Free water elimination tractometry reveals local and remote white matter alterations in diffuse gliomas

J Neurooncol. 2025 Dec 10;176(1):115. doi: 10.1007/s11060-025-05370-w.

Abstract

Purpose: To apply free water elimination (FWE) tractometry to a real-world clinical imaging dataset to quantify pathology-specific patterns of white matter involvement and peritumoral tissue alterations in diffuse gliomas.

Methods: The University of California San Francisco Preoperative Diffuse Glioma MRI dataset was analyzed using FWE tractometry. Twenty major white matter tracts were reconstructed and each divided into 100 equidistant nodes. Direct tumor involvement was quantified across enhancing tumor, necrotic core, and edema regions. Remote white matter tissue properties were assessed through hemispheric asymmetry analysis of free water-corrected fractional anisotropy (FW-FA), mean diffusivity (FW-MD), and free water fraction (FWF) in non-tumor involved regions at standardized distances from radiological tumor margins.

Results: 459 patients with unilateral glioma were included (361 glioblastoma, 87 astrocytoma, 11 oligodendroglioma). Glioblastoma demonstrated greater direct white matter involvement in enhancing tumor and necrotic core compared to astrocytoma and oligodendroglioma (q < 0.001, q = 0.01, respectively). Beyond radiological tumor margins, glioblastoma and astrocytoma exhibited decreased FW-FA, while oligodendroglioma showed increased FW-FA (q = 0.008, q = 0.04, respectively). Distance-based analysis revealed that this effect was most prominent in the proximal peritumoral region and diminished with increasing distance from tumor margins.

Conclusion: Using FWE tractometry on a large clinical repository, we identified distinct pathology-specific patterns of white matter alteration. Glioblastoma showed extensive direct involvement and peritumoral microstructural changes, while oligodendroglioma demonstrated relatively preserved white matter architecture near tumor margins. These patterns reflect expected biological differences and provide a reproducible framework for characterizing extent of white matter involvement, with potential applications in presurgical planning and understanding recurrence patterns.

Keywords: Diffusion MRI; Free water elimination; Glioma; Tractometry; White matter.

MeSH terms

  • Adult
  • Aged
  • Brain Neoplasms* / diagnostic imaging
  • Brain Neoplasms* / metabolism
  • Brain Neoplasms* / pathology
  • Diffusion Tensor Imaging* / methods
  • Female
  • Glioma* / diagnostic imaging
  • Glioma* / metabolism
  • Glioma* / pathology
  • Humans
  • Magnetic Resonance Imaging / methods
  • Male
  • Middle Aged
  • Water / metabolism
  • White Matter* / diagnostic imaging
  • White Matter* / metabolism
  • White Matter* / pathology
  • Young Adult

Substances

  • Water