Multiparametric magnetic resonance in the assessment of the gender differences in a high-grade glioma rat model

Background: Glioblastoma, the most frequent and aggressive of all astrocytomas, presents a clear predominance in male humans, but the assessment of sexual differences in its tumourigenesis and growth has received little attention so far. In this study, we aim to identify gender-dependent surrogate markers in an animal model of this cancer by means of magnetic resonance (MR) imaging and biochemical and behavioural studies. Methods: A high-grade glioma model developed in male and female rats was used. Multiparametric magnetic resonance images and localized spectra were acquired. The MR parameters linked to tumoural features were quantified. Motor and metabolic activity was also assessed. Postmortem analyses were carried out to measure indicators of malignancy, tumoural metabolism and viability of the blood-brain barrier (BBB). Results: Statistically significant differences dependent on the animal sex were found in the study of pathological indicators like oedema, inflammation, cellularity and microvasculature. Results suggest higher cell proliferative rate, inflammation and vasogenic oedema and or necrosis in glioma-bearing male rats. Haemodynamic parameters measured indicated a major disruption of the BBB, postmortem confirmed, in this sex. Metabolomic and energetic metabolism activity data are in agreement with a major malignancy and aggressiveness of this cancer model on males. Conclusions: Gender differences should be taken into account in preclinical studies of glioblastoma models, in the characterization of the tumoural behaviour and consequently in the development and validation of new therapeutic approaches. MR imaging and spectroscopy allow to non-invasively monitor this sexual dimorphism in the diagnosis and prognosis of brain cancer.