A Window on the Lung: Molecular Imaging as a Tool to Dissect Pathophysiologic Mechanisms of Acute Lung Disease

Abstract

In recent years, imaging has given a fundamental contribution to our understanding of the pathophysiology of acute lung diseases. Several methods have been developed based on computed tomography (CT), positron emission tomography (PET), and magnetic resonance (MR) imaging that allow regional, in vivo measurement of variables such as lung strain, alveolar size, metabolic activity of inflammatory cells, ventilation, and perfusion. Because several of these methods are noninvasive, they can be successfully translated from animal models to patients. The aim of this paper is to review the advances in knowledge that have been accrued with these imaging modalities on the pathophysiology of acute respiratory distress syndrome (ARDS), ventilator-induced lung injury (VILI), asthma and chronic obstructive pulmonary disease (COPD).

Figure 1

Positron emission tomography image representing pulmonary [¹⁸F]FDG activity 4 hours after unilateral cotton smoke inhalation to the left lung of a sheep (positioned on the right side in the figure). Note higher activity in the smoke exposed than in the control lung. Reproduced from Musch et al (Reference [34]).

Figure 2

Micropositron emission tomographic image of 9-(4-[¹⁸F]fluoro-3-[hydroxymethyl]butyl)guanine ([¹⁸F]FHBG) activity in a herpes simplex virus thymidine kinase (HSV-tk) reporter mice after smoke inhalation injury. [¹⁸F]FHBG activity is proportional to nuclear factor-kappa B (NF-κB)-mediated gene expression. The arrow indicates the location of the lungs. Note increased pulmonary NF-κB activation, and hence HSV-tk expression, at 24 and 48 hours after smoke inhalation. Reproduced from Syrkina et al. (Reference [35]).

Figure 3

[¹³N]nitrogen (¹³N₂) positron emission tomography images from a sheep with lavage-induced lung injury. A bolus of ¹³N₂ in saline solution was infused intravenously over 3 seconds at the beginning of a 60-second apnea. The distribution of ¹³N₂ during early apnea (between 5 and 10 seconds) reflects regional perfusion (peak apnea image). The distribution of ¹³N₂ at the end of apnea (between 40 and 60 seconds) is proportional to perfusion only to aerated alveolar units, which retain ¹³N₂ during apnea (end-apnea image). The decrease in tracer activity between peak and end-apnea images in the dorsal, dependent lung (arrowheads) reflects the presence of shunt in this part of the lung because alveoli that are perfused but not aerated do not retain ¹³N₂ during apnea. Modified from Musch et al (Reference [12]).