Infiltrative drug delivery by additional application of shock wave on pulsed water jet.

• Project/Area Number: 15H04945
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Neurosurgery
• Research Institution: Tohoku University
• Principal Investigator: NAKAGAWA Atsuhiro 東北大学, 大学病院, 特任准教授 (10447162)
• Co-Investigator(Kenkyū-buntansha): 中川 桂一 東京大学, 大学院工学系研究科(工学部), 講師 (00737926) ; 川口 奉洋 東北大学, 医学系研究科, 非常勤講師 (10723447) ; 大谷 清伸 東北大学, 流体科学研究所, 特任准教授 (80536748)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥16,640,000 (Direct Cost: ¥12,800,000、Indirect Cost: ¥3,840,000); Fiscal Year 2017: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2016: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2015: ¥7,540,000 (Direct Cost: ¥5,800,000、Indirect Cost: ¥1,740,000)
• Keywords: 薬剤デリバリー / 医工連携 / ジェットメス / 医療機器開発 / 衝撃波 / ドラッグデリバリー

Outline of Final Research Achievements

Water jet dissection has been clinically applied to achieve maximum resection of well-demarcated lesion under preservation of small vessels. However, removal of infiltered lesion is still challenging. On the other hands, shock waves (SW) changes permeability of membrane transiently. The purpose of present study is to develop pulsed water jet that can infilter the liquid from the surface of dissection plane using low overpressure SW which do not cause brain damage.
Pulsed water jet+ SW have been applied in the swine brain after development of prototype of generator. Relationship between energy, frequency, and water amount were evaluated by high speed photography, pressure measurement, and test in phantom model. The histological specimen and intraoperative finding showed the infiltration of pigmented liquid into brain parenchyma without significant damage as deep as 3 mm. Present results showed possibility of injecting drug into brain parenchyma without significant brain damage using SW.

Research Products

• [Journal Article] Water veil effect to control splashing from the pulsed water jet device: Minimization of the potential risk of dissemination using surgical aspirators. (2018)
  • Author(s): Nakayashiki A, Kawaguchi T, Nakagawa A, Sato M, Mochizuki F, Endo T, Tominaga T.
  • Journal Title: J Neurol Surg A Cent Eur Neurosurg (2018, in press) Volume: 印刷中 Issue: 04 Pages: 309-315
  • DOI: 10.1055/s-0037-1608836
  • Peer Reviewed
• [Journal Article] Application of actuator-driven pulsed water jet for coronary artery bypass grafting: assessment in a swine model. (2018)
  • Author(s): Suzuki T. Kawamoto S, Nakagawa A, Endo T, Tominaga T, Akiyama M, Adachi O, Kumagai K, Saiki Y.
  • Journal Title: J Artif Organ Volume: 21(2) Issue: 2 Pages: 247-253
  • DOI: 10.1007/s10047-017-1008-z
  • Peer Reviewed
• [Journal Article] Pulsed laser-induced liquid jet: Evolution from shock / bubble interaction to neurosurgical application. (2017)
  • Author(s): Nakagawa A, Kumabe T, Ogawa Y, Hirano T, Kawaguchi T, Ohtani K, Nakano T, Sato C, Yamada M, Washio T, Arafune T, Tsujita T, Konno A, Satomi S, Takayama K, Tominaga T.
  • Journal Title: Shock Waves Volume: 27 Pages: 1-14
  • Peer Reviewed
• [Journal Article] Primary blast-induced traumatic brain injury: lessons from lithotripsy. (2017)
  • Author(s): Nakagawa A, Ohtani K, Armonda R, Tomita H, Sakuma A, Mugikura S, Takayama K, Kushimoto S, Tominaga T.
  • Journal Title: Shock Waves Volume: 27(6) Pages: 863-878
  • Peer Reviewed
• [Journal Article] Application of actuator-driven pulsed water jet in aneurysmal subarachnoid hemorrhage surgery: its effectiveness for dissection around ruptured aneurysmal walls and subarachnoid clot removal. (2017)
  • Author(s): Endo H, Endo T, Nakagawa A, Fujimura M, Tominaga T.
  • Journal Title: Neurosurg Rev. Volume: 印刷中 Issue: 3 Pages: 485-493
  • DOI: 10.1007/s10143-016-0809-5
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] The Piezo Actuator-Driven Pulsed Water Jet System for Minimizing Renal Damage after Off-Clamp Laparoscopic Partial Nephrectomy (2017)
  • Author(s): Kamiyama Y, Yamashita S, Nakagawa A, Fujii S, Mitsuzuka K, Kaiho Y, Ito A, Abe T, Tominaga T, Arai Y.
  • Journal Title: The Tohoku Journal of Experimental Medicine Volume: 243 Issue: 1 Pages: 57-65
  • DOI: 10.1620/tjem.243.57
  • NAID: 130006088851
  • ISSN: 0040-8727, 1349-3329
  • Peer Reviewed
• [Journal Article] Clinical Characteristics and Outcome in Elderly Patients with Traumatic Brain Injury: For Establishment of Management Strategy (2017)
  • Author(s): Karibe H, Hayashi T, Narisawa A, Kameyama M, Nakagawa A, Tominaga T.
  • Journal Title: Neurologia medico-chirurgica Volume: 57 Issue: 8 Pages: 418-425
  • DOI: 10.2176/nmc.st.2017-0058
  • NAID: 130005974098
  • ISSN: 0470-8105, 1349-8029
  • Peer Reviewed
• [Journal Article] New Application of Actuator-Driven Pulsed Water Jet for Spinal Cord Dissection: An Experimental Study in Pigs. (2017)
  • Author(s): Endo T, Wenting J, Nakagawa A, Endo H, Sagae Y, Iwasaki M, Tominaga T.
  • Journal Title: J Neurol Surg A Cent Eur Neurosurg. Volume: 78(2) Issue: 02 Pages: 137-143
  • DOI: 10.1055/s-0036-1584919
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] A laser-induced pulsed water jet for layer-selective submucosal dissection of the esophagus. (2016)
  • Author(s): Nakano T, Sato C, Yamada M, Nakagawa A, Yamamoto H, Fujishima F, Tominaga T, Satomi S, Ohuchi N.
  • Journal Title: Laser Ther. Volume: 25(3) Pages: 185-191
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Use of water jet instruments in gastrointestinal endoscopy. (2016)
  • Author(s): Nakano T, Sato C, Sakurai T, Kamei T, Nakagawa A, Ohuchi N
  • Journal Title: World Journal of Gastrointestinal Endoscopy Volume: 8 Issue: 3 Pages: 122-127
  • DOI: 10.4253/wjge.v8.i3.122
  • Peer Reviewed / Open Access
• [Journal Article] Evaluation of a newly developed piezo actuator-driveb pulsed water jet system for liver resection in a surviving swine model. (2016)
  • Author(s): Nakanishi C, Nakano T, Nakagawa A, Sato C, Yamada M, Kawagishi N, Tomonaga T, Ohuchi N
  • Journal Title: BioMedical Engineering OnLine Volume: 15 Issue: 1 Pages: 9-9
  • DOI: 10.1186/s12938-016-0126-9
  • Peer Reviewed / Open Access
• [Journal Article] Ventricle wall dissection and vascular preservation with the pulsed water jet device: novel tissue dissector for flexible neuroendoscopic surgery. (2016)
  • Author(s): Kawaguchi T, Nakagawa A, Endo T, Fujimura M, Sonoda Y, Tominaga T.
  • Journal Title: J Neurosurg. Volume: 124(3) Issue: 3 Pages: 817-22
  • DOI: 10.3171/2015.3.jns142121
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Local convection-enhanced delivery of an anti-CD40 agonistic monoclonal antibody induces antitumor effects in mouse glioma models. (2016)
  • Author(s): Shoji T, Saito R, Chonan M, Shibahara I, Sato A, Kanamori M, Sonoda Y, Kondo T, Ishii N, Tominaga T.
  • Journal Title: Neuro Oncol. Volume: 18(8) Issue: 8 Pages: 1120-8
  • DOI: 10.1093/neuonc/now023
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Intraparenchymal ultrasound application and improved distribution of infusate with convection-enhanced delivery in rodent and nonhuman primate brain. (2016)
  • Author(s): Mano Y, Saito R, Haga Y, Matsunaga T, Zhang R, Chonan M, Haryu S, Shoji T, Sato A, Sonoda Y, Tsuruoka N, Nishiyachi K, Sumiyoshi A, Nonaka H, Kawashima R, Tominaga T.
  • Journal Title: J Neurosurg. Volume: 124(5) Issue: 5 Pages: 1490-500
  • DOI: 10.3171/2015.3.jns142152
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] 「真の」アンメットニーズに基づいた医療機器開発：東北大学病院ベッドサイドソリューションプログラム（ASU）とバイオデザイン． (2016)
  • Author(s): 中川敦寛、池田浩治、池野文昭、伊藤香織、五十嵐修一、高橋千明、冨永悌二．
  • Journal Title: 機能的脳神経外科 Volume: 55 Pages: 73-9
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] パルスレーザージェットメス：原理開発から臨床試験まで． (2016)
  • Author(s): 中川敦寛、川口奉洋、遠藤俊毅、小川欣一、山下慎一、荒船龍彦、加藤峰士、鷲尾利克、荒井陽一、冨永悌二．
  • Journal Title: The review of laser engineering : レーザー学会誌 Volume: 44(3) Pages: 165-168
  • NAID: 130007957190
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Pulsed Laser-induced Liquid Jet System for Treatment of Sellar and Parasellar Tumors: Safety Evaluation. (2015)
  • Author(s): Nakagawa A, Ogawa Y, Amano K, Ishii Y, Tahara S, Horiguchi K, Kawamata T, Yano S, Arafune T, Washio T, Kuratsu JI, Saeki N, Okada Y, Teramoto A, Tominaga T.
  • Journal Title: J Neurol Surg A Cent Eur Neurosurg. Volume: 76（6） Pages: 473-482
  • Peer Reviewed
• [Journal Article] Use of Actuator-Driven Pulsed Water Jet in Brain and Spinal Cord Cavernous Malformations Resection. (2015)
  • Author(s): Endo. T, Takahashi Y, Nakagawa A, Niizuma K, Fujimura M, Tominaga T.
  • Journal Title: Neurosurgery Volume: 11(Suppl 3) Pages: 394-403
  • Peer Reviewed
• [Journal Article] Intraventricular hemorrhage on initial computed tomography as marker of diffuse axonal injury after traumatic brain injury. (2015)
  • Author(s): Mata-Mbenba D, Mugikura S, Nakagawa A, Murata T, Kato Y, Tatewaki Y, Li Li, Takase K, Ishii K, Kushimoto S, Tominaga T, Takahashi S.
  • Journal Title: J Neurotrauma Volume: 32(5) Pages: 359-365
  • Peer Reviewed
• [Journal Article] パルスウォータージェットメスを用いた精密手術用治療器. (2015)
  • Author(s): 中川敦寛、遠藤敏毅、川口奉洋、冨永悌二．
  • Journal Title: 精密工学誌 Volume: 81(4) Pages: 293-297
  • NAID: 130005060668
  • Peer Reviewed
• [Journal Article] 生体模擬物質中の衝撃波伝播挙動． (2015)
  • Author(s): 大谷清伸, 中川敦寛, 中川桂一．
  • Journal Title: M&M2015 火薬学会秋季研究発表会 Volume: 2015 Pages: 1-4
  • Peer Reviewed
• [Journal Article] 模擬モデルを用いた爆風による外傷性脳損傷機序解明に関する数値模擬． (2015)
  • Author(s): 大谷清伸, 中川敦寛, 沼田大樹．
  • Journal Title: M&M2015 材料力学カンファレンスプロシーディング Volume: 2015 Pages: 369-371
  • Peer Reviewed
• [Presentation] 内視鏡分野における医療機器開発：最近の動向と今後の方向性 (2017)
  • Author(s): 中川敦寛、冨永悌二
  • Organizer: 第28回 中部神経内視鏡研究会 「新たな神経内視鏡手術の開発と発展」
• [Presentation] Biological effect of shock waves: Understanding of mechanism of blast-induced traumatic injury to medical application. (2017)
  • Author(s): Nakagawa A, Ohtani K, Armonda R, Takayama K, Tominaga T.
  • Organizer: The 31st International Symposium on Shock Waves (ISSW31)
  • Int'l Joint Research / Invited
• [Presentation] 頭部外傷後の社会復帰支援 (2017)
  • Author(s): 中川敦寛、富田博秋、麦倉俊司、古谷桂子、八木橋真央、佐久間篤、近田祐介、今井啓道、飯塚統、小林直也、工藤大介、 大沢伸一郎、刈部博、上之原広司、Geoffrey Manley、久志本成樹、冨永悌二．
  • Organizer: 日本脳神経外科学会第76回学術総会
• [Presentation] 社会復帰を目指す救急医療：長期予後を改善する (2017)
  • Author(s): 中川敦寛、富田博秋、麦倉俊司、古谷桂子、八木橋真央、佐久間篤、近田祐介、今井啓道、飯塚統、小林直也、工藤大介、 大沢伸一郎、刈部博、上之原広司、Geoffrey Manley、久志本成樹、冨永悌二．
  • Organizer: 第45回日本救急医学会総会
• [Presentation] 救急医療とICT：ビッグデータ臨床研究の現況と展望 (2017)
  • Author(s): 中川敦寛、小林直也、工藤大介、、近田祐介、麦倉俊司、古谷桂子、富田博秋、八木橋真央、佐久間篤、今井啓道、大沢伸一郎、刈部博、Geoffrey Manley、久志本成樹、冨永悌二．
  • Organizer: 第45回日本救急医学会総会
• [Presentation] Mechanism of shock wave propagation within the cell: Experimental model． (2017)
  • Author(s): Nakagawa A, Ohtani K, Tominaga T.
  • Organizer: ICFD 2017
  • Int'l Joint Research
• [Presentation] Mechanisms of Primary Blast-Induced Traumatic Brain Injury: Insights from 30 years of Shock-Wave Research at Tohoku University． (2017)
  • Author(s): Nakagawa A, Ohtani K, Takayama K, Tominaga T．
  • Organizer: The 6th International Symposium on Energetic Materials and their Applications Tohoku University
  • Int'l Joint Research
• [Presentation] last-induced traumatic brain injury: Clinical features, Mechanism, Prevention (2017)
  • Author(s): Nakagawa A, Ohtani K, Sakuma A, Yagihashi M, Nakanishi C, Karasawa H, Yamashita S, Matsui N, Terui Y, Kudo S, Saito A, Inoue S, Furuya K, Tsujita T, Konno A, Tominaga T
  • Organizer: 4ｔｈＡＣＤＴ
  • Int'l Joint Research
• [Presentation] ニーズに基づいた医療機器開発 - 東北大学ベッドサイドソリューションプログラム（インフラ）とバイオデザイン（方法） (2016)
  • Author(s): 中川敦寛、工藤大介、野村亮介、佐藤武揚、宮川乃理子、入野田崇、川副友、吉田良太朗、久志本成樹、冨永悌二．
  • Organizer: 第44回日本救急医学会学術総会
  • Place of Presentation: 新高輪プリンスホテル（東京都港区）
  • Year and Date: 2016-11-19
• [Presentation] 最大限の病変摘出と機能温存の両立を支援するパルスレーザージェットメス：薬事承認申請、市場創出に向けた取り組み. (2016)
  • Author(s): 中川敦寛、小川欣一、遠藤俊毅、川口奉洋、齋藤竜太、藤村幹、山下慎一、神山佳展、中野徹、中西史、櫻井直、國方彦志、鈴木智之、冨永悌二.
  • Organizer: 第37回 日本レーザー医学会総会
  • Place of Presentation: 旭川グランドホテル(北海道旭川市）
  • Year and Date: 2016-10-21
• [Presentation] Mechanism of shock wave propagation within the cell. (2016)
  • Author(s): Nakagawa A, Ohtani K, Harada N, Tominaga T.
  • Organizer: IFS Collaborative Research Forum (AFI-2016),
  • Place of Presentation: Sendai Kokusai Center（宮城県仙台市）
  • Year and Date: 2016-10-11
  • Int'l Joint Research
• [Presentation] 高齢者頭部外傷の現状 宮城県頭部外傷研究会2013年解析から． (2016)
  • Author(s): 中川敦寛、刈部博、亀山元信、麦倉俊司、Daddy Matas、古谷桂子、石ケ森朝香、上之原広司、吉田昌弘、荒井啓晶、西村真実、遠藤英徳、成田徳雄、石川修一、高橋康、川口奉洋、久志本成樹、冨永悌二．
  • Organizer: 第70回日本脳神経外科学会総会
  • Place of Presentation: 福岡国際会議場（福岡県福岡市）
  • Year and Date: 2016-09-28
• [Presentation] Maxillofacial fractures in patients with closed head trauma: prevalence and association with intracranial lesions (Dr. Daddy Mata-Mbembaの代行）． (2016)
  • Author(s): Matas D, Mugikura S, Nakagawa A, Tominaga T．
  • Organizer: 16th International Symposium on Intracranial Pressure（Boston）
  • Place of Presentation: MIT Boston, MA（USA Boston)
  • Year and Date: 2016-06-28
  • Int'l Joint Research
• [Presentation] Profile of traumatic brain injury in Miyagi prefecture 2013. (2016)
  • Author(s): Nakagawa A, Karibe H, Kameyama M, Uenohara H, Yoshida M, Arai M, Kawaguchi T, Tominaga T.
  • Organizer: 16th International Symposium on Intracranial Pressure（Boston）
  • Place of Presentation: MIT Boston, MA（USA Boston)
  • Year and Date: 2016-06-28
  • Int'l Joint Research
• [Presentation] Mechanism of bTBI: Evaluation of wave transmission by shock wave brain injury model． (2016)
  • Author(s): Nakagawa A, Ohtani K, Nakagawa K, Tominaga T．
  • Organizer: 16th International Symposium on Intracranial Pressure（Boston）
  • Place of Presentation: MIT Boston, MA（USA Boston)
  • Year and Date: 2016-06-28
  • Int'l Joint Research
• [Presentation] Mechanism of bTBI: Insights from shock wave research． (2016)
  • Author(s): Nakagawa A, Ohtani K, Armonda R, Tominaga T．
  • Organizer: Japan-US Technical Information Exchange Forum on Blast Injury (JUFBI 2016)
  • Place of Presentation: ニュー山王ホテル（東京都港区）
  • Year and Date: 2016-06-13
  • Int'l Joint Research
• [Presentation] 外傷性脳損傷 頭蓋顔面損傷の急性期から慢性期までの至適治療：神経外傷医の観点から． (2016)
  • Author(s): 中川敦寛、今井啓道、麦倉俊司、川口奉洋、工藤大介、Daddy Matas、佐藤顕光、館正弘、久志本成樹、冨永悌二．
  • Organizer: 第59回日本形成外科学会総会・学術集会
  • Place of Presentation: 福岡国際会議場（福岡県福岡市）
  • Year and Date: 2016-04-13
• [Book] 新NS NOWシリーズ14 脳・脊髄外傷の治療 (2018)
  • Author(s): 中川敦寛、大谷清伸、富田博秋、久志本成樹、Rocco Armonda、冨永悌二．
  • Publisher: メジカルビュー社
• [Patent(Industrial Property Rights)] 薬剤噴流生成装置、及び薬剤噴流生成装置の薬剤噴流生成方法 (2017)
  • Inventor(s): 中川敦寛、川口奉洋、冨永悌二、金田道寛
  • Industrial Property Rights Holder: 中川敦寛、川口奉洋、冨永悌二、金田道寛
  • Industrial Property Rights Type: 特許
  • Filing Date: 2017-01-20
  • Overseas
• [Patent(Industrial Property Rights)] 噴流生成装置、及び噴流生成装置の噴流生成方法 (2016)
  • Inventor(s): 中川敦寛、川口奉洋、冨永悌二、金田道寛
  • Industrial Property Rights Holder: 中川敦寛、川口奉洋、冨永悌二、金田道寛
  • Industrial Property Rights Type: 特許
  • Filing Date: 2016-08-25
  • Overseas