In vivo imaging is an important tool for preclinical studies of lung function and disease. The widespread availability of multimodal animal imaging systems and the rapid rate of diagnostic contrast agent development have empowered researchers to noninvasively study lung function and pulmonary disorders. Investigators can identify, track, and quantify biological processes over time. In this review, we highlight the fundamental principles of bioluminescence, fluorescence, planar X-ray, X-ray computed tomography, magnetic resonance imaging, and nuclear imaging modalities (such as positron emission tomography and single photon emission computed tomography) that have been successfully employed for the study of lung function and pulmonary disorders in a preclinical setting. The major principles, benefits, and applications of each imaging modality and technology are reviewed. Limitations and the future prospective of multimodal imaging in pulmonary physiology are also discussed. In vivo imaging bridges molecular biological studies, drug design and discovery, and the imaging field with modern medical practice, and, as such, will continue to be a mainstay in biomedical research.

Similar to effects of alcohol on the heart, liver, and brain, the effects of ethanol (EtOH) on lung injury are preventable. Unlike other vital organ systems, however, the lethal effects of alcohol on the lung are underappreciated, perhaps because there are no signs of overt pulmonary disorder until a secondary insult, such as a bacterial infection or injury, occurs in the lung. This paper provides overview of the complex changes in the alveolar environment known to occur following both chronic and acute alcohol exposures. Contemporary animal and cell culture models for alcohol-induced lung dysfunction are discussed, with emphasis on the effect of alcohol on transepithelial transport processes, namely, epithelial sodium channel activity (ENaC). The cascading effect of tissue and phagocytic Nadph oxidase (Nox) may be triggered by ethanol exposure, and as such, alcohol ingestion and exposure lead to a prooxidative environment; thus impacting alveolar macrophage (AM) function and oxidative stress. A better understanding of how alcohol changes the landscape of the alveolar epithelium can lead to improvements in treating acute respiratory distress syndrome (ARDS) for which hospitalized alcoholics are at an increased risk.

The lungs can undergo irreversible damage from chronic alcohol consumption. Herein, we developed an animal model predisposed for edematous lung injury following chronic ingestion of alcohol to better understand the etiology of alcohol-related disorders. Using animal modeling, alongside high-throughput proteomic and microarray assays, we identified changes in lung protein and transcript in mice and rats, respectively, following chronic alcohol ingestion or a caloric control diet. Liquid chromatography-mass spectrometry identified several mitochondrial-related proteins in which the expression was upregulated following long-term alcohol ingestion in mice. Consistent with these observations, rat gene chip microarray analysis of alveolar cells obtained from animals maintained on a Lieber-DeCarli liquid alcohol diet confirmed significant changes in mitochondrial-related transcripts in the alcohol lung. Transmission electron microscopy revealed significant changes in the mitochondrial architecture in alcohol mice, particularly following lipopolysaccharide exposure. Chronic alcohol ingestion was also shown to worsen mitochondrial respiration, mitochondrial membrane polarization, and NAD(+)-to-NADH ratios in alveolar type 2 cells. In summary, our studies show causal connection between chronic alcohol ingestion and mitochondrial dysfunction, albeit the specific role of each of the mitochondrial-related proteins and transcripts identified in our study requires additional study.

It is clear that a critical component of salt and water transport by the lungs depends on precise control of epithelial sodium channel (ENaC) activity, which generates the osmotic driving force for net transport of solute out of the air space. Chronic ethanol (EtOH) ingestion alters the signal transduction pathway leading to normal ENaC activity. We show that chronic EtOH ingestion in 12 week old C57BL/6 mice increases expression of ENaC, NADPH oxidase (Nox) 2, and Nox 4 protein (1.7, 1.5, and 2.8 fold, respectively) using western blot analysis. Real time PCR analysis of Rac‐guanine nucleotide exchange factors (which mediate activation of Nox) reveals that Arhgef7, Sos1, Sos2, Tiam1, and Ras‐GRF2 transcripts are significantly down‐regulated in EtOH lung compared to normal healthy lung. In vivo radiographic imaging indicates that these changes in cellular signaling lead to an enhanced rate of lung fluid clearance in EtOH animals following a tracheal saline challenge of 5uL/g body weight. We conclude that chronic ethanol ingestion activates NADPH oxidase, which oxidizes the alveolar environment in order to stimulate redox sensitive ENaC activity. This research was supported by SIRE awarded to DT, and R00‐HL‐09222601.