Imaging crossing fibers in mouse, pig, monkey, and human brain using small-angle X-ray scattering

Georgiadis, Marios; Menzel, Miriam; Reuter, Jan A.; Born, Donald E.; Kovacevich, Sophie R.; Alvarez, Dario; Taghavi, Hossein Moein; Schroeter, Aileen; Rudin, Markus; Gao, Zirui; Guizar-Sicairos, Manuel; Weiss, Thomas M.; Axer, Markus; Rajkovic, Ivan; Zeineh, Michael M.

doi:10.1016/j.actbio.2023.04.029

Title: Imaging crossing fibers in mouse, pig, monkey, and human brain using small-angle X-ray scattering

Journal Article · 23 April 2023 · Acta Biomaterialia

DOI: https://doi.org/10.1016/j.actbio.2023.04.029 · OSTI ID:1996020

^[1];

^[2];

^[3]; Born, Donald E. ^[4];

^[4]; Alvarez, Dario ^[4];

^[4]; Schroeter, Aileen ^[5]; Rudin, Markus ^[5];

^[5]; Guizar-Sicairos, Manuel ^[6]; Weiss, Thomas M. ^[7];

^[3];

^[7];

^[4]

Stanford Univ., CA (United States). School of Medicine; Eidgenoessische Technische Hochschule (ETH), Zurich (Switzerland); Univ. of Zurich (Switzerland)
Forschungszentrum Juelich (Germany); Delft Univ. of Technology (Netherlands)
Forschungszentrum Juelich (Germany)
Stanford Univ., CA (United States). School of Medicine
Eidgenoessische Technische Hochschule (ETH), Zurich (Switzerland); Univ. of Zurich (Switzerland)
Paul Scherrer Inst. (PSI), Villigen (Switzerland)
SLAC National Accelerator Laboratory (SLAC), Menlo Park, CA (United States). Stanford Synchrotron Radiation Lightsource (SSRL)

Myelinated axons (nerve fibers) efficiently transmit signals throughout the brain via action potentials. Multiple methods that are sensitive to axon orientations, from microscopy to magnetic resonance imaging, aim to reconstruct the brain's structural connectome. As billions of nerve fibers traverse the brain with various possible geometries at each point, resolving fiber crossings is necessary to generate accurate structural connectivity maps. However, doing so with specificity is a challenging task because signals originating from oriented fibers can be influenced by brain (micro)structures unrelated to myelinated axons. X-ray scattering can specifically probe myelinated axons due to the periodicity of the myelin sheath, which yields distinct peaks in the scattering pattern. Here, in this work, we show that small-angle X-ray scattering (SAXS) can be used to detect myelinated, axon-specific fiber crossings. We first demonstrate the capability using strips of human corpus callosum to create artificial double- and triple-crossing fiber geometries, and we then apply the method in mouse, pig, vervet monkey, and human brains. We compare results to polarized light imaging (3D-PLI), tracer experiments, and to outputs from diffusion MRI that sometimes fails to detect crossings. Given its specificity, capability of 3-dimensional sampling and high resolution, SAXS could serve as a ground truth for validating fiber orientations derived using diffusion MRI as well as microscopy-based methods.

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Research Organization:: SLAC National Accelerator Laboratory (SLAC), Menlo Park, CA (United States)

Sponsoring Organization:: USDOE Office of Science (SC), Biological and Environmental Research (BER); National Institutes of Health (NIH)

Grant/Contract Number:: AC02-76SF00515; R01NS088040; P41EB017183; R01AG061120-01; R01MH092311; 5P40OD010965; S10OD021512; P30GM133894

OSTI ID:: 1996020

Alternate ID(s):: OSTI ID: 2001421

Journal Information:: Acta Biomaterialia, Vol. 164; ISSN 1742-7061

Publisher:: Acta Materialia, Inc.Copyright Statement

Country of Publication:: United States

Language:: English

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59 BASIC BIOLOGICAL SCIENCES
animal and human brain
crossing fibers
diffusion MRI
fiber orientation mapping
human hippocampus
imaging myelinated axons
mouse/pig/vervet monkey brain
scanning small-angle X-ray scattering (SAXS)

Title: Imaging crossing fibers in mouse, pig, monkey, and human brain using small-angle X-ray scattering

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