Detection of blood-brain barrier disruption by contrast-enhanced high frequency ultrasound image: Small animals study

Contrast-enhanced magnetic resonance imaging was used to detect the increase of BBB permeability induced by high intensity focus ultrasound (HIFU) with ultrasound contrast agents (UCAs). In this study, contrast-enhanced high-frequency ultrasound imaging was used to detect the enhancement of BBB permeability in small animal experiments. The higher temporal resolution of high-frequency ultrasound imaging provides a potential to monitor the UCAs leakage into the surrounding brain parenchyma. Sprague-Dawley rats were performed craniotomy before the HIFU sonication. One 1.5 MHz HIFU was delivered to the left hemisphere brain with 2.45 MPa pressure. Prior to sonication, UCAs was injected to enhance BBB permeability. Control group rats were sonicated without UCAs injection. Before and after sonications, the rats were individually injected UCAs and immediately a sequence of B-mode images were acquired at 7 fps. Note that the UCAs act as imaging indicators at this moment. We monitored the BBB disruption 6 hours in total and repeated the above mentioned process every hour. The BBB disruptions were verified by means of Evans blue extravasation. To map contrast replenishment after UCAs injection, the echo power in each voxel was summed over the time direction. The results show the power intensity in experiment group is higher than the control group ones. In experiment group, the power intensity in left hemisphere brain is higher than the right side and the power intensity decreases over time. In addition, the spatial map of power consists with the Evans blue histology results. The conclusion is the contrast-enhanced high-frequency ultrasound imaging is feasible to detect the enhancement of BBB permeability.