Advanced MRI, Radiomics and Radiogenomics in Unravelling Incidental Glioma Grading and Genetic Status: Where Are We?

The 2021 WHO classification of brain tumours revolutionised the oncological field by emphasising the role of molecular, genetic and pathogenetic advances in classifying brain tumours. In this context, incidental gliomas have been increasingly identified due to the widespread performance of standard and advanced MRI sequences and represent a diagnostic and therapeutic challenge. The impactful decision to perform a surgical procedure deeply relies on the non-invasive identification of features or parameters that may correlate with brain tumour genetic profile and grading. Therefore, it is paramount to reach an early and proper diagnosis through neuroradiological techniques, such as MRI. Standard MRI sequences are the cornerstone of diagnosis, while consolidated and emerging roles have been awarded to advanced sequences such as Diffusion-Weighted Imaging/Apparent Diffusion Coefficient (DWI/ADC), Perfusion-Weighted Imaging (PWI), Magnetic Resonance Spectroscopy (MRS), Diffusion Tensor Imaging (DTI) and functional MRI (fMRI). The current novelty relies on the application of AI in brain neuro-oncology, mainly based on radiomics and radiogenomics models, which enhance standard and advanced MRI sequences in predicting glioma genetic status by identifying the mutation of multiple key biomarkers deeply impacting patients' diagnosis, prognosis and treatment, such as IDH, EGFR, TERT, MGMT promoter, p53, H3-K27M, ATRX, Ki67 and 1p19. AI-driven models demonstrated high accuracy in glioma detection, grading, prognostication, and pre-surgical planning and appear to be a promising frontier in the neuroradiological field. On the other hand, standardisation challenges in image acquisition, segmentation and feature extraction variability, data scarcity and single-omics analysis, model reproducibility and generalizability, the black box nature and interpretability concerns, as well as ethical and privacy challenges remain key issues to address. Future directions, rooted in enhanced standardisation and multi-institutional validation, advancements in multi-omics integration, and explainable AI and federated learning, may effectively overcome these challenges and promote efficient AI-based models in glioma management. The aims of our multidisciplinary review are to: (1) extensively present the role of standard and advanced MRI sequences in the differential diagnosis of iLGGs as compared to HGGs (High-Grade Gliomas); (2) give an overview of the current and main applications of AI tools in the differential diagnosis of iLGGs as compared to HGGs (High-Grade Gliomas); (3) show the role of MRI, radiomics and radiogenomics in unravelling glioma genetic profiles. Standard and advanced MRI, radiomics and radiogenomics are key to unveiling the grading and genetic profile of gliomas and supporting the pre-operative planning, with significant impact on patients' differential diagnosis, prognosis prediction and treatment strategies. Today, neuroradiologists are called to efficiently use AI tools for the in vivo, non-invasive, and comprehensive assessment of gliomas in the path towards patients' personalised medicine.