Correlation of FDG PET and MR Apparent Diffusion Coefficient Histogram Metrics with Survival in Diffuse Intrinsic Pontine Glioma: A Report from the Pediatric Brain Tumor Consortium

Objectives To describe the baseline FDG PET histogram metrics in pediatric diffuse intrinsic pontine glioma and to correlate these metrics with the baseline MR apparent diffusion coefficient (ADC) metrics, progression-free survival (PFS) and overall survival (OS).

Methods Baseline quantitative FDG PET, post-gadolinium (PG) MR and ADC images were registered to the baseline FLAIR MR images using FSL in the Functional Magnetic Resonance Imaging of the Brain Software Library[1]. 3D ROIs of the FLAIR and PG images of the tumor were generated using a semi-automated thresholding technique using ImageJ[2]. FDG PET and ADC histograms were retrospectively generated using these ROIs in 33 children with diffuse intrinsic pontine glioma (DIPG). Metrics evaluated included number of peaks, skewness and kurtosis. Correlation between PET and ADC histogram metrics was evaluated using Spearman’s rank correlation. PET pixel values within the ROI for each tumor were plotted against ADC values, and their correlation was captured as a separate imaging marker. Association of these imaging markers with PFS and OS was described using Cox Proportional Hazards Models.

Results PET histograms were almost always unimodal (94% vs. 6% bimodal). PET FLAIR histogram skewness was negatively correlated with ADC PG skewness (Spearman’s Rho=-0.56; p=0.025) and PET PG skewness tended towards a negative correlation with ADC FLAIR kurtosis (Spearman’s Rho=-0.49; p=0.075). None of the PET histogram parameters (skewness or kurtosis) had a significant association with PFS, although higher PET PG skewness tended towards less favorable PFS distribution (Hazard Ratio (95% CI)=3.48 (0.75,16.28); p=0.11). There was a significant association of higher ADC PG skewness with shorter PFS (Hazard Ratio (95% CI)=2.56 (1.11,5.91); p=0.028) and the suggestion that this also led to shorter OS (Hazard Ratio (95% CI)=2.18 (0.95,5.04); p=0.067). Higher ADC PG kurtosis tended towards shorter PFS (Hazard Ratio (95% CI)=1.30 (0.98,1.74); p=0.073). In a number of cases, PET and ADC pixel values were negatively correlated using the Pearson correlation coefficient. Further, the PET and ADC correlation coefficient was significantly associated with PFS; tumors with higher ADC-PET correlation had more favorable PFS (Hazard Ratio (95% CI)=0.17 (0.03, 0.89), p=0.036), suggesting higher negative correlation leads to less favorable PFS. Higher negative correlation may indicate higher grade elements within the tumor thus leading to poorer outcomes. There was no significant hazard ratio for OS.

Conclusions PET and ADC histogram metrics in DIPG demonstrate different characteristics with often significant negative correlation between PET and ADC pixel values using 3D FLAIR ROIs. Higher negative correlation is significantly associated with less favorable PFS which may indicate higher grade elements within the tumor. This work was supported in part by NIH grant U01 CA81457 for the Pediatric Brain Tumor Consortium (PBTC), The Pediatric Brain Tumor Consortium Foundation 1. Poussaint TY, Vajapeyam S, Ricci KI, et al. Apparent diffusion coefficient histogram metrics correlate with survival in diffuse intrinsic pontine glioma: a report from the Pediatric Brain Tumor Consortium. Neuro Oncol. 2015 Oct 20. PMID: 26487690 Epub ahead of print 2. Jenkinson M, Beckmann CF, Behrens TE, et al. FSL. NeuroImage. 2012;62(2):782-790.