(A) Coronal CT section from a TB patient with newly diagnosed cavitary TB demonstrating pathologically distinct TB lesions — granulomas (blue), pneumonia-like disease (blue), or cavities (red) — compared with unaffected lung (yellow). These different lesions demonstrate distinct pathological characteristics. (B) Radiolabeled ¹¹C-rifampin PET/CT demonstrates spatially compartmentalized rifampin exposures in the pathologically distinct TB lesions within the same patient, with low cavity wall rifampin exposures. The ¹¹C-rifampin AUC is shown as a heatmap overlay in the selected transverse section. A and B were adapted with permission from Nature Medicine (13). (C) MRI (T2 flair) demonstrates heterogeneous brain inflammation (arrow) in a patient with TB meningitis with the corresponding spatially heterogeneous ¹¹C-rifampin AUC exposures. Adapted with permission from Science Translational Medicine (78). (D) Longitudinal ¹⁸F-FDG PET/CT in a cavitary TB patient over 6 months of standard treatment. Increased ¹⁸F-FDG uptake (compared with month 1) is noted at 6 months into treatment, coincident with treatment failure. D was adapted with permission from EJNMMI Research (108). (E) Fluorescence microscopy allows longitudinal imaging of the brain (dashed line) and eye (solid line) of a zebrafish larva infected i.v. with approximately 100 CFU of fluorescent Mycobacterium marinum:tdTomato. Infection began in the hindbrain ventricle (arrowheads). (F) Ex vivo H&E staining of a large rabbit necrotic TB granuloma (left), matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) ion map of moxifloxacin in the same section (middle), and coregistration and overlay of moxifloxacin ion image with H&E staining (in grayscale) demonstrating accumulation in macrophage-rich regions (right). Scale bar: 2 mm. Images in F are courtesy of Drs. Landry Blanc and Véronique Dartois.