Resting state functional MRI as imaging biomarker for preclinical Alzheimer disease

• Project/Area Number: 15K09348
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Neurology
• Research Institution: Teikyo University (2017-2018); The University of Tokyo (2015-2016)
• Principal Investigator: Toshihiro Hayashi 帝京大学, 医学部, 教授 (60505890)
• Project Period (FY): 2015-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: 神経機能画像法 / アルツハイマー病 / 安静時fMRI

Outline of Final Research Achievements

Pathological changes of Alzheimer's disease precede onset of clinical symptoms by more than ten years. Biomarkers for the disease progression are requisite for any disease-modifying therapeutic trials on preclinical Alzheimer's disease, because no clinical symptoms are noted at that stage. Functional connectivity of large-scale brain networks, especially default mode network, is known to be affected even at the preclinical stage. Functional connectivity on resting state functional MRI is one of candidate biomarkers, which is noninvasive and suitable for longitudinal observation. However, connectivity signals, which are small, are overlaid by physiological noises such as respiratory and cardiac cycles and motions. The current research developed preprocessing methods to deal with artefacts from physiological noises and extract robust signals for connectivity analyses.

Academic Significance and Societal Importance of the Research Achievements

安静時fMRIによる脳の大域的神経結合（コネクティビティ）はアルツハイマー病を始めとする神経精神疾患の病態を評価する研究手法として急速に普及してきた．しかしコネクティビティに関連する微弱な信号を多くの生理学的ノイズのなかから抽出する必要がある．特に高齢者は撮像中の体動が若年者よりも大きくノイズの混入も多いため，強力な画像前処理が必要となる．本研究はそれに対応しうる解析方法を開発した．安静時fMRIが非侵襲的で経時的観察が出来るバイオマーカーとして確立すれば，神経精神疾患の治療薬開発に有用と期待する．

Research Products

• [Journal Article] Aphasic status epilepticus preceding tumefactive left hemisphere lesion in anti-MOG antibody associated disease (2019)
  • Author(s): Katsuse Kazuto、Kurihara Masanori、Sugiyama Yusuke、Kodama Satoshi、Takahashi Miwako、Momose Toshimitsu、Yumoto Masato、Kaneko Kimihiko、Takahashi Toshiyuki、Kubota Akatsuki、Hayashi Toshihiro、Toda Tatsushi
  • Journal Title: Multiple Sclerosis and Related Disorders Volume: 27 Pages: 91
  • DOI: 10.1016/j.msard.2018.10.012
  • Peer Reviewed
• [Journal Article] Ketotic hyperglycemia-related seizure with reversible white matter lesion: Metabolic implication of its reversibility based on magnetic resonance spectroscopy study (2018)
  • Author(s): Satoshi Kodama, Tatsuo Mano, Toshiyuki Kakumoto, Hiroyuki Ishiura, Akifumi Hagiwara, Kouhei Kamiya, Toshihiro Hayashi, Shoji Tsuji
  • Journal Title: Journal of the Neurological Sciences Volume: 390 Pages: 20
  • DOI: 10.1016/j.jns.2018.04.006
  • Peer Reviewed
• [Journal Article] Longitudinally extensive vasogenic edema following spinal cord infarction (2018)
  • Author(s): Gondo Takashi、Kurihara Masanori、Sugiyama Yusuke、Mano Tatsuo、Mori Harushi、Hayashi Toshihiro、Tsuji Shoji
  • Journal Title: Neurology and Clinical Neuroscience Volume: 6 Issue: 5 Pages: 143
  • DOI: 10.1111/ncn3.12215
  • Peer Reviewed
• [Journal Article] Severe visual impairment and subclinical encephalitis preceding clinical signs of chondritis in relapsing polychondritis (2018)
  • Author(s): Miyano Ryoji、Kurihara Masanori、Orimo Kenta、Mano Tatsuo、Kaburaki Toshikatsu、Tanaka Rie、Nishijima Hironobu、Ikemura Masako、Takahashi Miwako、Mori Harushi、Mutoh Tatsuro、Hamada Masashi、Hayashi Toshihiro、Toda Tatsushi
  • Journal Title: Neurology and Clinical Neuroscience Volume: 7 Issue: 2 Pages: 75
  • DOI: 10.1111/ncn3.12243
  • Peer Reviewed
• [Journal Article] “Localized” chronic invasive fungal rhinosinusitis without serological abnormalities (2018)
  • Author(s): Uchigami Hirokazu、Sato Kenichiro、Kubota Akatsuki、Hayashi Toshihiro、Shimizu Jun、Ikemura Masako、Toda Tatsushi
  • Journal Title: Neurology and Clinical Neuroscience Volume: 7 Issue: 2 Pages: 96
  • DOI: 10.1111/ncn3.12252
  • Peer Reviewed
• [Journal Article] Novel De Novo KCND3 Mutation in a Japanese Patient with Intellectual Disability, Cerebellar Ataxia, Myoclonus, and Dystonia (2017)
  • Author(s): Kurihara Masanori、Ishiura Hiroyuki、Sasaki Takuya、Otsuka Juuri、Hayashi Toshihiro、Terao Yasuo、Matsukawa Takashi、Mitsui Jun、Kaneko Juntaro、Nishiyama Kazutoshi、Doi Koichiro、Yoshimura Jun、Morishita Shinichi、Shimizu Jun、Tsuji Shoji
  • Journal Title: Cerebellum Volume: 17 Issue: 2 Pages: 237
  • DOI: 10.1007/s12311-017-0883-4
  • Peer Reviewed
• [Journal Article] Recovered recall memory after decompression of the fornix by surgical removal of pineal tumor (2016)
  • Author(s): Yoshida, M., Hayashi, T., Fujii, K., Kawai, K., Tsuji, S., Iwata, A.
  • Journal Title: Neurology Volume: 86 Issue: 8 Pages: 790
  • DOI: 10.1212/wnl.0000000000002394
  • Peer Reviewed
• [Presentation] 脳アミロイドアンギオパチーにおける皮質微小梗塞・白質病変の検討． (2018)
  • Author(s): 小林敬, 栗原正典, 神澤彩, 織茂賢太, 宮川統爾, 石浦浩之, 森墾, 林俊宏, 岩田淳, 戸田達史．
  • Organizer: 第59回日本神経学会学術大会
• [Presentation] 安静時fMRIと認知症の病態評価． (2016)
  • Author(s): 林 俊宏
  • Organizer: 第40回日本高次脳機能障害学会学学術総会
  • Place of Presentation: 松本
  • Year and Date: 2016-11-11
  • Invited