Different stages of invasive pulmonary aspergillosis (IPA) and the potential therapeutic importance of different tissue subcompartments. Different stages of invasive pulmonary aspergillosis (IPA) and the potential therapeutic importance of different tissue subcompartments. (A) In the very earliest stages of disease, the relevant subcompartments include epithelial lining fluid, alveolar epithelial cells, pulmonary endothelial cells, and pulmonary alveolar macrophages (PAMs). (B) In the early stages of established disease, a halo sign may be seen that consists of a nodule (n) surrounded by a halo (h), which is caused by active infection and inflammation around the nodule. In this case, the relevant subcompartments are within the nodule and contiguous lung. (C) In late disease, an air crescent sign may be present, which represents an organizing sequestrum. (A pulmonary sequestrum [s] is surrounded by an air crescent [ac].) The therapeutic challenge in this case is the achievement of antifungal drug concentrations within a relatively avascular area. (Reprinted from reference 262 with permission; imaging and details kindly provided by Reginald Greene.)‏ Timothy Felton et al. Clin. Microbiol. Rev. 2014; doi:10.1128/CMR.00046-13