Metabolic Habitat Imaging with Hemodynamic Heterogeneity Predicts Individual Progression-free Survival in High-grade Glioma

Abstract

Objective

We design a feasibility study to obtain a set of metabolic-hemodynamic habitats for tackling tumor spatial metabolic pattern with hemodynamic information.

Methods

Preoperative data from 69 HGG patients with subsequent histologic confirmation of HGG were prospectively collected (January 2016 to March 2020) after CCRT. Four vascular habitats were automatically segmentation by Multiparametric MRI. The metabolic information either at enhancing or edema tumor regions obtain by two neuroradiologists. The relative habitat volumes were used for weight estimation procedures for computing the coefficients of a linear regression model using weighted least squares (WLS) for metabolites semi-quantifications (i.e., Cho/NAA ratio and the Cho/Cr ratio) at vascular habitats. Multivariate Cox proportional hazard regression analyses to obtain odds ratio (OR) and develop a nomogram using weighted estimators corresponding to each covariate derived from Cox regression coefficients.

Results

There were strongly correlation between perfusion indexes and Cho/Cr ratio (rCBV, r=0.71) or Cho/NAA ratio (rCBV, r=0.66) at HAT habitat. Compared IDH mutation to their wild type, the IDH wild type had significantly decreased Cho/Cr ratio (IDH mutation: Cho/Cr ratio = 2.44 ± 0.33, IDH wildtype: Cho/Cr ratio = 2.66 ± 0.36, p=0.02) and Cho/NAA ratio (IDH mutation: Cho/Cr ratio = 4.59 ± 0.61, IDH wildtype: Cho/Cr ratio = 4.99 ± 0.66, p=0.022,) at the HAT. The C-index for the median PFS prediction were 0.769 for Cho/NAA nomogram and 0.747 for Cho/Cr nomogram through 1000 bootstrapping validation.

Conclusions

Our findings suggest that spatial metabolism combined with hemodynamic heterogeneity is associated with individual PFS to HGG patient post CCRT.