Validating DCE-MRI estimates of leakage volumes associated with subtle blood-brain barrier dysfunction using two-photon microscopy.

Motivation: DCE-MRI can be used to quantify subtle blood-brain barrier disruption. In this setting, it is generally assumed that contrast agent has access to the entire interstitial space. Prior work from our group indicates that contrast agent has access to a leakage volume much smaller than the interstitial space. Goal(s): To provide independent validation of DCE-MRI leakage-to-vessel volume ratios (ve/vb) in the case of subtle BBB impairment. Approach: The ve/vb ratio of Sulphorhodamine-101 (MW = 606.7g/mol) was measured in mouse brain using two-photon microscopy and compared to DCE-MRI estimates. Results: The ve/vb ratio of sulphorhodamine-101 agrees well with DCE-MRI estimates. Impact: Our results indicate that DCE-MRI kinetic models that assume infinite leakage volume (e.g. Patlak model) do not accurately reflect how Gd-DOTA distributes within the brain when BBB impairment is subtle.