The Relationship between Neurite Density Measured with Confocal Microscopy in a Cleared Mouse Brain and Metrics Obtained from Diffusion Tensor and Diffusion Kurtosis Imaging

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Author(s)

    • Irie Ryusuke
    • Department of Radiology, Juntendo University School of Medicine|Department of Radiology, The University of Tokyo Graduate School of Medicine
    • Sato Kanako
    • Department of Radiology, Juntendo University School of Medicine
    • Hori Masaaki
    • Department of Radiology, Juntendo University School of Medicine
    • Arikawa-Hirasawa Eri
    • Research Institute for Diseases of Old Age, Juntendo University Graduate School of Medicine
    • Aoki Shigeki
    • Department of Radiology, Juntendo University School of Medicine
    • Kamagata Koji
    • Department of Radiology, Juntendo University School of Medicine
    • Kerever Aurelien
    • Research Institute for Diseases of Old Age, Juntendo University Graduate School of Medicine
    • Ueda Ryo
    • Department of Radiological Sciences, Tokyo Metropolitan University Graduate School of Human Health Sciences
    • Yoshizawa Hidekazu
    • Department of Plastic and Reconstructive Surgery, Juntendo University Graduate School of Medicine
    • Hayashi Ayato
    • Department of Plastic and Reconstructive Surgery, Juntendo University Urayasu Hospital

Abstract

<p>Purpose: Diffusional kurtosis imaging (DKI) enables sensitive measurement of tissue microstructure by quantifying the non-Gaussian diffusion of water. Although DKI is widely applied in many situations, histological correlation with DKI analysis is lacking. The purpose of this study was to determine the relationship between DKI metrics and neurite density measured using confocal microscopy of a cleared mouse brain.</p><p>Methods: One thy-1 yellow fluorescent protein 16 mouse was deeply anesthetized and perfusion fixation was performed. The brain was carefully dissected out and whole-brain MRI was performed using a 7T animal MRI system. DKI and diffusion tensor imaging (DTI) data were obtained. After the MRI scan, brain sections were prepared and then cleared using aminoalcohols (CUBIC). Confocal microscopy was performed using a two-photon confocal microscope with a laser. Forty-eight ROIs were set on the caudate putamen, seven ROIs on the anterior commissure, and seven ROIs on the ventral hippocampal commissure on the confocal microscopic image and a corresponding MR image. In each ROI, histological neurite density and the metrics of DKI and DTI were calculated. The correlations between diffusion metrics and neurite density were analyzed using Pearson correlation coefficient analysis.</p><p>Results: Mean kurtosis (MK) (<i>P</i> = 5.2 × 10<sup>−9</sup>, <i>r</i> = 0.73) and radial kurtosis (<i>P</i> = 2.3 × 10<sup>−9</sup>, <i>r</i> = 0.74) strongly correlated with neurite density in the caudate putamen. The correlation between fractional anisotropy (FA) and neurite density was moderate (<i>P</i> = 0.0030, <i>r</i> = 0.42). In the anterior commissure and the ventral hippocampal commissure, neurite density and FA are very strongly correlated (<i>P</i> = 1.3 × 10<sup>−5</sup>, <i>r</i> = 0.90). MK in these areas were very high value and showed no significant correlation (<i>P</i> = 0.48).</p><p>Conclusion: DKI accurately reflected neurite density in the area with crossing fibers, potentially allowing evaluation of complex microstructures.</p>

Journal

  • Magnetic Resonance in Medical Sciences

    Magnetic Resonance in Medical Sciences 17(2), 138-144, 2018

    Japanese Society for Magnetic Resonance in Medicine

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