Abstract
242590
Introduction: Multiple sclerosis (MS) is an immune driven disease of the central nervous system. As an important component of neuroinflammation, microglia in MS have been widely investigated. Positron emission tomography (PET) imaging of the 18-kDa translocator protein (TSPO), is a widely used method to detect neuroinflammation in vivo, with recent work in MS indicating that TSPO accurately reflects microglial density. Numerous studies have utilized TSPO PET to investigate neuroinflammation in MS. However, outcomes and approaches vary greatly. Optimal tracer, quantification methods, and populations/disease stage for TSPO PET remains to be determined. This systematic review and meta-analysis aims to compile existing studies to investigate the utility of TSPO PET in MS and identify the most effective approaches for future MS research.
Methods: The current study adhered to PRISMA guidelines. Databases of Scopus, Medline, Web of Science and Embase were systematically searched until July 16th, 2023, using predetermined keywords related to MS, TSPO and TSPO PET (Fig. 1a). Titles and abstracts were screened by two independent researchers based on the inclusion (studies evaluating TSPO PET outcomes in MS patients) and exclusion criteria (review articles, case reports, studies using the same samples, and conference abstracts). Studies investigating MS patients only that reported individual patient data and disease severity outcomes were also included for correlation analyses. PET quantification data, demographics, and ROIs were analyzed using R statistical software (version 4.1.1). A random-effects model assessed the pooled standardized mean difference (SMD) in TSPO-PET signal with a 95% confidence interval (95% CI). Heterogeneity was evaluated using I2 statistics, with subsequent meta-regression and subgroup analyses to determine sources of heterogeneity including PET quantification method. Risk of bias was evaluated using appropriate NIH study quality assessment tools.
Results: Systematic search yielded 3996 articles, from which 1596 duplicates were removed. After screening, 2134 articles were excluded, leaving 272 full texts for further assessment. Applying our inclusion and exclusion criteria, 38 studies were included in our review (Fig. 1b). Initial meta-analyses on 29 articles that compared MS and control subjects revealed significantly higher brain TSPO PET signal in MS patients compared to healthy controls (SMD = 0.55; 95% CI: 0.31, 0.80, p<0.001, I2=99.38%, Fig. 1c). PET quantification method represented significant heterogeneity (26%). Thus, subgroup analysis was performed to stratify the data by PET quantification method. Five PET quantification outcomes were reported across the 29 articles including binding potential (BP, n=5), distribution volume ratio (DVR, n=14), standardized uptake value ratio (SUVR, n=4), total volume of distribution (Vt, n=7), and tracer uptake (n=2). Subgroup analysis demonstrated significantly elevated brain TSPO PET signal in MS compared to control subjects across BP (SMD=0.80; 95% CI: 0.15, 1.44, p=0.03), DVR (SMD = 0.79; 95% CI: 0.40, 1.17, p<0.001), and SUVR (SMD=0.55; 95% CI: 0.30, 0.80, p=0.009, Fig. 2).
Conclusions: The preliminary results of this study indicate that TSPO PET can successfully identify MS from control subjects, with increased brain TSPO PET signal consistently observed in MS populations. However, the existing research differs considerably in terms of tracers, ROIs, reference tissue, and other potentially influential factors in methods. We show that the type of PET quantification method reported is a significant source of heterogeneity. Our future work will investigate the impact of other variations within the studies by performing further subgroup analyses. In addition, we will investigate the relationship between indicators of disease severity and TSPO PET signal. Finally, we will rate quality of evidence using GRADE frameworks and evaluate publication bias.
In this issue
Jump to section
Related Articles
Cited By...
- No citing articles found.