The Use of Susceptibility-Weighted Magnetic Resonance Imaging to Characterize the Safety Window of Focused Ultrasound Exposure for Localized Blood—Brain-Barrier Disruption

Abstract

High‐intensity focused ultrasound has been discovered to be able to locally and reversibly increase the permeability of the blood—brain barrier (BBB), which can be detected using magnetic resonance imaging (MRI). However, side effects such as microhemorrhage, erythrocyte extravasations, or even extensive hemorrhage can also occur. Although current contrast‐enhanced T1‐weighted MRI can be used to detect the changes in BBB permeability, its efficacy in detecting tissue hemorrhage after focused‐ultrasound sonication remains limited. The purpose of this study was to determine the feasibility of using MR susceptibility‐weighted imaging (SWI) to identify tissue hemorrhage associated with the process of BBB permeability increase and characterize the safety window of acoustic pressure level. Brains of 42 Sprague‐Dawley rats were subjected to 107 sonications either unilaterally or bilaterally. Contrast‐enhanced T1‐weighted images, together with SWI were performed. Tissue damage and hemorrhage were analyzed histologically with light microscopy and staining by Evan’s blue, HE staining as well as TUNEL staining. Our results showed that contrast‐enhanced T1 weighted imaging is sensitive to the presence of the BBB disrupture, but was unable to differentiate from extensive tissue damage such as hemorrhage. Also, SWI proved to be a superior tool for the realtime monitoring of the presence of hemorrhage, which is essential to the clinical concerns. The safety operation window in vivo in our study indicated a pressure of 0.78 to 1.1 MPa. to increase the BBB permeability successfully without hemorrhage. Potential applications such as drug delivery in the brain might be benefited.