Quantification and visualization of metastatic lung tumors in mice

Ha Neul Lee; Seyl Kim; Sooah Park; Woonggyu Jung; Jin Seok Kang

doi:10.1007/s43188-022-00134-4

Quantification and visualization of metastatic lung tumors in mice

Toxicol Res. 2022 Apr 27;38(4):503-510. doi: 10.1007/s43188-022-00134-4. eCollection 2022 Oct.

Authors

Ha Neul Lee¹, Seyl Kim², Sooah Park³, Woonggyu Jung⁴, Jin Seok Kang¹

Affiliations

¹ Department of Biomedical Laboratory Science, Namseoul University, 91 Daehak-ro, Seonghwan-eup, Seobuk-gu, Cheonan-si, 31020 South Korea.
² Ferramed Inc., National Nanofab Center, KAIST, 291 Deahak-ro, Yuseong-gu, Deajeon, 34141 South Korea.
³ In Vivo Research Center, UNIST Central Research Facilities, Ulsan National Institute of Science and Technology, 50 UNIST-gil, Ulju-gun, Ulsan, 44919 South Korea.
⁴ Department of Biomedical Engineering, Ulsan National Institute of Science and Technology, 50 UNIST-gil, Ulju-gun, Ulsan, 44919 South Korea.

Abstract

Histopathological examination is important for the diagnosis of various diseases. Conventional histopathology provides a two-dimensional view of the tissues, and requires the tissue to be extracted, fixed, and processed using histotechnology techniques. However, there is an increasing need for three-dimensional (3D) images of structures in biomedical research. The objective of this study was to develop reliable, objective tools for visualizing and quantifying metastatic tumors in mouse lung using micro-computed tomography (micro-CT), optical coherence tomography (OCT), and field emission-scanning electron microscopy (FE-SEM). Melanoma cells were intravenously injected into the tail vein of 8-week-old C57BL/6 mice. The mice were euthanized at 2 or 4 weeks after injection. Lungs were fixed and examined by micro-CT, OCT, FE-SEM, and histopathological observation. Micro-CT clearly distinguished between tumor and normal cells in surface and deep lesions, thereby allowing 3D quantification of the tumor volume. OCT showed a clear difference between the tumor and surrounding normal tissues. FE-SEM clearly showed round tumor cells, mainly located in the alveolar wall and growing inside the alveoli. Therefore, whole-tumor 3D imaging successfully visualized the metastatic tumor and quantified its volume. This promising approach will allow for fast and label-free 3D phenotyping of diverse tissue structures.

Keywords: Field emission-scanning electron microscopy; Histopathology; Mice; Micro-computed tomography; Optical coherence tomography.