Monitoring of acoustic cavitation in microbubble-presented focused ultrasound exposure using gradient-echo MRI

Gadolinium-based contrast agents can be used to identify the blood-brain barrier (BBB) opening after inducing a focused ultrasound (FUS) cavitation effect in the presence of microbubbles. However, the use of gadolinium may be limited for frequent routine monitoring of the BBB opening in clinical applications.

To use a gradient-echo sequence without contrast agent administration for monitoring of acoustic cavitation.

Animal and phantom prospective.

Static and flowing gel phantoms; six normal adult male Sprague-Dawley rats.

3T, 7T; fast low-angle shot sequence.

Burst FUS with acoustic pressures = 1.5, 2.2, 2.8 MPa; pulse repetition frequencies = 1, 10,100 Hz; and duty cycles = 2%, 5%, 10% were transmitted to the chamber of a static phantom with microbubble concentrations = 10%, 1%, 0.1%. MR slice thicknesses = 3, 6, 8 mm were acquired. In flowing phantom experiments, 0.1%, 0.25%, 0.5%, 0.75%, and 1% microbubbles were infused and transmitted by burst FUS with an acoustic pressure = 0.4 and 1 MPa. In in vivo experiments, 0.25% microbubbles was infused and 0.8 MPa burst FUS was transmitted to targeted brain tissue beneath the superior sagittal sinus. The mean signal intensity (SI) was normalized using the mean SI from pre-FUS.

Two-tailed Student's t-test. P < 0.05 was considered statistically significant.

In the static phantom, the time courses of normalized SI decreases to minimum SI levels of 70-80%. In the flowing phantom, substantial normalized SI of 160-230% was present with variant acoustic pressures and microbubble concentrations. Compared with in vivo control rats, the brain tissue of experimental rats with transmission of FUS pulses exhibited considerable decreases of normalized SI (P < 0.001) because of the cavitation-induced perturbation of flow.

Observing gradient-echo SI changes can help monitor the targeted location of microbubble-enhanced FUS, which in turn assists the monitoring of the BBB opening.

2 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2020;51:311-318.