Visualization and quantification of microstructures of the brain: new concept using next-generation advanced diffusion MR imaging

• Project/Area Number: 18H02772
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 52040:Radiological sciences-related
• Research Institution: Juntendo University
• Principal Investigator: 青木 茂樹 順天堂大学, 医学(系)研究科(研究院), 教授 (80222470)
• Co-Investigator(Kenkyū-buntansha): 下地 啓五 地方独立行政法人東京都健康長寿医療センター(東京都健康長寿医療センター研究所), 東京都健康長寿医療センター研究所, 研究員 (20348931)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Project Status: Granted (Fiscal Year 2020)
• Budget Amount: ¥17,420,000 (Direct Cost: ¥13,400,000、Indirect Cost: ¥4,020,000); Fiscal Year 2020: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000); Fiscal Year 2019: ¥6,630,000 (Direct Cost: ¥5,100,000、Indirect Cost: ¥1,530,000); Fiscal Year 2018: ¥7,410,000 (Direct Cost: ¥5,700,000、Indirect Cost: ¥1,710,000)
• Keywords: 拡散MRI / 拡散時間 / 拡散テンソル / 定量ＭＲＩ / 神経疾患 / MRI / 拡散 / 次世代拡散MRI / microstructure / 脳 / 制限拡散 / 粘稠度 / epidermoid cyst / 微細構造

Outline of Annual Research Achievements

次世代拡散MRI（magnetic resonance imaging）により、広く使われている従来の拡散強
調像に関する過去の知見の限界が目立つようになってきた。従来の臨床機ではコントロール困難なため無視されてきた拡散時間の違いにより拡散MRIの定量値は変化する。今回我々は、次世代拡散MRIを用いて、拡散時間を考慮して従来の拡散強調像の概念の一新を行い、より病態を反映する新たな微細構造の解明を進める。その違いを加味した拡散MRIの新たな定量値と他の手法を合せ、最新技術を駆使して微細構造を明らかにする。
具体的には、短い拡散時間により粘稠度と空間的拡散の違いを明らかにして、従来の知見を一新するために、次世代MRIを用いて in vivoでヒトの軸索や神経突起の変化、線維のビーズ状変化などを考慮したより詳細な回路・微細構造の解明を行う。検証のために、Synthetic MRIなどによる定量値やマウス透明脳との比較検討も行う。
1）拡散時間を変えて粘稠度の違いと制限拡散の違いを持つファントムおよび、空間的制限拡散の脈絡叢肉芽腫などで、拡散時間と信号強度の詳細な検討を行う。短い拡散時間はOGSE,長い拡散時間は従来の方法やSTEAMなどで計測する。
2）従来の拡散強調像で高信号を示す疾患に絞って、OGSEで拡散時間を短くするとどのように信号強度が変化するかを検討し、粘稠度、空間的制限拡散のどちらによる高信号であったかを検討する。
3）OGSEを行った疾患で、次世代拡散MRIやSynthetic MRIなどの最新のMRIも行われている症例につき、さらに微細構造変化につき詳細な検討を行う。マウスでの実験の治験も合せ、MRIを用いた微細構造の研究をすすめる。

Current Status of Research Progress

2: Research has progressed on the whole more than it was originally planned.

Reason

拡散制限を来す疾患につき、Oscillating gradient spin-echo (OGSE)を行い、epidermoid cyst (Christina A, MRMS), 急性期脳梗塞（Boonrod A, Neuroradiology2018)で報告を行った。
粘稠度の異なる液体についての基礎的検討も行った（Maekawa T, Jpn J Radiol 2018)。
画像処理への人工知能の活用が急速に進んでいるため、その対応のため予算を残した。

Strategy for Future Research Activity

画像関連でのAIの進歩は著しく、拡散関係でもできるだけ取り入れて研究を進めたい。

Research Products

• [Int'l Joint Research] Department de genie electrique/Polytechnique/Montreal(カナダ)
• [Journal Article] Choroid plexus cysts analyzed using diffusion-weighted imaging with short diffusion-time (2019)
  • Author(s): Tomoko Maekawa, Masaaki Hori, Katsutoshi Murata, Thorsten Feiweier, Christina Andica, Issei Fukunaga, Saori Koshino, Akifumi Hagiwara, Kouhei Kamiya, Koji Kamagata, Akihiko Wada, Osamu Abe, Shigeki Aoki
  • Journal Title: Magn Reson Imaging Volume: 57 Pages: 323-327
  • DOI: 10.1016/j.mri.2018.12.010
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] The Relationship between Neurite Density Measured with Confocal Microscopy in a Cleared Mouse Brain and Metrics Obtained from Diffusion Tensor and Diffusion Kurtosis Imaging (2018)
  • Author(s): Irie R., Kamagata K., Kerever A., Ueda R., Yokosawa S., Otake Y., Ochi H., Yoshizawa H., Hayashi A., Tagawa K., Okazawa H., Takahashi K., Sato K., Hori M., Arikawa-Hirasawa E., Aoki S.
  • Journal Title: MRMS Volume: 17 Issue: 2 Pages: 128-144
  • DOI: 10.2463/mrms.mp.2017-0031
  • NAID: 130006685597
  • ISSN: 1347-3182, 1880-2206
  • Peer Reviewed / Open Access
• [Journal Article] Neurite orientation dispersion and density imaging of the nigrostriatal pathway in Parkinson's disease: Retrograde degeneration observed by tract-profile analysis (2018)
  • Author(s): Andica Christina、Kamagata Koji、Hatano Taku、Okuzumi Ayami、Saito Asami、Nakazawa Misaki、Ueda Ryo、Motoi Yumiko、Kamiya Kouhei、Suzuki Michimasa、Hori Masaaki、Kumamaru Kanako K.、Hattori Nobutaka、Aoki Shigeki
  • Journal Title: Parkinsonism Relat Disord Volume: in press Pages: 55-60
  • DOI: 10.1016/j.parkreldis.2018.02.046
  • Peer Reviewed / Open Access
• [Journal Article] Myelin Measurement : Comparison Between Simultaneous Tissue Relaxometry, Magnetization Transfer Saturation Index, and T(1)w/T(2)w Ratio Methods (2018)
  • Author(s): Hagiwara A., Hori M., Kamagata K., Warntjes M., Matsuyoshi D., Nakazawa M., Ueda R., Andica C., Koshino S., Maekawa T., Irie R., Takamura T., Kumamaru K. K., Abe O., Aoki S.
  • Journal Title: Sci Rep Volume: 8 Pages: 10554-10554
  • DOI: 10.1038/s41598-018-28852-6
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Diffusional kurtosis imaging and white matter microstructure modeling in a clinical study of major depressive disorder (2018)
  • Author(s): Kamiya K., Okada N., Sawada K., Watanabe Y., Irie R., Hanaoka S., Suzuki Y., Koike S., Mori H., Kunimatsu A., Hori M., Aoki S., Kasai K., Abe O.
  • Journal Title: NMR Biomed Volume: 31
  • DOI: 10.1002/nbm.3938
  • Peer Reviewed / Open Access
• [Journal Article] Changes in the ADC of diffusion-weighted MRI with the oscillating gradient spin-echo (OGSE) sequence due to differences in substrate viscosities (2018)
  • Author(s): Tomoko Maekawa, Masaaki Hori, Katsutoshi Murata, Thorsten Feiweier, Issei Fukunaga, Christina Andica, Akifumi Hagiwara, Koji Kamagata, Saori Koshino, Osamu Abe, Shigeki Aoki
  • Journal Title: Jpn J Radiol Volume: 36 Pages: 415-420
  • DOI: 10.1007/s11604-018-0737-0
  • Peer Reviewed / Open Access
• [Journal Article] Spatial Restriction within Intracranial Epidermoid Cysts Observed Using Short Diffusion-time Diffusion-weighted Imaging (2018)
  • Author(s): Christina Andica, Masaaki Hori, Kouhei Kamiya, Saori Koshino, Akifumi Hagiwara, Koji Kamagata, Issei Fukunaga, Nozomi Hamasaki, Michimasa Suzuki, Thorsten Feiweier, Katsutoshi Murata, Atsushi Arakawa, Akihide Kondo, Osamu Akiyama, Shigeki Aoki
  • Journal Title: MRMS Volume: 17 Issue: 3 Pages: 269-272
  • DOI: 10.2463/mrms.cr.2017-0111
  • NAID: 130007403806
  • ISSN: 1347-3182, 1880-2206
  • Peer Reviewed / Open Access
• [Journal Article] Reduced visualization of cerebral infarction on diffusion-weighted images with short diffusion times. (2018)
  • Author(s): Boonrod A, Hagiwara A, Hori M, Fukunaga I, Andica C, Maekawa T, Aoki S.
  • Journal Title: Neuroradiology Volume: 60 Pages: 979-982
  • DOI: 10.1007/s00234-018-2065-6
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Microstructural Damage in Normal-Appearing Brain Parenchyma and Neurocognitive Dysfunction in Adult Moyamoya Disease (2018)
  • Author(s): Hara S., Hori M., Murata S., Ueda R., Tanaka Y., Inaji M., Maehara T., Aoki S., Nariai T.
  • Journal Title: Stroke Volume: 49 Pages: 2504-2507
  • DOI: 10.1161/strokeaha.118.022367
  • Peer Reviewed / Open Access
• [Journal Article] The Advantage of Synthetic MRI for the Visualization of Anterior Temporal Pole Lesions on Double Inversion Recovery (DIR), Phase-sensitive Inversion Recovery (PSIR), and Myelin Images in a Patient with CADASIL (2018)
  • Author(s): Wallaert L, Hagiwara A, Andica C, Hori M, Yamashiro K, Koshino S, Maekawa T, Kamagata K, Aoki S.
  • Journal Title: MRMS Volume: 印刷中 Issue: 4 Pages: 275-276
  • DOI: 10.2463/mrms.ci.2017-0110
  • NAID: 130006251645
  • ISSN: 1347-3182, 1880-2206
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Differentiating Alzheimer's Disease from Dementia with Lewy Bodies Using a Deep Learning Technique Based on Structural Brain Connectivity. (2018)
  • Author(s): Wada A, Tsuruta K, Irie R, Kamagata K, Maekawa T, Fujita S, Koshino S, Kumamaru K, Suzuki M, Nakanishi A, Hori M, Aoki S.
  • Journal Title: Magn Reson Med Sci Volume: 18 Pages: 1-6
  • DOI: 10.2463/mrms.mp.2018-0091
  • NAID: 130007679745
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] Brain volumetry and myelin estimation derived from synthetic MRI with various in-plane resolutions at 3 T. (2019)
  • Author(s): Hagiwara A, Hori M, Ozaki Y, Maekawa T, Andica C, Horita M, Fujita S, Aoki S.
  • Organizer: European Congress of Radiology2019
  • Int'l Joint Research
• [Presentation] Diffusion Time Dependence of Diffusion Tensor Parameters in Choroid Plexus Cysts. (2019)
  • Author(s): Maekawa T, Hori M, Murata K, Andica C, Hagiwara A, Kamiya K, Kamagata K, Wada A, Aoki S.
  • Organizer: European Congress of Radiology2019
  • Int'l Joint Research
• [Presentation] Diffusion-weighted MRI with Oscillating Gradient Spin Echo (OGSE) sequence: Changes of ADC due to differences in the viscosity of substrates. (2018)
  • Author(s): Maekawa T, Hori M, Fukunaga I, Murata K, Koshino S, Andica C, Irie R, Hagiwara A,Murata S, Hamasaki N, Horita M, Takenaka Y, Aoki S.
  • Organizer: The 6th international congress on magnetic resonance imaging & 23rd annual scientific meeting of KSMRM
  • Int'l Joint Research
• [Presentation] White Matter Alterations in Parkinson’s Disease Analyzed with Combined Diffusion Magnetic Resonance Imaging and Magnetization Transfer Saturation Imaging: A Tract-Based Spatial Statistics Analysis. (2018)
  • Author(s): Andica C, Kamagata K, Hatano T, Saito A, Takenaka Y, Hagiwara A, Hori M, Irie R, Wada A, Kumamaru K, Hattori N, Aoki S.
  • Organizer: Joint Annual Meeting ISMRM-ESMRMB2018
  • Int'l Joint Research
• [Presentation] Oscillating gradient spin echo (OGSE) diffusion weighted imaging of the epidermoid cysts: simulation application. (2018)
  • Author(s): Koshino S, Sakakibara A, Choppin A, Andica C, Hagiwara A, Maekawa T, Takemori A, Arakawa A, Chougar L, Hori M, Aoki S.
  • Organizer: Joint Annual Meeting ISMRM-ESMRMB2018
  • Int'l Joint Research
• [Presentation] Rapid Myelin Measurement: Comparison Between SyMRI (Simultaneous Tissue Relaxometry), Magnetization Transfer Saturation Index, and T1w/T2w Ratio Methods. (2018)
  • Author(s): Hagiwara A, Hori M, Kamagata K, Nakazawa M, Andica C, Maekawa T, Koshino S, Irie R, Chougar L, Abe O, Aoki S.
  • Organizer: Joint Annual Meeting ISMRM-ESMRMB2018
  • Int'l Joint Research
• [Presentation] Diffusion kurtosis imaging and white matter model analysis of the brains of patients with major depressive disorder. (2018)
  • Author(s): Kamiya K, Okada N, Sawada K, Watanabe Y, Irie R, Suzuki Y, Hanaoka S, Watadani T, Koike S, Mori H, Kunimatsu A, Hori M, Aoki S, Kasai K, Abe O.
  • Organizer: Joint Annual Meeting ISMRM-ESMRMB2018
  • Int'l Joint Research
• [Presentation] Radiologic-Pathologic Correlation for Differential Diagnosis Using Diffusion MRI with a Short Diffusion Time. (2018)
  • Author(s): Koshino S, Takemori M, Andica C, Hori M, Kamagata K,. Kumamaru KK, Wada A, Watadani T, Mori H, Abe O, Aoki S.
  • Organizer: Ragiological Society of North America 104th Scientific Assembly and Annual Meeting
  • Int'l Joint Research