Regional Vulnerability to Brain Metastases Reflects Structural, Metabolic and Genetic Organization of the Healthy Brain

Brain metastases are more frequent near the gray-white matter junction and in high-perfusion, high-glucose-metabolism regions, with mitochondrial density linked to vulnerability in 1,406 patients.

• Why it matters: Brain metastases show non-uniform regional localization, but the healthy-brain structural, metabolic, and molecular features that shape this vulnerability are not well defined.
• What they did: Voxelwise BM distribution from 1,406 patients was compared with normative atlases of microstructure, vasculature, metabolism, cell-type composition, and gene expression, then tested for replication in 1,209 patients.
• The result: Seventeen genes spatially associated with BM vulnerability replicated in validation, and LAG3 ranked among the top ten with r = 0.40–0.45 (p < 0.001), with elevated LAG3 in peritumoral metastasis tissue in an independent spatial transcriptomic dataset.

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