Metabolic habitat imaging with hemodynamic heterogeneity predicts individual progression-free survival in high-grade glioma

Abstract

We design a feasibility study to obtain a set of metabolic-hemodynamic habitats for tackling tumor spatial metabolic patterns with hemodynamic information. Preoperative data from 69 high-grade gliomas (HGG) patients with subsequent histologic confirmation of HGG were prospectively collected (January 2016 to March 2020) after concurrent chemoradiotherapy (CCRT). Four vascular habitats were automatically segmented by multiparametric magnetic resonance imaging (MRI). The metabolic information, either at enhancing or edema tumor regions, was obtained 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 metabolite semiquantifications (i.e. the Cho/NAA ratio and the Cho/Cr ratio) at vascular habitats. Multivariate Cox proportional hazard regression analyses are used to obtain the odds ratio (OR) and develop a nomogram using weighted estimators corresponding to each covariate derived from Cox regression coefficients. There was a strongly correlation between perfusion indexes and the Cho/Cr ratio (rCBV, r=0.71) or Cho/NAA ratio (rCBV, r=0.66) at high-angiogenic enhancing tumor habitats (HAT) habitat. Compared isocitrate dehydrogenase (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 progression-free survival (PFS) prediction was 0.769 for the Cho/NAA nomogram and 0.747 for the Cho/Cr nomogram through 1000 bootstrapping validation. Our findings suggest that spatial metabolism combined with hemodynamic heterogeneity is associated with individual PFS to HGG patients post-CCRT.