Edema is not a reliable diagnostic sign to exclude small brain metastases.

No prior systematic study on the extent of vasogenic edema (VE) in patients with brain metastases (BM) exists. Here, we aim to determine 1) the general volumetric relationship between BM and VE, 2) a threshold diameter above which a BM shows VE, and 3) the influence of the primary tumor and location of the BM in order to improve diagnostic processes and understanding of edema formation. This single center, retrospective study includes 173 untreated patients with histologically proven BM. Semi-manual segmentation of 1416 BM on contrast-enhanced T1-weighted images and of 865 VE on fluid-attenuated inversion recovery/T2-weighted images was conducted. Statistical analyses were performed using a paired-samples t-test, linear regression/generalized mixed-effects model, and receiver-operating characteristic (ROC) curve controlling for the possible effect of non-uniformly distributed metastases among patients. For BM with non-confluent edema (n = 545), there was a statistically significant positive correlation between the volumes of the BM and the VE (P < 0.001). The optimal threshold for edema formation was a diameter of 9.4 mm for all BM. The primary tumors as interaction term in multivariate analysis had a significant influence on VE formation whereas location had not. Hence VE development is dependent on the volume of the underlying BM and the site of the primary neoplasm, but not from the location of the BM.