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

Steven S Hou1, Joyce Yang1, Yeseo Kwon1

  • 1Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02129.

Biorxiv : the Preprint Server for Biology
|February 3, 2025
PubMed

Insights

Researchers developed a novel cannula system for low-angle brain access in mice, enabling simultaneous multiphoton microscopy and direct drug/agent delivery. This technique facilitates longitudinal studies of neurodegenerative diseases and brain oxygen levels.

Area of Science:

  • Neuroscience
  • Biomedical Engineering
  • Optical Imaging

Background:

  • Multiphoton microscopy is vital for high-resolution live mouse brain imaging.
  • Cranial window surgery, while common, limits physical access and direct delivery of agents.
  • Existing methods pose challenges for simultaneous imaging and targeted substance administration.

Purpose of the Study:

  • To develop an improved surgical method for accessing the mouse brain.
  • To enable simultaneous multiphoton microscopy and direct delivery of substances.
  • To facilitate longitudinal studies of brain function and disease.

Main Methods:

  • Developed a low-profile cannula delivery system for implantation at shallow angles (as low as 8 degrees).
  • Ensured compatibility of the cannula system with multiphoton microscopy.
  • Validated the system through direct infusion and imaging of fluorescent markers, tracking degenerating neurons (Fluoro-Jade C), and longitudinal oxygen sensing.

Main Results:

  • Successfully implanted cannulas at shallow angles, allowing parallel brain surface access.
  • Demonstrated effective direct infusion and imaging of various fluorescent cell markers.
  • Successfully tracked degenerating neurons in Alzheimer's disease mouse models over time.
  • Achieved longitudinal imaging of brain tissue oxygen partial pressure.

Conclusions:

  • The developed cannula delivery system overcomes limitations of traditional cranial window surgery.
  • This technique enables simultaneous in vivo imaging and targeted delivery for diverse neurobiological research.
  • The system opens new avenues for longitudinal studies of the mouse brain, including disease progression and physiological monitoring.
Keywords:
braincannulacell deathchemical sensorscranial windowfluorescencein vivo imagingmultiphoton microscopyoxygenphosphorescence

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