Semi-Automated Quantification of 18F-FDG PET-CT in Pulmonary TB Contacts and Its Association with Prospective...

Positron emission tomography-computed tomography (PET-CT) has shown potential as a research tool to characterize heterogeneity in tuberculosis (TB) infection. Prospective utilisation of this technology will require standardization of imaging protocols, interpretation, and analysis of PET-CT images to improve generalizability and data assimilation between discrete cohorts. We evaluated a semi-automated approach using open-source software to minimize inter-operator variability of imaging interpretation and use reference organ normalization to lower variability in physiological uptake. We quantified ¹⁸F-Fluorodeoxyglucose (FDG) uptake in intrathoracic lymph nodes (ITLNs) of eleven interferon-gamma release assay (IGRA) positive TB contacts that enrolled on a prospective observational study, including eight contacts with serial PET-CT scans. The imaging was analyzed using 3D Slicer, an open-source medical imaging platform designed for biomedical and clinical research, that provides semi-automated segmentation and automated liver quantification. The extracted data included ITLN maximum standardized uptake value (SUVmax), mean standardized uptake value (SUVmean), metabolic volume (MV), and total lesion glycolysis (TLG), and liver SUVmean. We compared its performance to that of clinical software, both with and without standardizing to liver uptake (as a physiological reference), and assessed operator variability. Then, we evaluated the association between multiple quantitative PET metrics and prospective outcomes in pulmonary TB contacts. We report strong agreement between open-source and clinical image evaluation platforms. We find semi-automated PET quantification can lower inter-operator variability, and standardizing to reference organs increases the sensitivity of imaging analysis. Specifically, we report preliminary findings that increasing metabolic activity on serial PET-CT in early infection is associated with detectable Mycobacterium tuberculosis (Mtb) at the anatomical site of FDG uptake, consistent with a progressive phenotype of infection.