He Xuan, Wedekind Franziska, Kroll Tina, Oskamp Angela, Beer Simone, Drzezga Alexander, Ermert Johannes, Neumaier Bernd, Bauer Andreas, Elmenhorst David
Institut für Neurowissenschaften und Medizin (INM-2), Forschungszentrum Jülich, Jülich, Germany.
Department of Neurophysiology, Institute of Zoology (Bio-II), RWTH Aachen University, Aachen, Germany.
Front Physiol. 2020 Jan 29;10:1617. doi: 10.3389/fphys.2019.01617. eCollection 2019.
imaging for the A adenosine receptors (AARs) with positron emission tomography (PET) using 8-cyclopentyl-3-(3-[F]fluoropropyl)-1-propylxan- thine ([F]CPFPX) has become an important tool for studying physiological processes quantitatively in mice. However, the measurement of arterial input functions (AIFs) on mice is a method with restricted applicability because of the small total blood volume and the related difficulties in withdrawing blood. Therefore, the aim of this study was to extract an appropriate [F]CPFPX image-derived input function (IDIF) from dynamic PET images of mice.
In this study, five mice were scanned with [F]CPFPX for 60 min. Arterial blood samples ( = 7 per animal) were collected from the femoral artery and corrected for metabolites. To generate IDIFs, three different approaches were selected: (A) volume of interest (VOI) placed over the heart (cube, 10 mm); (B) VOI set over abdominal vena cava/aorta region with a cuboid (5 × 5 × 15 mm); and (C) with 1 × 1 × 1 mm voxels on five consecutive slices. A calculated scaling factor (α) was used to correct for partial volume effect; the method of obtaining the total metabolite correction of [F]CPFPX for IDIFs was developed. Three IDIFs were validated by comparison with AIF. Validation included the following: visual performance; computing area under the curve (AUC) ratios (IDIF/AIF) of whole-blood curves and parent curves; and the mean distribution volume ( ) ratios (IDIF/AIF) of AARs calculated by Logan plot and two-tissue compartment model.
Compared with the AIF, the IDIF with VOI over heart showed the best performance among the three IDIFs after scaling by 1.77 (α) in terms of visual analysis, AUC ratios (IDIF/AIF; whole-blood AUC ratio, 1.03 ± 0.06; parent curve AUC ratio, 1.01 ± 0.10) and ratios (IDIF/AIF; Logan ratio, 1.00 ± 0.17; two-tissue compartment model ratio, 1.00 ± 0.13) evaluation. The AARs distribution of average parametric images was in good accordance to autoradiography of the mouse brain.
The proposed study provides evidence that IDIF with VOI over heart can replace AIF effectively for quantification of AARs using PET and [F]CPFPX in mice brains.
使用8-环戊基-3-(3-[F]氟丙基)-1-丙基黄嘌呤([F]CPFPX)通过正电子发射断层扫描(PET)对A腺苷受体(AARs)进行成像已成为定量研究小鼠生理过程的重要工具。然而，由于小鼠总血容量小以及采血相关困难，测量小鼠动脉输入函数(AIFs)是一种适用性受限的方法。因此，本研究的目的是从小鼠动态PET图像中提取合适的[F]CPFPX图像衍生输入函数(IDIF)。
在本研究中，五只小鼠用[F]CPFPX扫描60分钟。从股动脉采集动脉血样(每只动物7份)并进行代谢物校正。为了生成IDIF，选择了三种不同的方法：(A)在心脏上方放置感兴趣体积(VOI)(立方体，10 mm)；(B)在腹静脉/主动脉区域设置长方体(5×5×15 mm)的VOI；(C)在连续五个切片上使用1×1×1 mm体素。使用计算的缩放因子(α)校正部分容积效应；开发了获得IDIF的[F]CPFPX总代谢物校正的方法。通过与AIF比较验证了三种IDIF。验证包括以下内容：视觉性能；计算全血曲线和母体曲线的曲线下面积(AUC)比值(IDIF/AIF)；以及通过Logan图和双组织隔室模型计算的AARs的平均分布容积()比值(IDIF/AIF)。
与AIF相比，在视觉分析、AUC比值(IDIF/AIF；全血AUC比值，1.03±0.06；母体曲线AUC比值，1.01±0.10)和比值(IDIF/AIF；Logan比值，1.00±0.17；双组织隔室模型比值，1.00±0.13)评估方面，心脏上方有VOI的IDIF在按1.77(α)缩放后的三种IDIF中表现最佳。平均参数图像的AARs分布与小鼠脑放射自显影结果良好一致。
本研究提供的证据表明，心脏上方有VOI的IDIF可以有效地替代AIF，用于在小鼠脑中使用PET和[F]CPFPX对AARs进行定量分析。
