An MRI Atlas of Regional Brain Vulnerability to Metastatic Disease

Are some brain regions intrinsically more vulnerable to metastatic colonization? We sought to characterize the spatial distribution of brain metastases and determine whether regional patterns vary according to primary tumor origin.

We analyzed baseline MRI scans and expert tumor segmentations from 906 patients with 3,492 brain metastases treated with stereotactic radiosurgery. Lesions were normalized to MNI152 standard space and superimposed to generate probabilistic atlases of metastatic occurrence. Regional metastatic burden was quantified using anatomical and vascular atlases. Spatial distributions were additionally compared between lung cancer and melanoma metastases.

Metastatic burden was distributed nonuniformly throughout the brain. The cerebellum demonstrated the strongest enrichment relative to its anatomical volume (fold change 1.61, p < 0.001), accompanied by overrepresentation of the vertebrobasilar circulation (fold change 1.49, p < 0.001). Spatial distribution also varied by primary tumor type. Lung cancer metastases demonstrated greater infratentorial involvement than melanoma metastases (16.6% vs. 8.7%, p < 0.05), with a corresponding increase in cerebellar burden (14.8% vs. 6.8%, p < 0.05), whereas melanoma metastases were relatively concentrated within the frontal lobe (37.7% vs. 24.6%, p < 0.01). Infratentorial enrichment was observed across all carcinoma subgroups, with the greatest enrichment seen in gastrointestinal metastases (32.9% infratentorial).

Brain metastases exhibit nonrandom spatial distributions, with preferential involvement of posterior and infratentorial structures. Regional patterns vary according to primary tumor origin, supporting the existence of region-specific vulnerability to metastatic disease.