Post-mortem 11.7 T DTI validation of myeloarchitectural changes in glioblastoma infiltration: Correlation with histology and PLI

Abstract

Ultra-high field MRI is believed to hold potential for detecting microstructural changes that occur in light of tumor infiltration in glioblastoma patients, although studies with histological validation are lacking. This study, therefore, used 11.7 T diffusion tensor imaging (DTI) to determine the extent of infiltration in post-mortem glioblastoma-affected brain with histological validation. Three post-mortem specimens with glioblastoma underwent 11.7 T DTI from which mean diffusivity (MD), radial diffusivity (RD), axial diffusivity (AD) and fractional anisotropy (FA) were extracted. Tissue samples were also investigated using hematoxylin-eosin (HE) and luxol fast blue (LFB) stains, as well as Polarized Light Imaging (PLI) microscopy. Regions of interest (ROIs) of normal white matter (NWM) and tumor infiltration were generated on HE stain-based nucleus density maps. The metrics of the NWM ROIs were compared to the metrics of the ROIs covering the regions with tumor infiltration. Metrics were subjected to a correlation analysis to assess the correlation between nucleus density data, diffusion-, PLI- and LFB data. Significant differences were found between NWM and regions of tumor infiltration for MD-, RD-, LFB- and PLI-retardance values (p = 0.036, p = 0.010, p = 0.007 and p < 0.001, respectively). A correlation between nucleus density and diffusivity metrics was found, but not with measures for myeloarchitectural changes (LFB and PLI). Also, a significant correlation between PLI-retardance values and LFB values was found (p < 0.001). Based on DTI metrics and histological validation methods, myeloarchitectural alterations (e.g., fiber displacement) were considered the prime driver of measurable changes in the regions of tumor invasion in glioblastoma patients. Although this study shows the potential of ultra-high field MRI in detecting microstructural changes caused by glioblastoma infiltration, future studies are needed to assess these results in the clinical setting.