Neurochemistry of mouse model investigated with 7T MR spectroscopy

• Project/Area Number: 24591790
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Radiation science
• Research Institution: Tokyo Women's Medical University (2014-2015); Toho University (2012-2013)
• Principal Investigator: Takanashi Jun-ichi 東京女子医科大学, 医学部, 教授 (00302555)
• Co-Investigator(Kenkyū-buntansha): Terada Hitoshi 東邦大学, 医学部, 教授 (90227520)
• Co-Investigator(Renkei-kenkyūsha): Aoki Ichio 国立研究開発法人放射線医学総合研究所, 分子イメージング研究センター, チームリーダー (10319519)
• Project Period (FY): 2012-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2015: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2014: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2013: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2012: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: MRスペクトルスコピー / 核磁気共鳴画像（MRI） / 先天性大脳白質形成不全症 / Pelizaeus-Merzbacher 病 / N-acetylaspartate (NAA) / choline (Cho) / モデルマウス / Pelizaeus-Merzbacher病 / Choline / マウスモデル / 副腎白質ジストロフィー / 18q-症候群 / 大脳白質形成不全症 / 磁気共鳴画像 / ＭＲスペクトルスコピー / 脳代謝 / 髄鞘形成不全

Outline of Final Research Achievements

Proton MR spectroscopy (MRS) of a hypomyelinating mouse model, a myelin synthesis-deficient mouse, a model of connatal Pelizaeus-Merzbacher disease (PMD) with mutation of the Plp1 gene, revealed increased N-acetylaspartate (NAA) and creatine (Cr) and decreased choline (Cho). That of a shiverer mouse with an autosomal recessive mutation of the Mbp gene showed decreased Cho with normal NAA and Cr. Accordingly, the reduction of Cho on MRS might be a common marker for hypomyelinating disorders. NAA concentrations range from normal to increased, probably depending upon the underlying pathology of oligodendrocytes. NAA may be increased in hypomyelination with a reduced number of mature oligodendrocytes, such as PMD.
The MRS pattern with reduced Cho and normal to increased NAA may lead to a diagnosis of hypomyelinating disorders, which is difficult to differentiate from demyelinating disorders on MR imaging.

Research Products

• [Journal Article] The magnetic resonance imaging spectrum of Pelizaeus-Merzbacher disease: A multicenter study of 19 patients. (2016)
  • Author(s): Sumida K, Inoue K, Takanashi JI, Sasaki M, Watanabe K, Suzuki M, Kurahashi H, Omata T, Tanaka M, Yokochi K, Iio J, Iyoda K, Kurokawa T, Matsuo M, Sato T, Iwaki A, Osaka H, Kurosawa K, Yamamoto T, Matsumoto N, Maikusa N, Mastuda H, Sato N
  • Journal Title: Brain Dev Volume: in press Issue: 6 Pages: 571-80
  • DOI: 10.1016/j.braindev.2015.12.007
  • Peer Reviewed
• [Journal Article] Drugs indicated for mitochondrial dysfunction as treatments for acute encephalopathy with onset of febrile convulsive status epileptics (2016)
  • Author(s): Omata T, Fujii K, Takanashi J, Murayama K, Takayanagi M, Muta K, Kodama K, Iida Y, Watanabe Y, Shimojo N.
  • Journal Title: J Neurol Sci Volume: 360 Pages: 57-60
  • DOI: 10.1016/j.jns.2015.11.043
  • Peer Reviewed / Open Access
• [Journal Article] Neurochemistry of Hypomyelination Investigated with MR Spectroscopy (2015)
  • Author(s): Takanashi J.
  • Journal Title: Magnetic Resonance in Medical Sciences Volume: 14 Issue: 2 Pages: 85-91
  • DOI: 10.2463/mrms.2014-0064
  • NAID: 130005069922
  • ISSN: 1347-3182, 1880-2206
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Disrupted glutamate-glutamine cycle in acute encephalopathy with biphasic seizures and late reduced diffusion. (2015)
  • Author(s): Takanashi JI, Mizuguchi M, Terai M, Barkovich AJ.
  • Journal Title: Neuroradiology Volume: 57 Issue: 11 Pages: 1163-1168
  • DOI: 10.1007/s00234-015-1573-x
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Predictive score for early diagnosis of acute encephalopathy with biphasic seizures and late reduced diffusion (AESD). (2015)
  • Author(s): Tada H, Takanashi J, Okuno H, Kubota M, Yamagata T, Kawano G, Shiihara T, Hamano S, Hirose S, Hayashi T, Osaka H, Mizuguchi M.
  • Journal Title: NEUROL SCI. Volume: 358(1-2) Issue: 1-2 Pages: 62-5
  • DOI: 10.1016/j.jns.2015.08.016
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Diffusion-weighted MRI for early diagnosis of neonatal herpes simplex encephalitis. (2015)
  • Author(s): Okanashi T, Yamamoto H, Hosokawa T, Ando N, Nagayama Y, Hashimoto Y, Maihara T, Goto T, Kutota M, Kawaguchi C, Yoshida H, Sugiura K, Itomi S, Ohno K, Takanashi J, Hayakawa M, Otsubo H, Okumura A.
  • Journal Title: Brain Dev Volume: 37 Issue: 4 Pages: 423-431
  • DOI: 10.1016/j.braindev.2014.07.006
  • Peer Reviewed
• [Journal Article] Clinical and radiologic features of encephalopathy during 2011 E coli O111 outbreak in Japan. (2014)
  • Author(s): Takanashi JI, Taneichi H, Misaki T, Yahata Y, Okumura A, Ishida YI, Miyawaki T, Okabe N, Sata T, Mizuguchi M.
  • Journal Title: Neurology Volume: 82 Issue: 7 Pages: 564-572
  • DOI: 10.1212/wnl.0000000000000120
  • Peer Reviewed
• [Journal Article] Expanding the phenotypic spectrum of TUBB4A-associated (2014)
  • Author(s): Miyatake S, Osaka H, Shiina M, Sasaki M, Takanashi J, Haginoya K, Wada T,
  • Journal Title: Neurology Volume: 82(24) Issue: 24 Pages: 2230-7
  • DOI: 10.1212/wnl.0000000000000535
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] けいれん・意識障害 画像検査の選択と解釈 (2014)
  • Author(s): 髙梨潤一
  • Journal Title: 小児内科 Volume: 46 Pages: 1152-1156
• [Journal Article] 神経画像検査 (1) MRI, CT. (2014)
  • Author(s): 髙梨潤一
  • Journal Title: 日本臨床 Volume: 72 Pages: 819-826
• [Journal Article] Neurochemistry in Shiverer mouse depicted on MR spectroscopy. (2014)
  • Author(s): Takanashi J, Nitta N, Iwasaki N, saito S, Tanaka R, Aoki I.
  • Journal Title: J Magn Reson Imaging Volume: 39 Issue: 6 Pages: 1550-1557
  • DOI: 10.1002/jmri.24306
  • Peer Reviewed
• [Journal Article] Epidemiological, clinical, and genetic landscapes of hypomyelinating leukodystrophies. (2014)
  • Author(s): Numata Y, Gotoh L, Iwaki A, Kurosawa K, Takanashi J, Deguchi K, Yamamoto T, Osaka H, Inoue K.
  • Journal Title: J Neurol. Volume: 261(4) Issue: 4 Pages: 752-758
  • DOI: 10.1007/s00415-014-7263-5
  • Peer Reviewed
• [Journal Article] MR spectroscopy in 18q- syndrome suggesting other than hypomyelination. (2014)
  • Author(s): Tada H, Takanashi J.
  • Journal Title: Brain Dev Volume: 36 Issue: 1 Pages: 57-60
  • DOI: 10.1016/j.braindev.2012.12.003
  • Peer Reviewed
• [Journal Article] Intragenic mutations in SMN1may contribute more significantly to clinical severity than SMN2 copy numbers in some spinal muscular atrophy (SMA) patients (2014)
  • Author(s): Yamamoto T, Sato H, Lai PS, Nurputra DK, Harahap NIF, Morikawa S, Nishimura N, Kurashige T, Tomohiko O, Nakajima H, Yamada H, Nishida Y, Toda S, Takanashi J, Takeuchi A, Tohyama Y, Kubo Y, Saito K, Takeshima Y, Matsuo M, Nishio H
  • Journal Title: Brain Dev Volume: 未 Issue: 10 Pages: 914-920
  • DOI: 10.1016/j.braindev.2013.11.009
  • Peer Reviewed
• [Journal Article] C5orf42 is the major gene responsible for OFD syndrome type VI. (2014)
  • Author(s): Lopez E, Thauvin-Robinet C, Reversade B, Khartoufi NE, Devisme L, Holder M, Ansart-Franquet H, Avila M, Lacombe D, Kleinfinger P, Kaori I, Takanashi JI, Le Merrer M, Martinovic J, Noël C, Shboul M, Ho L, Güven Y, Razavi F, Burglen L, Faivre L, Attié-Bitach T
  • Journal Title: Hum Genet Volume: 未 Issue: 3 Pages: 367-377
  • DOI: 10.1007/s00439-013-1385-1
  • Peer Reviewed
• [Journal Article] Different patterns of cerebellar abnormality and hypomyelination between POLR3A and POLR3B mutations. (2013)
  • Author(s): 98. Takanashi JI, Osaka H, Saitsu H, Sasaki M, Mori H, Shibayama H, Tanaka M,
  • Journal Title: Brain Dev. Volume: May 3 Issue: 3 Pages: 259-263
  • DOI: 10.1016/j.braindev.2013.03.006
  • Peer Reviewed
• [Journal Article] Phenotypic spectrum of COL4A1 mutations: porencephaly to schizencephaly (2013)
  • Author(s): Yoneda Y, Haginoya K,…..*Saitsu H
  • Journal Title: Ann Neurol Volume: 73(1):48-57 Issue: 1 Pages: 48-57
  • DOI: 10.1002/ana.23736
  • Peer Reviewed
• [Journal Article] 先天性大脳白質形成不全症―ゲノム解析から診断、治療への取り組み (2013)
  • Author(s): 井上健、岩城明子、黒澤健司、髙梨潤一、出口貴美子、山本俊至、小坂仁
  • Journal Title: 脳と発達 Volume: 45 Pages: 122-126
• [Journal Article] Clinical value of routine use of thin-section 3D MRI using 3D FSE sequences with a variable flip angle technique for internal derangements of the knee joint at 3T. (2013)
  • Author(s): Kudo H, Inaoka T, Kitamura N, Nakatsuka T, Kasuya S, Kasai R, Tozawa M, Nakagawa K, Terada H.
  • Journal Title: Magn Reson Imaging Volume: 31 Issue: 8 Pages: 1309-1317
  • DOI: 10.1016/j.mri.2013.02.003
  • Peer Reviewed
• [Journal Article] MRI, MR spectroscopyによる先天性大脳白質形成不全症の診断、病態解明 (2013)
  • Author(s): 高梨潤一
  • Journal Title: 脳と発達 Volume: 45 Pages: 132-136
  • NAID: 10031156275
• [Journal Article] Metabolic changes in early childhood using LCModel with corrected water scaling method. (2012)
  • Author(s): Takanashi J, Somazawa F, Maruyama K,Terada H, Xu D, A. Barkovich AJ.
  • Journal Title: J Magn Reson Imaging Volume: 35 Issue: 1 Pages: 174-180
  • DOI: 10.1002/jmri.22802
  • Peer Reviewed
• [Journal Article] Brain N-acetylaspartate is increased in mice with hypomyelination (2012)
  • Author(s): Takanashi J, Saito S, Aoki I, Barkovich J, Itoh Y, Inoue K.
  • Journal Title: J Magn Reson Imaging Volume: 35 Issue: 2 Pages: 418-425
  • DOI: 10.1002/jmri.22817
  • Peer Reviewed
• [Journal Article] Hypoyelination in I-cell disease; MRI, MR spectroscopy and neuropathological correlation. (2012)
  • Author(s): Takanashi J, Hayashi M, Yuasa S, Satoh H, Terada H.
  • Journal Title: Brain Dev Volume: 34 Issue: 9 Pages: 780-783
  • DOI: 10.1016/j.braindev.2011.12.013
  • Peer Reviewed
• [Presentation] Neuroimaging in acute encephalopathy with biphasic seizures and late reduced diffusion (AESD) (2015)
  • Author(s): 高梨潤一
  • Organizer: 10th Asian Oceanian Congress of Neuroradiology (AOCNR)
  • Place of Presentation: Hilton Fukuoka Sea Hawk（福岡県福岡市）
  • Year and Date: 2015-11-05
  • Int'l Joint Research / Invited
• [Presentation] MR spectroscopyで診る脳病態 (2015)
  • Author(s): 高梨潤一
  • Organizer: 第8回Neuro-imaging Refresher Club
  • Place of Presentation: 東京コンファレンスセンター・品川（東京都品川区）
  • Year and Date: 2015-11-01
  • Invited
• [Presentation] MRで診る脳代謝：MRスペクトルスコピーのあれこれ (2015)
  • Author(s): 高梨潤一
  • Organizer: 第56回神奈川小児神経懇話会
  • Place of Presentation: ホテル横浜キャメロットジャパン（神奈川県横浜市）
  • Year and Date: 2015-07-25
  • Invited
• [Presentation] 臨床から迫る白質変性症 (2015)
  • Author(s): 高梨潤一
  • Organizer: 第57回日本小児神経学会学術集会
  • Place of Presentation: 帝国ホテル大阪（大阪府大阪市）
  • Year and Date: 2015-05-27
  • Invited
• [Presentation] Neurochenistry in hypomyelination on MR spectroscopy (2015)
  • Author(s): 高梨潤一
  • Organizer: 第56回日本神経学会学術大会
  • Place of Presentation: 新潟コンベンションセンター（新潟県新潟市）
  • Year and Date: 2015-05-20
  • Invited
• [Presentation] Neuroimaging findings in children with acute encephalopathy (2015)
  • Author(s): 高梨潤一
  • Organizer: 13th Asian Oceanian Congress of Child Neurology (AOCCN)
  • Place of Presentation: 台北（台湾）
  • Year and Date: 2015-05-13
  • Int'l Joint Research / Invited
• [Presentation] MR spectroscopyを用いた神経疾患モデルマウス脳代謝解析 (2015)
  • Author(s): 高梨潤一
  • Organizer: 第3回 日本生物物理学会九州支部・熊本大学イメージングセミナー
  • Place of Presentation: 熊本大学（熊本県熊本市）
  • Year and Date: 2015-05-07
  • Invited
• [Presentation] 小児の白質病変 (2014)
  • Author(s): 髙梨潤一
  • Organizer: 第7回 Neuro-Imaging Refresher Club
  • Place of Presentation: 東京コンファレンスセンター・品川（東京都）
  • Year and Date: 2014-11-23
  • Invited
• [Presentation] 小児神経疾患における proton MR spectroscopy の臨床応用 (2014)
  • Author(s): 髙梨潤一
  • Organizer: 第42回日本磁気共鳴医学会総会
  • Place of Presentation: ホテルグランビア京都（京都市）
  • Year and Date: 2014-09-18 – 2014-09-20
  • Invited
• [Presentation] Neurochemistry in hypomyelination depicted on MR spectroscopy. (2014)
  • Author(s): Takanashi J, Nitta N, Terada H, Barkovich AJ, Tada H, Aoki I.
  • Organizer: 20th Symposium Neuroradiologicum
  • Place of Presentation: イスタンブール（トルコ）
  • Year and Date: 2014-09-07 – 2014-09-12
• [Presentation] Proton MR spectroscopy in neurological disorders. (2014)
  • Author(s): 髙梨潤一
  • Organizer: 第50回日本小児放射線学会学術集会
  • Place of Presentation: 神戸国際会議場（神戸市）
  • Year and Date: 2014-06-27 – 2014-06-28
  • Invited
• [Presentation] How to read/interplete neuroimagings? (2014)
  • Author(s): 髙梨潤一
  • Organizer: 第56回日本小児神経学会学術集会
  • Place of Presentation: アクトシティー浜松（浜松市）
  • Year and Date: 2014-05-28 – 2014-05-31
  • Invited
• [Presentation] 小児神経放射線 Topics
  • Author(s): 高梨潤一
  • Organizer: 第55回日本小児神経学会学術集会
  • Place of Presentation: 大分オアシスタワーホテル（大分市）
  • Invited
• [Presentation] 白質病変の新しい病態解析とMRマーカー：hypomyelinationのMRを用いたneurochemistry.
  • Author(s): 高梨潤一
  • Organizer: 第41回日本磁気共鳴医学会大会
  • Place of Presentation: アスティーとくしま（徳島市）
  • Invited
• [Presentation] Clinical keys for the diagnosis of pediatrics leukodystrophy
  • Author(s): 高梨潤一
  • Organizer: 第73回日本医学放射線学会
  • Place of Presentation: パシフィコ横浜（横浜市）
  • Invited
• [Presentation] 小児神経疾患の画像診断 up to date
  • Author(s): 高梨潤一
  • Organizer: 第46回新潟小児神経研究会
  • Place of Presentation: コープシシティー花岡ガレッソホール（新潟市）
  • Invited
• [Presentation] MRI, MR spectroscopyによる先天性大脳白質形成不全症の診断、病態解明
  • Author(s): 高梨潤一
  • Organizer: 第54回日本小児神経学会
  • Place of Presentation: ホテルロイトン札幌（北海道）
  • Invited
• [Presentation] H-MRS in neurodegeneration
  • Author(s): Takanashi J
  • Organizer: 12th International Child Neurology Congress
  • Place of Presentation: Brisbane Convention & Exhibition Center（ブリスベン・オーストラリア））
  • Invited
• [Presentation] シバラーマウスにおけるMR spectroscopyによる脳代謝解析
  • Author(s): 高梨潤一、岩崎信明、齋藤茂芳、新田展大、青木伊知男、多田弘子、寺田一志
  • Organizer: 第40回日本磁気共鳴医学会
  • Place of Presentation: 国立京都国際会館（京都府）
• [Presentation] 髄鞘低形成のMR spectroscopy を用いた neurochemistry
  • Author(s): 高梨潤一
  • Organizer: 第41回日本磁気共鳴医学会
  • Place of Presentation: アスティ徳島（徳島県）
  • Invited
• [Book] 続・イメージからせまる小児神経疾患 (2015)
  • Author(s): 高梨潤一
  • Total Pages: 119
  • Publisher: 診断と治療社
• [Book] 疾患から見る画像診断の進め方・読み方 (2015)
  • Author(s): 高梨潤一
  • Total Pages: 348
  • Publisher: 診断と治療社
• [Book] Proton MRS の臨床有用性コンセンサスガイド 2013年度版 (2013)
  • Author(s): 高梨潤一（日本磁気共鳴医学会 Proton MRS の臨床有用性検討会編集）
  • Total Pages: 81
  • Publisher: 日本磁気共鳴医学会
• [Book] これでわかる拡散MRI 第３版 (2013)
  • Author(s): 高梨潤一（青木茂樹、阿部修、増谷佳孝、高原太郎 編集）
  • Total Pages: 487
  • Publisher: 秀潤社
• [Book] 3-2-6 小児脳、発達（磁気共鳴スペクトルの医学応用） (2013)
  • Author(s): 髙梨潤一（成瀬昭二、梅田雅宏、原田雅史、田中忠蔵編）
  • Publisher: インナービジョン
• [Remarks] 先天性大脳白質形成不全症：PMDと類縁疾患に関するネットワーク
  • URL: http://plaza.umin.ac.jp/~pmd/
• [Remarks] 遺伝性白質疾患の診断・治療・研究システムの構築班
  • URL: http://plaza.umin.ac.jp/~pmd/iden_introduction.html
• [Remarks] 先天性大脳白質形成不全症：PMDと類縁疾患に関するネットワーク
  • URL: http://kcmc.jp/pmd/about.html
• [Remarks] 先天性大脳白質形成不全症：PMDと類縁疾患に関するネットワーク
  • URL: http://kcmc.jp/pmd/about.html