Permeability Imaging using Simultaneous Dynamic PET and Arterial Spin Labeling MRI

摘要 应聘者职业目标：韩博士在磁共振成像、影像方面有很强的背景 重建和动脉自旋标记(ASL)，拥有生物和脑工程博士学位。韩博士目前在 马萨诸塞州综合医院(MGH)初级教员级别的讲师。他的目标是拓展自己的未来 从多模式正电子发射断层扫描(PET)-磁共振成像到转化性研究和临床 进步。他的长期目标是成为一名独立的、有成就的调查员，能够领导未来 科学和临床成像项目充分利用多模式PET-MR成像。 职业发展计划：建议对以下人员进行PET/PET-MR成像和神经学的基础培训 候选人，这是候选人目前缺乏知识和经验的领域。这位候选人计划 参与正式的课程工作/研讨会，通过与导师和合作者一对一的指导进行研究， 会议/演示、稿件/助学金准备以及教学/领导角色 在PET-MR成像和神经学领域的独立研究员。 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示踪剂的渗透表面积(PS)，这是新的 仅用PET或MR无法获得的生理信息。PS描述了单向通量 大分子从血浆进入细胞组织间隙的速率是关键的指标 用于评估血脑屏障(BBB)的完整性。了解PET示踪剂的PS可提供强大的 能够探索与发病有关的必需大分子的生理递送过程 与血脑屏障有关的疾病，由于理论上设计的放射性类似物的无限潜力 重要的生物化合物。我们计划开发一种PET示踪PS映射方法，实现第一个体模 并对人体进行PS标测，研究tau神经原纤维缠结的空间分布变化 (Tau)和淀粉样β蛋白(A？)斑块沉积与病理事件中BBB完整性变化的关系 通过使用18F-T807和11C-T807进行动态PET/mPLD-ASL研究，与AD的进展相关。 匹兹堡化合物B(PIB)在AD和正常受试者上的PET示踪。 环境：麻省理工学院为开展MR、PET和PET-MR成像研究提供了理想的环境，因为 多种最先进的成像系统可用于临床前/临床前磁共振扫描仪和临床前 同步PET-MR扫描仪。有一个动态流动体模，旨在模拟两个人的血液流动 连续血液的室间药代动力学及MR兼容泵和检测系统 适用于动脉采样的ASL血流和PET成像研究。此外，还有一个共享的 内存超级计算机是项目中提出的图像重建的理想选择。麻省理工学院也是许多 PET-MR成像和神经学方面的专家，他们可以为这个项目提供专业知识。

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.