Radio-Pathomic Maps of Cell Density Identify Brain Tumor Invasion beyond Traditional MRI-Defined Margins

AJNR Am J Neuroradiol. 2022 May;43(5):682-688. doi: 10.3174/ajnr.A7477. Epub 2022 Apr 14.

Abstract

Background and purpose: Currently, contrast-enhancing margins on T1WI are used to guide treatment of gliomas, yet tumor invasion beyond the contrast-enhancing region is a known confounding factor. Therefore, this study used postmortem tissue samples aligned with clinically acquired MRIs to quantify the relationship between intensity values and cellularity as well as to develop a radio-pathomic model to predict cellularity using MR imaging data.

Materials and methods: This single-institution study used 93 samples collected at postmortem examination from 44 patients with brain cancer. Tissue samples were processed, stained with H&E, and digitized for nuclei segmentation and cell density calculation. Pre- and postgadolinium contrast T1WI, T2 FLAIR, and ADC images were collected from each patient's final acquisition before death. In-house software was used to align tissue samples to the FLAIR image via manually defined control points. Mixed-effects models were used to assess the relationship between single-image intensity and cellularity for each image. An ensemble learner was trained to predict cellularity using 5 × 5 voxel tiles from each image, with a two-thirds to one-third train-test split for validation.

Results: Single-image analyses found subtle associations between image intensity and cellularity, with a less pronounced relationship in patients with glioblastoma. The radio-pathomic model accurately predicted cellularity in the test set (root mean squared error = 1015 cells/mm2) and identified regions of hypercellularity beyond the contrast-enhancing region.

Conclusions: A radio-pathomic model for cellularity trained with tissue samples acquired at postmortem examination is able to identify regions of hypercellular tumor beyond traditional imaging signatures.

MeSH terms

  • Brain Neoplasms* / diagnostic imaging
  • Brain Neoplasms* / pathology
  • Cell Count
  • Glioblastoma* / diagnostic imaging
  • Glioblastoma* / pathology
  • Glioma* / diagnostic imaging
  • Glioma* / pathology
  • Humans
  • Magnetic Resonance Imaging / methods
  • Margins of Excision