# Exploring the Role of Advanced MRI in Understanding Glioblastoma Biology: A Scoping Review

## TL;DR

This review explores how advanced MRI techniques can reveal the biology of glioblastoma, a deadly brain tumor, and how they might improve diagnosis and treatment.

## Contribution

The paper synthesizes advanced MRI findings in IDHwt glioblastoma and aligns them with the 2021 WHO classification to guide future research and clinical use.

## Key findings

- APTw imaging correlates with Ki-67 expression and tumor cellularity.
- DWI and PWI show variable but meaningful links to MGMTp status and tumor biology.
- QSM features correlate with Ki-67, ferritin, and immune markers in glioblastoma.

## Abstract

This review brings together past imaging research and aligns it with the 2021 World Health Organization classification to provide a clearer picture of glioblastoma biology. Glioblastoma is the deadliest brain tumour in adults, and traditional imaging often fails to reveal its complex biology. We explore how advanced magnetic resonance imaging techniques can uncover features such as cell growth, blood supply, and immune response without invasive procedures. For example, amide proton transfer-weighted imaging detects elevated protein and peptide content in highly proliferative tumour regions, correlating with the histological proliferation marker Ki-67. By identifying the most promising methods and highlighting gaps in knowledge, this work aims to guide future studies. If adopted clinically, these techniques could improve diagnosis, enable personalised treatment, and help predict outcomes, ultimately advancing care for people with glioblastoma.

Background: Among adult primary brain tumours, glioblastoma (GBM) carries the worst prognosis. Magnetic resonance imaging (MRI) serves to diagnose and guide treatment, despite recognised constraints. Advanced MRI techniques—magnetic resonance spectroscopy (MRS), amide proton transfer-weighted imaging (APTw), diffusion-weighted imaging (DWI), perfusion-weighted imaging (PWI), and quantitative susceptibility mapping (QSM)—reveal GBM characteristics that conventional sequences cannot detect. The 2021 World Health Organization reclassification disrupted established imaging–biology relationships, necessitating isocitrate dehydrogenase wildtype (IDHwt) GBM-specific evidence integration. This review synthesises biological insights provided by advanced MRI in preoperative IDHwt GBM. Methods: We conducted a scoping review following the PRISMA-ScR framework, querying five databases (PubMed, Scopus, Cochrane, EBSCO, and Embase) to identify literature using advanced MRI to investigate biological correlates in IDHwt GBM. Results: MRS ratios were associated with tumour presence and Ki-67 expression. APTw demonstrated robust associations with cellularity but failed to predict O6-methylguanine-DNA methyltransferase promoter (MGMTp) methylation. DWI exhibited variable utility; certain metrics linked to cellularity, while apparent diffusion coefficient values were inconsistent but useful for predicting MGMTp status, telomerase reverse transcriptase promoter mutations, and CD163+ macrophage infiltration. PWI showed relationships with cellularity, micro-vessel area, and MGMTp status. QSM features correlated with Ki-67, ferritin, and immune markers. Conclusions: Advanced MRI demonstrates potential for biological stratification of GBM, though protocol variability and limited reproducibility hinder clinical translation. Standardised pipelines and prospective multicentre validation must precede clinical adoption, before these techniques can benefit patients.