’s disease, supporting the concept that ISQR is useful for the evaluation of 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 (PSN_D and PSN_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, R2(ISQR)∗ values significantly increased in the substantia nigra (PSN_D and PSN_ND < 0.0001) when comparing all Parkinson’s disease patients to controls.
R2(ISQR)∗ values in the substantia nigra significantly increased with the disease duration (PSN_D = 0.01; PSN_ND = 0.03) as well as the severity of the disease (Hoehn & Yahr scale <2 and ≥ 2, PSN_D = 0.02). Additionally, correlations between R2(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.