High-Resolution Fiber Tract Reconstruction in the Human Brain by Means of Three-Dimensional Polarized Light Imaging

Abstract

Functional interactions between different brain regions require connecting fiber tracts, the structural basis of the human connectome. To assemble a comprehensive structural understanding of neural network elements from the microscopic to the macroscopic dimensions, a multimodal and multiscale approach has to be envisaged. However, the integration of results from complementary neuroimaging techniques poses a particular challenge. In this paper, we describe a steadily evolving neuroimaging technique referred to as three-dimensional polarized light imaging (3D-PLI). It is based on the birefringence of the myelin sheaths surrounding axons, and enables the high-resolution analysis of myelinated axons constituting the fiber tracts. 3D-PLI provides the mapping of spatial fiber architecture in the postmortem human brain at a sub-millimeter resolution, i.e., at the mesoscale. The fundamental data structure gained by 3D-PLI is a comprehensive 3D vector field description of fibers and fiber tract orientations – the basis for subsequent tractography. To demonstrate how 3D-PLI can contribute to unravel and assemble the human connectome, a multiscale approach with the same technology was pursued. Two complementary state-of-the-art polarimeters providing different sampling grids (pixel sizes of 100 and 1.6 μm) were used. To exemplarily highlight the potential of this approach, fiber orientation maps and 3D fiber models were reconstructed in selected regions of the brain (e.g., Corpus callosum, Internal capsule, Pons). The results demonstrate that 3D-PLI is an ideal tool to serve as an interface between the microscopic and macroscopic levels of organization of the human connectome.

Quantitative Comparison of Reconstruction Methods for Intra-Voxel Fiber Recovery From Diffusion MRI

“…In the first case, the fiber configurations estimated from dMRI are compared with the results of histological or tracerinjection studies [43]- [46], either in vivo or ex vivo, performed on the same biological sample. In particular, an emerging technique called three-dimensional Polarized Light Imaging (3D-PLI) [47] is capable of providing the directionality of the axons in postmortem human brains at ultra-high resolution, i.e. sub-millimeter scale.…”

Mapping the connectome: Multi-level analysis of brain connectivity

“…Axer et al (2011a) demonstrate automated 3-D reconstruction of fiber orientations across multiple histological sections in the human brain stem, yielding highly resolved datasets that are useful complements for both conventional histological stains and DTI data (Figures 1C,D). Using the same approach, Axer et al (2011b) show how 3-D PLI derived fiber orientation vectors can subsequently be used as a basis for high-resolution tractography of fiber tracts, potentially suitable for bridging microscopic and macroscopic connectome representations. The importance of correlating various non-invasive MRI derived measurements to cellular-level morphological data is also emphasized by Annese (2012), presenting the perspective that whole-brain histological maps (Figures 1E,F) created using large-scale digital microscopy spanning several histological modalities will support the analysis and interpretation of MRI-based connectivity studies.…”

“…This Research Topic of Frontiers in Neuroinformatics, dedicated to the memory of Rolf Kötter (1961Kötter ( -2010 and his pioneering work in the field of brain connectomics, comprises contributions that elucidate different levels of connectivity analysis (from MRIbased methods, through axonal tracing techniques, to mapping of functional connectivity in relation to detailed 3-D reconstructions Gorbach et al, 2011;Yendiki et al, 2011] to ex vivo mapping of detailed fiber architectures [(C,e) Axer et al, 2011b; (e,F) Annese, 2012]. (g-H) Novel experimental methods in animal models include combined optogenetic and functional MRI mapping of specific connections (g) (Lee, 2011) (Borisyuk et al, 2011).…”

The human brain project: neuroscience perspectives and German contributions

“…Research on unstained sections with polarized light, specifically, 3D polarized light imaging (3D-PLI), allow the study of fiber tracts and nerve fibers at a microscopic level with a spatial resolution of up to 1.5 microns [3,4]. Markus Axer, Karl Zilles and Katrin Amunts (Research Centre Jülich) work in this field.…”

“…The quantitative in vitro receptor autoradiography [19] is a method to quantify differences in regional and laminar distribution Fig. 2 9 Three-dimensional polarized light imaging (3D-PLI) [3,4] represents a novel neuroimaging technique to map nerve fibers, i.e., myelinated axons, and fiber pathways in human postmortem brains with a resolution at the micrometer scale. This is possible through the detection of the birefringence properties of the nerve fibers, which is given especially by their myelin sheaths patterns of single receptors in the cerebral cortex.…”