To redefine blood-brain-barrier (BBB)
Project/Area Number |
18K19510
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Research Category |
Grant-in-Aid for Challenging Research (Exploratory)
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Allocation Type | Multi-year Fund |
Review Section |
Medium-sized Section 52:General internal medicine and related fields
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Research Institution | Nagoya University |
Principal Investigator |
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Co-Investigator(Kenkyū-buntansha) |
田岡 俊昭 名古屋大学, 医学系研究科, 特任教授 (30305734)
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Project Period (FY) |
2018-06-29 – 2021-03-31
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Project Status |
Completed (Fiscal Year 2020)
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Budget Amount *help |
¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000)
Fiscal Year 2020: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2019: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2018: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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Keywords | 血液脳関門 / ガドリニウム造影剤 / 磁気共鳴画像 / 血液迷路関門 / 血液脳関門(BBB) / ガドリニウム造影剤(Gd) |
Outline of Final Research Achievements |
To redefine blood-brain-barrier (BBB), we used advanced MRI techniques that were developed by us. We utilized extremely sensitive pulse sequences, which visualize ultra-low concentration gadolinium-based contrast agent (GBCA) in fluid. In human subjects, we found that intravenously injected GBCA slightly leaks to brain parenchyma of the subjects with normal BBB. Leaked GBCA exit brain through parevenous pial sheath to meningeal lymphatics along superior sagittal sinus. This leakage is closely related to aging and cyst formation along cortical veins. We also found that the age dependence of GBCA leakage to CSF is more prominent in ventricular CSF than in subarachnoid space of the brain surface. The results of this project were greatly influence the future research of BBB, drug delivery system and neurodegenerative disease.
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Academic Significance and Societal Importance of the Research Achievements |
人類全体にとって大きな問題である認知症などの神経変性疾患には血液脳関門の透過性亢進が関与していると推定されている。また脳の疾患の治療には薬剤の血液脳関門の通過が必須である。我々は先進磁気共鳴画像技術を用いて、従来考えられていたよりも血液脳関門は盤石ではなく、脳脊髄液を介して比較的自由に脳内に到達することを見出した。またこれが年齢依存性が強いことも示した。さらに頭頂部における静脈周囲の嚢胞形成が、血液脳関門の透過性を修飾することを世界で初めて示した。これらの結果は、血液脳関門に関する研究のブレークスルーをさらに加速させるものと思われる。将来的に神経疾患の治療に結びつく意義が大きな結果と考える。
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Report
(4 results)
Research Products
(179 results)
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[Journal Article] Intracranial Distribution of Intravenously Administered Gadolinium-based Contrast Agent over a Period of 24 Hours: Evaluation with 3D-real IR Imaging and MR Fingerprinting2021
Author(s)
Shinji Naganawa,, Rintaro Ito, Yutaka Kato , Hisashi Kawai , Toshiaki Taoka, Tadao Yoshida, Katsuya Maruyama, Katsutoshi Murata , Gregor Korzdorfer , Josef Pfeuffer, Mathias Nittka , Michihiko Sone
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Journal Title
Magnetic Resonance in Medical Sciences
Volume: 20
Issue: 1
Pages: 91-98
DOI
NAID
ISSN
1347-3182, 1880-2206
Related Report
Peer Reviewed / Open Access
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[Journal Article] Effects of Head Motion on the Evaluation of Age-related Brain Network Changes Using Resting State Functional MRI2021
Author(s)
Sanae Kato, Epifanio Bagarinao, Haruo Isoda, Shuji Koyama, Hirohisa Watanabe, Satoshi Maesawa, Daisuke Mori, Kazuhiro Hara, Masahisa Katsuno, Minoru Hoshiyama, Shinji Naganawa, Norio Ozaki, Gen Sobue
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Journal Title
Magnetic Resonance in Medical Sciences
Volume: 20
Issue: 4
Pages: 338-346
DOI
NAID
ISSN
1347-3182, 1880-2206
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[Journal Article] Three Dimensional Ultra-short Echo Time MRI Can Depict Cholesterol Components of Gallstones Bright2021
Author(s)
Mamoru Takahashi, Yasuo Takehara, Kenji Fujisaki, Tomoyuki Okuaki, Yukiko Fukuma, Norihiro Tooyama, Katsutoshi Ichijo, Tomoyasu Amano, Satoshi Goshima, Shinji Naganawa
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Journal Title
Magnetic Resonance in Medical Sciences
Volume: 20
Issue: 4
Pages: 359-370
DOI
NAID
ISSN
1347-3182, 1880-2206
Related Report
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[Journal Article] Detection of IV-gadolinium Leakage from the Cortical Veins into the CSF Using MR Fingerprinting2020
Author(s)
Shinji Naganawa, Toshiki Nakane, Hisashi Kawai, Toshiaki Taoka, Hirokazu Kawaguchi, Katsuya Maruyama, Katsutoshi Murata, Gregor Korzdorfer, Josef Pfeuffer, Mathias Nittka, Michihiko Sone
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Journal Title
Magnetic Resonance in Medical Sciences
Volume: 19
Issue: 2
Pages: 141-146
DOI
NAID
ISSN
1347-3182, 1880-2206
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[Journal Article] Abnormal Flow Dynamics Result in Low Wall Shear Stress and High Oscillatory Shear Index in Abdominal Aortic Dilatation: Initial in vivo Assessment with 4D-flow MRI2020
Author(s)
Yasuo Takehara, Haruo Isoda, Mamoru Takahashi, Naoki Unno, Norihiko Shiiya, Takasuke Ushio, Satoshi Goshima, Shinji Naganawa , Marcus Alley, Tetsuya Wakayama, Atsushi Nozaki
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Magn Reson Med Sci .
Volume: 19(3)
Issue: 3
Pages: 235-246
DOI
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[Journal Article] Optimal Plane Selection for Measuring Post-prandial Blood Flow Increase within the Superior Mesenteric Artery: Analysis Using 4D Flow and Computational Fluid Dynamics2020
Author(s)
Masataka Sugiyama, Yasuo Takehara, Masanori Kawate, Naoki Ooishi, Masaki Terada, Haruo Isoda, Harumi Sakahara, Shinji Naganawa, Kevin M. Johnson, Oliver Wieben, Tetsuya Wakayama, Atsushi Nozaki, Hiroyuki Kabasawa
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Journal Title
Magnetic Resonance in Medical Sciences
Volume: 19
Issue: 4
Pages: 366-374
DOI
NAID
ISSN
1347-3182, 1880-2206
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[Journal Article] Comprehensive Evaluation of B<sub>1</sub><sup>+</sup>-corrected FISP-based Magnetic Resonance Fingerprinting: Accuracy, Repeatability and Reproducibility of T<sub>1</sub> and T<sub>2</sub> Relaxation Times for ISMRM/NIST System Phantom and Volunteers2020
Author(s)
Yutaka Kato, Kazushige Ichikawa, Kuniyasu Okudaira, Toshiaki Taoka, Hirokazu Kawaguchi, Katsutoshi Murata, Katsuya Maruyama, Gregor Koerzdoerfer, Josef Pfeuffer, Mathias Nittka, Shinji Naganawa
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Journal Title
Magnetic Resonance in Medical Sciences
Volume: 19
Issue: 3
Pages: 168-175
DOI
NAID
ISSN
1347-3182, 1880-2206
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[Journal Article] Change of White Matter Integrity in Children With Hematopoietic Stem Cell Transplantation.2020
Author(s)
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Volume: 111
Pages: 78-84
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[Journal Article] Identifying the brain's connector hubs at the voxel level using functional connectivity overlap ratio.2020
Author(s)
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Journal Title
Neuroimage .
Volume: 222
Pages: 117241-117241
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[Journal Article] Changes in white matter fiber density and morphology across the adult lifespan: A cross-sectional fixel-based analysis.2020
Author(s)
Shao Wei Choy, Epifanio Bagarinao, Hirohisa Watanabe, Eric Tatt Wei Ho, Satoshi Maesawa, Noritaka Yoneyama, Kazunori Imai, Michihito Masuda, Toshiaki Taoka, Shuji Koyama, Hiroki C Tanabe, Masahisa Katsuno, Toshihiko Wakabayashi, Masafumi Kuzuya, Minoru Hoshiyama, Haruo Isoda, Shinji Naganawa, Norio Ozaki, Gen Sobue
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Journal Title
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Volume: 41(12)
Issue: 12
Pages: 3198-3211
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[Journal Article] Efficacy and safety of accelerated fractionated radiotherapy without elective nodal irradiation for T3N0 glottic cancer without vocal cord fixation.2020
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Pages: 1775-1782
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[Journal Article] Aging Impacts the Overall Connectivity Strength of Regions Critical for Information Transfer Among Brain Networks2020
Author(s)
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Volume: 12
Pages: 592469-592469
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[Journal Article] Evaluation of magnetic resonance angiography as a possible alternative to rotational angiography or computed tomography angiography for assessing cerebrovascular computational fluid dynamics.2020
Author(s)
Yuya Yoneyama, Haruo Isoda, Kenta Ishiguro, Masaki Terada, Masaki Kamiya, Kenichi Otsubo, Roshani Perera, Takashi Mizuno, Atsushi Fukuyama, Kazuya Takiguchi, Tomoya Watanabe, Takafumi Kosugi, Yoshiaki Komori, Shinji Naganawa
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Journal Title
Phys Eng Sci Med.
Volume: 43(4)
Issue: 4
Pages: 1327-1337
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[Journal Article] Assessing the Risk of Intracranial Aneurysm Rupture Using Morphological and Hemodynamic Biomarkers Evaluated from Magnetic Resonance Fluid Dynamics and Computational Fluid Dynamics2020
Author(s)
Roshani Perera, Haruo Isoda, Kenta Ishiguro, Takashi Mizuno, Yasuo Takehara, Masaki Terada, Chiharu Tanoi, Takehiro Naito, Harumi Sakahara, Hisaya Hiramatsu, Hiroki Namba, Takashi Izumi, Toshihiko Wakabayashi, Takafumi Kosugi, Yuki Onishi, Marcus Alley, Yoshiaki Komori, Mitsuru Ikeda, Shinji Naganawa
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Journal Title
Magnetic Resonance in Medical Sciences
Volume: 19
Issue: 4
Pages: 333-344
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ISSN
1347-3182, 1880-2206
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[Journal Article] Pharmacologic and non-pharmacologic interventions to prevent hypersensitivity reactions of non-ionic iodinated contrast media: a systematic review protocol.2020
Author(s)
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Volume: 10(3)
Issue: 3
Pages: e033023-e033023
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[Journal Article] Reorganization of brain networks and its association with general cognitive performance over the adult lifespan.2019
Author(s)
Epifanio Bagarinao, Hirohisa Watanabe, Satoshi Maesawa, Daisuke Mori, Kazuhiro Hara, Kazuya Kawabata, Noritaka Yoneyama, Reiko Ohdake,…他 Haruo Isoda, Shinji Naganawa, Gen Sobue
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Sci Rep.
Volume: 9(1)
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[Journal Article] A plea for systematic literature analysis and conclusive study design, comment on: "Systematic review of magnetic resonance imaging for diagnosis of Meniere disease".2019
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Journal Title
Nagoya Journal of Medical Science
Volume: 81
Issue: 2
Pages: 233-239
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2186-3326
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Volume: 37(6)
Issue: 6
Pages: 437-448
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Volume: 81(5)
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[Journal Article] Corpus callosal involvement is correlated with cognitive impairment in multiple system atrophy.2018
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Hara K, Watanabe H, Bagarinao E, Kawabata K, Yoneyama N, Ohdake R, Imai K, Masuda M, Yokoi T, Ogura A, Tsuboi T, Ito M, Atsuta N, Niwa H, Taoka T, Maesawa S, Naganawa S, Katsuno M, Sobue G.
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Volume: 265
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Volume: 39(10)
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Volume: 19(5)
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[Presentation] Development of Three-Dimensional Printed Compensator for Improvement of Dose Distribution in Boron Neutron Capture Therapy: A Preliminary Study2019
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[Presentation] Should Small Cell Carcinoma of the Cervix be Treated As Localized Small Cell Cancer or Advanced Cervical Cancer: A Retrospective Multi-Institutional Cohort Study2019
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[Presentation] MR Fingerprinting Evaluation for the Early Changes of Relaxation Time in the Brain Tumor and Surrounding White Matter After Stereotactic Radiotherapy.2019
Author(s)
Toshiaki Taoka, Kazuhiro Ohtakara, Hisashi Kawai, Yutaka Kato, Yoshiyuki Itoh, Shinji Naganawa, Toshiki Nakane, Rintaro Ito, Kazushige Ichikawa, Kuniyasu Okudaira, Katsutoshi Murata, Katsuya Maruyama, Hirokazu Kawaguchi, Gregor Koerzdoerfer, Josef Pfeuffer, Mathias Nittka
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[Presentation] Evaluation of haemodynamic and morphological biomarkers to assess the rupture risk of intracranial aneurysms using magnetic resonance fluid dynamics and computational fluid dynamics.2019
Author(s)
Roshani Perera, Haruo Isoda, Shunsuke Tajima, Takashi Mizuno, Masaki Terada, Takehiro Naito, Chiharu Tanoi, Takashi Izumi, Yasuo Takehara, Toshihiko Wakabayashi, Harumi Sakahara, Shinji Naganawa
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第85回東海総合画像医学研究会
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[Presentation] Feasibility of novel thin bolus using tungsten functional paper for electron beam radiotherapy.2018
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18th Asia-Oceania Congress of Medical Physics (AOCMP) & 16th South-East Asia Congress of Medical Physics (SEACOMP)
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