Spatial lung imaging in clinical and translational settings

Abstract

For many severe lung diseases, non-invasive biomarkers from imaging could improve early detection of lung injury or disease onset, establish a diagnosis, or help follow-up disease progression and treatment strategies. Imaging of the thorax and lung is challenging due to its size, respiration movement, transferred cardiac pulsation, vast density range and gravitation sensitivity. However, there is extensive ongoing research in this fast-evolving field. Recent improvements in spatial imaging have allowed us to study the three-dimensional structure of the lung, providing both spatial architecture and transcriptomic information at single-cell resolution. This fast progression, however, comes with several challenges, including significant image file storage and network capacity issues, increased costs, data processing and analysis, the role of artificial intelligence and machine learning, and mechanisms to combine several modalities. In this review, we provide an overview of advances and current issues in the field of spatial lung imaging.

FIGURE 1

Numbers of published articles on imaging techniques in respiratory medicine from 2014 to 2024. Illustration of the increasing frequency of articles employing imaging technology, published over the past decade. The numbers of retrieved articles were generated from the database PubMed using the search terms “imaging technique” [All Fields] AND “chest” [All Fields] OR “lung” [All Fields] OR “pulmonary” [All Fields] OR “respiratory” [All Fields] OR “thorax” [All Fields] OR “thoracic” [All Fields] OR “pneumonia” [All Fields] OR “pneumonitis” [All Fields] OR “bronchiectasis” [All Fields] OR “bronchiolitis” [All Fields] OR “cystic fibrosis” [All Fields] OR “tuberculosis” [All Fields] OR “mycobacteria” [All Fields] OR “asthma” [All Fields] OR “copd” [All Fields] OR “pleural” [All Fields] OR “sarcoidosis” [All Fields] OR “lung fibrosis” [All Fields] OR “ILD” [All Fields] OR “ventilation” [All Fields]. The search was performed on 16 May 2024.

FIGURE 2

Imaging newly synthesised collagen type I. The small peptide, named CBP8, was conjugated to radioactive nuclei for assessment of early fibrogenesis by positron emission tomography (PET) imaging. a) Increased lung uptake of the collagen tracer in a mouse model of fibrosis, comparing a healthy control mouse (sham) to a bleomycin-exposed mouse (BM). Reproduced from [51] with permission. Data are expressed as percent injected dose per cm³ of tissue (% ID/cc). The tracer uptake for each scan is indicated by the colour bar next to the lung image. b) The same fibrosis model in rats, where the same collagen tracer was employed. Reproduced from [52] with permission. c–e) The first-in-human study where the same collagen tracer was used to assess early fibrogenesis, in terms of collagen type I synthesis. c) A healthy subject was undergoing a PET scan which was compared to d) an idiopathic pulmonary fibrosis (IPF) patient. The increased PET signal at certain hotspots (white arrows) in the IPF patient were not indicated as areas of fibrogenesis within e) the same patient's computed tomography (CT) lung scan. Red arrows show matching disease areas, found by both PET and CT. Reproduced from [9] with permission.

FIGURE 3

Schematic illustration describing how the imaging field has progressed from being able to image simple two-dimensional structures to advanced imaging of whole organs and the human body in three dimensions. Figure created with BioRender.com.