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MRI-guided focused ultrasound combined with microbubbles can open the blood-brain barrier (BBB) and allow therapeutic drugs to reach the diseased brain location under the direction of MRI. This is a promising technique that has been shown to be safe in patients with various brain diseases, such as Alzheimer’s disease, Parkinson’s disease, ALS, and glioblastoma. While MRI has been commonly used for the guidance and evaluation of treatment in preclinical research and clinical studies, until now, researchers have not known the impact of the static magnetic field generated by the MRI scanner. on the size of the opening of the BBB and the efficiency of drug administration.
In new research published in Radiology, Hong Chen and his laboratory at Washington University in St. Louis first discovered that the magnetic field of the MRI scanner decreased the opening volume of the BBB from 3.3 times to 11.7 times, according to the strength of the magnetic field, in a mouse model.
Chen, associate professor of biomedical engineering at the McKelvey School of Engineering and radiation oncology at the School of Medicine, and his lab conducted the study in 30 mice in four groups. After the mice were injected with the microbubbles, three groups received sonication with focused ultrasound at different magnetic field intensities: 1.5 T (teslas), 3 T and 4.7 T, while one group n never entered the magnetic field.
They found that the activity of microbubble cavitation, or the expansion, contraction and collapse of microbubbles, decreased by 2.1 decibels at 1.5 T; 2.9 decibels at 3 T; and 3 decibels at 4.7 T, compared to those dosed outside the magnetic field. In addition, the magnetic field decreased the opening volume of the BBB by 3.3 times at 1.5 T; 4.4 times at 3 T; and 11.7 times at 4.7 T. None of the mice showed tissue damage due to the procedure.
After focused ultrasound sonication, the team injected a model drug, Evans blue, to test whether the static magnetic field affects the efficiency of trans-BBB drug delivery. The images showed that the fluorescence intensity of Evans blue was lower in mice treated in any of the three magnetic field strengths compared to mice treated outside the magnetic field. Evans blue trans-BBB administration was reduced 1.4-fold at 1.5 T, 1.6-fold at 3.0 T, and 1.9-fold at 4.7 T compared to those treated in outside the magnetic field.
The damping effect of the magnetic field on the microbubble is probably caused by the loss of kinetic energy of the bubble due to the Lorentz force acting on the charged lipid molecules moving on the shell of the microbubble and the molecules of dipolar water surrounding the microbubbles.
Yaoheng (Mack) Yang, senior study author and doctoral student, Washington University in St Louis
“The results of this study suggest that the impact of the magnetic field should be considered in clinical applications of focused ultrasound in drug delivery to the brain,” Chen said.
In addition to drug delivery to the brain, cavitation is also the fundamental physical mechanism of several other therapeutic techniques, such as histotripsy, the use of cavitation to mechanically destroy regions of tissue, and sonothrombolysis, a therapy. used after acute ischemic stroke. The magnetic field-induced damping effect on cavitation is expected to affect treatment results of other cavitation-induced techniques when MRI-guided focused ultrasound systems are used.
Source:
Washington University at St. Louis
Journal reference:
Yang, Y., et al. (2021) Static magnetic fields attenuate the opening of the blood-brain barrier by focused ultrasound. Radiology. doi.org/10.1148/radiol.2021204441.
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