Imaging Pulmonary Inflammation

Abstract

Lung inflammatory diseases contribute significantly to the socioeconomic burden of disease. Yet very few new, effective therapies for respiratory disease have been approved for use. A major contributing factor is the lack of biomarkers that can accurately quantify the lung inflammatory burden and can be used to understand the contribution of lung inflammation to loss in lung function. Molecular imaging approaches can detect and quantify the recruitment and activation of specific immune cells in lung inflammation. We review the clinical techniques used to image lung inflammation, provide an overview of clinical and emerging PET techniques for quantifying lung inflammation, and discuss potential clinical applications.

Keywords: lung inflammation; molecular imaging; positron emission tomography; pulmonary.

FIGURE 1.

CT manifestations of inflammatory lung disease. (A) Organizing pneumonia is characterized by left lower lobe focal consolidation with peripheral ground-glass opacity and air bronchograms. Chronic eosinophilic pneumonia and adenocarcinoma in situ can appear similar. (B) Diffuse, confluent ground-glass opacity and interlobular septal thickening with a “crazy paving” pattern in right lung, with lesser involvement of left lung can reflect multifocal pneumonia, atypical edema pattern, or pulmonary parenchymal hemorrhage. Pleural effusions are also present bilaterally. (C) Nonspecific interstitial pneumonia exhibits predominantly peripheral ground-glass opacity with fine reticulation and subpleural sparring in lower lobes, right greater than left. Absence of honeycombing makes usual interstitial pneumonia unlikely.

FIGURE 2.

PET/CT images in COPD and age-matched healthy volunteers in pilot study assessing reproducibility of ¹⁸F-FDG uptake in COPD lungs. (A) Representative PET and CT images from healthy volunteer and volunteers with COPD without or with chronic bronchitis symptoms. PET images shown are sum of last 5 min of data from 60-min dynamic acquisition. COPD participant without chronic bronchitis had emphysema diffusely throughout both lungs on CT. COPD participant with chronic bronchitis had more heterogeneously distributed emphysema. Units of intercept-normalized K_i (K_iN) = min⁻¹. (B) All data points in healthy volunteers (n = 7) and COPD participants without (n = 6) and with chronic bronchitis symptoms (n = 4). (Data reported in abstract form in Chen et al. (52)).

FIGURE 3.

PET and CT images from 2 patients obtained within 24 h of being placed on ventilator. Images on left demonstrate no abnormal ¹⁸F-FDG uptake within lungs. Images on right demonstrate visibly increased ¹⁸F-FDG uptake in both lungs. SUVs of whole lung were not different between patients, demonstrating relative insensitivity of SUV for quantifying whole-lung inflammation compared with whole-lung K_i, which is higher in patient on right. K_ir and SUV_r are K_i and SUV in 50% of pixels with highest activity within each region of interest (in white). Images obtained in collaboration with Brian Fuller, MD, Washington University School of Medicine.

FIGURE 4.

High-resolution CT and ¹⁸F-FDG PET/CT in usual interstitial pneumonia. (A) Axial high-resolution CT image of chest demonstrates honeycombing, fibrosis, and traction bronchiectasis, most evident in lingula. There is also emphysema. (B and C) Axial attenuation-corrected PET and fused PET/CT images demonstrate mild, diffusely increased ¹⁸F-FDG uptake throughout lung parenchy3ma, with more focally increased ¹⁸F-FDG uptake in area of honeycombing and fibrosis in lingula.

FIGURE 5.

High-resolution CT and ¹⁸F-FDG PET/CT in ILD. (A) Coronal maximum-intensity-projection PET image demonstrates diffusely increased ¹⁸F-FDG uptake in left lung, with lesser involvement in right lung. (B and C) Axial PET and PET/CT fused images shows heterogeneously increased ¹⁸F-FDG uptake, suggesting active inflammation or possible active fibrosis. (D) CT images demonstrate regions of diffuse ground-glass opacity with honeycombing, interlobular septal thickening, and bronchiectasis, more pronounced on right, in areas of increased ¹⁸F-FDG uptake. Although usual interstitial pneumonia was suspected due to presence of honeycombing, left lung biopsies demonstrated emphysematous changes, subpleural and interstitial fibrosis, and focal organizing pneumonitis, with considerations including hypersensitivity pneumonitis or smoking-related ILD.