Radiomics-based tumor phenotype determination based on medical imaging and tumor microenvironment in a preclinical setting

Radiother Oncol. 2022 Apr:169:96-104. doi: 10.1016/j.radonc.2022.02.020. Epub 2022 Feb 19.

Abstract

Background and purpose: Radiomics analyses have been shown to predict clinical outcomes of radiotherapy based on medical imaging-derived biomarkers. However, the biological meaning attached to such image features often remains unclear, thus hindering the clinical translation of radiomics analysis. In this manuscript, we describe a preclinical radiomics trial, which attempts to establish correlations between the expression of histological tumor microenvironment (TME)- and magnetic resonance imaging (MRI)-derived image features.

Materials & methods: A total of 114 mice were transplanted with the radioresistant and radiosensitive head and neck squamous cell carcinoma cell lines SAS and UT-SCC-14, respectively. The models were irradiated with five fractions of protons or photons using different doses. Post-treatment T1-weighted MRI and histopathological evaluation of the TME was conducted to extract quantitative features pertaining to tissue hypoxia and vascularization. We performed radiomics analysis with leave-one-out cross validation to identify the features most strongly associated with the tumor's phenotype. Performance was assessed using the area under the curve (AUCValid) and F1-score. Furthermore, we analyzed correlations between TME- and MRI features using the Spearman correlation coefficient ρ.

Results: TME and MRI-derived features showed good performance (AUCValid,TME = 0.72, AUCValid,MRI = 0.85, AUCValid,Combined=0.85) individual tumor phenotype prediction. We found correlation coefficients of ρ=-0.46 between hypoxia-related TME features and texture-related MRI features. Tumor volume was a strong confounder for MRI feature expression.

Conclusion: We demonstrated a preclinical radiomics implementation and notable correlations between MRI- and TME hypoxia-related features. Developing additional TME features may help to further unravel the underlying biology.

Keywords: Head and neck; Hypoxia; Preclinical; Radiomics; Tumor microenvironment.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Head and Neck Neoplasms* / diagnostic imaging
  • Head and Neck Neoplasms* / radiotherapy
  • Humans
  • Hypoxia
  • Magnetic Resonance Imaging / methods
  • Mice
  • Phenotype
  • Retrospective Studies
  • Squamous Cell Carcinoma of Head and Neck / diagnostic imaging
  • Tumor Microenvironment*