Multiscale mapping of venous remodelling in idiopathic pulmonary fibrosis
Abstract
The integrity of the pulmonary vasculature is a key determinant of lung health, yet challenges in visualisation and quantification have hindered interrogation of its pathophysiological role in chronic lung disease. Here, we align recent advances in microscale image acquisition with novel computer vision-based vessel segmentation models to demonstrate expansion of the bronchial and pulmonary veins across varying severities of tissue remodelling in idiopathic pulmonary fibrosis (IPF). Relating these imaging findings to molecular data in control, mild, and severe fibrosis, we show that bronchial venous endothelial cells expand beyond their physiological peribronchial niche even in mild disease, acquiring persistent angiogenic, inflammatory, and matrix-remodelling programmes that define a specialised fibrovascular-immune interface. Finally, we relate these microscale and molecular observations to clinical CT imaging, demonstrating that intrapulmonary vein enlargement independently associates with worsened survival across three IPF cohorts. Collectively, our multimodal, multiscale approach connects previously unresolved three-dimensional venous architecture to its molecular endothelial correlate, establishing venous enlargement as a prognostically significant and clinically relevant feature of IPF. Our analytical approach also demonstrates how biological discoveries made in intact ex vivo human organs can translate into measurable phenotypes in living patients, providing a template for other organs and diseases.
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BibTeX
@misc{yamada2026multiscale,
title = {{Multiscale mapping of venous remodelling in idiopathic pulmonary fibrosis}},
author = {D. Yamada and H. Wang and A. Szmul and J. Riese and R. Egashira and C. H. M. van Moorsel and N. Mogulkoc and B. Gokce and S. Aslani and D. Cheng and Y. Chen and R. Bodenmann and M. Brunner and B. Tielemans and J. Brunet and T. Urban and J. Purzycka and H. Dejea and P. Tafforeau and M. Vermant and F. T. van Beek and B. Maurer and S. Krattli and M. Kreuzer and R. Bruggmann and T. Follet and M. Veltkamp and T. Goos and K. Anseele and M. Vander Kuylen and H. W. van Es and K. Engel and R. Savas and J. M. Brenes and J. M. Hendriks and T. S. Lapperre and C. L. Walsh and D. Jonigk and L. Neubert and C. Werlein and H. Freitag and S. Dettmer and J. C. Schupp and L. J. de Sadeleer and Robin},
howpublished = {bioRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.17.752253},
url = {https://www.biorxiv.org/content/10.64898/2026.09.17.752253v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - Multiscale mapping of venous remodelling in idiopathic pulmonary fibrosis
AU - D. Yamada
AU - H. Wang
AU - A. Szmul
AU - J. Riese
AU - R. Egashira
AU - C. H. M. van Moorsel
AU - N. Mogulkoc
AU - B. Gokce
AU - S. Aslani
AU - D. Cheng
AU - Y. Chen
AU - R. Bodenmann
AU - M. Brunner
AU - B. Tielemans
AU - J. Brunet
AU - T. Urban
AU - J. Purzycka
AU - H. Dejea
AU - P. Tafforeau
AU - M. Vermant
AU - F. T. van Beek
AU - B. Maurer
AU - S. Krattli
AU - M. Kreuzer
AU - R. Bruggmann
AU - T. Follet
AU - M. Veltkamp
AU - T. Goos
AU - K. Anseele
AU - M. Vander Kuylen
AU - H. W. van Es
AU - K. Engel
AU - R. Savas
AU - J. M. Brenes
AU - J. M. Hendriks
AU - T. S. Lapperre
AU - C. L. Walsh
AU - D. Jonigk
AU - L. Neubert
AU - C. Werlein
AU - H. Freitag
AU - S. Dettmer
AU - J. C. Schupp
AU - L. J. de Sadeleer
AU - Robin
PY - 2026
DA - 2026/09/17
PB - bioRxiv
DO - 10.64898/2026.09.17.752253
UR - https://www.biorxiv.org/content/10.64898/2026.09.17.752253v1
AB - The integrity of the pulmonary vasculature is a key determinant of lung health, yet challenges in visualisation and quantification have hindered interrogation of its pathophysiological role in chronic lung disease. Here, we align recent advances in microscale image acquisition with novel computer vision-based vessel segmentation models to demonstrate expansion of the bronchial and pulmonary veins across varying severities of tissue remodelling in idiopathic pulmonary fibrosis (IPF). Relating these imaging findings to molecular data in control, mild, and severe fibrosis, we show that bronchial venous endothelial cells expand beyond their physiological peribronchial niche even in mild disease, acquiring persistent angiogenic, inflammatory, and matrix-remodelling programmes that define a specialised fibrovascular-immune interface. Finally, we relate these microscale and molecular observations to clinical CT imaging, demonstrating that intrapulmonary vein enlargement independently associates with worsened survival across three IPF cohorts. Collectively, our multimodal, multiscale approach connects previously unresolved three-dimensional venous architecture to its molecular endothelial correlate, establishing venous enlargement as a prognostically significant and clinically relevant feature of IPF. Our analytical approach also demonstrates how biological discoveries made in intact ex vivo human organs can translate into measurable phenotypes in living patients, providing a template for other organs and diseases.
ER -