Lung [18F]fluorodeoxyglucose Uptake and Ventilation–Perfusion Mismatch in the Early Stage of Experimental Acute Smoke Inhalation

Abstract

Background Acute lung injury (ALI) occurs in a third of patients with smoke inhalation injury. Its clinical manifestations usually do not appear until 48 to 72 h after inhalation. Identifying inflammatory changes that occur in pulmonary parenchyma earlier than that could provide insight into the pathogenesis of smoke-induced ALI. Furthermore, noninvasive measurement of such changes might lead to earlier diagnosis and treatment. Because glucose is the main source of energy for pulmonary inflammatory cells, we hypothesized that its pulmonary metabolism is increased shortly after smoke inhalation, when classic manifestations of ALI are not yet expected. Methods In five sheep we induced unilateral injury with 48 breaths of cotton smoke while the contralateral lung served as control. We used positron emission tomography with: 1) [18F]fluorodeoxyglucose to measure pulmonary inflammatory cell metabolic activity; and 2) [13N]nitrogen in saline to measure shunt and ventilation-perfusion distributions separately in the smoke-exposed and control lungs. Results The pulmonary [18F]fluorodeoxyglucose uptake rate was increased at 4 h after smoke inhalation (mean ± SD: 0.0031 ± 0.0013 vs. 0.0026 ± 0.0010 min−1, P < 0.05) mainly as a result of increased glucose phosphorylation. At this stage there was no worsening in lung aeration or shunt. However, there was a shift of perfusion toward units with lower ventilation-to-perfusion ratio (mean ratio ± SD: 0.82 ± 0.10 vs. 1.12 ± 0.02, P < 0.05) and increased heterogeneity of the ventilation-perfusion distribution (mean ± SD: 0.21 ± 0.07 vs. 0.13 ± 0.01, P < 0.05). Conclusion Using noninvasive imaging we demonstrated that increased pulmonary [18F]fluorodeoxyglucose uptake and ventilation-perfusion mismatch occur early after smoke inhalation.

Positron Emission Tomography With 18F-Fluorodeoxyglucose in Patients With Sickle Cell Acute Chest Syndrome

“…As compared to other inflammatory nontumoral conditions and as quantified with SUVmax, lung 18 F-FDG uptake of patients with ACS (median 2.5 [0.6–1.0]) was in the range of that reported in patients having lung contusion (2.2) 24 or idiopathic pulmonary fibrosis (2.8), 23 but lower than that reported in the pulmonary parenchyma of patients with sarcoidosis (5.1). 25 Lung 18 F-FDG uptake has been associated with lung neutrophilic inflammation in various conditions of acute lung injury, including experimental models of pneumococcal pneumonia, 9 , 26 bleomycin pneumonitis, 9 , 26 endotoxemia, 27 , 28 ventilator-induced lung injury, 12 smoke inhalation, 29 and airway instillation of endotoxin in humans. 11 Because increased bronchoalveolar fluid neutrophilia has been reported during ACS, 8 one can hypothesize that neutrophils are the main cells accounting for lung 18 F-FDG uptake during ACS.…”

Novel outcome measures for clinical trials in cystic fibrosis

“… 83 Furthermore, FDG-PET/CT imaging could be enhanced by quantitative measurements of regional ventilation and perfusion, to increase sensitivity for detecting functional changes in the lungs, as demonstrated previously for PET scanning. 84 – 86 …”

New Frontiers in Functional and Molecular Imaging of the Acutely Injured Lung: Pathophysiological Insights and Research Applications

“…Inflammatory cell metabolic activation is an early event in the pathogenesis of lung injury, as increased [ 18 F]FDG uptake precedes impairment of pulmonary gas exchange in an acute smoke inhalation model of lung injury ( Musch et al, 2014 ) and development of lung densities in an endotoxemia model with superimposed mechanical ventilation ( Wellman et al, 2016 );…”