The role of molecular imaging in predicting the development of aortic aneurysm.

• Project/Area Number: 18K07770
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 52040:Radiological sciences-related
• Research Institution: Keio University
• Principal Investigator: Nakahara Takehiro 慶應義塾大学, 医学部(信濃町), 特任助教 (00599540)
• Co-Investigator(Kenkyū-buntansha): 中原 理紀 慶應義塾大学, 医学部(信濃町), 准教授 (10317240) ; 岩渕 雄 慶應義塾大学, 医学部(信濃町), 助教 (90573262) ; 陣崎 雅弘 慶應義塾大学, 医学部(信濃町), 教授 (80216259)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: PET / Aortic aneurysm / NaF / FDG / 大動脈瘤 / CT / 石灰化 / 微小石灰化 / PET/CT / 分子イメージング

Outline of Final Research Achievements

Abdominal aortic aneurysms (AAAs) expand over time and increase the risk of fatal rupture. We studied the role of inflammation, using 18F-FDG PET/CT and lesion necrosis, using 18F-NaF PET/CT in the evolution of experimental abdominal aortic aneurysm (AAA).
We employed male rats and simulated in the lower abdominal aorta by placing of 0.5M CaCl2 soaked gauze while the control group were simulated with gauze soaked in saline. The animals were imaged on a micro PET/CT with both NaF and FDG at 1, 2, 4, 6, and 8 weeks after surgery. Abdominal cross-section area increased in each group and was significantly higher in all aneurysm groups compared with the vehicle control animals. Abdominal FDG uptake was significantly higher at 1 and 2 weeks compared with control, while abdominal NaF uptake was significantly higher at all time points.
In conclusion, NaF uptake was elevated at all time points, and appears to be a more sensitive indicator of evolution of the aneurysm in this model.

Academic Significance and Societal Importance of the Research Achievements

大動脈瘤は、突然破裂し死亡率は高いが、増大や破裂を予測する検査は今のところ確立されていない。血管径の増大から破裂の確率を推定するに留まる。同じ血管径でも、どの症例が破裂するか予測する検査が必要である。大動脈瘤の動物モデルを用いた今回の検討では、大動脈瘤の進展予測にFDG・NaFを用いた核医学的評価（PET/CT）が有益であることが示された。今後は臨床研究に発展させ、実臨床において同様にFDG・NaFを用いた核医学的評価（PET/CT）が有益かを検討していく。もし、臨床においても同様の結果が示されれば、患者ごとにより適した治療法が導きだされ、大動脈瘤の死亡率低下に寄与すると考えている。

Research Products

• [Journal Article] Temporal relationship between 18F-sodium fluoride uptake in the abdominal aorta and evolution of CT-verified vascular calcification. (2019)
  • Author(s): Nakahara T, Narula J, Fox JJ, Jinzaki M, Strauss HW.
  • Journal Title: J Nucl Cardiol. Volume: Inpress Issue: 5 Pages: 1936-1945
  • DOI: 10.1007/s12350-019-01934-2
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Vascular Calcification: The Evolving Relationship of Vascular Calcification to Major Acute Coronary Events. (2019)
  • Author(s): Strauss HW, Nakahara T, Narula N, Narula J.
  • Journal Title: J Nucl Med Volume: 60 Issue: 9 Pages: 1207-1212
  • DOI: 10.2967/jnumed.119.230276
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] 18F-Fluoride Positron Emission Tomographic Imaging of Penile Arteries and Erectile Dysfunction (2019)
  • Author(s): Nakahara Takehiro、Narula Jagat、Tijssen Jan G.P.、Agarwal Sunil、Chowdhury Mohammed M.、Coughlin Patrick A.、Dweck Marc R.、Rudd James H.F.、Jinzaki Masahiro、Mulhall John、Strauss H. William
  • Journal Title: Journal of the American College of Cardiology Volume: 73 Issue: 12 Pages: 1386-1394
  • DOI: 10.1016/j.jacc.2018.10.076
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] NaF uptake in unstable plaque: what does fluoride uptake mean? (2018)
  • Author(s): Nakahara T, Narula J, Strauss HW.
  • Journal Title: Eur J Nucl Med Mol Imaging. Volume: 45 Issue: 13 Pages: 2250-2252
  • DOI: 10.1007/s00259-018-4177-y
  • Peer Reviewed / Int'l Joint Research
• [Presentation] The combination of 18F-FDG and 18F-NaF uptake predict the development of abdominal aortic aneurysm in rat model (2020)
  • Author(s): Takehiro Nakahara
  • Organizer: the 2020 SNMMI (Society of Nuclear Medicine and Molecular Imaging) Annual Meeting
  • Int'l Joint Research
• [Presentation] 分子イメージングによる不安定プラークの検出 ：基礎から臨床へ (2019)
  • Author(s): 中原健裕、中原理紀、陣崎 雅弘
  • Organizer: 第29回日本心臓核医学会総会・学術大会
  • Invited
• [Presentation] Molecular imaging for vulnerable plaque (2019)
  • Author(s): 中原健裕
  • Organizer: PCI Optimization by Physiology And Imaging
  • Invited
• [Presentation] 18F-Flouride Uptake in Penile Arteries Does it Represent Atherosclerotic Basis of Erectile Dysfunction in Patients with Prostate Cancer (2018)
  • Author(s): Nakahara T, Narula J, Tijssen JGP, Agarwal S, Chowdhury MM, Coughlin PA, Dweck MR, Rudd JHF, Jinzaki M, Mulhall J, Strauss HW.
  • Organizer: The American College of Cardiology's 68th Annual Scientific Session
  • Int'l Joint Research
• [Presentation] 18F-fluoride uptake in Penile Arteries and Erectile Dysfunction. (2018)
  • Author(s): Takehiro Nakahara, Jagat Narula, Sunil Agarwal, Mohammed M. Chowdhury, Patrick A. Coughlin, Marc Dweck, James Rudd, Masahiro Jinzaki,, John Mulhall, H. William Strauss
  • Organizer: SNMMI 2018 Philadelphia USA June 23-26
  • Int'l Joint Research
• [Presentation] Molecular imaging for vulnerable plaque (2018)
  • Author(s): Takehiro Nakahara
  • Organizer: PCI Optimization by Physiology And Imaging 2018
  • Invited
• [Presentation] 99mTc-Duramycin imaging detects doxorubicin cardiotoxicity before onset of ventricular dysfunction. (2018)
  • Author(s): Takehiro Nakahara1,2,3, Artiom D. Petrov1, Takashi Tanimoto1, Nezam Haider1, Navneet Narula4, Farhan Chaudhry1, Jeffrey A Mattis5, Brian D. Gray5, Koon Yan Pak5, Gagan Sahai1, Anry Terersten1, Aarti Bhardwaj1, Partho P. Sengupta1, Marc R Dweck1, H. William Strauss1,2, and Jagat Narula1
  • Organizer: 第58回日本核医学会学術総会