Permeability Imaging using Simultaneous Dynamic PET and Arterial Spin Labeling MRI

摘要 候选人的职业目标：韩博士在磁共振（MR）成像、图像方面拥有深厚的背景 重建和动脉自旋标记（ASL），拥有博士学位。在生物和脑工程领域。韩博士目前在 马萨诸塞州总医院 (MGH) 初级教员级别的讲师。他的目标是拓展自己的未来 用于转化研究和临床的多模态正电子发射断层扫描 (PET)-MR 成像 改善。他的长期目标是成为一名独立、有成就的调查员，能够领导未来 充分利用多模态 PET-MR 成像的科学和临床成像项目。 职业发展计划：建议进行 PET/PET-MR 成像以及神经病学的基础培训 候选人目前缺乏知识和经验的领域。候选人计划 参与正式课程/研讨会，通过与导师和合作者的一对一指导进行研究， 会议/演讲、手稿/赠款准备以及教学/领导角色，以成长为 PET-MR 成像和神经病学领域的独立研究者。 研究项目：拟议研究的总体目标是利用同步动态 PET 和 ASL-MR 成像来估计 PET 示踪剂的渗透性表面积 (PS)，这是一种新方法 单独使用 PET 或 MR 无法获得的生理信息。 PS 描述单向通量 大分子从血浆进入细胞组织间隙的速率，是关键指标 用于评估血脑屏障（BBB）的完整性。了解 PET 示踪剂的 PS 可以提供强大的帮助 能够探测参与发病机制的重要大分子的生理传递过程 与 BBB 相关的疾病，由于理论上在设计放射性类似物方面具有无限的潜力 重要的生物化合物。我们计划开发一种PET示踪剂PS映射方法，实现第一个体模 和人体研究PS图谱，研究tau神经原纤维缠结的空间分布变化 (tau) 和淀粉样蛋白-β (Aß) 斑块沉积与 BBB 完整性随病理事件变化的关系 与 AD 进展相关，通过使用 18F-T807 和 11C- 进行动态 PET/mPLD-ASL 研究 AD 和正常受试者的匹兹堡化合物 B (PiB) PET 示踪剂。 环境：MGH 为开展 MR、PET 和 PET-MR 成像研究提供了理想的环境 多种最先进的成像系统可用于临床前/临床 MR 扫描仪和临床前 同步 PET-MR 扫描仪。有一个动态流动模型，旨在模拟两个人的血流 用于连续血液的隔室药代动力学和 MR 兼容泵和检测系统 适合通过动脉采样进行 ASL 血流和 PET 成像研究的采样。另外，还有一个共享 内存超级计算机非常适合该项目中提出的图像重建。 MGH 也是许多人的家 PET-MR 成像和神经病学专家可以为该项目提供专业知识。

Abstract Candidate's Career Goals: Dr. Han has a strong background in magnetic resonance (MR) imaging, image reconstruction and arterial spin labeling (ASL), with a Ph.D. in bio and brain engineering. Dr. Han is currently at a junior-faculty rank of instructor at Massachusetts General Hospital (MGH). His goal is to expand his future career to multi-modality positron emission tomography (PET)-MR imaging for translational research and clinical improvement. His long-term goal is to become an independent, accomplished investigator that can lead future scientific and clinical imaging projects taking full advantage of multi-modality PET-MR imaging. Career Development Plan: Foundational training in PET/PET-MR imaging as well as neurology is proposed for the candidate, an area that the candidate currently lacks knowledge and experience in. The candidate plans to engage in formal course work/seminars, research via one-on-one instructions with mentors and collaborators, conferences/presentations, manuscript/grant preparations, and teaching/leadership roles to grow as an independent investigator in the field of PET-MR imaging and neurology. Research Project: The overall goal of the proposed research is to take advantage of simultaneous dynamic PET and ASL-MR imaging to estimate the permeability surface product (PS) of the PET tracer, which is new physiological information that cannot be obtained with PET or MR alone. PS describes the unidirectional flux rate of macromolecules from the blood plasma into the interstitial space of cellular tissue and is the key metric for assessing the integrity of the blood-brain barrier (BBB). Knowing the PS of the PET tracer provides powerful capability to probe the physiological delivery process of essential macromolecules involved in the pathogenesis of diseases in relation to BBB, due to the theoretically unlimiting potential in the design of radioactive analogs of important biological compounds. We plan to develop a PET tracer PS mapping method, achieve the first phantom and human study with PS mapping, and study the changes in the spatial distribution of tau neurofibrillary tangles (tau) and amyloid-beta (Aß) plaque depositions in relation to the BBB integrity changes with pathological events associated with the progression of AD, by performing dynamic-PET/mPLD-ASL studies using 18F-T807 and 11C- Pittsburgh compound B (PiB) PET tracers on AD and normal subjects. Environment: MGH provides an ideal setting for conducting research in MR, PET, and PET-MR imaging since multiple state-of-the-art imaging systems are available for preclinical/clinical MR scanners and preclinical simultaneous PET-MR scanners. There is a dynamic flow phantom designed to simulate blood flow for two compartment pharmacokinetics and an MR-compatible pump and detection system for continuous blood sampling suitable for performing ASL flow and PET imaging studies with arterial sampling. Also, there is a shared memory supercomputer ideal for the image reconstruction proposed in the project. MGH is also home to many experts in both PET-MR imaging and neurology who can provide their expertise to this project.