Journal
NATURE COMMUNICATIONS
Volume 10, Issue -, Pages -Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/s41467-019-13374-0
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Funding
- National Institute of Health [R01-NS095985, R01-MH111444, R01-AG061120, R0-1NS093057]
- Stanford Radiology Angel Funds
- Stanford Neurosciences Institute
- HHMI
- Defense Advanced Research Projects Agency [W911NF-14-2-0013]
- American Society for Neuroradiology
- Boerger Research Fund for Alzheimer's Disease and Neurocognitive Disorders
- GE Healthcare
- William Randolph Hearst Foundation
- U.S. Army Research Laboratory
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3D histology, slice-based connectivity atlases, and diffusion MRI are common techniques to map brain wiring. While there are many modality-specific tools to process these data, there is a lack of integration across modalities. We develop an automated resource that combines histologically cleared volumes with connectivity atlases and MRI, enabling the analysis of histological features across multiple fiber tracts and networks, and their correlation with in-vivo biomarkers. We apply our pipeline in a murine stroke model, demonstrating not only strong correspondence between MRI abnormalities and CLARITY-tissue staining, but also uncovering acute cellular effects in areas connected to the ischemic core. We provide improved maps of connectivity by quantifying projection terminals from CLARITY viral injections, and integrate diffusion MRI with CLARITY viral tracing to compare connectivity maps across scales. Finally, we demonstrate tract-level histological changes of stroke through this multimodal integration. This resource can propel investigations of network alterations underlying neurological disorders.
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