Lung function measurements in preclinical research: What has been done and where is it headed?

Due to the close interaction of lung morphology and functions, repeatable measurements of pulmonary function during longitudinal studies on lung pathophysiology and treatment efficacy have been a great area of interest for lung researchers. Spirometry, as a simple and quick procedure that depends on the maximal inspiration of the patient, is the most common lung function test in clinics that measures lung volumes against time. Similarly, in the preclinical area, plethysmography techniques offer lung functional parameters related to lung volumes. In the past few decades, many innovative techniques have been introduced for in vivo lung function measurements, while each one of these techniques has their own advantages and disadvantages. Before each experiment, depending on the sensitivity of the required pulmonary functional parameters, it should be decided whether an invasive or non-invasive approach is desired. On one hand, invasive techniques offer sensitive and specific readouts related to lung mechanics in anesthetized and tracheotomized animals at endpoints. On the other hand, non-invasive techniques allow repeatable lung function measurements in conscious, free-breathing animals with readouts related to the lung volumes. The biggest disadvantage of these standard techniques for lung function measurements is considering the lung as a single unit and providing only global readouts. However, recent advances in lung imaging modalities such as x-ray computed tomography and magnetic resonance imaging opened new doors toward obtaining both anatomical and functional information from the same scan session, without the requirement for any extra pulmonary functional measurements, in more regional and non-invasive manners. Consequently, a new field of study called pulmonary functional imaging was born which focuses on introducing new techniques for regional quantification of lung function non-invasively using imaging-based techniques. This narrative review provides first an overview of both invasive and non-invasive conventional methods for lung function measurements, mostly focused on small animals for preclinical research, including discussions about their advantages and disadvantages. Then, we focus on those newly developed, non-invasive, imaging-based techniques that can provide either global or regional lung functional readouts at multiple time-points.