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) 参与其在生物发现、医疗保健和商业化中的应用来推进分子成像。注意：需要明确的是，混合 PET/MRI 是在同一解剖结构（例如心脏）上同时采集 PET 和 MRI 数据/图像。 所需的基础设施：我建立了一个领先的混合 PET/MRI 项目以及最先进的医疗回旋加速器和放射化学设施，包括招募八名博士科学家（三名放射化学家、两名 PET/MRI 成像生物物理学家和三名分子生物学家）。假设：混合 PET/MRI 有可能显着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：我们将使用这种聚合方法来解决心脏 PET 的两个局限性：a) 仅限于区分一个 PET 探头，因为所有 PET 探头均由相同信号（湮灭辐射）检测到；b) 采集动态 PET 采集来测量心肌血流量，无需对体积、心脏和呼吸运动进行校正。我们提出同时收集的 MRI 数据如何解决这些心脏 PET 局限性。具体来说，我们将重点关注使用 13N-氨 (13NA) 进行心肌动态血流测量。注意：在我的上一个 NSERC/DG（截至 2020 年 6 月）中，我 a) 完成了关于磁场转导的生物物理机制的发现工作（发表了 4 篇论文；77 次引用）和 b) 开发了 MRI 报告基因； （发表 5 篇论文，提交 2 篇；53 次引用）如果获得资助，该 NSERC 将继续支持正在完成这项工作的博士生。 具体的新目标： 1.我将继续研究使用心脏功能 MRI BOLD (cfBOLD) 作为 13NA 的替代品。原理验证已在狗身上建立[Sci Transl Med，2019 年 5 月]。在人类中实施将使目前需要 200 分钟的炎症 PET/MRI 评估在 50 分钟内完成。 2.我将开发一种方法来执行两次血流测量（休息和压力，使用两次注射13NA），目前需要70分钟，只需20分钟。这将使用减法技术，该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.我将开发一种使用同时采集的 MRI 数据来校正 13NA 图像的大部分心脏和呼吸模糊的方法。我将采用低阶张量 (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) 减少采集时间（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.