Cover Image

Characterization of transient and progressive pulmonary fibrosis by spatially correlated phase contrast microCT, classical histopathology and atomic force microscopy

Pulmonary fibrosis (PF) is a severe and progressive condition in which the lung becomes scarred over time resulting in pulmonary function impairment. Classical histopathology remains an important tool for micro-structural tissue assessment in the diagnosis of PF. A novel workflow based on spatial co...

Full description

Saved in:
Bibliographic Details
Main Authors: D'Amico, Lorenzo (Author) , Svetlove, Angelika (Author) , Longo, Elena (Author) , Meyer, Ruth (Author) , Senigagliesi, Beatrice (Author) , Saccomano, Giulia (Author) , Nolte, Philipp (Author) , Wagner, Willi Linus (Author) , Wielpütz, Mark Oliver (Author) , Leitz, Dominik (Author) , Dürr, Julia (Author) , Mall, Marcus A. (Author) , Casalis, Loredana (Author) , Köster, Sarah (Author) , Alves, Frauke (Author) , Tromba, Giuliana (Author) , Dullin, Christian (Author)
Format: Article (Journal)
Language:English
Published: 8 January 2024
In: Computers in biology and medicine
Year: 2024, Volume: 169, Pages: 1-11
ISSN:1879-0534
DOI:10.1016/j.compbiomed.2024.107947
Online Access:Verlag, kostenfrei, Volltext: https://doi.org/10.1016/j.compbiomed.2024.107947
Verlag, kostenfrei, Volltext: https://www.sciencedirect.com/science/article/pii/S0010482524000313
Get full text
Author Notes:Lorenzo D’Amico, Angelika Svetlove, Elena Longo, Ruth Meyer, Beatrice Senigagliesi, Giulia Saccomano, Philipp Nolte, Willi L. Wagner, Mark O. Wielpütz, Dominik H.W. Leitz, Julia Duerr, Marcus A. Mall, Loredana Casalis, Sarah Köster, Frauke Alves, Giuliana Tromba, Christian Dullin
Description
Summary:Pulmonary fibrosis (PF) is a severe and progressive condition in which the lung becomes scarred over time resulting in pulmonary function impairment. Classical histopathology remains an important tool for micro-structural tissue assessment in the diagnosis of PF. A novel workflow based on spatial correlated propagation-based phase-contrast micro computed tomography (PBI-microCT), atomic force microscopy (AFM) and histopathology was developed and applied to two different preclinical mouse models of PF - the commonly used and well characterized Bleomycin-induced PF and a novel mouse model for progressive PF caused by conditional Nedd4-2 KO. The aim was to integrate structural and mechanical features from hallmarks of fibrotic lung tissue remodeling. PBI-microCT was used to assess structural alteration in whole fixed and paraffin embedded lungs, allowing for identification of fibrotic foci within the 3D context of the entire organ and facilitating targeted microtome sectioning of planes of interest for subsequent histopathology. Subsequently, these sections of interest were subjected to AFM to assess changes in the local tissue stiffness of previously identified structures of interest. 3D whole organ analysis showed clear morphological differences in 3D tissue porosity between transient and progressive PF and control lungs. By integrating the results obtained from targeted AFM analysis, it was possible to discriminate between the Bleomycin model and the novel conditional Nedd4-2 KO model using agglomerative cluster analysis. As our workflow for 3D spatial correlation of PBI, targeted histopathology and subsequent AFM is tailored around the standard procedure of formalin-fixed paraffin-embedded (FFPE) tissue specimens, it may be a powerful tool for the comprehensive tissue assessment beyond the scope of PF and preclinical research.
Item Description:Gesehen am 16.09.2024
Physical Description:Online Resource
ISSN:1879-0534
DOI:10.1016/j.compbiomed.2024.107947

Similar Items