An official ATS conference proceedings: Advances in small-animal imaging application to lung pathophysiology

The American Thoracic Society convened a workshop, "Advances in Small Animal Imaging: Application to Lung Pathophysiology," to identify cutting-edge research in imaging technology and the potential applicability to the study of lung pathophysiology in small-animal models. The goals of the conference were as follows: (1) to summarize the current state of small-animal models of lung pathophysiology and their applicability to human disease; (2) to identify all potentialmodes of noninvasive imaging; (3) to explore the potential for current and future applications; (4) to discuss and debate current controversies; and (5) to identify future research directions and opportunities for, and applications of, imaging technology to facilitate the use of small-animal models for the study of lung diseases. The first part of the workshop focused on the current state of knowledge of mouse models with an emphasis on "What are the big questions?" and "How good are the models?" Presentations described four major animal model systems of lung disease: (1) reactive airway disease, (2) chronic obstructive pulmonary disease (COPD) and emphysema, (3) interstitial lung disease, and (4) acute lung injury (ALI). The second part of the workshop reviewed those "state of the art" imaging modalities that would be most likely applicable to lung disease with an emphasis on the questions "What is the cutting edge of the imaging modality?" and "What can we measure with this imaging modality?" The related presentations focused on six imaging modalities that have received the most recent attention: (1) videomicroscopy, (2) magnetic resonance imaging (MRI), (3) micro-computed tomography (micro-CT), (4) micro-positron emission tomography (micro-PET), (5) optical imaging, and (6) molecular markers. The final part of the workshop was devoted to discussion and interaction between those investigators focused on development of imaging modalities and those using small-animal models of lung disease. The discussion included (1) the quality and applicability of current small-animal models of lung disease and (2) how to better adapt currently available imaging modalities to study lung disease in small-animal models. Workshop participants concluded that noninvasive imaging of health and disease in living organisms can span several domains, including anatomic, physiologic, metabolic, and molecular imaging. In parallel, technologies have evolved that allow us to query biological processes at multiple levels, including X-ray/CT, MRI, nuclear imaging (single photon emission CT [SPECT]/PET), ultrasound, and optical imaging (bioluminescence/fluorescence). "Molecular imaging" refers to the measurement and characterization of specific molecules, molecular processes, and molecular events, over time and space, in living organisms. Furthermore, whereas imaging modalities may be applicable to small animals, the currently used small-animal models of common human lung diseases remain limited in terms of their ability to truly recapitulate human pathophysiologic conditions. Further development is required for small-animal models of human lung disease as well as the integrated use of imaging modalities. The following recommendations were made for future work on animal models: • Continually reassess current animal models of lung disease. • Delineate appropriate criteria for animal models of lung disease. • Develop animal models that better duplicate human respiratory disease. • Focus on an integrated approach, from the submolecular level up to the organ level, in the animal models of lung disease. For imaging modalities, the workshop ended with the following recommendations: • Increase interaction between the integrative biological science community and the imaging science community. • Utilize imaging modalities to investigate the topography of the lung pathophysiology. • Utilize imaging modalities to investigate intracellular lung pathophysiology in vivo and in real time. • Utilize imaging modalities to investigate and study temporal pathophysiological events. • Utilize combined imaging modalities to better relate spatial and temporal events (e.g., CT with PET or SPECT). • Utilize imaging modalities to determine how well various animal models reproduce the human disease condition. • Explore technical advances for several imaging techniques, such as validation, increased resolution, and increased speed of data acquisition, to name a few. • Develop better quantitative analysis tools for image analysis - for example, the application of stereological techniques to imaging datasets. • Investigate the use of bioinformatics analysis techniques to the large datasets produced by image acquisition. • Expand future workshops to include other imaging modalities and their potential application to respiratory disease.