Quantitative Methods for Clinical Whole Body Dynamic PET

描述(由申请人提供)：正电子发射断层扫描(PET)是肿瘤学中的主要分子成像工具，应用范围从诊断和分期到患者管理。尽管PET在临床环境中得到了广泛的应用，但目前还没有一种可用于常规临床实践的定量PET成像方法。目前使用的静态扫描可以为全身扫描提供半定量的测量标准摄取值(SUV)。然而，它完全忽略了放射性药物动力学的动态本质。流行的半定量双时间点方法可以通过比较活动来逼近两个时间点的动力学差异，但通常需要较长的等待时间才能进行第二次扫描。多时间点方法可以计算净流入率，但仍然需要较长的扫描时间，使全身扫描不可行。定量全身动态PET扫描的挑战在于如何使用短采集周期的数据来估计诸如净流量等定量函数值，以及如何加速计算以使其在临床环境中具有实用性。我们通过开发和优化一种新的数据分析方法并使用高性能计算工具来实现它，从而解决了这一挑战。我们利用Patlak图形分析的线性，将每个体素中的示踪剂活动建模为血液输入函数及其积分的线性组合，并通过包括净流入速率在内的Patlak参数进行加权。此外，我们还推导了血液输入函数的简化模型，该模型基于用于从动力学隔室模型推导Patlak参数的相同假设。然后，我们使用列表模式数据及其相关的非齐次Poisson统计模型在惩罚极大似然估计框架中估计Patlak参数和血液输入函数中的参数。我们还从理论上分析了我们的Patlak估计器在噪声、分辨率和信噪比(SNR)方面的性能，并利用这些结果来指导我们优化扫描持续时间和成像床的任何运动，以获得最佳的SNR。先进的估计算法，加上精确的成像系统模型，可以在不需要测量血液输入功能的情况下，在短时间内使用列表模式数据稳健地计算净流入率，使全身动态扫描变得实用。我们的算法将在基于NVIDIA Tesla GPU(图形处理单元)的工作站上实现，这是一种新的计算工具，提供以前只能在迷你超级计算机上使用的计算能力。我们将使用列表模式数据的有效表示和系统矩阵的组合来进一步加速我们的算法。我们将使用模拟和临床数据来评估该方法的性能，并将其与SUV、双时间点方法和传统的Patlak方法进行比较。我们将使用一系列性能指标，包括感兴趣区域(ROI)偏差、ROI方差、病变可检测性以及计算机和人类观察者。该项目最终将提供一种定量的动态全身PET成像方案，该方案可能会提高PET成像在肿瘤学中的敏感性和特异性。 公共卫生相关性：正电子发射断层扫描(PET)已广泛应用于癌症的诊断、分期、治疗计划、管理和评估。然而，它的潜力还没有完全实现，部分原因是我们无法充分利用PET扫描仪可以收集的动态信息。在这个项目中，我们将开发一种新的方法来获取和分析PET数据，这将使我们能够第一次扫描患者的全身，并从动态获取的数据中生成PET示踪剂摄取的定量估计。这些措施可能是肿瘤存在和代谢活动的更敏感的指标，因此它们的使用将导致对原发和转移肿瘤的更好的检测、分期和监测。

DESCRIPTION (provided by applicant): Positron Emission tomography (PET) is a major molecular imaging tool in oncology, with applications ranging from diagnosis and staging to patient management. Despite the broad use of PET in the clinical environment, there is no quantitative PET imaging method available for routine clinical practice. The currently used static scan can provide a semi-quantitative measurement, standardized uptake value (SUV), for a whole body scan. However, it completely ignores the dynamic nature of radiopharmaceutical kinetics. The popular semi-quantitative dual time point method can approximate the kinetic differences at two time points by comparing activities but usually requires an extended waiting time for the second scan. The multiple time point method can calculate the net influx rate but still requires long scan duration and makes a whole body scan infeasible. The challenge of a quantitative whole body dynamic PET scan lies in how to estimate the quantitative functional values, such as net flux rate, using data from a short acquisition period, and how to accelerate the computation to make it practical in a clinical setting. We address this challenge by developing and optimizing a novel data analysis method and implementing it using a high performance computing tool. We take advantage of the linearity of Patlak graphic analysis to model the tracer activity in each voxel as a linear combination of the blood input function and its integral, weighted by the Patlak parameters including net influx rate. In addition, we derive a simplified model of the blood input function, based on the same assumptions used to derive Patlak parameters from the kinetic compartment model. We then estimate the Patlak parameters and the parameters in the blood input function in a penalized maximum likelihood estimation framework using the list mode data and its associated inhomogeneous Poisson statistical model. We also theoretically analyze the performance of our Patlak estimator in terms of noise, resolution and signal-to-noise ratio (SNR), and use the results to guide us in optimizing the scan duration and any movement of imaging bed to achieve the best SNR. The advanced estimation algorithm, along with an accurate imaging system model, can robustly compute the net influx rate using the list mode data in a short acquisition without a measured blood input function, and make whole body dynamic scans practical. Our algorithms will be implemented on an Nvidia Tesla GPU (graphics processing unit) based workstation, a new computing tool that provides computational power previously available only on a mini super computer. We will further accelerate our algorithms using a combination of efficient representation of the list mode data and the system matrix. We will evaluate the performance of the proposed method and compare it with SUV, the dual time point method, and the traditional Patlak method, using simulated and clinical data. We will use a range of performance metrics, including region of interest (ROI) bias, ROI variance, lesion detectability, and computer and human observers. This project will eventually provide a quantitative dynamic whole body PET imaging protocol that can potentially improve the sensitivity and specificity of PET imaging in oncology. PUBLIC HEALTH RELEVANCE: Positron Emission Tomography (PET) has been widely used in cancer diagnosis, staging, treatment planning, management and evaluation. However, its potential is not yet fully realized, in part because we are not able to take full advantage of the dynamic information that can be collected by the PET scanner. In this project we will develop a new approach to the acquisition and analysis of PET data that will allow us for the first time to scan the whole body of the patient and produce quantitative estimates of PET tracer uptake from dynamically acquired data. These measures may be more sensitive indicators of the presence and metabolic activity of tumors, so that their use would lead to improved detection, staging and monitoring of primary and metastatic tumors.