@article{Koo2018,

title = {Small airways disease in mild and moderate chronic obstructive pulmonary disease: a cross-sectional study.},

author = {Hyun-Kyoung Koo and Dragoş M Vasilescu and Steven Booth and Aileen Hsieh and Orestis L Katsamenis and Nick Fishbane and W Mark Elliott and Miranda Kirby and Peter Lackie and Ian Sinclair and Jane A Warner and Joel D Cooper and Harvey O Coxson and Peter D Paré and James C Hogg and Tillie-Louise Hackett},

doi = {10.1016/S2213-2600(18)30196-6},

issn = {2213-2619},

year  = {2018},

date = {2018-08-01},

journal = {The Lancet. Respiratory medicine},

volume = {6},

issue = {8},

pages = {591–602},

abstract = {The concept that small conducting airways less than 2 mm in diameter become the major site of airflow obstruction in chronic obstructive pulmonary disease (COPD) is well established in the scientific literature, and the last generation of small conducting airways, terminal bronchioles, are known to be destroyed in patients with very severe COPD. We aimed to determine whether destruction of the terminal and transitional bronchioles (the first generation of respiratory airways) occurs before, or in parallel with, emphysematous tissue destruction. In this cross-sectional analysis, we applied a novel multiresolution CT imaging protocol to tissue samples obtained using a systematic uniform sampling method to obtain representative unbiased samples of the whole lung or lobe of smokers with normal lung function (controls) and patients with mild COPD (Global Initiative for Chronic Obstructive Lung Disease [GOLD] stage 1), moderate COPD (GOLD 2), or very severe COPD (GOLD 4). Patients with GOLD 1 or GOLD 2 COPD and smokers with normal lung function had undergone lobectomy and pneumonectomy, and patients with GOLD 4 COPD had undergone lung transplantation. Lung tissue samples were used for stereological assessment of the number and morphology of terminal and transitional bronchioles, airspace size (mean linear intercept), and alveolar surface area. Of the 34 patients included in this study, ten were controls (smokers with normal lung function), ten patients had GOLD 1 COPD, eight had GOLD 2 COPD, and six had GOLD 4 COPD with centrilobular emphysema. The 34 lung specimens provided 262 lung samples. Compared with control smokers, the number of terminal bronchioles decreased by 40% in patients with GOLD 1 COPD (p=0·014) and 43% in patients with GOLD 2 COPD (p=0·036), the number of transitional bronchioles decreased by 56% in patients with GOLD 1 COPD (p=0·0001) and 59% in patients with GOLD 2 COPD (p=0·0001), and alveolar surface area decreased by 33% in patients with GOLD 1 COPD (p=0·019) and 45% in patients with GOLD 2 COPD (p=0·0021). These pathological changes were found to correlate with lung function decline. We also showed significant loss of terminal and transitional bronchioles in lung samples from patients with GOLD 1 or GOLD 2 COPD that had a normal alveolar surface area. Remaining small airways were found to have thickened walls and narrowed lumens, which become more obstructed with increasing COPD GOLD stage. These data show that small airways disease is a pathological feature in mild and moderate COPD. Importantly, this study emphasises that early intervention for disease modification might be required by patients with mild or moderate COPD. Canadian Institutes of Health Research.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Wollatz2017,

title = {3D Histopathology—a Lung Tissue Segmentation Workflow for Microfocus X-ray-Computed Tomography Scans},

author = {Lasse Wollatz and Steven J Johnston and Peter M Lackie and Simon J Cox},

url = {https://link.springer.com/article/10.1007/s10278-017-9966-5},

doi = {10.1007/s10278-017-9966-5},

year  = {2017},

date = {2017-01-01},

journal = {Journal of Digital Imaging},

pages = {1–10},

publisher = {Springer},

abstract = {Lung histopathology is currently based on the analysis of 2D sections of tissue samples. The use of microfocus X-ray-computed tomography imaging of unstained soft tissue can provide high-resolution 3D image datasets in the range of 2–10 μm without affecting the current diagnostic workflow. Important details of structural features such as the tubular networks of airways and blood vessels are contained in these datasets but are difficult and time-consuming to identify by manual image segmentation. Providing 3D structures permits a better understanding of tissue functions and structural interrelationships. It also provides a more complete picture of heterogeneous samples. In addition, 3D analysis of tissue structure provides the potential for an entirely new level of quantitative measurements of this structure that have previously been based only on extrapolation from 2D sections. In this paper, a workflow for segmenting such 3D images semi-automatically has been created using and extending the ImageJ open-source software and key steps of the workflow have been integrated into a new ImageJ plug-in called LungJ. Results indicate an improved workflow with a modular organization of steps facilitating the optimization for different sample and scan properties with expert input as required. This allows for incremental and independent optimization of algorithms leading to faster segmentation. Representation of the tubular networks in samples of human lung, building on those segmentations, has been demonstrated using this approach.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Apps2016,

title = {Imaging Invasion: Micro-CT imaging of adamantinomatous craniopharyngioma highlights cell type specific spatial relationships of tissue invasion.},

author = {John R. Apps and J. Ciaran Hutchinson and Owen J. Arthurs and Alex Virasami and Abhijit Joshi and Berit Zeller-Plumhoff and Dale Moulding and Thomas S. Jacques and Neil J. Sebire and Juan Pedro Martinez-Barbera},

url = {https://actaneurocomms.biomedcentral.com/articles/10.1186/s40478-016-0321-8},

doi = {10.1186/s40478-016-0321-8},

issn = {2051-5960},

year  = {2016},

date = {2016-06-01},

journal = {Acta neuropathologica communications},

volume = {4},

issue = {1},

pages = {57},

abstract = {Tissue invasion and infiltration by brain tumours poses a clinical challenge, with destruction of structures leading to morbidity. We assessed whether micro-CT could be used to map tumour invasion in adamantinomatous craniopharyngioma (ACP), and whether it could delineate ACPs and their intrinsic components from surrounding tissue.Three anonymised archival frozen ACP samples were fixed, iodinated and imaged using a micro-CT scanner prior to the use of standard histological processing and immunohistochemical techniques.We demonstrate that micro-CT imaging can non-destructively give detailed 3D structural information of tumours in volumes with isotropic voxel sizes of 4-6 microns, which can be correlated with traditional histology and immunohistochemistry.Such information complements classical histology by facilitating virtual slicing of the tissue in any plane and providing unique detail of the three dimensional relationships of tissue compartments.},

keywords = {},

pubstate = {epublish},

tppubtype = {article}

}

@article{Jones2016,

title = {Three-dimensional characterization of fibroblast foci in idiopathic pulmonary fibrosis},

author = {Mark G Jones and Aurélie Fabre and Philipp Schneider and Francesco Cinetto and Giacomo Sgalla and Mark Mavrogordato and Sanjay Jogai and Aiman Alzetani and Ben G Marshall and Katherine MA O’Reilly and others},

url = {https://insight.jci.org/articles/view/86375},

doi = {10.1172/jci.insight.86375},

year  = {2016},

date = {2016-01-01},

journal = {JCI insight},

volume = {1},

number = {5},

publisher = {NIH Public Access},

abstract = {In idiopathic pulmonary fibrosis (IPF), the fibroblast focus is a key histological feature representing active fibroproliferation. On standard 2D pathologic examination, fibroblast foci are considered small, distinct lesions, although they have been proposed to form a highly interconnected reticulum as the leading edge of a “wave” of fibrosis. Here, we characterized fibroblast focus morphology and interrelationships in 3D using an integrated micro-CT and histological methodology. In 3D, fibroblast foci were morphologically complex structures, with large variations in shape and volume (range, 1.3 × 104 to 9.9 × 107 μm3). Within each tissue sample numerous multiform foci were present, ranging from a minimum of 0.9 per mm3 of lung tissue to a maximum of 11.1 per mm3 of lung tissue. Each focus was an independent structure, and no interconnections were observed. Together, our data indicate that in 3D fibroblast foci form a constellation of heterogeneous structures with large variations in shape and volume, suggesting previously unrecognized plasticity. No evidence of interconnectivity was identified, consistent with the concept that foci represent discrete sites of lung injury and repair.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{ScottVasilescuSealEtAl2015,

title = {Three dimensional imaging of paraffin embedded human lung tissue samples by micro-computed tomography},

author = {A. E. Scott and D. M. Vasilescu and K. A. D. Seal and S. D. Keyes and M. N. Mavrogordato and J. C. Hogg and I. Sinclair and J. A. Warner and T. L. Hackett and P. M. Lackie},

url = {http://eprints.soton.ac.uk/381745/},

year  = {2015},

date = {2015-06-01},

journal = {PLoS ONE},

pages = {1–10},

abstract = {Background: understanding the three-dimensional (3-D) micro-architecture of lung tissue can provide insights into the pathology of lung disease. Micro computed tomography (mu CT) has previously been used to elucidate lung 3D histology and morphometry in fixed samples that have been stained with contrast agents or air inflated and dried. However, non-destructive microstructural 3D imaging of formalin-fixed paraffin embedded (FFPE) tissues would facilitate retrospective analysis of extensive tissue archives of lung FFPE lung samples with linked clinical data. Methods: FFPE human lung tissue samples (n = 4) were scanned using a Nikon metrology mu CT scanner. Semi-automatic techniques were used to segment the 3D structure of airways and blood vessels. Airspace size (mean linear intercept, Lm) was measured on mu CT images and on matched histological sections from the same FFPE samples imaged by light microscopy to validate mu CT imaging. 

Results: the mu CT imaging protocol provided contrast between tissue and paraffin in FFPE samples (15mm x 7mm). Resolution (voxel size 6.7 mu m) in the reconstructed images was sufficient for semi-automatic image segmentation of airways and blood vessels as well as quantitative airspace analysis. The scans were also used to scout for regions of interest, enabling time-efficient preparation of conventional histological sections. The Lm measurements from mu CT images were not significantly different to those from matched histological sections. 

Conclusion: we demonstrated how non-destructive imaging of routinely prepared FFPE samples by laboratory mu CT can be used to visualize and assess the 3D morphology of the lung including by morphometric analysis.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}