A prospective study to support validation of lung deposition models with nuclear medicine imaging methods

项目摘要 在这个项目中，我们建议开发和执行核成像沉积研究的协议，使用 单光子发射计算机断层扫描（SPECT）或优选正电子发射断层扫描（PET）， 其目的是支持沉积的计算机模拟模型的验证。这些协议是在 与FDA的合作，将进行优化，以1）收集可用作输入参数的数据， 模型使用这些数据进行验证，2）利用SPECT和PET的最新进展 技术，以获得比以前更高的空间和时间分辨率的图像 可能基于主要由研究人员弗莱明，蒙特桑托斯和格林布拉特开发的方法，我们 将开发方法，从所得图像中获得更准确的分支级沉积估计 通过1）利用我们在肺结构的定量CT分割方面的经验，2）利用 提高图像分辨率，优化气道内放射性示踪剂活性定位， 3）将放射性示踪剂活性定位在肺的解剖隔室内，小至节段性 水平，以及4）更准确地反映气道形态学中的疾病特异性变化， 弗莱明和蒙特桑托斯工作的假设。 这些方案将与核医学人员合作制定和执行， 伊拉斯谟医学中心放射学和药理学系的副获奖者。这些研究人员将 主要负责开发、验证和实施生产放射性标记的 一种适合使用的经口吸入制剂（OIDP）以及适当的SPECT或PET 为满足整个项目的需求而优化的协议。健康志愿者和哮喘或COPD受试者 将从位于比利时孔蒂奇的单一中心招募。通过招募患有哮喘和COPD的受试者， 我们希望开发出一种方法，可以解释通气和沉积的临床显著差异， 这在以前的工作中没有考虑到，特别是肺气肿和气体滞留。 所得到的数据，包括1）标准化的协议和程序，2）获得的图像，3）方法和 代码，以及4）分析结果将提供给FDA，并在18个月后公开传播 完成研究，以满足提供数据以促进计算机模型验证的目标。

Project Summary In this project we propose to develop and execute protocols for a nuclear imaging deposition study using either single-photon emission computed tomography (SPECT) or, preferably, positron emission tomography (PET), with the goal of supporting validation of in-silico models of deposition. These protocols, developed in collaboration with the FDA, will be optimized to 1) collect data which may be used as input parameters for the models which use this data for validation purposes and 2) leverage recent advances in SPECT and PET technology to achieve images with significantly higher spatial and temporal resolution than was previously possible. Building on approaches developed primarily by researchers Fleming, Montesantos, and Greenblatt, we will develop methods to derive more accurate estimations of branch-level deposition from the resulting images by 1) leveraging our experience in quantitative CT segmentation of lung structure, 2) making use of improvements in image resolution to optimize radiotracer activity localization within airways as small as the 4th generation, 3) localizing radiotracer activity within anatomic compartments of the lung as small as the segmental level, and 4) more accurately reflecting disease-specific variations in airway morphology which violate key assumptions of the work of Fleming and Montesantos. These protocols will be developed and executed in collaboration with personnel from the Nuclear Medicine and Radiology and Pharmacology faculty at Erasmus Medical Center as subawardees. These researchers will be primarily responsible for developing, validating, and implementing a process to produce a radiolabeled formulation of one orally inhaled drug product (OIDP) which is fit-for-use, as well as appropriate SPECT or PET protocols optimized for the needs of the overall project. Healthy volunteers and subjects with asthma or COPD will be recruited from a single center located in Kontich, Belgium. By recruiting subjects with asthma and COPD, we hope to develop methods which can account for clinically significant differences in ventilation and deposition which are not accounted for in previous work, specifically emphysema and gas trapping. The resulting data, including 1) standardized protocols and procedures, 2) images acquired, 3) methods and code, and 4) results of analysis will be made available to the FDA to disseminate publicly 18 months following completion of the study, to meet the objective of providing data to facilitate in-silico model validation.