4.6 Article

Mouse lung automated segmentation tool for quantifying lung tumors after micro-computed tomography

Journal

PLOS ONE
Volume 16, Issue 6, Pages -

Publisher

PUBLIC LIBRARY SCIENCE
DOI: 10.1371/journal.pone.0252950

Keywords

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Funding

  1. Pfizer, Inc.
  2. Pfizer Inc.

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This study discusses the use of genetically engineered mice tumor models and microCT imaging for lung cancer research, as well as the development of the automated image analysis tool MLAST to improve data analysis efficiency and accuracy. The application of MLAST in efficacy trials showed high precision and sensitivity in quantifying tumor growth inhibition after drug treatment, accelerating the analysis of microCT data and allowing for larger study sizes and mid-study readouts. This approach demonstrates the potential of automated image analysis tools for high throughput and quantitative results in preclinical imaging studies.
Unlike the majority of cancers, survival for lung cancer has not shown much improvement since the early 1970s and survival rates remain low. Genetically engineered mice tumor models are of high translational relevance as we can generate tissue specific mutations which are observed in lung cancer patients. Since these tumors cannot be detected and quantified by traditional methods, we use micro-computed tomography imaging for longitudinal evaluation and to measure response to therapy. Conventionally, we analyze microCT images of lung cancer via a manual segmentation. Manual segmentation is time-consuming and sensitive to intra- and inter-analyst variation. To overcome the limitations of manual segmentation, we set out to develop a fully-automated alternative, the Mouse Lung Automated Segmentation Tool (MLAST). MLAST locates the thoracic region of interest, thresholds and categorizes the lung field into three tissue categories: soft tissue, intermediate, and lung. An increase in the tumor burden was measured by a decrease in lung volume with a simultaneous increase in soft and intermediate tissue quantities. MLAST segmentation was validated against three methods: manual scoring, manual segmentation, and histology. MLAST was applied in an efficacy trial using a Kras/Lkb1 non-small cell lung cancer model and demonstrated adequate precision and sensitivity in quantifying tumor growth inhibition after drug treatment. Implementation of MLAST has considerably accelerated the microCT data analysis, allowing for larger study sizes and mid-study readouts. This study illustrates how automated image analysis tools for large datasets can be used in preclinical imaging to deliver high throughput and quantitative results.

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