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Whole-brain tissue mapping toolkit using large-scale highly multiplexed immunofluorescence imaging and deep neural
Dragan Maric1, Jahandar Jahanipour2,3, Xiaoyang Rebecca Li3
1National Institute of Neurological Disorders and Stroke, Bethesda, MD, 20892, USA. maricd@ninds.nih.gov.
Nature Communications
|March 11, 2021
Summary
This study introduces a new method for detailed brain tissue analysis using advanced imaging and computational techniques. It enables comprehensive mapping of biological processes across all cell types and brain regions.
Area of Science:
- Neuroscience
- Histology
- Biomarker Analysis
Background:
- Mapping biological processes in brain tissues is complex, requiring integration of numerous histological observations from multiple samples.
- Current methods face challenges in comprehensive, multi-scale analysis of brain tissues.
Purpose of the Study:
- To present a direct method for generating comprehensive biomarker readouts from serial whole-brain slices.
- To characterize all major brain cell types at multiple scales, from subcellular to whole-brain regions.
Main Methods:
- Iterative cycles of optimized 10-plex immunostaining and 10-color epifluorescence imaging.
- Computational isolation of specific fluorescent signals, rejecting noise and artifacts.
- Deep neural networks for reliable large-scale cell detection, segmentation, and phenotyping.
Main Results:
- Generation of highly enriched image datasets from individual whole-brain slices.
- Reconstruction of seamless, signal-corrected mosaics of brain tissue.
- Simultaneous profiling of multiple biological processes within their native anatomical context.
Conclusions:
- This approach accelerates pre-clinical drug evaluation and system-level brain histology studies.
- Enables detailed characterization of brain cell types and biological processes at unprecedented scale.
