Abstract

BackgroundGenetic profiling represents the future of neuro-oncology but suffers from inadequate biopsies in heterogeneous tumors like Glioblastoma (GBM). Contrast-enhanced MRI (CE-MRI) targets enhancing core (ENH) but yields adequate tumor in only ~60% of cases. Further, CE-MRI poorly localizes infiltrative tumor within surrounding non-enhancing parenchyma, or brain-around-tumor (BAT), despite the importance of characterizing this tumor segment, which universally recurs. In this study, we use multiple texture analysis and machine learning (ML) algorithms to analyze multi-parametric MRI, and produce new images indicating tumor-rich targets in GBM.MethodsWe recruited primary GBM patients undergoing image-guided biopsies and acquired pre-operative MRI: CE-MRI, Dynamic-Susceptibility-weighted-Contrast-enhanced-MRI, and Diffusion Tensor Imaging. Following image coregistration and region of interest placement at biopsy locations, we compared MRI metrics and regional texture with histologic diagnoses of high- vs low-tumor content (≥80% vs <80% tumor nuclei) for corresponding samples. In a training set, we used three texture analysis algorithms and three ML methods to identify MRI-texture features that optimized model accuracy to distinguish tumor content. We confirmed model accuracy in a separate validation set.ResultsWe collected 82 biopsies from 18 GBMs throughout ENH and BAT. The MRI-based model achieved 85% cross-validated accuracy to diagnose high- vs low-tumor in the training set (60 biopsies, 11 patients). The model achieved 81.8% accuracy in the validation set (22 biopsies, 7 patients).ConclusionMulti-parametric MRI and texture analysis can help characterize and visualize GBM’s spatial histologic heterogeneity to identify regional tumor-rich biopsy targets.

Highlights

  • Glioblastoma (GBM) represents one of the most genetically heterogeneous, resistant, and lethal of all human cancers [1,2]

  • The MRI-based model achieved 85% cross-validated accuracy to diagnose high- vs low-tumor in the training set (60 biopsies, 11 patients)

  • contrast-enhanced MRI (CE-MRI) poorly localizes tumor within surrounding non-enhancing parenchyma, or Brain Around Tumor (BAT), which appears indistinguishable from nontumoral vasogenic edema [5]

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Summary

Introduction

Glioblastoma (GBM) represents one of the most genetically heterogeneous, resistant, and lethal of all human cancers [1,2]. Recent landmark initiatives by the National Cancer Institute (NCI) and The Cancer Genome Atlas (TCGA) have sought to catalog GBM’s diverse genetic landscape, giving insight to pathogenesis, prognosis and therapeutic susceptibility This should help guide risk stratification for existing protocols and help identify key driver genes as potential therapeutic targets in the future [4]. Securing tumor-rich biospecimens for genomic profiling remains a significant challenge In their initial report, TCGA found that only 35% of submitted biopsy samples contained adequate tumoral content and/or genetic material [4]. TCGA found that only 35% of submitted biopsy samples contained adequate tumoral content and/or genetic material [4] This low yield relates to GBM’s profound histologic heterogeneity and the limitations of contrast-enhanced MRI (CE-MRI)guided biopsies to distinguish enhancing tumor from non-tumoral tissue (e.g., reactive gliosis, microscopic necrosis). We use multiple texture analysis and machine learning (ML) algorithms to analyze multi-parametric MRI, and produce new images indicating tumor-rich targets in GBM

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