Combining image-derived and venous input functions enables quantification of serotonin-1A receptors with [carbonyl-11C]WAY-100635 independent of arterial sampling
Combining image-derived and venous input functions enables quantification of serotonin-1A receptors with [carbonyl-11C]WAY-100635 independent of arterial sampling
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DOI：
10.1016/j.neuroimage.2012.04.047
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发表时间：
2012-08-01
期刊：
影响因子：
5.7
通讯作者：
Lanzenberger, Rupert
中科院分区：
文献类型：
--
作者：
Hahn, Andreas;Nics, Lukas;Lanzenberger, Rupert
与动脉插管相比，图像衍生输入函数 (IDIF) 代表了一种有前途的技术，可以更简单、侵入性更小地对 PET 研究进行量化。然而，许多限制使 IDIF 在临床研究方案中的常规使用变得复杂，并且几乎没有对静脉样本完全替代手动动脉样本进行评估。本研究旨在直接验证 IDIF 和静脉数据，以量化激素治疗前后与 [羰基-C-11]WAY-100635 的 5-羟色胺-1A 受体结合 (5-HT1A)。 方法：从 10 名健康女性中获得 15 次动脉和静脉血采样 PET 测量结果，在激素替代治疗前 8 周和之后 7 次进行扫描。图像衍生的输入函数自动从脑血管中导出，校正部分容量效应，并与 10 分钟以后的静脉手动样本相结合 (IDIF + VIF)。分别对动脉和静脉样本进行血浆/全血比率和代谢物的校正。使用两组织室模型通过动脉输入功能 (AIF) 和 IDIF + VIF 实现 5-HT1A 受体定量。结果：动脉和静脉手工血样之间的比较具有出色的重现性。全血活性的变异性 (VAR) 低于 10% (p > 0.4)，血浆与全血比率的变异性 (VAR) 低于 2% (p > 0.4)。母体分数的变异性稍高（5 分钟时 VARmax = 24%，p < 0.05，20 分钟后 VAR < 13%，p > 0.1），但仍在先前报告的值内。部分体积校正后的 IDIF 具有与 AIF 相当的峰值（平均差 Delta = -7.6 +/- 16.9 kBq/ml，p > 0.1），而 AIF 表现出延迟（Delta = 4 +/- 6.4s，p < 0.05）和更高的峰宽（Delta = 15.9 +/- 5.2 s，p < 0.001）。线性回归分析显示，AIF 和 IDIF + VIF 在基线时 (R-2 = 0.95)、治疗后 (R-2 = 0.93) 以及合并所有扫描时 (R-2 = 0.93) 获得的 5-HT1A 结合具有很强的一致性，斜率和截距分别在 0.97 至 1.07 和 -0.05 至 0.16 范围内。除了感兴趣区域分析之外，与 AIF 相比，该方法在体素定量方面产生了几乎相同的结果。 结论：尽管放射性配体的代谢速度很快，但手动动脉血样本可以用静脉血样本代替母体部分和血浆与全血的比率。此外，图像衍生功能和静脉输入功能的结合提供了 5-HT1A 受体的可靠定量。这对于基于兴趣区域和体素建模的治疗前后的 5-HT1A 结合估计都是正确的。总而言之，该方法通过完全独立于动脉插管提供侵入性较小的受体定量。这为临床研究方案的常规使用提供了巨大的潜力，并鼓励对具有不同动力学特征的其他放射性配体进行进一步研究。 (C) 2012 Elsevier Inc. 保留所有权利。
Image-derived input functions (IDIFs) represent a promising technique for a simpler and less invasive quantification of PET studies as compared to arterial cannulation. However, a number of limitations complicate the routine use of IDIFs in clinical research protocols and the full substitution of manual arterial samples by venous ones has hardly been evaluated. This study aims for a direct validation of IDIFs and venous data for the quantification of serotonin-1A receptor binding (5-HT1A) with [carbonyl-C-11]WAY-100635 before and after hormone treatment.Methods: Fifteen PET measurements with arterial and venous blood sampling were obtained from 10 healthy women, 8 scans before and 7 after eight weeks of hormone replacement therapy. Image-derived input functions were derived automatically from cerebral blood vessels, corrected for partial volume effects and combined with venous manual samples from 10 min onward (IDIF + VIF). Corrections for plasma/whole-blood ratio and metabolites were done separately with arterial and venous samples. 5-HT1A receptor quantification was achieved with arterial input functions (AIF) and IDIF + VIF using a two-tissue compartment model.Results: Comparison between arterial and venous manual blood samples yielded excellent reproducibility. Variability (VAR) was less than 10% for whole-blood activity (p > 0.4) and below 2% for plasma to whole-blood ratios (p > 0.4). Variability was slightly higher for parent fractions (VARmax = 24% at 5 min, p < 0.05 and VAR < 13% after 20 min, p > 0.1) but still within previously reported values. IDIFs after partial volume correction had peak values comparable to AIFs (mean difference Delta = -7.6 +/- 16.9 kBq/ml, p > 0.1), whereas AIFs exhibited a delay (Delta = 4 +/- 6.4s, p < 0.05) and higher peak width (Delta = 15.9 +/- 5.2 s, p < 0.001). Linear regression analysis showed strong agreement for 5-HT1A binding as obtained with AIF and IDIF + VIF at baseline (R-2 = 0.95), after treatment (R-2 = 0.93) and when pooling all scans (R-2 = 0.93), with slopes and intercepts in the range of 0.97 to 1.07 and -0.05 to 0.16, respectively. In addition to the region of interest analysis, the approach yielded virtually identical results for voxel-wise quantification as compared to the AIF.Conclusions: Despite the fast metabolism of the radioligand, manual arterial blood samples can be substituted by venous ones for parent fractions and plasma to whole-blood ratios. Moreover, the combination of image-derived and venous input functions provides a reliable quantification of 5-HT1A receptors. This holds true for 5-HT1A binding estimates before and after treatment for both regions of interest-based and voxel-wise modeling. Taken together, the approach provides less invasive receptor quantification by full independence of arterial cannulation. This offers great potential for the routine use in clinical research protocols and encourages further investigation for other radioligands with different kinetic characteristics. (C) 2012 Elsevier Inc. All rights reserved.