Advances in Hybrid PET/MRI Cardiac Imaging

研究项目愿景：通过以下途径推进分子成像：a)心脏PET/MRI混合方法的发展；b)参与其在生物发现、医疗保健和商业化中的应用。注：需要澄清的是，混合PET/MRI是同时获取同一解剖结构（例如心脏）的PET和MRI数据/图像。必要的基础设施：我建立了一个领先的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：PET/MRI的混合有潜力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：我们将使用这种收敛的方法来解决心脏PET的两个局限性：a)由于所有PET探针都是通过相同的信号（湮灭辐射）检测，因此只能区分一个PET探针；b)动态PET采集来测量心肌血流，而不需要校正体积、心脏和呼吸运动。我们建议如何同时收集MRI数据来解决这些心脏PET限制。具体来说，我们将重点关注使用13n -氨（13NA）测量心肌的动态血流量。注：在我的上一个NSERC/DG（结束2020年6月），我a)完成了我对磁场转导的生物物理机制的发现工作（发表了4篇论文，引用了77次）和b)开发了MRI报告基因；（5篇论文发表，2篇提交，53次引用）如果获得资助，NSERC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：我将继续研究心脏功能MRI BOLD （cfBOLD）作为13NA的替代方法。在狗身上已经建立了原理证明[Sci Transl Med， 2019年5月]。在人体上的应用将允许PET/MRI评估炎症，目前需要200分钟，在50分钟内完成。我将开发一种方法来进行两次血流量测量（休息和压力使用两次注射13NA），目前需要70分钟，只需要20分钟。这将使用一种减法技术，该技术依赖于使用同时获得的MRI数据检测和校正大块心脏运动。3.我将开发一种方法，使用同时获取的MRI数据来纠正13NA图像的大部分心脏和呼吸模糊。我将使用低秩张量（LRT）公式从MRI数据中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)降低辐射剂量（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标记的细胞。

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.