PDF(Pubmed)
Abstract：
Myocardial perfusion imaging by positron emission tomography (PET-MPI) is the current gold standard for quantification of myocardial blood flow. 18F-flurpiridaz was recently introduced as a valid alternative to currently used PET-MPI probes. Nonetheless, optimum scan duration and time interval for image analysis are currently unknown. Further, it is unclear whether rest/stress PET-MPI with 18F-flurpiridaz is feasible in mice.
Rest/stress PET-MPI was performed with 18F-flurpiridaz (0.6-3.0 MBq) in 27 mice aged 7-8 months. Regadenoson (0.1 µg/g) was used for induction of vasodilator stress. Kinetic modeling was performed using a metabolite-corrected arterial input function. Image-derived myocardial 18F-flurpiridaz uptake was assessed for different time intervals by placing a volume of interest in the left ventricular myocardium.
Tracer kinetics were best described by a two-tissue compartment model. K1 ranged from 6.7 to 20.0 mL·cm-3·min-1, while myocardial volumes of distribution (VT) were between 34.6 and 83.6 mL·cm-3. Of note, myocardial 18F-flurpiridaz uptake (%ID/g) was significantly correlated with K1 at rest and following pharmacological vasodilation for all time intervals assessed. However, while Spearman\'s coefficients (rs) ranged between 0.478 and 0.681, R2 values were generally low. In contrast, an excellent correlation of myocardial 18F-flurpiridaz uptake with VT was obtained, particularly when employing the averaged myocardial uptake from 20 to 40 min post tracer injection (R2 ≥ 0.98). Notably, K1 and VT were similarly sensitive to pharmacological vasodilation induction. Further, mean stress-to-rest ratios of K1, VT, and %ID/g 18F-flurpiridaz were virtually identical, suggesting that %ID/g 18F-flurpiridaz can be used to estimate coronary flow reserve (CFR) in mice.
Our findings suggest that a simplified assessment of relative myocardial perfusion and CFR, based on image-derived tracer uptake, is feasible with 18F-flurpiridaz in mice, enabling high-throughput mechanistic CFR studies in rodents.
Rest/stress PET-MPI was performed with 18F-flurpiridaz (0.6-3.0 MBq) in 27 mice aged 7-8 months. Regadenoson (0.1 µg/g) was used for induction of vasodilator stress. Kinetic modeling was performed using a metabolite-corrected arterial input function. Image-derived myocardial 18F-flurpiridaz uptake was assessed for different time intervals by placing a volume of interest in the left ventricular myocardium.
Tracer kinetics were best described by a two-tissue compartment model. K1 ranged from 6.7 to 20.0 mL·cm-3·min-1, while myocardial volumes of distribution (VT) were between 34.6 and 83.6 mL·cm-3. Of note, myocardial 18F-flurpiridaz uptake (%ID/g) was significantly correlated with K1 at rest and following pharmacological vasodilation for all time intervals assessed. However, while Spearman\'s coefficients (rs) ranged between 0.478 and 0.681, R2 values were generally low. In contrast, an excellent correlation of myocardial 18F-flurpiridaz uptake with VT was obtained, particularly when employing the averaged myocardial uptake from 20 to 40 min post tracer injection (R2 ≥ 0.98). Notably, K1 and VT were similarly sensitive to pharmacological vasodilation induction. Further, mean stress-to-rest ratios of K1, VT, and %ID/g 18F-flurpiridaz were virtually identical, suggesting that %ID/g 18F-flurpiridaz can be used to estimate coronary flow reserve (CFR) in mice.
Our findings suggest that a simplified assessment of relative myocardial perfusion and CFR, based on image-derived tracer uptake, is feasible with 18F-flurpiridaz in mice, enabling high-throughput mechanistic CFR studies in rodents.
摘要：
背景：通过正电子发射断层扫描（PET-MPI）进行的心肌灌注成像是当前量化心肌血流量的金标准。18F-flurpiridaz最近被引入作为当前使用的PET-MPI探针的有效替代品。尽管如此，图像分析的最佳扫描持续时间和时间间隔目前未知。Further,目前尚不清楚在小鼠中使用18F-flurpiridaz的休息/应激PET-MPI是否可行。
方法：在27只7-8月龄小鼠中使用18F-flurpiridaz（0.6-3.0MBq）进行休息/应激PET-MPI。Regadenoson（0.1µg/g）用于诱导血管扩张剂应激。使用代谢物校正的动脉输入功能进行动力学建模。通过在左心室心肌中放置感兴趣的体积，在不同的时间间隔内评估图像衍生的心肌18F-flurpiridaz摄取。
结果：示踪剂动力学最好通过双组织区室模型来描述。K1范围为6.7至20.0mL·cm-3·min-1，而心肌分布体积（VT）为34.6至83.6mL·cm-3。值得注意的是，在所有评估的时间间隔内,静息时和药理学血管舒张后,心肌18F-flurpiridaz摄取(%ID/g)与K1显著相关.然而,虽然Spearman系数（rs）介于0.478和0.681之间，但R2值普遍较低。相比之下,获得了心肌18F-flurpiridaz摄取与VT的极好相关性，特别是当使用示踪剂注射后20至40分钟的平均心肌摄取时（R2≥0.98）。值得注意的是,K1和VT对药理学血管舒张诱导同样敏感。Further,K1、VT、和%ID/g18F-flurpiridaz几乎相同，提示%ID/g18F-flurpiridaz可用于估计小鼠冠状动脉血流储备(CFR)。
结论：我们的研究结果表明，对相对心肌灌注和CFR的简化评估，基于图像衍生的示踪剂摄取，在小鼠中使用18F-flurpiridaz是可行的，在啮齿动物中实现高通量机械CFR研究。
方法：在27只7-8月龄小鼠中使用18F-flurpiridaz（0.6-3.0MBq）进行休息/应激PET-MPI。Regadenoson（0.1µg/g）用于诱导血管扩张剂应激。使用代谢物校正的动脉输入功能进行动力学建模。通过在左心室心肌中放置感兴趣的体积，在不同的时间间隔内评估图像衍生的心肌18F-flurpiridaz摄取。
结果：示踪剂动力学最好通过双组织区室模型来描述。K1范围为6.7至20.0mL·cm-3·min-1，而心肌分布体积（VT）为34.6至83.6mL·cm-3。值得注意的是，在所有评估的时间间隔内,静息时和药理学血管舒张后,心肌18F-flurpiridaz摄取(%ID/g)与K1显著相关.然而,虽然Spearman系数（rs）介于0.478和0.681之间，但R2值普遍较低。相比之下,获得了心肌18F-flurpiridaz摄取与VT的极好相关性，特别是当使用示踪剂注射后20至40分钟的平均心肌摄取时（R2≥0.98）。值得注意的是,K1和VT对药理学血管舒张诱导同样敏感。Further,K1、VT、和%ID/g18F-flurpiridaz几乎相同，提示%ID/g18F-flurpiridaz可用于估计小鼠冠状动脉血流储备(CFR)。
结论：我们的研究结果表明，对相对心肌灌注和CFR的简化评估，基于图像衍生的示踪剂摄取，在小鼠中使用18F-flurpiridaz是可行的，在啮齿动物中实现高通量机械CFR研究。
