This article details a method for treating brain tumors in mice using magnetic resonance-guided focused ultrasound (MRgFUS) combined with sonodynamic therapy. The approach involves the use of a sonosensitizer that targets tumor cells, leading to oxidative stress and cell death.
Begin with an anesthetized nude mouse bearing a brain tumor in a magnetic resonance-guided focused ultrasound (MRgFUS) system.
The mouse has been previously injected with a sonosensitizer precursor.
This precursor accumulates in the mitochondria of tumor cells due to their high metabolic activity and is converted into a sonosensitizer.
Apply ultrasound gel to the scalp and place a water bath with its bottom membrane in contact with the gel.
Submerge the ultrasound transducer in the water bath.
Using previously acquired MR images of the brain, identify the tumor.
Position the transducer over the tumor site and deliver focused ultrasound waves to perform
sonodynamic therapy.
The coupled water bath and gel serve as an acoustic medium for efficient ultrasound transmission.
The ultrasound activates the sonosensitizer, which converts molecular oxygen into reactive oxygen species (ROS).
These sonosensitizer-generated ROS induce oxidative stress, leading to cell death and reduced tumor proliferation.
Place a dab of centrifuged ultrasound gel on the animal's head, such that the gel covers the entire scalp above the skull. Then fill 80%of the water bath with deionized and degassed water and place the water bath onto its corresponding columns on the platform.
Lower the water bath until the bottom membrane touches the ultrasound gel on the animal's head, forming a coupling surface between the water and the gel. Submerge the ultrasound transducer into the water bath, ensuring no air bubbles are forming on the transducer surface. After lowering the transducer arm, align the magnetic slots with each other while the transducer surface remains submerged.
For burst mode, go to the sonication settings tab and enter the sonication time. Click on the target icon in the top middle of the page and select the proper locations on the correct MRI slice where the FUS focal region is to be aimed. Clicking the focal spot will highlight the coordinates and the corresponding focal region on the image will turn blue.
The last column on the table shows the power level to be sonicated at each focal spot. Once satisfied with all focal regions, select motion test. Once ready, select start sonication to begin the sonication protocol, moving the transducer and applying the FUS parameters at each focal region selected.
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