Multi-Parametric MRI and Texture Analysis to Visualize Spatial Histologic Heterogeneity and Tumor Extent in Glioblastoma

<div><p>Background</p><p>Genetic 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.</p><p>Methods</p><p>We 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.</p><p>Results</p><p>We 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).</p><p>Conclusion</p><p>Multi-parametric MRI and texture analysis can help characterize and visualize GBM’s spatial histologic heterogeneity to identify regional tumor-rich biopsy targets.</p></div

ML-based MRI invasion maps show tumor-rich (>80% tumor nuclei) extent throughout ENH and BAT.

<p>(A,B,C,E) Biopsy locations within the non-enhancing BAT zone (green dots, arrows) on T1+C (A,D) and T2W (B,E) images correspond with high-tumor (>80% tumor nuclei) and low-tumor (<80% tumor nuclei) tissue samples on histologic analysis. (C,F) Color overlay maps with manual tracings (green) around BAT show the probability (range 0–1) of tumor-rich (red) vs tumor-poor (green/blue) content, based on ML analysis and multi-parametric MRI in 60 training biopsies and 22 validation biopsies. The maps show correspondence between tumor-rich (B, red) and tumor-poor (D, blue/gray) biopsy samples.</p

Summary of selected MRI-based texture features to optimize CV training accuracy.

<p>Machine learning (ML) selected the 3 MRI-based texture features that optimized cross validation (CV) accuracy based on leave-one-out cross validation (LOOCV) of the training set data (60 biopsies, 11 patients). The overall CV accuracy based on the 3 features is 85%.</p><p>Summary of selected MRI-based texture features to optimize CV training accuracy.</p

ML-based model improves tumor-rich biopsy delineation compared with CE-MRI.

<p>(A) ML-based MRI texture model in the full dataset (n = 82, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0141506#pone.0141506.t001" target="_blank">Table 1</a>) shows higher positive predictive values (PPV) (66.7% in BAT, 81.3% in ENH) for recovering tumor-rich samples compared with CE-MRI (21.2% in BAT, 59.2% in ENH). These PPVs suggest that the ML-based model would help recover tumor-rich BAT samples with over three times greater efficiency compared with CE-MRI guidance. (B) ML-based MRI texture model in the subanalysis (n = 76, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0141506#pone.0141506.s002" target="_blank">S2 Appendix</a>) provides higher positive predictive values (PPV) (57.1% in BAT, 80.6% in ENH) for recovering tumor-rich samples (>80% tumor nuclei) compared with CE-MRI (13.8% in BAT, 59.6% in ENH). Based on these PPVs, the ML-based model would enable four times more efficient tumor-rich recovery from BAT compared with CE-MRI guidance.</p