1 Section on Neuroadaptation & Protein Metabolism, National Institute of Mental Health, Bethesda, MD, USA.
2 Department of Neuroimaging, IoPPN, King's College London, London, UK.
J Cereb Blood Flow Metab. 2019 Sep;39(9):1849-1863. doi: 10.1177/0271678X18771242. Epub 2018 Apr 17.
We developed and validated a method to estimate input functions for determination of regional rates of cerebral protein synthesis (rCPS) with L-[1-C]leucine PET without arterial sampling. The method is based on a population-derived input function (PDIF) approach, with venous samples for calibration. Population input functions were constructed from arterial blood data measured in 25 healthy 18-24-year-old males who underwent L-[1-C]leucine PET scans while awake. To validate the approach, three additional groups of 18-27-year-old males underwent L-[1-C]leucine PET scans with both arterial and venous blood sampling: 13 awake healthy volunteers, 10 sedated healthy volunteers, and 5 sedated subjects with fragile X syndrome. Rate constants of the L-[1-C]leucine kinetic model were estimated voxel-wise with measured arterial input functions and with venous-calibrated PDIFs. Venous plasma leucine measurements were used with venous-calibrated PDIFs for rCPS computation. rCPS determined with PDIFs calibrated with 30-60 min venous samples had small errors (RMSE: 4-9%), and no statistically significant differences were found in any group when compared to rCPS determined with arterial input functions. We conclude that in young adult males, PDIFs calibrated with 30-60 min venous samples can be used in place of arterial input functions for determination of rCPS with L-[1-C]leucine PET.
我们开发并验证了一种方法，无需动脉采样即可使用 L-[1-C]亮氨酸 PET 估算脑蛋白质合成率 (rCPS) 的输入函数。该方法基于群体推导的输入函数 (PDIF) 方法，采用静脉样本进行校准。群体输入函数是从 25 名年龄在 18-24 岁之间的健康男性的动脉血数据中构建的，这些男性在清醒状态下接受了 L-[1-C]亮氨酸 PET 扫描。为了验证该方法，另外三组 18-27 岁的男性在清醒状态下接受了 L-[1-C]亮氨酸 PET 扫描，并进行了动脉和静脉采血：13 名健康志愿者，10 名镇静志愿者，和 5 名脆性 X 综合征的镇静受试者。使用测量的动脉输入函数和静脉校准的 PDIF 以体素为单位估算 L-[1-C]亮氨酸动力学模型的速率常数。使用静脉校准的 PDIF 和静脉血浆亮氨酸测量值来计算 rCPS。用 30-60 分钟静脉样本校准的 PDIF 确定的 rCPS 误差较小 (RMSE：4-9%)，与用动脉输入函数确定的 rCPS 相比，在任何组中均未发现统计学差异。我们得出结论，在年轻成年男性中，用 30-60 分钟静脉样本校准的 PDIF 可以代替动脉输入函数，用于 L-[1-C]亮氨酸 PET 确定 rCPS。
