Imaging the Evolution of Reactivation Pulmonary Tuberculosis in Mice Using 18F-FDG PET

Latent tuberculosis infection affects one third of the world's population and can reactivate (relapse) decades later. However, current technologies, dependent on postmortem analyses, cannot follow the temporal evolution of disease. Methods: C3HeB/FeJ mice, which develop necrotic and hypoxic tuberculosis lesions, were aerosol-infected with Mycobacterium tuberculosis. PET and CT were used to serially image the same cohort of infected mice through pretreatment, tuberculosis treatment, and subsequent development of relapse. Results: A novel diffeomorphic registration was successfully used to monitor the spatial evolution of individual pulmonary lesions. Although most lesions during relapse developed in the same regions as those noted during pretreatment, several lesions also arose de novo within regions with no prior lesions. Conclusion: This study presents a novel model that simulates infection and reactivation disease as seen in humans and could prove valuable to study tuberculosis pathogenesis and evaluate novel therapeutics.