ArticleScientific reports2019
Correlative 3D Imaging and Microfluidic Modelling of Human Pulmonary Lymphatics using Immunohistochemistry and High-resolution μCT.
Article in Scientific reports, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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Who cites it
6 citing papers in PubMed.
- Computational Modeling Meets 3D Bioprinting: Emerging Synergies in Cardiovascular Disease Modeling.Advanced healthcare materials · 2026Review
- The lymphatic vasculature in lung function and respiratory disease.Frontiers in medicine · 2023Review
- Volumetric Imaging of Lung Tissue at Micrometer Resolution: Clinical Applications of Micro-CT for the Diagnosis of Pulmonary Diseases.Diagnostics (Basel, Switzerland) · 2021Review
- Immunofluorescence-guided segmentation of three-dimensional features in micro-computed tomography datasets of human lung tissue.Royal Society open science · 2021Article
- Tutorial: methods for three-dimensional visualization of archival tissue material.Nature protocols · 2021Review
- Pulmonary Interstitial Matrix and Lung Fluid Balance From Normal to the Acutely Injured Lung.Frontiers in physiology · 2021Review
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Authors and funding
5 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Lung lymphatics maintain fluid homoeostasis by providing a drainage system that returns fluid, cells and metabolites to the circulatory system. The 3D structure of the human pulmonary lymphatic network is essential to lung function, but it is poorly characterised. Image-based 3D mathematical modelling of pulmonary lymphatic microfluidics has been limited by the lack of accurate and representative image geometries. This is due to the microstructural similarity of the lymphatics to the blood vessel network, the lack of lymphatic-specific biomarkers, the technical limitations associated with image resolution in 3D, and sectioning artefacts present in 2D techniques. We present a method that combines lymphatic specific (D240 antibody) immunohistochemistry (IHC), optimised high-resolution X-ray microfocus computed tomography (μCT) and finite-element mathematical modelling to assess the function of human peripheral lung tissue. The initial results identify lymphatic heterogeneity within and between lung tissue. Lymphatic vessel volume fraction and fractal dimension significantly decreases away from the lung pleural surface (p < 0.001, n = 25 and p < 0.01, n = 20, respectively). Microfluidic modelling successfully shows that in lung tissue the fluid derived from the blood vessels drains through the interstitium into the lymphatic vessel network and this drainage is different in the subpleural space compared to the intralobular space. When comparing lung tissue from health and disease, human pulmonary lymphatics were significantly different across five morphometric measures used in this study (p ≤ 0.0001). This proof of principle study establishes a new engineering technology and workflow for further studies of pulmonary lymphatics and demonstrates for the first time the combination of correlative μCT and IHC to enable 3D mathematical modelling of human lung microfluidics at micrometre resolution.
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