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Nat Commun. 2019 Dec 3;10(1):5504. doi: 10.1038/s41467-019-13374-0.

Multimodal image registration and connectivity analysis for integration of connectomic data from microscopy to MRI.

Author information

1
Department of Radiology, Stanford University, Stanford, CA, 94035, USA. maged.goubran@sri.utoronto.ca.
2
Department of Radiology, Stanford University, Stanford, CA, 94035, USA.
3
Department of Bioengineering, Stanford University, Stanford, CA, 94035, USA.
4
CNC Program, Stanford University, Stanford, CA, 94035, USA.
5
Department of Neurosurgery and Stanford Stroke Center, Stanford University, Stanford, CA, 94035, USA.
6
Department of Electrical Engineering, Stanford University, Stanford, CA, 94035, USA.
7
Department of Psychiatry, Stanford University, Stanford, CA, 94035, USA.
8
Howard Hughes Medical Institute, Stanford University, Stanford, CA, 94035, USA.
9
Department of Radiology, Stanford University, Stanford, CA, 94035, USA. mzeineh@stanford.edu.

Abstract

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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