The role of myelination in measures of white matter integrity: Combination of diffusion tensor imaging and two-photon microscopy of CLARITY intact brains

Eric H. Chang, Miklos Argyelan, Manisha Aggarwal, Toni Shay S Chandon, Katherine H. Karlsgodt, Susumu Mori, Anil K. Malhotra

Research output: Research - peer-reviewArticle

Abstract

Diffusion tensor imaging (DTI) is used extensively in neuroscience to noninvasively estimate white matter (WM) microarchitecture. However, the diffusion signal is inherently ambiguous because it infers WM structure from the orientation of water diffusion and cannot identify the biological sources of diffusion changes. To compare inferred WM estimates to directly labeled axonal elements, we performed a novel within-subjects combination of high-resolution ex vivo DTI with two-photon laser microscopy of intact mouse brains rendered optically transparent by Clear Lipid-exchanged, Anatomically Rigid, Imaging/immunostaining compatible, Tissue hYdrogel (CLARITY). We found that myelin basic protein (MBP) immunofluorescence significantly correlated with fractional anisotropy (FA), especially in WM regions with coherent fiber orientations and low fiber dispersion. Our results provide evidence that FA is particularly sensitive to myelination in WM regions with these characteristics. Furthermore, we found that radial diffusivity (RD) was only sensitive to myelination in a subset of WM tracts, suggesting that the association of RD with myelin should be used cautiously. This combined DTI-CLARITY approach illustrates, for the first time, a framework for using brain-wide immunolabeling of WM targets to elucidate the relationship between the diffusion signal and its biological underpinnings. This study also demonstrates the feasibility of a within-subject combination of noninvasive neuroimaging and tissue clearing techniques that has broader implications for neuroscience research.

LanguageEnglish (US)
Pages119-124
Number of pages6
JournalNeuroImage
Volume147
DOIs
StatePublished - Feb 15 2017

Fingerprint

Diffusion Tensor Imaging
Hydrogel
Photons
Microscopy
Lipids
Brain
White Matter
Anisotropy
Neurosciences
Myelin Basic Protein
Myelin Sheath
Confocal Microscopy
Neuroimaging
Fluorescent Antibody Technique
Water
Research

Keywords

  • Fractional anisotropy
  • Multimodal imaging
  • Myelin basic protein
  • Neuroimaging
  • Tissue clearing
  • Whole brain immunolabeling

ASJC Scopus subject areas

  • Neurology
  • Cognitive Neuroscience

Cite this

The role of myelination in measures of white matter integrity : Combination of diffusion tensor imaging and two-photon microscopy of CLARITY intact brains. / Chang, Eric H.; Argyelan, Miklos; Aggarwal, Manisha; Chandon, Toni Shay S; Karlsgodt, Katherine H.; Mori, Susumu; Malhotra, Anil K.

In: NeuroImage, Vol. 147, 15.02.2017, p. 119-124.

Research output: Research - peer-reviewArticle

Chang, Eric H. ; Argyelan, Miklos ; Aggarwal, Manisha ; Chandon, Toni Shay S ; Karlsgodt, Katherine H. ; Mori, Susumu ; Malhotra, Anil K./ The role of myelination in measures of white matter integrity : Combination of diffusion tensor imaging and two-photon microscopy of CLARITY intact brains. In: NeuroImage. 2017 ; Vol. 147. pp. 119-124
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