Abstract
Understanding brain vasculature in metastases requires correlating MRI resolution limitations with microscopic ground truth. Using the BRIDGE framework, we correlated two-photon (2P) microscopy with MRI (T2, T2*, TOF) to analyze vessel visibility. High-resolution 3D T2w imaging (40 µm) enabled visualization of vessels down to ~20 µm, revealing a significant inverse correlation between vessel volume density and T2w intensity. TOF sequences reflected blood flow velocity but not vessel diameter, while T2w sequences captured vascular structure. In a breast cancer brain metastases model (Jimt1), ex vivo MRI identified progressive T2*-hypointense lesions. Our in vivo BRIDGE pipeline linked T2* positivity to reduced blood flow velocity in perimetastatic capillaries <12 µm. Ex vivo analysis confirmed increased metastatic and erythrocyte clustering, with electron microscopy revealing vascular stasis. These findings validate MRI-based vascular signatures at microscopic resolution, highlighting microvascular dysfunction as a key factor in metastatic progression.