Volumetric and linear measurements of lung tumor burden from non-gated micro-CT imaging correlate with histological analysis in a genetically engineered mouse model of non-small cell lung cancer

Abstract

In vivo micro-computed tomography (CT) imaging allows longitudinal studies of pulmonary neoplasms in genetically engineered mouse models. Respiratory gating increases the accuracy of lung tumor measurements but lengthens anesthesia time in animals that may be at increased risk for complications. We hypothesized that semiautomated, volumetric, and linear tumor measurements performed in micro-CT images from non-gated scans would have correlation with histological findings. Primary lung tumors were induced in eight FVB mice with two transgenes (FVB/N-Tg(tetO-Kras2)12Hev/J; FVB.Cg-Tg(Scgb1a1-rtTA)1Jaw/J). Non-gated micro-CT scans were performed and the lungs were subsequently harvested. In the acquired micro-CT scans, measurements of all identified tumors were determined using the following methods: semiautomated three-dimensional (3D) volume, ellipsoid volume, Response Evaluation Criteria in Solid Tumors (RECIST; sum of largest axial (i.e., transverse) diameter from five tumors), sum of largest axial diameters from all tumors (modified RECIST), and average axial diameter. For histological analysis, all five lung lobes were analyzed and the tumor area was summed from measurements made on five histological sections that were 300 µm apart from each other (covering a total depth of 1200 µm). All micro-CT measurement methods had very strong correlation with histological tumor burden (Pearson’s correlation coefficient, 0.87 ( p = 0.0053) −0.98 ( p < 0.0001)). The only methods found to have different correlations were the semiautomated 3D method and the RECIST method (Williams’ test for dependent overlapping correlations, p = 0.013). Our results suggest quantification of lung tumor burden from non-gated micro-CT imaging will reflect histological differences between mice and can therefore be used for between-group comparisons or when concerns about systemic health of research animals may limit lengthy anesthetic procedures.