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Articles, Neurobiology of Disease

Application of q-Space Diffusion MRI for the Visualization of White Matter

Kanehiro Fujiyoshi, Keigo Hikishima, Jin Nakahara, Osahiko Tsuji, Junichi Hata, Tsunehiko Konomi, Toshihiro Nagai, Shinsuke Shibata, Shinjiro Kaneko, Akio Iwanami, Suketaka Momoshima, Shinichi Takahashi, Masahiro Jinzaki, Norihiro Suzuki, Yoshiaki Toyama, Masaya Nakamura and Hideyuki Okano
Journal of Neuroscience 2 March 2016, 36 (9) 2796-2808; DOI: https://doi.org/10.1523/JNEUROSCI.1770-15.2016
Kanehiro Fujiyoshi
1Departments of Orthopedic Surgery,
2Physiology,
6Department of Orthopedic Surgery, National Hospital Organization Murayama Medical Center, Tokyo 208-0011, Japan,
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Keigo Hikishima
2Physiology,
7Central Institute for Experimental Animals, Kanagawa 210-0821, Japan, and
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Jin Nakahara
3Neurology, and
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Osahiko Tsuji
1Departments of Orthopedic Surgery,
2Physiology,
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Junichi Hata
2Physiology,
8Laboratory for Marmoset Neural Architecture, RIKEN Brain Science Institute, Saitama 351-0198, Japan
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Tsunehiko Konomi
1Departments of Orthopedic Surgery,
2Physiology,
6Department of Orthopedic Surgery, National Hospital Organization Murayama Medical Center, Tokyo 208-0011, Japan,
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Toshihiro Nagai
5Electron Microscopic Laboratory, Keio University School of Medicine, Tokyo 160-8582, Japan,
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Shinsuke Shibata
2Physiology,
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Shinjiro Kaneko
6Department of Orthopedic Surgery, National Hospital Organization Murayama Medical Center, Tokyo 208-0011, Japan,
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Akio Iwanami
1Departments of Orthopedic Surgery,
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Suketaka Momoshima
4Radiology, and
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Shinichi Takahashi
3Neurology, and
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Masahiro Jinzaki
4Radiology, and
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Norihiro Suzuki
3Neurology, and
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Yoshiaki Toyama
1Departments of Orthopedic Surgery,
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Masaya Nakamura
1Departments of Orthopedic Surgery,
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Hideyuki Okano
2Physiology,
8Laboratory for Marmoset Neural Architecture, RIKEN Brain Science Institute, Saitama 351-0198, Japan
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Abstract

White matter abnormalities in the CNS have been reported recently in various neurological and psychiatric disorders. Quantitation of non-Gaussianity for water diffusion by q-space diffusional MRI (QSI) renders biological diffusion barriers such as myelin sheaths; however, the time-consuming nature of this method hinders its clinical application. In the current study, we aimed to refine QSI protocols to enable their clinical application and to visualize myelin signals in a clinical setting. For this purpose, animal studies were first performed to optimize the acquisition protocol of a non-Gaussian QSI metric. The heat map of standardized kurtosis values derived from optimal QSI (myelin map) was then created. Histological validation of the myelin map was performed in myelin-deficient mice and in a nonhuman primate by monitoring its variation during demyelination and remyelination after chemical spinal cord injury. The results demonstrated that it was sensitive enough to depict dysmyelination, demyelination, and remyelination in animal models. Finally, its utility in clinical practice was assessed by a pilot clinical study in a selected group of patients with multiple sclerosis (MS). The human myelin map could be obtained within 10 min with a 3 T MR scanner. Use of the myelin map was practical for visualizing white matter and it sensitively detected reappearance of myelin signals after demyelination, possibly reflecting remyelination in MS patients. Our results together suggest that the myelin map, a kurtosis-related heat map obtainable with time-saving QSI, may be a novel and clinically useful means of visualizing myelin in the human CNS.

SIGNIFICANCE STATEMENT Myelin abnormalities in the CNS have been gaining increasing attention in various neurological and psychiatric diseases. However, appropriate methods with which to monitor CNS myelin in daily clinical practice have been lacking. In the current study, we introduced a novel MRI modality that produces the “myelin map.” The myelin map accurately depicted myelin status in mice and nonhuman primates and in a pilot clinical study of multiple sclerosis patients, suggesting that it is useful in detecting possibly remyelinated lesions. A myelin map of the human brain could be obtained in <10 min using a 3 T scanner and it therefore promises to be a powerful tool for researchers and clinicians examining myelin-related diseases.

  • demyelination
  • MRI
  • multiple sclerosis
  • myelin
  • remyelination
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The Journal of Neuroscience: 36 (9)
Journal of Neuroscience
Vol. 36, Issue 9
2 Mar 2016
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Application of q-Space Diffusion MRI for the Visualization of White Matter
Kanehiro Fujiyoshi, Keigo Hikishima, Jin Nakahara, Osahiko Tsuji, Junichi Hata, Tsunehiko Konomi, Toshihiro Nagai, Shinsuke Shibata, Shinjiro Kaneko, Akio Iwanami, Suketaka Momoshima, Shinichi Takahashi, Masahiro Jinzaki, Norihiro Suzuki, Yoshiaki Toyama, Masaya Nakamura, Hideyuki Okano
Journal of Neuroscience 2 March 2016, 36 (9) 2796-2808; DOI: 10.1523/JNEUROSCI.1770-15.2016

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Application of q-Space Diffusion MRI for the Visualization of White Matter
Kanehiro Fujiyoshi, Keigo Hikishima, Jin Nakahara, Osahiko Tsuji, Junichi Hata, Tsunehiko Konomi, Toshihiro Nagai, Shinsuke Shibata, Shinjiro Kaneko, Akio Iwanami, Suketaka Momoshima, Shinichi Takahashi, Masahiro Jinzaki, Norihiro Suzuki, Yoshiaki Toyama, Masaya Nakamura, Hideyuki Okano
Journal of Neuroscience 2 March 2016, 36 (9) 2796-2808; DOI: 10.1523/JNEUROSCI.1770-15.2016
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Keywords

  • demyelination
  • MRI
  • multiple sclerosis
  • myelin
  • remyelination

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