The relationship between radiomics and pathomics in Glioblastoma patients: Preliminary results from a cross-scale association study

Abstract

Glioblastoma multiforme (GBM) typically exhibits substantial intratumoral heterogeneity at both microscopic and radiological resolution scales. Diffusion Weighted Imaging (DWI) and dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) are two functional MRI techniques that are commonly employed in clinic for the assessment of GBM tumor characteristics. This work presents initial results aiming at determining if radiomics features extracted from preoperative ADC maps and post-contrast T1 (T1C) images are associated with pathomic features arising from H&E digitized pathology images. 48 patients from the public available CPTAC-GBM database, for which both radiology and pathology images were available, were involved in the study. 91 radiomics features were extracted from ADC maps and post-contrast T1 images using PyRadiomics. 65 pathomic features were extracted from cell detection measurements from H&E images. Moreover, 91 features were extracted from cell density maps of H&E images at four different resolutions. Radiopathomic associations were evaluated by means of Spearman's correlation (ρ) and factor analysis. p values were adjusted for multiple correlations by using a false discovery rate adjustment. Significant cross-scale associations were identified between pathomics and ADC, both considering features (n = 186, 0.45 < ρ < 0.74 in absolute value) and factors (n = 5, 0.48 < ρ < 0.54 in absolute value). Significant but fewer ρ values were found concerning the association between pathomics and radiomics features (n = 53, 0.5 < ρ < 0.65 in absolute value) and factors (n = 2, ρ = 0.63 and ρ = 0.53 in absolute value). The results of this study suggest that cross-scale associations may exist between digital pathology and ADC and T1C imaging. This can be useful not only to improve the knowledge concerning GBM intratumoral heterogeneity, but also to strengthen the role of radiomics approach and its validation in clinical practice as "virtual biopsy", introducing new insights for omics integration toward a personalized medicine approach.

Keywords: MRI; WSI (whole slide image); correlation; digital pathology; glioblastoma; pathomics; radiomics; radiopathomics.

Figure 1

Workflow of the radiopathomic analysis implemented in the study. On the first row the radiomic analysis steps. On the second row the pathomic analysis steps.

Figure 2

Radiopathomic analysis between ADC radiomic features and pathomic features. Correlation matrix filtered from nonsignificant correlations (rows and columns with non significant values were deleted, while nonsignificant values surviving were set to zero). CD, Cellular Density; ADC, Apparent Diffusion Coefficient; LALGLE, Large Area Low Gray Level Emphasis; IMOC, Information Measure Of Correlation; ASM, Angular Second Moment; LDLGLE, Large Dependence Low Gray Level Emphasis; LDHGLE, Large Dependence High Gray Level Emphasis; SDLGLE, Small Dependence Low Gray Level Emphasis; LALGLE, Large Area Low Gray Level Emphasis; GLNUN, Gray level non uniformity normalized; glcm, gray level co-occurrence matrix; gldm, Gray Level Dependence Matrix; glszm, Gray Level Size Zone Matrix; ngtdm, Neighbouring Gray Tone Difference Matrix; glrlm, Gray Level Run Length Matrix.

Figure 3

Radiopathomic analysis between T1C radiomic features and pathomic features. Correlation matrix filtered from nonsignificant correlations (rows and columns with non-significant values were deleted, while surviving nonsignificant values were set to zero). DNU, Dependence non uniformity; GLNU, gray-level non-uniformity; IMOC, Information Measure Of Correlation; ASM, Angular Second Moment; SRLGLE, Short Run Low Gray Level Emphasis; SDLGLE, Small Dependence Low Gray Level Emphasis; T1C, post-contrast T1; SALGLE, Small Area Low Gray Level Emphasis; LALGLE, Large Area Low Gray Level Emphasis; glcm, gray level co-occurrence matrix; gldm, Gray Level Dependence Matrix; glszm, Gray Level Size Zone Matrix; ngtdm, Neighbouring Gray Tone Difference Matrix; glrlm, Gray Level Run Length Matrix.