Factors Affecting the Detection of Permeability Derangements in Perfusion Imaging of Stroke Patients

Background: In acute ischemic stroke (AIS) patients, damage to the bloodbrain barrier (BBB) can ultimately lead to the most feared complication of thrombolytic therapy, intracranial hemorrhage (ICH). MRI evidence of breakdown in the BBB has been linked to subsequent ICH in animals and in humans. Recent studies have demonstrated that leakage of contrast during PWI of AIS patients due to increased permeability may be a sensitive predictor of subsequent hemorrhagic transformation.(1;2) Currently, however, no technique using perfusion-based permeability imaging (PPI) in stroke patients has been able to quantify permeability. Furthermore published methods for PPI in AIS have been poorly described and not rigorously tested with basic MR principles. Hypothesis: The signal change caused by contrast leakage through the BBB is dependent on the parameters of the acquisition which need be corrected for in order to quantify permeability. Methods: PPI algorithm: Damage to the BBB results in contrast extravasation into the parenchyma during the course of a PWI acquisition. This affects the recorded signal by introducing a T1 component to what is primarily a T2* weighted signal. In the absence of BBB derangements, changes in tissue contrast agent concentration are measured as changes in relaxivity with the equation:(3) 1) ∆R2*(t) = (-1/TE)ln(S(t)/S0) Where TE is the time to echo, S(t) is the signal intensity in the voxel at time t, and S0 is the baseline signal intensity prior to delivery of the contrast bolus. When taking into consideration the effects of extravasation, the measured signal is more accurately characterized by adding a term to equation (1) to account for T1 effects:(3)