A novel brain imaging study has uncovered slight yet informative differences in the brains of individuals with Parkinson’s Disease (PD), offering new hope for earlier detection and more accurate tracking of this debilitating condition.
PD is a progressive neurological disorder that destroys dopamine-producing neurons, mainly causing movement difficulties, and people tend to have tremors, stiffness, and impaired posture. Even though researchers have investigated this over several decades, the fine-scale in vivo brain changes underlying these symptoms have remained elusive, limiting clinicians to late-stage diagnosis and hampering assessment of new therapies.
A team of scientists at the Shaare Zedek Medical Center in Jerusalem aimed to overcome these limitations using advanced multiparametric quantitative MRI (qMRI). They focused on the putamen, which is one of the most critical structures of the brain that is involved in motor coordination with the basal ganglia, which is among the earliest regions affected by dopamine depletion. In healthy brains, the putamen exhibits clear microstructural gradients along its length, but it remained unclear whether these gradients are disrupted in PD.
The study involved 62 patients diagnosed with PD and 28 healthy controls. There was no significant difference between the groups in terms of age (t (88) = -0.68, P = 0.50) and sex (χ2(88) = – 2.11, P = 0.15). Unsurprisingly, the PD group exhibited a much higher level of motor impairment (MDS-UPDRS III: t (83) = 11.29, P < 10-17) and lower cognitive function scores (MoCA: t(85) =−4.29, P < 0.00005).
The researchers measured several properties of brain tissue including relaxation rates (R1, R2, R2*), water fraction (WF), susceptibility, magnetization transfer (MTsat), mean diffusivity (MD), and fractional anisotropy (FA) using qMRI along the anterior- post (AP) axis of the putamen. Healthy subjects had significant spatial gradients, e.g., relaxation rates, susceptibility, MTsat, and FA increased toward more posterior putamen, whereas water fraction and mean diffusivity decreased. Importantly, the PD patients experienced significant disruptions in these gradients. Water fraction was the most influential effect: spatial gradient of WF was significantly reduced (β= 0.46, 95 CI: 0.33-0.59, p < 10-10). Significant changes were observed in the posterior half of the putamen, and predominantly in the 0.75-1.00 positions, where the maximum amount of water was found.
Another key finding was the altered gradient of R2*—a marker associated with iron—which was significantly different in PD patients (β = -0.47, 95% CI: -0.63 to -0.32, p < 10⁻⁷), indicating unexpected reductions in iron-related signals. Interestingly, similar findings were not detected by conventional MRI measures of whole-putamen volume or median values, which did not significantly differ (P > 0.14). The researchers explain that this proves the strength of fine-grained spatial pattern analysis over averaged measures for the early detection of brain pathology. The research further revealed that motor asymmetry was intertwined with water levels in the body, a condition characteristic of Parkinsonism, which manifests in one side of the body more than in the other. Among patients with motor asymmetry (n = 45), water fraction increased in the more-affected side of the putamen, mostly in the posterior portion (positions 0.65-0.70/1.00). This asymmetry was associated with poorer scores on the opposite body side motor examination.
The study did not find a strong relationship between qMRI markers and cognitive decline, but the distinct structural patterns in the putamen suggest a potential early imaging “fingerprint” of Parkinson’s disease.
The authors acknowledge certain limitations, such as the scans being time-consuming and movement sensitive, and the cross-sectional design does not allow representation of changes in the brain over time. However, the group is optimistic to extend their imaging methodology to other brain regions such as the substantia nigra to investigate PD across interconnected neural networks.
Improved imaging techniques like qMRI may one day enable earlier diagnosis of PD, more precisely target therapies, and better evaluation of treatment efficacy in slowing disease progression.
References: Drori E, Cohen L, Arkadir D, et al. Multiparametric quantitative MRI uncovers putamen microstructural changes in Parkinson’s disease. NPJ Parkinsons Dis. 2025;11:197.
doi:10.1038/s41531-025-01020-0
