Evaluating the Clinical Utility of TSPO-PET in MS and the Influence of Methodological Heterogeneity

BACKGROUND AND OBJECTIVES: vivo and shows promise for detecting innate inflammatory activity in multiple sclerosis (MS). However, TSPO-PET findings in MS vary substantially across studies. We performed a systematic review and meta-analysis to quantify TSPO-PET signal differences between people with MS (PwMS) and healthy controls (HCs) and to evaluate the impact of methodological factors on study outcomes. METHODS: statistics. Meta-regression and subgroup analyses investigated methodological sources of heterogeneity. Patient-level data were analyzed for associations with clinical and demographic variables. Risk of bias and certainty of evidence were assessed using quality assessment of diagnostic accuracy studies 2 tool and GRADE framework, respectively. RESULTS: -weighted white matter lesion regions. Patient-level analyses, while limited in power, showed significant associations between TSPO-PET signal (DVR) and disability measures (expanded disability status scale). DISCUSSION: TSPO-PET effectively distinguishes PwMS from HC and differentiates MS subtypes. However, radiotracer, quantification method, image analysis method, reference tissue, and region of interest significantly impact TSPO-PET outcomes and must be considered when designing and interpreting studies. Methodological standardization and improved reporting will be essential to enhance cross-study comparability and clinical interpretability.