Advancements in Neuroimaging to Unravel Biological and Molecular Features of Brain Tumors

Simple Summary Advanced neuroimaging is gaining increasing relevance for the characterization and the molecular profiling of brain tumor tissue. On one hand, for some tumor types, the most widespread advanced techniques, investigating diffusion and perfusion features, have been proven clinically feasible and rather robust for diagnosis and prognosis stratification. In addition, 2-hydroxyglutarate spectroscopy, for the first time, offers the possibility to directly measure a crucial molecular marker. On the other hand, numerous innovative approaches have been explored for a refined evaluation of tumor microenvironments, particularly assessing microstructural and microvascular properties, and the potential applications of these techniques are vast and still to be fully explored. In recent years, the clinical assessment of primary brain tumors has been increasingly dependent on advanced magnetic resonance imaging (MRI) techniques in order to infer tumor pathophysiological characteristics, such as hemodynamics, metabolism, and microstructure. Quantitative radiomic data extracted from advanced MRI have risen as potential in vivo noninvasive biomarkers for predicting tumor grades and molecular subtypes, opening the era of "molecular imaging" and radiogenomics. This review presents the most relevant advancements in quantitative neuroimaging of advanced MRI techniques, by means of radiomics analysis, applied to primary brain tumors, including lower-grade glioma and glioblastoma, with a special focus on peculiar oncologic entities of current interest. Novel findings from diffusion MRI (dMRI), perfusion-weighted imaging (PWI), and MR spectroscopy (MRS) are hereby sifted in order to evaluate the role of quantitative imaging in neuro-oncology as a tool for predicting molecular profiles, stratifying prognosis, and characterizing tumor tissue microenvironments. Furthermore, innovative technological approaches are briefly addressed, including artificial intelligence contributions and ultra-high-field imaging new techniques. Lastly, after providing an overview of the advancements, we illustrate current clinical applications and future perspectives.