Enhancement of drug induction into brain parenchyma using shock wave delivery system

• Project/Area Number: 18390388
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Cerebral neurosurgery
• Research Institution: Tohoku University
• Principal Investigator: TOMINAGA Teiji Tohoku University, 大学院医学系研究科, 教授 (00217548)
• Co-Investigator(Kenkyū-buntansha): IKOHAGI Toshiaki 東北大学, 流体科学研究所, 教授 (90091652) ; TAKAYAMA Kazuyoshi 東北大学, 流体科学研究所, 教授 (40006193) ; MAKISHI Wataru 東北大学, 大学院工学系研究科, 助教 (60400454) ; MATSUURA Yuji 東北大学, 医工学研究科, 准教授 (10241530)
• Project Period (FY): 2006 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥17,100,000 (Direct Cost: ¥15,300,000、Indirect Cost: ¥1,800,000); Fiscal Year 2008: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000); Fiscal Year 2007: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2006: ¥9,300,000 (Direct Cost: ¥9,300,000)
• Keywords: 医療工学 / 高エネルギー外傷 / 対側損傷 / 低侵襲外科 / 頭部外傷モデル / 衝撃波工学 / レーザー光学 / アジ化銀 / 高速度撮影 / 過剰圧 / レーザー工学 / 低侵襲医療 / Ho: YAGレーザー / ラット

Research Abstract

衝撃波損傷ラットモデルでは10-15MPa以上で照射側に脳内出血・壊死が認められた。その周囲では脳梁を介して反対側におよぶ広範囲で色素漏出とmatrix metalloproteinase発現増加が認められ、血管透過性亢進を示唆する所見と考えられた。対側には神経細胞の紡錘化を認め、頭蓋模擬モデル実験から頭蓋骨に反射した反射波とキャビテーションの発生が部位特有の損傷に関与するものと考えられた。グリオーマ細胞株への照射により種々の薬剤のうち、ブレオマイシンのみが照射回数依存的に細胞増殖能抑制効果を示した。

Research Products

• [Journal Article] Traumatic brain injury by blast waves.Insight from perspectives from shock wave physics (2009)
  • Author(s): Nakagawa A, Manley GT, Gean AD, Armonda R, Takayama K, Tominaga T
  • Journal Title: Shock Waves
  • Peer Reviewed
• [Journal Article] パルスHo : YAGレーザーを用いた微小ジェットの臨床応用 : 東北大学における医工学連携の取り組み (2009)
  • Author(s): 中川敦寛, 隈部俊宏, 小川欣一, 平野孝幸, 橋本時忠, 中野徹, 亀井尚, 上之原広司, 高山和喜, 冨永悌二
  • Journal Title: 日本レーザー医学会誌
  • Peer Reviewed
• [Journal Article] Pulsed laser-induced liquid jet : evolution from shock/ bubble interaction to neurosurgical application (2009)
  • Author(s): Nakagawa A, Kumabe T, Ogawa Y, Hirano T, Nakano T, Takayama K, Tominaga T
  • Journal Title: Shock Waves
  • Peer Reviewed
• [Journal Article] Clinical implications of intraoperative infrared brain surface monitoring during superficial temporal artery-middle cerebral artery anastomosis in patients with moyamoya disease (2009)
  • Author(s): Nakagawa A, Fujimura M, Arafune T, Sakuma I, Tominaga T
  • Journal Title: J Neurosurg[Epub ahead of print]
  • Peer Reviewed
• [Journal Article] Magnetic resonance imaging for preoperative identification of the lenticulstriate arteries in insular glioma surgery (2009)
  • Author(s): Saito R, Kumabe T, Inoue T, Takada S, Yamashita Y, Kanamori M, Sonoda Y, Tominaga T
  • Journal Title: J Neurosurg[Epub ahead of print]
  • Peer Reviewed
• [Journal Article] Therapeutic efficacy of a polymeric micellar doxorubicin infused by convection-enhanced delivery against intracranial 9L brain tumor models (2009)
  • Author(s): Inoue T, Yamashita Y, Nishihara M, Sugiyama S, Sonoda Y, Kumabe T, Yokoyama M, Tominaga T
  • Journal Title: Neuol Oncol 11 Pages: 151-157
  • Peer Reviewed
• [Journal Article] Traumatic brain injury by blast waves. Insight from perspectives from shock wave physics (2009)
  • Author(s): Nakagawa A Manley GT Gean AD Rosenthal G Takayama K Tominaga T
  • Journal Title: Shock Waves (in press)
  • Peer Reviewed
• [Journal Article] パルスHo : YAGレーサーを用いた微小ジェットの臨床応用 : 東北大学における医工学連携の取り組み (2009)
  • Author(s): 中川敦寛, 隈部俊宏, 小川欣一, 平野孝幸, 橋本時忠, 中野徹, 亀井尚, 上之原広司, 高山和喜, 冨永悌二
  • Journal Title: 日本レーザー医学会誌 (in press)
• [Journal Article] Therapeutic efficacy of a polymeric micellar doxorubicin infused by convection-enhanced delivery against intracranial 9L brain tumor models (2009)
  • Author(s): Inoue T, Yamashita Y, Nishihara M, Sugiyama S, Sonoda Y, Kumabe T, Yokoyama M, Tominaga T.
  • Journal Title: Neuro Oncology 12(2) Pages: 151-157
  • Peer Reviewed
• [Journal Article] パルスレーザージェットメス : 神経膠腫手術への臨床応用 (2008)
  • Author(s): 中川敦寛, 隈部俊宏, 金森政之, 斎藤竜太, 平野孝幸, 高山和喜, 冨永悌二
  • Journal Title: No Shinkei Geka 36 Pages: 1005-1010
  • Peer Reviewed
• [Journal Article] Shock wave-induced brain injury in rat : Novel traumatic brain injury animal model (2008)
  • Author(s): Nakagawa A, Fujimura M, Kato K, Okuyama H, Hashimoto T, Takayama K, Tominaga T
  • Journal Title: Acta Neurochir (Suppl) 102 Pages: 421-424
  • Peer Reviewed
• [Journal Article] Intraoperative dynamic infrared brain surface blood flow monitoring during superficial temporal artery-middle cerebral artery anastomosis in patients with childhood moyamoya disease (2008)
  • Author(s): Nakagawa A, Fujimura M, Arafune T, Sakuma I, Tominaga T
  • Journal Title: Child's Nerv Syst 24 Pages: 1299-1305
  • Peer Reviewed
• [Journal Article] Intraoperative infrared brain surface blood flow monitoring during superficial temporal artery-middle cerebral artery anastomosis in a patient with moyamoya disease : Clinical implication of the gradation value in postoperative clinical course (2008)
  • Author(s): Nakagawa A, Fujimura M, Arafune T, Suzuki H, Sakuma I, Tominaga T
  • Journal Title: Acta Neurochir (Suppl) 102 Pages: 159-163
  • Peer Reviewed
• [Journal Article] Convection-enhanced delivery of polyethylene glycol-coated liposomal doxorubicin : characterization and efficacy in rat intracranial glioma models (2008)
  • Author(s): Kikuchi T, Saito R, Sugiyama S, Yamashita Y, Kumabe T, Krauze M, Bankiewicz K, Tominaga T
  • Journal Title: J Neurosurg 109 Pages: 867-873
  • Peer Reviewed
• [Journal Article] Clinical features and significance of negative motor response in intraoperative language mapping during awake craniotomy (2008)
  • Author(s): Nagamatsu K, Kumabe T, Suzuki K, Nakasato N, Sato K, Iizuka O, Kanamori M, Sonoda Y, Tominaga T
  • Journal Title: No Shinkei Geka 36 Pages: 693-700
  • Peer Reviewed
• [Journal Article] Pulsed laser-induced liquid jet microcatheter system for rapid and reliable fibrinolysis in acute cerebral embolisms (2008)
  • Author(s): Hirano T, Nakagawa A, Sato Y, Uenohara H, Takahashi A, Takayama K, Tominaga T
  • Journal Title: Minim Invas Neurosurg 51 51 Pages: 324-328
  • Peer Reviewed
• [Journal Article] Predictive factors for overall and progression-free survival, and dissemination in oligodendlial tumors (2008)
  • Author(s): Kanamori M, Kumabe T, Sonoda Y, Nishino Y, Watanabe M, Tominaga T
  • Journal Title: J Neurooncol [Epub ahead of print]
  • Peer Reviewed
• [Journal Article] Enhanced antitumor effect of combined-modality treatment using convection-enhanced delivery of hydrophilic nitrosourea with irradiation or systemic administration of temozolomide in intracranial brain tumor xenografts (2008)
  • Author(s): Sugiyama S, Yamashita Y, Kikuchi T, Sonoda Y, Kumabe T, Tominaga T
  • Journal Title: Neurol Res 30 Pages: 960-967
  • Peer Reviewed
• [Journal Article] Convection-enhanced delivery of polyethylene glycol-coated liposomal doxorubicin : characterization and efficacy in rat intracranial glioma models (2008)
  • Author(s): Kikuchi T Saito R Sugiyama S Yamashita Y Kumabe T Krauze M Bankiewicz K Tominaga T
  • Journal Title: Journal of Neurosurgery 109 Pages: 867-873
  • Peer Reviewed
• [Journal Article] Shock wave-induced brain injury in rat : Novel traumatic brain injury animal model (2008)
  • Author(s): Nakagawa A Fujimura M Kato K Okuyam H Hashimoto T Takayama K Tominaga T
  • Journal Title: Acta Neurochir (Wien) Suppl 102 Pages: 421-424
• [Journal Article] Intraoperative dynamic infrared brain surface blood flow monitoring during superficial temporal artery-middle cerebral artery anastomosis in patients with childhood moyamoya disease (2008)
  • Author(s): Nakagawa A Fujimura M Arafune T Sakuma I Tominaga T
  • Journal Title: Child's Nervous System 24 Pages: 1299-1305
  • Peer Reviewed
• [Journal Article] パルスレーザージェットメス : 神経膠腫手術への臨床応用 (2008)
  • Author(s): 中川敦寛, 隈部俊宏, 金森政之, 斎藤竜太, 平野孝幸, 高山和喜, 冨永悌二
  • Journal Title: 脳神経外科 36 Pages: 1005-1010
  • Peer Reviewed
• [Journal Article] Enhanced antitumor effect of combined-modality treatment using convection-enhanced delivery of hydrophilic nitrosourea with irradiation or systemic administration of temozolomide in intracranial brain tumor xenografts (2008)
  • Author(s): Sugiyama S, Yamashita Y, Kikuchi T, Sonoda Y, Kumabe T, Tominaga T.
  • Journal Title: Neurological Research 30 Pages: 960-967
  • Peer Reviewed
• [Journal Article] Pulsed laser-induced liquid jet microcatheter system for rapid and reliable fibrinolysis in acute cerebral embolisms (2008)
  • Author(s): Hirano T Nakagawa A Sato Y Uenohara H Takahashi A Takayama K Tominaga T
  • Journal Title: Minimally Invasive Neurosurgery 51 Pages: 324-328
  • Peer Reviewed
• [Journal Article] Intraoperative infrared brain surface blood flow monitoring during superficial temporal artery-middle cerebral artery anastomosis in a patient with moyamoya disease: Clinical implication of the gradation value in postoperative clinical course. (2008)
  • Author(s): Nakagawa A, Fujimura M, Arafune T, Suzuki H, Sakuma I, Tominaga T.
  • Journal Title: Acta Neurochir(Wien) (In press)
  • Peer Reviewed
• [Journal Article] Pressure-dependent effect of shock waves on rat brain : induction of neuronal apoptosis mediated by a caspase-dependent pathway (2007)
  • Author(s): Kato K, Fujimura M, Nakagawa A, Saito T, Ohki T, Takayama K, Tominaga T.
  • Journal Title: J Neurosurg 106 Pages: 667-676
  • Peer Reviewed
• [Journal Article] Pulsed Laser-Induced Liquid Jet Microcatheter System for Rapid and Reliable Fibrinolysis in Acute Cerebral Embolisms : Experiments on Safety and Preliminary Application in Porcine Cranial Vessels (2007)
  • Author(s): Sato Y, Nakagawa A, Hirano T, Ohki H, Uenohara H, Takayama K, Tominaga T
  • Journal Title: Minim Invas Neurosurg 50 Pages: 212-218
  • Peer Reviewed
• [Journal Article] Pressure-dependent effect of shock waves on rat brain: induction of neuronal apoptosismediated by a caspase-dependent pathway. (2007)
  • Author(s): Kato K, Fujimura M, Nakagawa A, Saito T, Ohki T, Takayama K, Tominaga T.
  • Journal Title: Journal of Neurosurgery 106 Pages: 667-676
  • Peer Reviewed
• [Journal Article] Pulsed Laser-Induced Liquid Jet Microcatheter System for Rapid and Reliable Fibrinolysis in Acute Cerebral Embolisms: Experiments on Safety and Preliminary Application in Porcine Cranial Vessels. (2007)
  • Author(s): Sato Y, Nakagawa A, Hirano T, Ohki H, Uenohara H, Takayama K, Tominaga T.
  • Journal Title: Minimally Invasive Neurosurgery 50 Pages: 212-218
  • Peer Reviewed
• [Journal Article] Pressure-dependent effect of shock wave on rat brain : induction of neuronal apoptosis mediated by caspase-dependent pathway. (2007)
  • Author(s): Kato K, Fujimura M, Nakagawa A, Saito A, Ohki T, Takayama K, Tominaga T
  • Journal Title: J Neurosurg (in press)
• [Journal Article] Application of Shock Waves for the Treatment of Bone Defect in the Skull : Experiment on Young Rat Calvalium. (2006)
  • Author(s): Nakagawa A, Hirano T, Ezura M, Takahashi A, Takayama K, Tominaga T
  • Journal Title: Future Medical Engineering Based on Bionanotechnology. Proceedings of the Final Symposium of the Tohoku University 21 st Century Center of Excellence Program. Pages: 1107-1114
• [Journal Article] Biological Effect of Shock Waves : Brain Damage By Shock Waves in Rats - Pressure Dependence. (2006)
  • Author(s): Kato K, Fujimura M, Nakagawa A, Saito A, Tominaga T
  • Journal Title: Future Medical Engineering Based on Bionanotechnology. Proceedings of the Final Symposium of the Tohoku University 21 st Century Center of Excellence Program. Pages: 949-954
• [Journal Article] Application of Underwater Shock Wave and Laser-Induced Liquid Jet to Neurosurgery. (2006)
  • Author(s): Tominaga T, Nakagawa A, Hirano T, Sato J, Kato K, Takayama K
  • Journal Title: Shock Waves 15 Pages: 55-67
• [Journal Article] Development of shock wave assisted therapeutic devices and establishment of shock wave therapy. (2006)
  • Author(s): Hosseini SH, Menezes V, Moosagi-Nejad S, Ohki T, Nakagawa A, Tominaga T, Takayama K.
  • Journal Title: Minim Invasive Ther Allied Technol 15 Pages: 230-240
• [Journal Article] Disease targeting therapy for neurosurgical disorders : molecular targeting and drug delivery (2006)
  • Author(s): Saito R, Kumabe T, Tominaga T.
  • Journal Title: No Shinkei Geka 34 Pages: 1157-1165
• [Presentation] パルスHo : YAGレーザーを用いた微小噴流生成装置の臨床応用:東北大学における医工学連携の取り組み (2008)
  • Author(s): 中川敦寛, 隈部俊宏, 金森政之, 小川欣一, 橋本時忠, 渡辺みか, 斉藤竜太, 平野孝幸, 高山和喜, 冨永悌二
  • Organizer: 第29回日本レーザー医学会総会
  • Place of Presentation: 東京 東京工科大学
  • Year and Date: 2008-11-15
• [Presentation] パルスHo : YAGレーザーを用いた微小噴流生成装置の臨床応用 : 東北大学における医工学連携の取り組み (2008)
  • Author(s): 中川敦寛, 隈部俊宏, 金森政之, 小川欣一, 橋本時忠, 渡辺みか, 斉藤竜太, 平野孝幸, 高山和喜, 冨永悌二
  • Organizer: 第29回日本レーザー医学会総会
  • Place of Presentation: 東京東京工科大学
  • Year and Date: 2008-11-15
• [Presentation] びまん性軸索損傷症例におけるdiffusion tensor imagingを用いた白質損傷評価 : 高次脳機能との関連 (2008)
  • Author(s): 中川敦寛, 野村亮介, 杉山鎌, 湯澤寛尚, 山本修三, 日向野修一, 篠澤洋太郎, 冨永悌二
  • Organizer: 第36回日本救急医学会総会学術集会
  • Place of Presentation: 札幌ロイトン札幌
  • Year and Date: 2008-10-14
• [Presentation] 細血管温存可能な内視鏡手術デバイス(パルスレーザージェットメス)の開発 (2008)
  • Author(s): 中川敦寛, 芳賀洋一, 孫明宇, 藤村幹, 隈部俊宏, 金森政之, 小川欣一,中野徹, 橋本時忠, 船本健一, 高山和喜, 冨永悌二
  • Organizer: 東北大学若手研究者萌芽研究育成プログラム研究成果発表会
  • Place of Presentation: 仙台 東北大学 さくらホール
  • Year and Date: 2008-07-16
• [Presentation] 細血管温存可能な内視鏡手術デバイス(パルスレーザージエットメス)の開発 (2008)
  • Author(s): 中川敦寛, 芳賀洋一, 孫明宇, 藤村幹, 隈部俊宏, 金森政之, 小川欣一, 金森政之, 中野徹, 橋本時船, 本健一, 高山和喜, 冨永悌二
  • Organizer: 東北大学若手研究者萌芽研究育成プログラム研究成果発表会
  • Place of Presentation: 仙台東北大学さくらホール
  • Year and Date: 2008-07-16
• [Presentation] びまん性軸索損傷存在診断/高次脳機能障害との関連 (2008)
  • Author(s): 中川敦寛, 杉山謙, 冨永悌二
  • Organizer: 第15回仙台外傷症例検討会
  • Place of Presentation: 仙台東北大学医学部
  • Year and Date: 2008-06-21
• [Presentation] レーザージェットメスによる穿通枝温存下悪性神経膠腫摘出術 : 8例の経験を踏まえて (2008)
  • Author(s): 中川敦寛, 隈部俊宏, 金森政之, 渡辺みか, 斉藤竜太, 平野孝幸, 高山和喜, 冨永悌二
  • Organizer: 第17回脳神経外科手術と機器学会
  • Place of Presentation: 長崎ブリックホール
  • Year and Date: 2008-04-19
• [Presentation] Application of pulsed laser-induced liquid jet for glioma surgery (2007)
  • Author(s): Nakagawa A, Kumabe T, Kanamori M, Sasaki K, Saito R, Takayama K, Tominaga T
  • Organizer: Society for Medical Innovation and Techonology
  • Place of Presentation: Sendai, Tokyu Hotel
  • Year and Date: 2007-11-21
• [Presentation] Intraoperative brain surface monitoring using IRIS-V infrared imaging in neurological procedures : Experience in moyamoya disease (2007)
  • Author(s): Nakagawa A, Fujimura M, Arafune T, Yamaguchi T, Kobayashi E, Sakuma I, Tominaga T
  • Organizer: Society for Medical Innovation and Techonology
  • Place of Presentation: Sendai, Tokyu Hotel
  • Year and Date: 2007-11-21
• [Presentation] 衝撃波による脳組織損傷 : 圧損傷閾値の同定と損傷機序に関する検討 (2007)
  • Author(s): 中川敦寛, 藤村幹, 加藤薫子, 奥山洋信, 斉藤敦志, 高山和喜, 冨永悌二
  • Organizer: 第8回日本分子脳神経外科学会
  • Place of Presentation: 神戸兵庫医科大学平成記念会館
  • Year and Date: 2007-08-31
• [Presentation] 衝撃波による脳組織損傷:圧損傷閾値の同定と損傷機序に関する検討 (2007)
  • Author(s): 中川敦寛, 藤村幹, 加藤薫子, 奥山洋信, 斉藤敦志, 高山和喜, 冨永悌二
  • Organizer: 第8回日本分子脳神経外科学会
  • Place of Presentation: 神戸
  • Year and Date: 2007-08-31
• [Presentation] Shock Wave induced brain injury : Pathological evaluation using rat (2007)
  • Author(s): Nakagawa A, Fujimura M, Kato K, Okuyama H, Takayama K, Tominaga T
  • Organizer: 13 th International Symposium on ICP and Brain Monitoring
  • Place of Presentation: The Palace Hotel,San Francisco
  • Year and Date: 2007-07-25
• [Presentation] Shock Wave induced brain injury: Pathological evaluation using rat (2007)
  • Author(s): Nakagawa A, Fujimura M, Kato K, Okuyama H, Takayama K, Tominaga T.
  • Organizer: 13 th International Symposium on ICP and Brain Monitoring
  • Place of Presentation: San Francisco
  • Year and Date: 2007-07-25
• [Presentation] Intraoperative brain surface monitoring using IRIS-V infrared imaging system in moyamoya disease (2007)
  • Author(s): Nakagawa A, Fujimura M, Arafune T, Yamaguchi T, Sakuma I, Tominaga T
  • Organizer: 13 th International Symposium on ICP and Brain Monitoring
  • Place of Presentation: The Palace Hotel, San Francisco
  • Year and Date: 2007-07-23
• [Presentation] 衝撃波による脳神経組織損-閾値・機序の解明- (2007)
  • Author(s): 加藤薫子, 藤村幹, 中川敦寛, 斉藤敦志, 奥山洋信, 高山和喜, 冨永悌二
  • Organizer: 第26回日本脳神経超音波学会総会
  • Place of Presentation: 横浜 パシフィコ横浜
  • Year and Date: 2007-07-09
• [Presentation] 衝撃波による脳神経組織損傷 : 過剰圧依存的損傷とアポトーシス発現に関する検討 (2007)
  • Author(s): 加藤薫子, 中川敦寛, 藤村幹, 斉藤敦志, 奥山洋信, 高山和喜, 冨永悌二
  • Organizer: 第46回日本生体医工学会
  • Place of Presentation: 仙台 仙台国際センター
  • Year and Date: 2007-04-25
• [Remarks] 衝撃波損傷(blast wave injury)モデルにおける高次脳機能解析、分子生物学的解析に関しては今後、Walter Reed Army Medical Center / National Naval Medical Center(Bethesda, MD)の支援を得て、カリフォルニア大学サンフランシスコ校・脳脊髄外傷センター(San Francisco, CA)との共同研究へ発展・継続の見込み。
• [Remarks] 本研究を含む研究内容はNational Navy Medical Center(2009年8月26日:Bethesda, MD)、National Institute of Health(2010年4月)に招待講演として発表決定。
• [Remarks] 2009年米国Congress of Neurosurgeons(2009年10月24-29日 New Orleans)で本研究を含む内容はTop Ten Abstractに選出された(Nakagawa A, Fujimura M, Kato K, Okuyama H, Hashimoto T, Takayama K, Tominaga T. Mechanism of Primary Blast Injury : Insight from Microexplosive Generated Shock Wave-induced Brain Injury Animal Model and Engineering Experiments)
• [Patent(Industrial Property Rights)] 流体噴射装置とその駆動方法 (2008)
  • Inventor(s): セイコーエプソン株式会社高山和喜, 冨永悌二, 平野孝幸, 中川敦寛
  • Industrial Property Rights Holder: セイコーエプソン株式会社
  • Filing Date: 2008-10-20
  • Overseas