Noninvasive quantification of macrophagic lung recruitment during experimental ventilation-induced lung injury

Abstract

Macrophagic lung infiltration is pivotal in the development of lung biotrauma because of ventilation-induced lung injury (VILI). We assessed the performance of [¹¹C](R)-PK11195, a positron emission tomography (PET) radiotracer binding the translocator protein, to quantify macrophage lung recruitment during experimental VILI. Pigs (n = 6) were mechanically ventilated under general anesthesia, using protective ventilation settings (baseline). Experimental VILI was performed by titrating tidal volume to reach a transpulmonary end-inspiratory pressure (∆P_L) of 35-40 cmH₂O. We acquired PET/computed tomography (CT) lung images at baseline and after 4 h of VILI. Lung macrophages were quantified in vivo by the standardized uptake value (SUV) of [¹¹C](R)-PK11195 measured in PET on the whole lung and in six lung regions and ex vivo on lung pathology at the end of experiment. Lung mechanics were extracted from CT images to assess their association with the PET signal. ∆P_L increased from 9 ± 1 cmH₂O under protective ventilation, to 36 ± 6 cmH₂O during experimental VILI. Compared with baseline, whole-lung [¹¹C](R)-PK11195 SUV significantly increased from 1.8 ± 0.5 to 2.9 ± 0.5 after experimental VILI. Regional [¹¹C](R)-PK11195 SUV was positively associated with the magnitude of macrophage recruitment in pathology (P = 0.03). Compared with baseline, whole-lung CT-derived dynamic strain and tidal hyperinflation increased significantly after experimental VILI, from 0.6 ± 0 to 2.0 ± 0.4, and 1 ± 1 to 43 ± 19%, respectively. On multivariate analysis, both were significantly associated with regional [¹¹C](R)-PK11195 SUV. [¹¹C](R)-PK11195 lung uptake (a proxy of lung inflammation) was increased by experimental VILI and was associated with the magnitude of dynamic strain and tidal hyperinflation.NEW & NOTEWORTHY We assessed the performance of [¹¹C](R)-PK11195, a translocator protein-specific positron emission tomography (PET) radiotracer, to quantify macrophage lung recruitment during experimental ventilation-induced lung injury (VILI). In this proof-of-concept study, we showed that the in vivo quantification of [¹¹C](R)-PK11195 lung uptake in PET reflected the magnitude of macrophage lung recruitment after VILI. Furthermore, increased [¹¹C](R)-PK11195 lung uptake was associated with harmful levels of dynamic strain and tidal hyperinflation applied to the lungs.

Keywords: inflammation; mechanical ventilation; medical imaging; positron emission tomography; ventilation-induced lung injury.