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Tuesday, October 15 • 11:15am - 11:30am
Brain Tissue Analytics for Accelerating Drug Discovery

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While international brain mapping initiatives remain focused on the structure and working of the healthy brain, the need to map the unhealthy brain is compelling and urgent. Pointedly, traumatic brain injury (TBI) inflicts pathological alterations in all types of brain cells, at scales ranging from individual cells to multi-cellular functional units, to the layered brain cytoarchitecture. Furthermore, it inflicts a mix of alterations due to the primary injury, secondary injuries, regenerative processes, inflammation, tissue remodeling, drug treatments, and drug side effects. Many of these alterations can be subtle and/or latent, only discernible by sensing changes in cell morphology and/or the expression and/or intra-cellular distribution of specific molecular markers, and can be distant from the injury/damage site. Unfortunately, current immunohistochemistry (IHC) methods reveal only a fraction of these alterations, and do not provide quantitative readouts.

We present an approach for comprehensive pathological brain tissue mapping with a focus on rational therapeutics development. Our method is based on imaging and analyzing highly multiplexed whole brain sections using 10 – 50 molecular markers. Analyzing these images is challenging due to their complexity, variability, and size. We describe a combination of morphology-driven signal reconstruction, deep cell detection and segmentation, and data analysis methods to generate quantitative readouts of cellular alterations at multiple scales ranging from individual cells to multi-cellular units, cortical layers, and atlas-defined brain regions. The results can be used for testing hypotheses, screening combination drug therapies, and system-level studies.



Tuesday October 15, 2019 11:15am - 11:30am
BRC 280

Attendees (5)