J Korean Neurosurg Soc.  2023 Mar;66(2):172-182. 10.3340/jkns.2022.0236.

Characteristics of Focused Ultrasound Mediated Blood-Brain Barrier Opening in Magnetic Resonance Images

• Chang KW
• Hong SW
• Chang WS
• Jung HH
• Chang JW

• KMID: 2539878
• DOI: http://doi.org/10.3340/jkns.2022.0236

Abstract

Objective
: The blood-brain barrier (BBB) is an obstacle for molecules to pass through from blood to the brain. Focused ultrasound is a new method which temporarily opens the BBB, which makes pharmaceutical delivery or removal of neurodegenerative proteins possible. This study was demonstrated to review our BBB opening procedure with magnetic resonance guided images and find specific patterns in the BBB opening.
Methods
: In this study, we reviewed the procedures and results of two clinical studies on BBB opening using focused ultrasound regarding its safety and clinical efficacy. Magnetic resonance images were also reviewed to discover any specific findings.
Results
: Two clinical trials showed clinical benefits. All clinical trials demonstrated safe BBB opening, with no specific side effects. Magnetic resonance imaging showed temporary T1 contrast enhancement in the sonication area, verifying the BBB opening. Several low-signal intensity spots were observed in the T2 susceptibility-weighted angiography images, which were also reversible and temporary. Although these spots can be considered as microbleeding, evidence suggests these are not ordinary microbleeding but an indicator for adequate BBB opening.
Conclusion
: Magnetic resonance images proved safe and efficient BBB opening in humans, using focused ultrasound.

Keyword

Blood brain barrier; Focused ultrasound; Drug delivery; Glioblastoma; Alzheimer’s disease

Figure

• 

  Fig. 1. Planning of blood-brain barrier opening area in Alzheimer’s disease study with focused ultrasound device. Area of grid with dots is the planned area for blood-brain barrier (BBB) opening. Area of BBB opening can be monitored in a heatmap shape by realtime acoustic emission monitoring.

• 

  Fig. 2. Sequential T1 contrast images of glioblastoma blood-brain barrier opening study. Each row is the follow up magnetic resonance image of each temozolomide cycle. Orange circle indicates the region of interest. The tumor size has been stable or partially reduced during the follow-up sequential images.

• 

  Fig. 3. T1 contrast image for Alzheimer’s disease clinical study. Immediate post focused ultrasound magnetic resonance imaging (MRI) image (left row) and 1 month follow up MRI (right row) are shown. The T1 contrast image shows gadolinium enhancement in the blood-brain barrier opening area (left row). White arrow indicates marked contrast enhancement. The enhancement disappeared in the following image. The patient dropped out of the study in case 6.

• 

  Fig. 4. Susceptibility-weighted angiography images of Alzheimer’s disease study. Immediate post focused ultrasound (FUS) magnetic resonance imaging (MRI) images (left row) show multiple dot shaped hypointense spots observed in the bilateral frontal lobes. Yellow circles indicate marked hypointense spots in the sonication area. The spot shape resembles the grid shape in the FUS system. Some spots attenuated and disappeared in the follow up MRI (right row). The patient dropped out in case 6.

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  Fig. 5. Sequential susceptibility-weighted angiography (SWAN) images of glioblastoma study. Each row is the SWAN image immediately after the focused ultrasound (FUS) sonication. Magnetic resonance imaging images show multiple dot shaped hypointense spot observed in the sonication sites (white arrows). The spots resemble the grid shape in the FUS system. Note that the spot differs in location according to the sonication area, and in the follow-up image, most of the spots disappeared.

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  Fig. 6. A new ongoing blood-brain barrier (BBB) opening clinical study of drug delivery in recurred glioblastoma (GBM). A wider BBB opening area can be achieved than in the GBM temozolomide clinical study. A : Planning image with grid. B : Post focused ultrasound MR images, susceptibility-weighted angiography, T1, T1 contrast. Red circles in the (B) indicate the region of interest in the post operative images.

Reference

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