Advances in Hybrid PET/MRI Cardiac Imaging

研究计划愿景：通过a)开发心脏混合PET/MRI方法和b)参与它们在生物发现、保健和商业化方面的应用，促进分子成像。注：明确地说，混合PET/MRI是在相同的解剖结构(例如心脏)上同时采集PET和MRI数据/图像。所需的基础设施：我建立了一个尖端的PET/MRI混合项目和最先进的医疗回旋加速器和放射化学设施，包括招聘了8名博士科学家(3名放射化学家、2名PET/MRI成像生物物理学家和3名分子生物学家)。假设：混合PET/MRI有可能极大地提高目前对心脏分子生物学的理解。然而，这需要PET和MRI的融合。背景：我们将使用这种会聚的方法来解决心脏PET的两个局限性：a)限于仅区分一个PET探头，因为所有的PET探头都是由相同的信号(湮没辐射)检测到的；b)采集动态PET以测量心肌血流时，无需校正整体运动、心脏和呼吸运动。我们提出了同时收集的MRI数据如何解决这些心脏PET的局限性。具体地说，我们将重点介绍使用13N-氨(13NA)对心肌进行动态血流量测量。注：在我的上一次NSERC/DG(截至2020年6月)中，a)完成了我在磁场传导生物物理机制方面的发现工作(发表了4篇论文；77篇引文)和b)开发了MRI报告基因；(发表了5篇论文，提交了2篇；53篇引文)这个NSERC，如果得到资助，将继续支持一名正在完成这项工作的博士生。具体的新目标：1.我将继续研究心脏功能磁共振成像BOLD(CfBOLD)作为13NA的替代品的使用。在狗身上已经建立了原则证明[科学翻译医学，2019年5月]。在人体上实施后，目前需要200分钟的PET/MRI炎症评估可以在50分钟内完成。2.我将开发一种方法来进行两次血流测量(使用两次13NA注射进行休息和应激)，目前需要70分钟，而只需要20分钟。这将使用一种减影技术，依赖于使用同时采集的MRI数据检测和校正大量心脏运动。3.我将开发一种方法，使用同时获得的MRI数据来纠正13NA图像的大部分心脏和呼吸模糊。我将使用低阶张量(LRT)公式从MRI数据生成三维心脏和呼吸运动场。这些运动场将用于校正13N-氨PET数据。影响：a)减少辐射剂量(CfBOLD)，b)提高心脏空间分辨率(cfBOLD，LRT方法)，c)缩短采集时间(cfBOLD，快速注射13NA)，d)增加每次检查的信息，e)允许准确跟踪PET标记细胞。

Research Program Vision: Advance molecular imaging through a) the development of cardiac hybrid PET/MRI methodologies and b) participate in their application to biological discovery, healthcare and commercialization. N.B. To be clear, hybrid PET/MRI is the simultaneous acquisition of PET and MRI data/images over the same anatomy (e.g. the heart). The Needed Infrastructure: I established a leading-edge hybrid PET/MRI program and state-of-the-art medical cyclotron and radiochemistry facility including the recruitment of eight PhD scientists (three radiochemists, two PET/MRI imaging biophysicists and three molecular biologists). Hypothesis: Hybrid PET/MRI has the potential to dramatically improve current understanding of the molecular biology of the heart. However, this requires a convergent incorporation of PET and MRI. Background: We will use this convergent approach to address two limitations of cardiac PET: a) restricted to distinguish only one PET probe as all PET probes are detected by the same signal (annihilation radiation) and b) dynamic PET acquisition to measure myocardial blood flow is collected without correction for bulk, cardiac and respiratory movement. We propose how the simultaneously collected MRI data could address these cardiac PET limitations. Specifically, we will focus on dynamic blood flow measurement of the myocardium using 13N-Ammonia (13NA). N.B. In my last NSERC/DG (ends June 2020) I a) completed my discovery work on biophysical mechanisms of magnetic field transduction (4 papers published; 77 citations) and b) for the development of an MRI reporter gene; (5 papers published, 2 submitted; 53 citations) this NSERC, if funded, would continue to support a PhD student who is completing this work. Specific New Objectives: 1.I will continue to investigate the use of cardiac functional MRI BOLD (cfBOLD) as an alternative to 13NA. Proof-of-principle has been established in dogs [Sci Transl Med, May 2019]. Implementation in humans would allow a PET/MRI evaluation of inflammation, that currently takes 200 min, to be done in 50 min. 2.I will develop a method to perform two measurements of blood flow (rest and stress using two injections of 13NA) that currently takes 70min to take only 20 min. This will use a subtraction technique dependent on detection and correction of bulk cardiac motion using simultaneously acquired MRI data. 3.I will develop a method using simultaneously acquired MRI data to correct for most of the cardiac and respiratory blurring of 13NA images. I will employ a low-rank tensor (LRT) formulation to generate the three-dimensional cardiac and respiratory motion fields from MRI data. These motion fields will be used to correct 13N-ammonia PET data. Impact: a) Reduce radiation dose (cfBOLD), b) Improved cardiac spatial resolution (cfBOLD, LRT approach), c) Reduce acquisition time (cfBOLD, rapid injections of 13NA), d) Increased information per examination, e) Allow accurate tracking of PET labeled cells.