Penetration of PZA in cellular and necrotic lesions. (A) Two left panels: ion maps of PZA [M+2H]⁺ in rabbit lung tissue sections that encompass cellular and necrotic granulomas. The PZA [M+2H]⁺ signal intensity scale is linear and shown to the left. Middle panels: H&E stains of the corresponding adjacent sections. N, necrotic core or caseum; C, cellular rim or fully cellular granuloma; L, uninvolved lung. Right panels: optical images of the sections used for MALDI-MSI. The necrotic core of caseous granulomas is highlighted by the black contour lines in the ion maps (left) and white contour lines in the H&E stained section and optical image. Scale bars: 5 mm. (B) Quantitation of PZA in the necrotic or caseous core, cellular rim, and surrounding lung tissue of four lesions collected in two rabbits, obtained by LCM coupled to HPLC/tandem mass spectrometry. Each value was normalized to plasma concentrations measured at the time of tissue sampling.