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Purpose <p>Systemic infiltration is a hallmark pathological feature of diffuse midline glioma (DMG), which may induce subtle alterations in cortical morphology. This study sought to characterize how the normal-appearing cortex is affected by the DMG, further hypothesizing that highly aggressive “DMG, H3 K27-altered” (DMG-A) would induce greater abnormalities than “DMG, H3 K27 wild-type” (DMG-W).</p> Methods <p>Fifty-five DMG-A patients, 40 DMG-W patients, and 50 age- and sex-matched healthy controls underwent three-dimensional T1-weighted imaging. Cortical thickness and local gyrification index were calculated using FreeSurfer. Structural covariance networks were constructed by assessing the interregional similarity of cortical thickness. Topological properties and important sub-networks were evaluated through graph theory and network-based statistics, respectively.</p> Results <p>Compared with healthy controls, both patient groups displayed widespread cortical thickening. The DMG-A group predominantly involved the precuneus, superior frontal gyrus, and medial orbitofrontal cortex, while the DMG-W group primarily involved the pars orbitalis. Network analysis revealed decreased structural covariance, especially in the default mode network and the visual network. Notably, comparison of the two patient groups demonstrated significantly lower local gyrification index in the DMG-A group, specifically in the right pars triangularis, precuneus, and lingual gyrus.</p> Conclusions <p>DMG patients exhibited widespread cortical alterations extending beyond the tumor location. Additionally, patients with H3 K27 alterations exhibited more extensive whole-brain morphological changes compared to those with wild-type H3 K27. These findings highlight the distributed nature of DMG-related cortical changes and suggest that whole-brain morphometric analyses may offer a useful framework for future studies investigating disease burden and treatment-related effects.</p>

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Unveiling the whole-brain impact of diffuse midline glioma: cortical morphological remodeling and network alterations driven by H3 K27 mutation

  • 期刊论文

  • 发表日期：

    2026年2月19日

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  • Di Chen,
  • Simin Zhang,
  • Dian Zhang,
  • Yuan Yang,
  • Xibiao Yang,
  • Yujiao Deng,
  • Ni Chen,
  • Yanhui Liu,
  • Qiang Yue

摘要

Purpose

Systemic infiltration is a hallmark pathological feature of diffuse midline glioma (DMG), which may induce subtle alterations in cortical morphology. This study sought to characterize how the normal-appearing cortex is affected by the DMG, further hypothesizing that highly aggressive “DMG, H3 K27-altered” (DMG-A) would induce greater abnormalities than “DMG, H3 K27 wild-type” (DMG-W).

Methods

Fifty-five DMG-A patients, 40 DMG-W patients, and 50 age- and sex-matched healthy controls underwent three-dimensional T1-weighted imaging. Cortical thickness and local gyrification index were calculated using FreeSurfer. Structural covariance networks were constructed by assessing the interregional similarity of cortical thickness. Topological properties and important sub-networks were evaluated through graph theory and network-based statistics, respectively.

Results

Compared with healthy controls, both patient groups displayed widespread cortical thickening. The DMG-A group predominantly involved the precuneus, superior frontal gyrus, and medial orbitofrontal cortex, while the DMG-W group primarily involved the pars orbitalis. Network analysis revealed decreased structural covariance, especially in the default mode network and the visual network. Notably, comparison of the two patient groups demonstrated significantly lower local gyrification index in the DMG-A group, specifically in the right pars triangularis, precuneus, and lingual gyrus.

Conclusions

DMG patients exhibited widespread cortical alterations extending beyond the tumor location. Additionally, patients with H3 K27 alterations exhibited more extensive whole-brain morphological changes compared to those with wild-type H3 K27. These findings highlight the distributed nature of DMG-related cortical changes and suggest that whole-brain morphometric analyses may offer a useful framework for future studies investigating disease burden and treatment-related effects.