From Mouse to Man and Back: Closing the Correlation Gap between Imaging and Histopathology for Lung Diseases

Abstract

Lung diseases such as fibrosis, asthma, cystic fibrosis, infection and cancer are life-threatening conditions that slowly deteriorate quality of life and for which our diagnostic power is high, but our knowledge on etiology and/or effective treatment options still contains important gaps. In the context of day-to-day practice, clinical and preclinical studies, clinicians and basic researchers team up and continuously strive to increase insights into lung disease progression, diagnostic and treatment options. To unravel disease processes and to test novel therapeutic approaches, investigators typically rely on end-stage procedures such as serum analysis, cyto-/chemokine profiles and selective tissue histology from animal models. These techniques are useful but provide only a snapshot of disease processes that are essentially dynamic in time and space. Technology allowing evaluation of live animals repeatedly is indispensable to gain a better insight into the dynamics of lung disease progression and treatment effects. Computed tomography (CT) is a clinical diagnostic imaging technique that can have enormous benefits in a research context too. Yet, the implementation of imaging techniques in laboratories lags behind. In this review we want to showcase the integrated approaches and novel developments in imaging, lung functional testing and pathological techniques that are used to assess, diagnose, quantify and treat lung disease and that may be employed in research on patients and animals. Imaging approaches result in often novel anatomical and functional biomarkers, resulting in many advantages, such as better insight in disease progression and a reduction in the numbers of animals necessary. We here showcase integrated assessment of lung disease with imaging and histopathological technologies, applied to the example of lung fibrosis. Better integration of clinical and preclinical imaging technologies with pathology will ultimately result in improved clinical translation of (therapy) study results.

Imaging Biomarkers in Animal Models of Drug-Induced Lung Injury: A Systematic Review

“…An additional aspect to highlight when implementing imaging in model validation is that incidence of induced disease may also differ or create subgroups of pathologies worth discussing, as well as enables selection of treatment groups when only animals are chosen for continuous intervention experiments, where disease successfully was induced. Here, imaging biomarkers are extremely valuable, without the need to terminate any groups for validation of disease incidence [ 27 , 47 ].…”

Longitudinal Imaging Using PET/CT with Collagen-I PET-Tracer and MRI for Assessment of Fibrotic and Inflammatory Lesions in a Rat Lung Injury Model

“…challenge model [ 16 , 25 , 26 , 29 , 34 , 35 ], but it has also been reported in other types of lung injury models [ 34 , 35 , 36 , 37 ]. This phenomenon is thought to be a compensatory mechanism to cope with the acutely induced vascular leak [ 35 , 38 ]. In the bleomycin model, this is mainly occurring during the first week after one i.t.…”

From Macroscopy to Ultrastructure: An Integrative Approach to Pulmonary Pathology

“…In addition, other promising tools are discussed in more detail including their potential applications. We acknowledge that a plethora of techniques has also been investigated in animal studies, which can readily be leveraged to combine imaging data with mechanistical insights ( 7 ); however, we deliberately focus on studies in humans that can be implemented more easily into routine clinical practice.…”