Thalamic Magnetic Susceptibility (χ) Alterations in Neurodegenerative Diseases: A Systematic Review and Meta-Analysis of Quantitative Susceptibility Mapping Studies

Background: Quantitative Susceptibility Mapping (QSM) provides a non-invasive post-processing method to investigate alterations in magnetic susceptibility (χ), reflecting iron content within brain regions implicated in neurodegenerative diseases (NDDs).

Purpose: To investigate alterations in thalamic χ in patients with NDDs using QSM.

Study type: Systematic review and meta-analysis.

Population: A total of 696 patients with NDDs and 760 healthy controls (HCs) were included in 27 studies.

Field strength/sequence: Three-dimensional multi-echo gradient echo sequence for QSM at mostly 3 Tesla.

Assessment: Studies reporting QSM values in the thalamus of patients with NDDs were included. Following PRISMA 2020, we searched the four major databases including PubMed, Scopus, Web of Science, and Embase for peer-reviewed studies published until October 2024.

Statistical tests: Meta-analysis was conducted using a random-effects model to calculate the standardized mean difference (SMD) between patients and HCs.

Results: The pooled SMD indicated a significant increase in thalamic χ in NDDs compared to HCs (SMD = 0.42, 95% CI: 0.05-0.79; k = 27). Notably, amyotrophic lateral sclerosis patients showed a significant increase in thalamic χ (1.09, 95% CI: 0.65-1.53, k = 2) compared to HCs. Subgroup analyses revealed significant χ alterations in younger patients (mean age ≤ 62 years; 0.56, 95% CI: 0.10-1.02, k = 11) and studies using greater coil channels (coil channels > 16; 0.64, 95% CI: 0.28-1.00, k = 9). Publication bias was not detected and quality assessment indicated that studies with a lower risk of bias presented more reliable findings (0.75, 95% CI: 0.32-1.18, k = 9). Disease type was the primary driver of heterogeneity, while other factors, such as coil type and geographic location, also contributed to variability.

Data conclusion: Our findings support the potential of QSM for investigating thalamic involvement in NDDs. Future research should focus on disease-specific patterns, thalamic-specific nucleus analysis, and temporal evolution.

Plain language summary: Our research investigated changes in iron levels within the thalamus, a brain region crucial for motor and cognitive functions, in patients with various neurodegenerative diseases (NDDs). The study utilized a specific magnetic resonance imaging technique called Quantitative Susceptibility Mapping (QSM) to measure iron content. It identified a significant increase in thalamic iron levels in NDD patients compared to healthy individuals. This increase was particularly prominent in patients with Amyotrophic Lateral Sclerosis, younger individuals, and studies employing advanced imaging equipment.

Level of evidence: 2 TECHNICAL EFFICACY: Stage 2.