Targeted Neuronal Injury for the Non-Invasive Disconnection of Brain Circuitry

Area of Science:

• Neurosurgery
• Neurology
• Biomedical Engineering

Background:

• Surgical interventions are effective for intractable neurological diseases like epilepsy and movement disorders.
• Current surgical methods are invasive, risking damage to non-target tissues.
• There is a need for non-invasive, neurotoxic surgical approaches.

Purpose of the Study:

• To present a novel non-invasive method for creating focal neuronal lesions in the brain.
• To utilize focused ultrasound and microbubbles to enable targeted drug delivery across the Blood-Brain Barrier (BBB).

Main Methods:

• Low-intensity focused ultrasound combined with intravenous microbubbles to transiently open the Blood-Brain Barrier (BBB).
• Focal delivery of the BBB-impermeable neurotoxin quinolinic acid (QA) to targeted brain regions.
• Confirmation of BBB opening via contrast-enhanced T1-weighted MRI and lesion localization via T2 imaging.

Main Results:

• Successful transient and focal opening of the BBB in rodent models.
• Targeted delivery of QA resulted in focal neuronal injury and loss in specific brain areas.
• Control animals receiving saline showed BBB opening but no neuronal injury, confirming QA's role.

Conclusions:

• Precise Intracerebral Non-invasive Guided surgery (PING) offers a non-invasive method for creating targeted neuronal lesions.
• This technique holds potential for treating neurological disorders linked to aberrant neural circuitry.
• PING allows for precise, localized neurotoxicity without systemic side effects.