Characterising Water Exchange in Gliomas Using Diffusion MRI with Free Gradient Waveforms

TL;DR

This study demonstrates that diffusion MRI with free gradient waveforms can non-invasively map water exchange in gliomas, revealing heterogeneity and potential biomarkers related to tumour progression and treatment planning.

Contribution

It introduces the ResEx diffusion MRI approach for quantifying water exchange in gliomas independently of restricted diffusion effects.

Findings

ResEx maps show heterogeneous water exchange patterns within gliomas.

Elevated exchange rates are observed in tumour margins and peritumoural regions.

Water exchange rates may serve as biomarkers for tumour aggressiveness and infiltration.

Abstract

Transmembrane water permeability, which regulates cellular water exchange and is influenced by water channels such as aquaporin-4 (AQP4), has been implicated in glioma progression and may affect tumour infiltration and treatment response. Non-invasive mapping of water exchange may therefore provide biomarkers of glioma pathology. This study investigates the feasibility of characterizing water exchange in gliomas using diffusion MRI with free gradient waveforms, known as the Restriction-Exchange (ResEx) approach, which enables exchange quantification independent of restricted diffusion effects. Thirteen patients with histologically confirmed gliomas (ten glioblastomas, three astrocytomas) underwent preoperative MRI at 3T using a custom ResEx protocol. Multiple diffusion-weighted acquisitions with selective exchange sensitivity were performed to estimate voxel-wise maps of the apparent diffusion coefficient (ADC), diffusion kurtosis, and water exchange rate. ResEx-derived maps revealed heterogeneous spatial patterns across and within tumours. Elevated exchange rates were commonly observed in enhancing tumour margins, potentially reflecting smaller cells, increased membrane permeability or AQP4 upregulation. In some cases, elevated exchange extended into non-enhancing peritumoural regions. Exchange values in oedema were slightly higher than in healthy tissue, suggesting potential infiltration or membrane disruption. Diffusion MRI with free gradient waveforms permits non-invasive mapping of water exchange in gliomas and reveals physiological information not captured by standard imaging. Exchange rate mapping may offer novel biomarkers of tumour aggressiveness, infiltration, and treatment response, and holds promise for surgical and radiotherapy planning.