title: Application of q-Space Diffusion MRI for the Visualization of White Matter.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Departments of Orthopedic Surgery, Physiology, Department of Orthopedic Surgery, National Hospital Organization Murayama Medical Center, Tokyo 208-0011, Japan.
authors.forename: Kanehiro
authors.initials: K
authors.lastname: Fujiyoshi
authors.affiliation: Physiology, Central Institute for Experimental Animals, Kanagawa 210-0821, Japan, and.
authors.forename: Keigo
authors.initials: K
authors.lastname: Hikishima
authors.affiliation: Neurology, and.
authors.forename: Jin
authors.initials: J
authors.lastname: Nakahara
authors.affiliation: Departments of Orthopedic Surgery, Physiology.
authors.forename: Osahiko
authors.initials: O
authors.lastname: Tsuji
authors.affiliation: Physiology, Laboratory for Marmoset Neural Architecture, RIKEN Brain Science Institute, Saitama 351-0198, Japan.
authors.forename: Junichi
authors.initials: J
authors.lastname: Hata
authors.affiliation: Departments of Orthopedic Surgery, Physiology, Department of Orthopedic Surgery, National Hospital Organization Murayama Medical Center, Tokyo 208-0011, Japan.
authors.forename: Tsunehiko
authors.initials: T
authors.lastname: Konomi
authors.affiliation: Electron Microscopic Laboratory, Keio University School of Medicine, Tokyo 160-8582, Japan.
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Nagai
authors.affiliation: Physiology.
authors.forename: Shinsuke
authors.initials: S
authors.lastname: Shibata
authors.affiliation: Department of Orthopedic Surgery, National Hospital Organization Murayama Medical Center, Tokyo 208-0011, Japan.
authors.forename: Shinjiro
authors.initials: S
authors.lastname: Kaneko
authors.affiliation: Departments of Orthopedic Surgery.
authors.forename: Akio
authors.initials: A
authors.lastname: Iwanami
authors.affiliation: Radiology, and.
authors.forename: Suketaka
authors.initials: S
authors.lastname: Momoshima
authors.affiliation: Neurology, and.
authors.forename: Shinichi
authors.initials: S
authors.lastname: Takahashi
authors.affiliation: Radiology, and.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Jinzaki
authors.affiliation: Neurology, and.
authors.forename: Norihiro
authors.identifier: http://orcid.org/0000-0002-0399-6590
authors.initials: N
authors.lastname: Suzuki
authors.affiliation: Departments of Orthopedic Surgery.
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Toyama
authors.affiliation: Departments of Orthopedic Surgery, masa@a8.keio.jp hidokano@a2.keio.jp.
authors.forename: Masaya
authors.identifier: http://orcid.org/0000-0001-7916-5497
authors.initials: M
authors.lastname: Nakamura
authors.affiliation: Physiology, Laboratory for Marmoset Neural Architecture, RIKEN Brain Science Institute, Saitama 351-0198, Japan masa@a8.keio.jp hidokano@a2.keio.jp.
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Okano
mesh_terms: D000328:Adult; D000818:Animals; D001931:Brain Mapping; D002144:Callithrix; D003711:Demyelinating Diseases / Q000139:chemically induced / Q000235:genetics / Q000473:pathology*; D038524:Diffusion Magnetic Resonance Imaging; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008244:Lysophosphatidylcholines / Q000633:toxicity; D008297:Male; D051379:Mice; D008816:Mice, Jimpy; D008817:Mice, Mutant Strains; D009103:Multiple Sclerosis / Q000473:pathology; D009154:Mutation / Q000235:genetics; D004676:Myelin Basic Protein / Q000235:genetics / Q000378:metabolism; D009186:Myelin Sheath / Q000473:pathology*; D013116:Spinal Cord / Q000378:metabolism / Q000473:pathology; D066127:White Matter / Q000473:pathology* / Q000648:ultrastructure
chemical_list: D008244:Lysophosphatidylcholines; D004676:Myelin Basic Protein
keywords: MRI; demyelination; multiple sclerosis; myelin; remyelination