Detection of transient ischemia and hemorrhage in blood-brain barrier disruption by high-frequency ultrasound imaging

Focused ultrasound (FUS) with microbubbles has been discovered to locally increase the permeability of blood-brain barrier (BBB). However, bioeffects such as erythrocyte extravasations and brain tissue damage may accompany. Therefore, development of a real-time imaging method to visualize occurrence of brain injury during opening of BBB by FUS is chief to improve the safety of this technology. The purpose of this study is to investigate the feasibility of using the high-frequency ultrasound imaging technique including contrast-enhanced and B-mode two images to monitor the transient responses of BBB disruption (BBBD) induced by FUS. We observed that BBBD with extensive hemorrhage and ischemia in 1-MHz FUS with 1.1 MPa. The bright spots from the blood clots scattering appeared in B-mode images and correspond to the map without perfusion in the contrast-enhanced images. In addition, a relative safe power to BBBD without such bioeffects was 0.3 MPa. The results indicated that location of hyperechoic spots correlates with hemorrhage areas and the ischemia region consistent with the BBBD areas under the cases of high FUS power. That reflected high-frequency ultrasound can provide the information of microhemorrhage and transient ischemia information during BBB open by FUS.