FUS-mediated BBB opening leads to transient perfusion decrease and inflammation without acute or chronic brain...

Area of Science:

• Neuroimaging
• Biomedical Engineering
• Pharmacology

Background:

• MR-guided focused ultrasound (FUS) offers a non-invasive method for opening the blood-brain barrier (BBB).
• Understanding hemodynamic changes post-BBB opening is crucial for optimizing therapeutic delivery and patient outcomes.
• Cerebral hemodynamic parameters and neuroinflammation require careful evaluation for clinical translation.

Purpose of the Study:

• To assess the impact of MR-guided FUS-induced BBB opening on cerebral hemodynamics.
• To monitor cavitation levels during FUS application.
• To quantify longitudinal neuroinflammation markers after BBB permeabilization.

Main Methods:

• MR-guided FUS was applied to the cortex or striatum to open the BBB.
• Cerebral blood flow (CBF), blood volume fraction (BVf), and apparent diffusion coefficient (ADC) were monitored using MRI.
• Cavitation was monitored using a passive cavitation detector (PCD) and classified using the International Ultrasound Diagnostics (IUD) index.

Main Results:

• Successful BBB opening was achieved in all subjects, with minimal adverse cavitation.
• Transient decreases in CBF (up to 54%) and BVf (up to 15%) were observed post-FUS, returning to baseline within 90 minutes.
• Neuroinflammation markers showed transient increases in astrocytic recruitment and microglial activation, resolving within 7 days.

Conclusions:

• MR-guided FUS-induced BBB opening causes temporary hemodynamic alterations in the CNS.
• These hemodynamic changes suggest a transient reduction in nutrient and oxygen supply.
• The findings are essential for refining FUS parameters for safe and effective therapeutic delivery.