Single-tracer Multiparametric PET Imaging

项目总结 血流和细胞新陈代谢是两个基本但至关重要的生理过程，通常是失调的 在重大疾病方面。血流-代谢不匹配或耦合的成像具有广泛的临床和研究价值 在许多疾病中的意义，例如，在缺血性心肌病中评估心肌活力，在 癌症用于肿瘤侵袭性分级，神经退行性疾病用于研究脑功能。一个 血流代谢的PET成像的主要挑战是扫描这两个过程需要两个 不同的放射性示踪剂-18F-氟代脱氧葡萄糖(FDG)用于代谢和第二流动放射性示踪剂 灌注成像。虽然FDG在临床上广泛用于代谢成像，但PET的灌注成像 在临床上是有限的，导致流动代谢成像在研究和临床上都没有得到充分利用。这个 该项目的目标是开发一种单示踪剂多参数PET成像解决方案，用于同时流动- 仅使用18F-FDG进行新陈代谢成像，不需要第二个血流特异性放射性示踪剂。早期尝试 其他人和我们的团队使用FDG血液到组织的转移率(K1)作为血流的替代指标。然而， FDG K1模拟血流的准确性在很大程度上取决于组织中FDG的提取分数 而且FDG K1和血糖水平之间的相关性也会影响到这一点。我们的前期工作 已经专门在心肌中解决了这些问题，并证明了将FDG用于 测量心肌血流量。这项提议的重点是将努力扩展到一项大型研究和 整个身体，并进一步开发使能技术，以改善FDG血流量化。我们将(1) 葡萄糖归一化提取分数校正用于FDG各器官血流定量 应用全身动态正电子发射计算机断层扫描；(2)改进的FDG血液的高时间分辨率动力学建模 血流定量；(3)使用先进图像改进FDG短程PET血流成像 重建。该项目的成功完成将发展18F-FDG的新技术能力，用于 在减少辐射剂量的情况下同时进行血流和葡萄糖代谢的多参数成像 成像时间和成本。这也将为临床应用开辟许多新的机会，这些应用需要 多参数成像生物标志物，但历史上一直受到灌注可获得性的限制 成像，因此在患者临床护理和研究的多种PET应用中产生了广泛的影响。

PROJECT SUMMARY Blood flow and cellular metabolism are two basic but vital physiological processes that are often dysregulated in major diseases. Imaging of flow-metabolism mismatch or coupling is of broad clinical and research significance in many diseases, for instance, in ischemic cardiomyopathy for assessing myocardial viability, in cancer for grading tumor aggressiveness, and in neurodegenerative diseases for studying brain function. A major challenge in PET imaging of flow-metabolism is that scanning for these two processes requires two different radiotracers–18F-fluorodeoxyglucose (FDG) for metabolism and a second flow radiotracer for perfusion imaging. While FDG is widely available in the clinic for metabolic imaging, perfusion imaging by PET is clinically limited, resulting in underutilization of flow-metabolism imaging in both research and clinics. The goal of this project is to develop a single-tracer multiparametric PET imaging solution for simultaneous flow- metabolism imaging using only 18F-FDG without the need for a second flow-specific radiotracer. Early attempts from others and our group have used FDG blood-to-tissue delivery rate (K1) as a proxy of blood flow. However, the accuracy of FDG K1 approximating blood flow largely depends on the FDG extraction fraction in tissues and is also compromised by the correlation between FDG K1 and blood glucose levels. Our preliminary work has tackled these problems specifically in the myocardium and demonstrated the feasibility of using FDG for measuring myocardial blood flow. The focus of this proposal is to extend the effort to a large study and to the whole body, and further develop the enabling techniques to improve FDG blood flow quantification. We will (1) develop glucose-normalized extraction fraction correction for FDG blood flow quantification in various organs using total-body dynamic PET; (2) develop high-temporal resolution kinetic modeling for improved FDG blood flow quantification; (3) improve FDG blood flow imaging on short PET scanners using advanced image reconstruction. Successful completion of this project will develop a new technical capability of 18F-FDG for simultaneous multiparametric imaging of blood flow and glucose metabolism with reduced radiation dose, imaging time and cost. This would also open up many new opportunities for clinical applications that require multiparametric imaging biomarkers but have been historically restricted by the accessibility of perfusion imaging, thus making a broad impact in multiple PET applications for patient clinical care and research.