Relationship between necrotic patterns in glioblastoma and patient survival: fractal dimension and lacunarity analyses using magnetic resonance imaging

Abstract

Necrosis is a hallmark feature of glioblastoma (GBM). This study investigated the prognostic role of necrotic patterns in GBM using fractal dimension (FD) and lacunarity analyses of magnetic resonance imaging (MRI) data and evaluated the role of lacunarity in the biological processes leading to necrosis. We retrospectively reviewed clinical and MRI data of 95 patients with GBM. FD and lacunarity of the necrosis on MRI were calculated by fractal analysis and subjected to survival analysis. We also performed gene ontology analysis in 32 patients with available RNA-seq data. Univariate analysis revealed that FD < 1.56 and lacunarity > 0.46 significantly correlated with poor progression-free survival (p = 0.006 and p = 0.012, respectively) and overall survival (p = 0.008 and p = 0.005, respectively). Multivariate analysis revealed that both parameters were independent factors for unfavorable progression-free survival (p = 0.001 and p = 0.015, respectively) and overall survival (p = 0.002 and p = 0.007, respectively). Gene ontology analysis revealed that genes positively correlated with lacunarity were involved in the suppression of apoptosis and necrosis-associated biological processes. We demonstrate that the fractal parameters of necrosis in GBM can predict patient survival and are associated with the biological processes of tumor necrosis.

Figure 1

Segmentation and fractal analysis procedures for the analysis of necrotic patterns in glioblastoma. (A) A post-contrast T1-weighted magnetic resonance image of a representative patient with glioblastoma. (B) Segmentation of the tumor (green mask) and necrotic ROIs (red mask). (C) The necrotic ROIs are extracted with the tumor ROIs as the border. (D) Fractal analysis was performed by using the box-counting method.

Figure 2

Kaplan-Meier curves showing the association of progression-free survival (PFS) and overall survival (OS) with the (A) fractal dimension (FD) and (B) lacunarity values.

Figure 3

Gene ontology analysis for the lacunarity of necrosis in patients with glioblastoma. Biological processes (A) and pathways (B) associated with necrosis are shown. Genes involved in the representative biological processes are shown in (C).