A method for determination of tracheobronchial airway geometries from four different strains of mice


Authored by  J Hoeng, C Foong, F Lucci, D Yeo, J Chua, A Kuczaj, M Peitsch

Presented at EB 2019    

Abstract 

Accurate lung morphometry is fundamental for predicting aerosol dosimetry. Currently, lung morphometry is only available for 2-3 species of mice (B6C3F1, BALB/c, and A/J).  Based upon in situ prepared silicone rubber mouse lung casts, a complete process, including their micro-CT scanning, segmentation, and automated algorithmic processing enabling the determination of airways geometries was developed for four strains of mice (BALB/c, A/J, ApoE-/-, and C57BL/6). 

Silicone rubber lung casts were prepared in situ from 20 ApoE-/- and C57BL/6 mice. The cured mouse lung casts were manually inspected for casting quality and manual morphometry measurements were performed (tracheobronchial generations 1-6) on selected lung casts prior to high resolution micro-CT scanning. Micro-CT scanning of existing in situ lung casts from BALB/c and A/J mice were also performed.  Micro-CT Images were then segmented to reconstruct a 3D model of the individual lung casts. A skeleton of each processed lung cast was automatically created by shrinking the 3D model of each airway to its centerline.  Algorithms were developed for automatic detection of possible skeleton exceptions like closed loops, trifurcations and isolated nodes to be subsequently manually resolved. Finally, the skeleton was automatically measured extracting major airway morphometry characteristics (e.g. airway generation number, length, diameter, bifurcation angles, and angle to gravity). 

The automated measurement procedure was tested/verified by comparing its measurements of airway length, diameter, and bifurcation angles with previous manual morphometry measurements from lung casts of identical BALB/c & A/J mice and the automated measurements of lung casts of two BALB/c mice.  Not surprisingly, tracheobronchial airway diameters for ApoE-/- and C57BL/6 mice were similar, but were significantly different from the other murine strains examined.  It is anticipated that these anatomical differences will result in different aerosol deposition as predicted by various dosimetry codes (NCRP, ICRP, and Multiple-Path Particle Dosimetry Model).