Development of core technologies for heart diagnostic imaging apparatus based on nanoanalysis

• Project/Area Number: 26560225
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Biomedical engineering/Biomaterial science and engineering
• Research Institution: Jikei University School of Medicine
• Principal Investigator: Fukuda Norio 東京慈恵会医科大学, 医学部, 准教授 (30301534)
• Co-Investigator(Kenkyū-buntansha): 照井 貴子 東京慈恵会医科大学, 医学部, 助手 (10366247) ; 小比類巻 生 東京慈恵会医科大学, 医学部, 助教 (40548905) ; 大山 廣太郎 東京慈恵会医科大学, 医学部, 特別研究員 (70632131)
• Co-Investigator(Renkei-kenkyūsha): ISHIWATA SHIN'ICHI 早稲田大学, 理工学術院, 名誉教授 (10130866)
• Project Period (FY): 2014-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000); Fiscal Year 2016: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2015: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2014: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
• Keywords: ナノバイオ / 先端機器デバイス / 循環器・高血圧 / 分子イメージング / 先端機能デバイス

Outline of Final Research Achievements

1）We developed an experimental system for simultaneous nano-imaging of intracellular Ca dynamics and single sarcomere length in rat neonatal cardiomyocytes. We achieved this by expressing a fluorescence resonance energy transfer-based Ca sensor yellow Cameleon-Nano fused to α-actinin in order to localize to the Z disks. 2）We developed a high-speed (100 fps), high-resolution (20 nm) nano-imaging system for myocardial sarcomeres in living mice. During imaging, we measured macroscopic parameters such as electrocardiogram and left ventricular pressure. 3) We developed a digitally-controlled image reconstruction system for in vivo nano-imaging. Namely, the position of the objective lens was moved downward in the Z-direction during imaging. After experimentation, the LVP record was divided into 17 phases (i.e., 10.2 ms per phase); best-focused images were selected at each phase, and then, combined to obtain an image sequence.

Research Products

• [Journal Article] Dynamic properties of bio-motile systems as a liquid-crystalline structure (2017)
  • Author(s): Shin'ichi Ishiwata, Makito Miyazaki, Katsuhiko Sato, Koutaro Nakagome, Seine A. Shintani, Fuyu Kobirumaki-Shimozawa, Norio Fukuda, Kazuya Suzuki, Jun Takagi, Yuta Shimamoto, and Takeshi Itabashi
  • Journal Title: Mol. Cryst. Liq. Cryst. Volume: 印刷中 Issue: 1 Pages: 127-150
  • DOI: 10.1080/15421406.2017.1289445
  • Peer Reviewed / Open Access
• [Journal Article] In vivo cardiac nano-imaging: A new technology for high-precision analyses of sarcomere dynamics in the heart (2017)
  • Author(s): Togo Shimozawa, Erisa Hirokawa, Fuyu Kobirumaki-Shimozawa, Kotaro Oyama, Seine A. Shintani, Takako Terui, Yasuharu Kushida, Seiichi Tsukamoto, Teruyuki Fujii, Shin'ichi Ishiwata, and Norio Fukuda
  • Journal Title: Prog. Biophys. Mol. Biol. Volume: 124 Pages: 31-40
  • DOI: 10.1016/j.pbiomolbio.2016.09.006
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Simultaneous imaging of local calcium and single sarcomere length in rat neonatal cardiomyocytes using yellow Cameleon-Nano140 (2016)
  • Author(s): Seiichi Tsukamoto, Teruyuki Fujii, Kotaro Oyama, Seine A. Shintani, Togo Shimozawa, Fuyu Kobirumaki-Shimozawa, Shin’ichi Ishiwata, and Norio Fukuda
  • Journal Title: J. Gen. Physiol. Volume: 148 Issue: 4 Pages: 341-355
  • DOI: 10.1085/jgp.201611604
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Nano-imaging of the beating mouse heart in vivo: Importance of sarcomere dynamics, as opposed to sarcomere length per se, in the regulation of cardiac function. (2016)
  • Author(s): Kobirumaki-Shimozawa F, Oyama K, Shimozawa T, Mizuno A, Ohki T, Terui T, Minamisawa S, Ishiwata S, Fukuda N
  • Journal Title: Journal of General Physiology Volume: 147 Issue: 1 Pages: 53-62
  • DOI: 10.1085/jgp.201511484
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] High-frequency sarcomeric auto-oscillations induced by heating in living neonatal cardiomyocytes of the rat (2015)
  • Author(s): Shintani, S., Oyama, K. Fukuda, N., and Ishiwata, S.
  • Journal Title: Biochem. Biophys. Res. Commun. Volume: 457 Issue: 2 Pages: 165-170
  • DOI: 10.1016/j.bbrc.2014.12.077
  • Peer Reviewed
• [Journal Article] Sarcomere length nanometry in rat neonatal cardiomyocytes expressed with α-actinin-AcGFP in Z-discs (2014)
  • Author(s): Shintani, S., Oyama, K., Kobirumaki, F., Shimozawa, F., Ohki, T., Ishiwata, S., and Fukuda, N.
  • Journal Title: J. Gen. Physiol. Volume: 143 Issue: 4 Pages: 513-524
  • DOI: 10.1085/jgp.201311118
  • Peer Reviewed
• [Journal Article] Cardiac thin filament regulation and the Frank-Starling mechanism (2014)
  • Author(s): Fuyu Kobirumaki-Shimozawa, Inoue, T. Shintani, S., Oyama, K., Terui, T. Minamisawa, S., Ishiwata, S., and Fukuda, N.
  • Journal Title: J. Physiol. Sci. Volume: 64 Issue: 4 Pages: 221-232
  • DOI: 10.1007/s12576-014-0314-y
  • Peer Reviewed / Open Access
• [Journal Article] Clinical definition and diagnostic criteria for sarcopenia (2014)
  • Author(s): Udaka J, Fukuda N, Yamauchi H, Marumo K.
  • Journal Title: The Journal of Physical Fitness and Sports Medicine Volume: 3 Issue: 3 Pages: 347-352
  • DOI: 10.7600/jpfsm.3.347
  • NAID: 130004972984
  • ISSN: 2186-8123, 2186-8131
  • Peer Reviewed / Acknowledgement Compliant
• [Presentation] ラット幼若心筋細胞のZ線におけるYellow Cameleon-Nano140融合α-actinin発現を用いたサルコメア動態と局所的カルシウムの同時観測 (2017)
  • Author(s): 塚本 精一，大山 廣太郎，藤井 輝之，小比類巻 生，石渡 信一，福田 紀男
  • Organizer: 第94回日本生理学会大会
  • Place of Presentation: アクトシティ浜松（静岡県浜松市）
  • Year and Date: 2017-03-28
• [Presentation] In vivo cardiac nano-imaging: high-resolution analysis of excitation-contraction coupling in the heart (2017)
  • Author(s): 小比類巻生、福田紀男
  • Organizer: 第94回日本生理学会大会
  • Place of Presentation: アクトシティ浜松（静岡県浜松市）
  • Year and Date: 2017-03-28
  • Invited
• [Presentation] マウス心筋における単一サルコメア動態のin vivoナノ解析 (2017)
  • Author(s): 小比類巻 生、大山廣太郎、下澤東吾、石渡信一、福田紀男
  • Organizer: 第95回日本生理学会大会
• [Presentation] 光熱変換顕微鏡を用いた温度センシングの一細胞解析 (2017)
  • Author(s): 大山廣太郎、Zeeb Vadim、新井智実、伊藤秀城、新谷正嶺、鈴木 団、福田紀男、石渡信一
  • Organizer: 第95回日本生理学会大会
  • Invited
• [Presentation] 悪性高熱症の原因となる骨格筋リアノジン受容体１変異体の熱刺激応答 (2017)
  • Author(s): 大山廣太郎、山澤德志子、村山尚、原田慶恵、飯野正光、福田紀男、石渡信一、鈴木 団
  • Organizer: 2018年生体運動研究合同班会議
• [Presentation] サルコメア収縮の蛍光イメージングと光操作技術の開発 (2017)
  • Author(s): 大山廣太郎、新谷正嶺、塚本精一、小比類巻 生、下澤東吾、鈴木 団、石渡信一、福田紀男
  • Organizer: 精神・神経疾患研究開発費「ジストロフィン欠損モデル動物を基盤とした筋ジストロフィーの新しい治療法開発」平成29年度研究班会議
  • Invited
• [Presentation] Yellow Cameleon-Nano140融合α-actininを用いた幼若心筋細胞におけるサルコメア動態と局所Ca2+濃度の同時観測 (2017)
  • Author(s): 塚本精一、藤井輝之、大山廣太郎、下澤東吾、小比類巻生、石渡信一、福田紀男
  • Organizer: 生理学研究所研究会「シグナル動態の可視化と操作に基づく多階層機能解析の新展開」
  • Invited
• [Presentation] In vivo 心筋ナノイメージング (2017)
  • Author(s): 下澤東吾、広川恵里沙、小比類巻生、大山廣太郎、照井貴子、石渡信一、福田紀男
  • Organizer: 生理学研究所研究会「シグナル動態の可視化と操作に基づく多階層機能解析の新展開」
  • Invited
• [Presentation] In vivoナノイメージングによる心筋収縮の可視化と熱による制御 (2016)
  • Author(s): 大山 廣太郎、小比類巻 生、下澤 東吾、福田 紀男
  • Organizer: 第93回日本生理学会年会
  • Place of Presentation: 北海道
  • Year and Date: 2016-03-22
  • Invited
• [Presentation] Yellow Cameleon-Nano140を用いたラット幼若心筋細胞のサルコメア長と細胞内カルシウムの同時観測系の開発 (2016)
  • Author(s): 塚本 精一、大山 廣太郎、藤井 輝之、小比類巻 生、石渡 信一、福田 紀男
  • Organizer: 第93回日本生理学会年会
  • Place of Presentation: 北海道
  • Year and Date: 2016-03-22
• [Presentation] マウス心臓上における移植ラット幼若心筋のサルコメア動態の定量的解析 (2016)
  • Author(s): 櫛田 康晴、塚本 精一、藤井 輝之、大山 廣太郎、小比類巻-下澤 生、福田 紀男
  • Organizer: 第93回日本生理学会年会
  • Place of Presentation: 北海道
  • Year and Date: 2016-03-22
• [Presentation] High-speed, high-performance real-time imaging of physiological sarcomere dynamics in the beating heart in vivo (2016)
  • Author(s): Fuyu Kobirumaki-Shimozawa, Kotaro Oyama, Togo Shimozawa, Takako Terui, Shin'ichi Ishiwata, Norio Fukuda
  • Organizer: Biophysical Society 60th Annual Meeting
  • Place of Presentation: Los Angels, Californiam USA
  • Year and Date: 2016-02-27
  • Int'l Joint Research
• [Presentation] SIMULTANEOUS HIGH-PRECISION IMAGING OF LOCAL CALCIUM AND SINGLE SARCOMERE LENGTH IN RAT NEONATAL CARDIOMYOCYTES VIA EXPRESSION OF YELLOW CAMELEON-NANO140 IN Z-DISCS (2016)
  • Author(s): Seiichi Tsukamoto, Kotaro Oyama, Teruyuki Fujii, Fuyu Kobirumaki-Shimozawa, Togo Shimozawa, Seine A. Shintani, Shin’ichi Ishiwata, Norio Fukuda
  • Organizer: Biophysical Society 60th Annual Meeting, Los Angeles, California, USA
  • Place of Presentation: Los Angels, Californiam USA
  • Year and Date: 2016-02-27
  • Int'l Joint Research
• [Presentation] ナノイメージングによるマウス心臓のin vivoサルコメア動態解析 (2015)
  • Author(s): 小比類巻生、大山廣太郎、下澤東吾、新谷正嶺、広川恵里沙、照井貴子、石渡信一、福田紀男
  • Organizer: 第53回日本生物物理学会年会
  • Place of Presentation: 金沢大学角間キャンパス、金沢市
  • Year and Date: 2015-09-13
• [Presentation] High-frequency sarcomeric auto-oscillations in living cardiomyocytes under hyperthermal conditions (2014)
  • Author(s): Shintani, S.A., Oyama, K., Fukuda, N., Ishiwata, S.
  • Organizer: 第52回日本生物物理学会
  • Place of Presentation: 札幌コンベンションセンター
  • Year and Date: 2014-09-25 – 2014-09-27
• [Presentation] ナノスケール高速ライブイメージングによるin vivoサルコメア計測 (2014)
  • Author(s): 小比類巻生、大山廣太郎、下澤東吾、照井貴子、南沢享、石渡信一、福田紀男
  • Organizer: 第12回ナノ学会大会
  • Place of Presentation: 京都大学宇治キャンパス
  • Year and Date: 2014-05-22 – 2014-05-24
• [Presentation] サルコメア長ナノ計測による心筋細胞内収縮ダイナミクスの系統的解明 (2014)
  • Author(s): 新谷正嶺、大山廣太郎、石渡信一、福田紀男
  • Organizer: 第12回ナノ学会大会
  • Place of Presentation: 京都大学宇治キャンパス
  • Year and Date: 2014-05-22 – 2014-05-24
• [Presentation] 高精度分子イメージングを用いた心臓拍動メカニズムの解析 (2014)
  • Author(s): 福田紀男
  • Organizer: 革新的分子イメージングで拓く医学新領域
  • Place of Presentation: 東京工業大学
  • Year and Date: 2014-04-22
  • Invited
• [Book] 曽我部正博編：メカノバイオロジー（第12章：横紋筋のメカノバイオフィジックス：マクロからミクロへ） (2015)
  • Author(s): 石渡信一、島本勇太、福田紀男
  • Total Pages: 368
  • Publisher: 化学同人
• [Book] メカノバイオロジー（第12章：横紋筋のメカノバイオフィジックス：マクロからミクロへ） (2015)
  • Author(s): 石渡信一、島本勇太、福田紀男
  • Total Pages: 13
  • Publisher: 化学同人