Pulse sequence and timing of contrast-enhanced MRI for assessing blood-brain barrier disruption after transcranial focused ultrasound in the presence of hemorrhage

Purpose: To optimize the timing of contrast-enhanced magnetic resonance imaging (MRI) that best indicates blood-brain barrier (BBB) disruption induced by focused ultrasound (FUS) along with an ultrasound contrast agent (UCA) and to verify that the contrast-enhanced spin-echo MRI sequence can indicate the degree and location of BBB disruption in the presence of hemorrhage better than a gradient-echo sequence. Materials and Methods: Sonication was applied to 12 rat brains with four different doses of UCA to cause variable degrees of hemorrhage. Two imaging sequences were performed to acquire T1-weighted (T1W) images at two timepoints after the administration of a T1-shortening contrast agent. The contrast enhancement at the sonicated regions was quantified and correlated against Evans blue (EB) staining. Results: The spin-echo T1W images at 10 minutes post-contrast enhancement showed the best correlation with EB staining in both quantity of EB extravasation (r = 0.812; P < 0.01) and spatial distribution (r = 0.528, P < 0.01). This capability was more robust than the gradientecho sequence. Conclusion: Our results suggest that contrast-enhanced T1W spin-echo sequence acquired in the early phase post-contrast enhancement should be considered to monitor the degree and location of BBB disruption under the possibility of hemorrhage induced by FUS.