Permeability Imaging using Simultaneous Dynamic PET and Arterial Spin Labeling MRI

摘要 候选人的职业目标：韩博士在磁共振成像（MR），影像学方面有很强的背景， 重建和动脉自旋标记（ASL），拥有博士学位在生物和大脑工程中。韩博士目前在 在马萨诸塞州总医院（MGH）担任初级教员的指导员。他的目标是拓展他的未来 职业生涯到多模态正电子发射断层扫描（PET）-MR成像的转化研究和临床 改进.他的长期目标是成为一名独立的，有成就的调查员，可以领导未来的研究。 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：PET/PET-MR成像以及神经病学的基础培训建议用于 候选人，候选人目前缺乏知识和经验的领域。候选人计划 参加正式的课程工作/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，以成长为一个 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），这是新的 这些生理信息不能单独用PET或MR获得。PS描述了单向通量 大分子从血浆进入细胞组织的间隙空间的速率，并且是 用于评估血脑屏障（BBB）的完整性。了解PET示踪剂的PS， 能够探测参与发病机制的重要大分子的生理传递过程 与血脑屏障有关的疾病，由于放射性类似物的设计在理论上无限的潜力， 重要的生物化合物。我们计划开发一种PET示踪PS标测方法，实现第一个体模 和人类的研究与PS映射，并研究tau神经元缠结的空间分布的变化 (tau)和β淀粉样蛋白（AAPs）斑块沉积与病理事件的BBB完整性变化有关 与AD进展相关，通过使用18F-T807和11 C- 匹兹堡化合物B（PiB）PET示踪剂对AD和正常受试者的影响。 环境：MGH为MR、PET和PET-MR成像研究提供了理想的环境， 多个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体模，设计用于模拟两个 用于连续血液的隔室药代动力学和MR兼容泵和检测系统 采样适用于使用动脉采样进行ASL血流和PET成像研究。此外，还有一个共享的 内存超级计算机的理想图像重建项目中提出的。MGH也是许多 PET-MR成像和神经病学的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.