Phenotypic and Genetic Heterogeneity of Glioblastoma: Comparison of MRI and PET/CT Parameters with the Molecular Genetic Characteristics of Tumors.

Glioblastoma (GB) is characterized by a high degree of heterogeneity in its development in space and time, which is due to genomic instability, high growth rates in individual regions, and heterogeneous neovascularization. The molecular genetic features of GB play an important role in the prognosis of the disease, which is reflected in the new (2021) WHO classification of central nervous system tumors. The aim of the present work was to compare MRI data on blood flow and diffusion parameters and PET/CT data on tumor tissue metabolism with the genetic profiles of GB. The study included 40 patients (age 55 ± 12 years, male:female = 31:9) with first diagnoses of GB who underwent evaluation of MRI parameters (apparent diffusion coefficient (ADC), cerebral blood flow velocity (CBF), ASL perfusion data) and PET/CT to acquire the methionine (MET) uptake index. All these volumetric profiles (VOI – 1 cm³) were automatically transferred using software (PMOD) to all map images and compared with each other; a total of nine parameters were obtained: METmax, METcbf, METadc, ADCmin, ADCmet, ADCcbf, CBFmax, CBFmet, and CBFadc. Comparative and correlation analysis of parameters was carried out, both in the overall GB group and separately in genetically different subgroups (MGMT^+/– and EGFR^+/–) and in groups defined by Ki67 level. The study showed that the locations of zones with high values for blood flow, cell density, and amino acid metabolism coincided in only 45% of cases, demonstrating the occurrence of differences in the structure and functional activity of GB areas. Data on the relationship between methylation of the MGMT gene promoter and ADC (ADCmin > 1.01 (10^–3 mm²/sec), Se = 78%, Sp = 74%, AUC = 0.77) confirmed results reported by other authors showing that this genetic subtype of GB has lower requirements for the construction of new membranes, due to inhibition of the mechanisms if the DNA repair system. Detection of amplification of the EGFR gene in our cohort was associated with a significant increase in MET metabolism (METmax > 3.29, Se = 88%, Sp = 70%, AUC = 0.82) and correlated with a higher Ki67 index [Rs = –0.85], confirming the fact of an increase in the consumption of amino acids by GB cells for membrane synthesis. The correlations between the MET uptake index and ADC and the absence of such with CBF parameters confirm the relationship of methionine metabolism in gliomas with the processes of building new cell membranes and not with neovascularization. The phenomenon of heterogeneity in the structure of GB was confirmed on the basis of differences found in the locations of the zones in which the standard MRI and PET/CT parameters had their maximum values, as well as significant differences between them in groups of patients with GB with different molecular genetic profiles. [ABSTRACT FROM AUTHOR]