TSPO PET brain inflammation imaging: A transdiagnostic systematic review and meta-analysis of 156 case-control studies.
Level 4 - case-series / case-control
Systematic review and meta-analysis of case-control observational studies
PubMed 37543251 · doi:10.1016/j.bbi.2023.07.023
What was done
Authors conducted a systematic review and random-effects meta-analysis of 156 human in vivo case-control TSPO PET studies across 11 central nervous system illness categories (139 meta-analysable, covering 2,381 healthy controls and 2,626 patients). Standardized mean differences (SMD) in TSPO PET signal between cases and controls were evaluated in cortical grey matter (cGM), cortico-limbic circuitry, and the thalamus. Subgroup and meta-regression analyses evaluated sources of heterogeneity, including radioligand generation, PET quantification method (volume of distribution [VT] vs reference tissue-based), age, sex, and publication year, using False Discovery Rate (FDR) correction (P < 0.05).
What was found
Across all illness categories combined, TSPO signal was elevated in cases compared to controls in cGM (n = 121 studies, SMD = 0.358, P FDR < 0.001, I2 = 68%), but category-specific cGM increases were significant only for Alzheimer's disease (SMD = 0.693, P FDR < 0.001, I2 = 64%) and other neurodegenerative disorders (SMD = 0.929, P FDR < 0.001, I2 = 73%). Cortico-limbic increases (n = 97 studies, SMD = 0.541, P < 0.001, I2 = 67%) were observed in Alzheimer's disease, mild cognitive impairment, other neurodegenerative disorders, mood disorders, and multiple sclerosis. Thalamic increases (n = 79 studies, SMD = 0.393, P < 0.001, I2 = 71%) were present in Alzheimer's disease, other neurodegenerative disorders, multiple sclerosis, and chronic pain and functional disorders (all P FDR < 0.05). Findings for systemic immunological disorders, viral infections, substance use disorders, schizophrenia, and traumatic brain injury were not significant. Quantification method accounted for 25% of between-study variance (VT-based SMD = 0.000 vs reference tissue-based SMD = 0.630; F = 20.49, P < 0.001), while patient age explained 9% and radioligand generation explained 5%.
Why it matters
This transdiagnostic analysis demonstrates that TSPO PET neuroinflammatory elevations are disorder- and region-specific rather than a universal hallmark of CNS disorders. It also highlights that quantification methods (reference tissue vs absolute VT modeling) introduce substantial bias into effect estimates.
Limits
All included data derive from cross-sectional case-control studies, which cannot establish causality or longitudinal disease dynamics. High statistical heterogeneity was present across all evaluated brain regions (I2 = 64% to 73%). The strong discrepancy between VT-based and reference tissue-based quantification methods complicates interpretation of true biological signal vs methodological artifact. Several illness categories had few studies.
Cited by
- supports Positive TSPO scans showing microglial activation are observed in Alzheimer's disease, Parkinson's disease, multiple system atrophy, progressive supranuclear palsy, major depressive disorder, PTSD, and long COVID.