Shallow-angle intracranial cannula for repeated infusion and in vivo imaging with multiphoton microscopy

Area of Science:

• Neuroscience
• Biomedical Engineering
• Optical Imaging

Background:

• Multiphoton microscopy is crucial for high-resolution live mouse brain imaging.
• Cranial window surgery, while common, limits direct agent delivery to the brain.
• Existing methods restrict access for repeated compound administration during imaging.

Purpose of the Study:

• To develop a method for repeated administration of imaging agents and compounds during in vivo multiphoton microscopy of the mouse brain.
• To overcome the limitations of cranial window surgery in delivering substances to the brain.
• To enable longitudinal studies with enhanced delivery capabilities.

Main Methods:

• Developed a low-profile cannula delivery system for implantation nearly parallel to the brain surface (as shallow as 8 degrees).
• Ensured compatibility of the cannula system with multiphoton microscopy setups.
• Validated the system through direct infusion and imaging of fluorescent markers.

Main Results:

• Demonstrated successful repeated administration of imaging agents and compounds.
• Tracked degenerating neurons in Alzheimer's disease mice using Fluoro-Jade C.
• Performed longitudinal imaging of oxygen partial pressure in brain tissue using a phosphorescent sensor.

Conclusions:

• The developed shallow-angle cannula system facilitates repeated delivery of agents during in vivo multiphoton imaging.
• This technique significantly enhances the capabilities for longitudinal imaging studies in the mouse brain.
• Opens new avenues for studying dynamic processes and therapeutic interventions in neurological research.