Algorithms for studying murine airway structure in microfocus computed tomography images

Abstract

Complex branching 3D structures, such as root systems, renal vasculature and pulmonary airways and vasculature, are prevalent throughout nature. The analysis and measurement of these structures and the development of automatic or semi-automatic algorithms to study Microfocus Computed Tomography (µCT) images is therefore an important requirement in this field.
Asthma is a prevalent chronic airway disease that is not yet fully understood. Murine models of lung diseases are used with increasing frequency. As the lung is a complex 3D structure, there are benefits to using 3D methodology to measure structural changes in these models. µCT is a valuable technique in non-destructive imaging that yields high resolution, high quality 3D images.
I describe a sphere inflation branching structure skeletonisation technique that uses radial ray-casting to detect branch points. Quantitative comparisons are made between this technique and three other algorithms: the medial axis transform, the scale axis transform, and a Hough transform for circles tracing technique, as well as manually-produced skeletons from a set of three filled lungs. The sphere growth tracer performs well against the other algorithms when compared to the manually-produced skeletons.
Mutations in A Disintegrin And Metalloprotease (ADAM) 33 gene have been linked to asthma and soluble ADAM33 causes airway remodelling in a transgenic mouse model. This work tests the hypothesis that the effects of human ADAM33 over-expression in transgenic mouse lungs are visible in µCT images as a thickening of the smooth muscle that lines the bronchi and bronchioles, resulting in thicker airway walls as well as narrower lumens than in control mice. Airways were extracted and analysed semi-autonomously for lumen radius, area and perimeter, and wall thickness at seven sites across four generations of branching in 14 murine lungs. However, in a small sample number with limited soft tissue resolution and contrast of the µCT images no significant differences in airway structure could be detected in ADAM33 overexpressing mice compared with control mice.

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ORCID for Philipp Thurner: orcid.org/0000-0001-7588-9041

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