Drug Development

Area of Science:

• Neuroscience
• Histology
• Drug Discovery

Background:

• Traditional 2D histology limits deep tissue imaging to specific regions.
• Advances in optical clearing and light sheet imaging enable 3D brain-wide cellular resolution.
• 3D histology is crucial for CNS therapeutic development, assessing target engagement and efficacy.

Purpose of the Study:

• To develop and disseminate advanced 3D tissue clearing and AI-powered quantification methodologies.
• To enable brain-wide, cellular resolution analysis of amyloid plaques and microglia.
• To facilitate unbiased mapping of CNS therapeutic efficacy in neuroinflammation and amyloid deposition.

Main Methods:

• Utilized iDISCO-based tissue clearing kits and light sheet microscopy for intact mouse brain imaging.
• Employed Translucence Teravoxel Toolkit (3TK) software for cell identification and 3D atlas registration.
• Developed AI-powered workflows for segmenting microglia (Iba1) and quantifying amyloid plaques.

Main Results:

• Achieved brain-wide segmentation of microglia, providing regional activation metrics.
• Successfully labeled and quantified amyloid plaques in 5xFAD mouse models.
• Identified and quantified plaque-associated microglia (PAMs), correlating their levels with plaque density.

Conclusions:

• Disseminated 3D histology technology via BRAIN Initiative-funded kits and cloud-based analysis.
• Enables neuroscientists to utilize next-generation 3D immunohistochemistry for comprehensive CNS analysis.
• Facilitates unbiased, anatomically precise mapping of therapeutic efficacy for amyloid and neuroinflammation.