Background: Parkinson’s disease (PD) is characterized by progressive degeneration of dopaminergic neurons in the substantia nigra pars compacta, accompanied by neuromelanin loss. Neuromelanin-sensitive magnetic resonance imaging (NM-MRI) enables in vivo visualization of these changes; however, its diagnostic and clinical utility remains incompletely defined. This study evaluated the feasibility, reliability, and biological sensitivity of semi-automated NM-MRI–based substantia nigra volumetry in PD. Methods: In this prospective case–control study, 50 participants (25 PD patients and 25 healthy controls) underwent 3T NM-sensitive MRI using a high-resolution T1-weighted spin-echo sequence. Semi-automated segmentation of hyperintense substantia nigra regions was performed using Mango v3.5.1, with intracranial volume normalization derived from FreeSurfer v7.3. Four participants were excluded due to motion artifacts, yielding a final cohort of 46 subjects. Clinical assessment included the Unified Parkinson’s Disease Rating Scale (UPDRS) Part III and Hoehn and Yahr (H&Y) staging. Group comparisons, receiver operating characteristic (ROC) analysis, and reliability testing using intraclass correlation coefficients (ICC) were performed. Results: Corrected substantia nigra volume was significantly reduced in PD patients compared with controls (18% reduction; p = 0.039, Mann–Whitney U test). Semi-automated measurements demonstrated excellent agreement with manual segmentation (ICC = 0.945). ROC analysis showed moderate discriminative performance for corrected volume (AUC = 0.700; sensitivity 68.4%, specificity 74.1%). No significant correlation was observed between corrected substantia nigra volume and UPDRS-III motor scores, while a trend toward lower SNc volume was observed with advancing H&Y stage. Conclusions: Semi-automated NM-MRI volumetry detects biologically meaningful substantia nigra volume loss in early-stage Parkinson’s disease with high measurement reliability. However, diagnostic performance was moderate and insufficient for standalone clinical diagnosis or motor severity prediction. These findings support the role of NM-MRI as a complementary imaging marker within multimodal diagnostic and research frameworks rather than as an independent diagnostic tool.

Background and Objectives: Enlarged perivascular spaces (ePVS) demonstrated by MRI have recently been associated with cerebral small vessel disease and glymphatic dysfunction, implicated in Parkinson’s disease (PD) pathophysiology. This study aimed to quantify the burden of ePVS in PD patients versus healthy controls and to examine associations with cognitive performance. Materials and Methods: A total of 51 participants underwent 3T MRI, including a T2-weighted sequence. Twenty-one patients with Parkinson’s disease and 21 age-matched healthy controls were included in the final analysis. The ePVS burden was assessed quantitatively by counting visible PVS in the basal ganglia and centrum semiovale, and qualitatively using Potter and Heier rating scales. Cognitive function was measured with the Montreal Cognitive Assessment (MoCA). Statistical analyses used Mann–Whitney U tests and Spearman correlations. Results: PD patients had significantly higher total PVS counts in the basal ganglia (84.8 vs. 48.0; p < 0.001) and centrum semiovale (290.6 vs. 143.9; p < 0.001). Potter scale ratings were higher in PD across regions (p ≤ 0.025). Largest per-slice PVS counts negatively correlated with MoCA scores in right basal ganglia (ρ = −0.362, p = 0.012) and bilateral centrum semiovale (right: ρ = −0.421, p = 0.003; left: ρ = −0.431, p = 0.002). Heier scale differences were significant only in the right centrum semiovale (p = 0.023). PVS diameters were larger in PD only in the centrum semiovale (right: p = 0.010; left: p = 0.040). Conclusions: In this cohort, increased ePVS burden in the basal ganglia and centrum semiovale was associated with cognitive impairment in PD patients. Qualitative and quantitative PVS assessment, notably the largest-per-slice counts, may serve as a sensitive, non-invasive imaging biomarker for neurodegeneration and cognitive decline in PD. Larger group studies and longitudinal data are needed to assess their prognostic value in the long term, as well as the development of automatic quantification applications for better reproducibility.

Background/Objectives: Perivascular spaces (PVS) are MRI-visible compartments surrounding cerebral vessels and are increasingly interpreted as markers of cerebral small-vessel disease and glymphatic-system dysfunction. PVS burden is multifactorial, with possible contributions from vascular risk, atrophy, white matter disease, sleep, inflammation, diabetes, pathological protein deposition, genetic susceptibility, and venous drainage anatomy. This study evaluated whether apolipoprotein E (APOE) ε4 carrier status and venous sinus volumes are associated with quantitative PVS burden in patients across the cognitive spectrum. Methods: In this cross-sectional observational MRI study, 110 participants with normal cognition or varying cognitive impairment underwent 3T brain MRI and cognitive assessment. PVS lesion count and total PVS volume were quantified from T2-weighted (T2W) imaging using an automated deep learning segmentation approach. Venous sinus volumes were derived for the transverse, straight, and superior sagittal sinus segments and reported in mm³. APOE genotype was analyzed as ε4 carrier status. Non-parametric correlations, ordered cognitive-stage trend tests, APOE group comparisons, and adjusted partial Spearman analyses were performed. Results: Dorsal superior sagittal sinus (SSS-D) volume was associated with PVS count (ρ = 0.353, p < 0.001) and total PVS volume (ρ = 0.285, p = 0.009). These associations persisted after adjustment for age, sex, medial temporal atrophy (MTA), Fazekas score, and estimated intracranial volume (eTIV). APOE ε4 carrier status was not associated with PVS volume or count. PVS burden tended to decrease with greater cognitive-stage severity, while MTA increased across cognitive stages. Conclusions: In this cohort, SSS-D volume was associated with automated 3T T2W MRI-detectable PVS burden, whereas APOE ε4 carrier status was not a dominant predictor. These findings support further study of venous sinus morphology as a potential contributor to MRI-visible PVS burden, while longitudinal and flow-sensitive studies are needed to clarify causality and glymphatic clearance mechanisms.