Journal Article Preprint Epublish 2 citations
PubMed: 40667045 DOI: 10.1101/2025.06.16.660017
A multimodal imaging approach for imaging the metabolic changes resulting from bronchopulmonary dysplasia.
bioRxiv
Authors: Brittney L Gorman, Zhi Li, Gail Deutsch, Heidi L Huyck, Niana Beishembieva, Heather Olson, Jorge Villazon, Ping Yu, Gloria S Pryhuber, Geremy Clair, Lingyan Shi, Christopher R Anderton
Affiliations
- Environmental and Biological Sciences Directorate, Pacific Northwest National Laboratory, Richland, WA, 99354, United States.
- Shu Chien-Gene Lay Department of Bioengineering, University of California San Diego, La Jolla, California 92093, United States.
- Seattle Children's Hospital, Seattle, WA 98105, United States.
- Department of Pediatrics, University of Rochester Medical Center, Rochester, NY 14642, United States.
Abstract
Lung tissue is composed of various functional units, each essential for maintaining the intricate functions of the lung. Disruptions in the molecular and cellular mechanisms in the lung can cause tissue fibrosis, inflammation, and severe breathing difficulties, which are common in conditions such as bronchopulmonary dysplasia (BPD). BPD's molecular changes are not well understood, which hinders effective diagnosis and treatment. Here, we present a new multimodal imaging workflow for detailed molecular and metabolic characterization of tissues at multiple spatial scales. We applied a combined imaging approach using matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) and ultrafast focused light-based imaging & photonics platform (U-FLIP) that included two-photon fluorescence (TPF), second harmonic generation (SHG), and stimulated Raman scattering (SRS). We also developed a hierarchical multimodal registration network (HiMReg) for the precise co-registration of each modality. This approach revealed previously unknown metabolic changes in distinct functional tissue units affected by BPD, including altered lipid distributions, reduced optical redox states, and specific collagen remodeling in bronchioles. Our findings evidenced alterations in lipid composition and metabolism of BPD-affected alveoli compared to healthy tissue, providing novel insights into disease pathophysiology. Our findings elucidate the intricate spatial and molecular complexity of BPD, building on prior research that did not provide the spatial resolution necessary to capture the nuances of metabolic alterations. This multimodal approach offers exceptional insights into disease exploration and could transform the way we study spatially heterogeneous conditions. By providing detailed maps of the metabolic shifts occurring in distinct tissue microanatomical features, the methods developed here could enable the discovery of new therapeutic avenues, making it highly attractive for the field of biomedical research.
MeSH
Lung, Multimodal Imaging, Research, Therapeutics, Tissues, Bronchopulmonary Dysplasia