iDetection of Early Alterations in Radiologically Normal-Appearing Brain Regions before Recurrence of High-Grade Glioma Using Multiparameter Mapping And Diffusion Tensor Imaging
Philipp Raffler, Severin Schramm, Cornelius Berberich, Daniele Calabro, Ronja Berg, Kirsten Jung, Julian Ziegenfeuter, Tim Herrmann, Claire Delbridge, Stephanie C Combs, Bernhard Meyer, Christine Preibisch, Benedikt Wiestler, Marie-Christin MetzAbstract
Background
Quantitative MRI (qMRI) might detect subtle changes in recurrent high-grade glioma earlier than conventional imaging. The purpose of this study was to investigate whether WHO grade 4 glioma patients demonstrate alterations in multiparameter mapping (MPM) and diffusion tensor imaging (DTI)-derived measures within radiologically normal-appearing brain regions that subsequently exhibit tumor recurrence in follow-up scans.
Methods
For 16 WHO grade 4 glioma patients with confirmed recurrence at follow-up, qMRI parametric maps (proton density (PD), longitudinal relaxation rate (R1), transverse relaxation rate (R2*)) were generated using a MPM protocol. Additionally, diffusion tensor imaging (DTI) -derived free water (FW) and FW-corrected tissue fractional anisotropy (FAt) were evaluated. We mapped recurrent tumor areas onto baseline scans to identify regions that subsequently progressed to contrast-enhancing tumor (CET) or FLAIR-hyperintense areas.
Results
Normal-appearing grey matter (NAGM) that progressed into FLAIR-hyperintense areas in follow-up scans showed significantly lower median PD values, while median FW was significantly elevated across all subregions compared to their reference regions. This potentially reflects an early redistribution of water from bound tissue compartments into the extracellular space, most evident in gray matter. R1 demonstrated significantly lower median values in NAGM progressing to tumor compared to stable NAGM. Variance was significantly increased for PD, R2*, and FW in multiple subregions, consistent with heterogeneous tumor infiltration.
Conclusions
MPM and DTI-derived metrics reveal subtle alterations in radiologically normal-appearing brain tissue months before recurrence becomes visible on conventional imaging. This could support earlier identification of subclinical progression and allow for personalized surveillance strategies.