Test-retest reproducibility of cannabinoid-receptor type 1 availability quantified with the PET ligand [¹¹C]MePPEP.
Test-retest reproducibility of cannabinoid-receptor type 1 availability quantified with the PET ligand [¹¹C]MePPEP.
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DOI：
10.1016/j.neuroimage.2014.04.020
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发表时间：
2014-08-15
期刊：
影响因子：
5.7
通讯作者：
Hammers A
中科院分区：
文献类型：
--
作者：
Riaño Barros DA;McGinnity CJ;Rosso L;Heckemann RA;Howes OD;Brooks DJ;Duncan JS;Turkheimer FE;Koepp MJ;Hammers A
内源性大麻素参与正常认知，大麻素受体介导的神经传递功能障碍已被认为是各种神经和精神病理学。1型大麻素受体（CB 1）在人类中枢神经系统中广泛表达。本研究的目的是量化PET配体[11 C]MePPEP测量的重测重现性，以评估人体内CB 1受体定量的稳定性。15名健康受试者（8名女性;中位年龄32岁，范围25至65岁）在注射中位剂量364 MBq的[11 C]MePPEP后进行了两次90分钟PET扫描。获得所有扫描的代谢物校正的动脉血浆输入函数。8个ROI，反映不同水平的受体密度/浓度，自动定义：海马，前扣带回，额下回，尾状核，苍白球，丘脑，脑桥。我们使用了七种定量方法：可逆房室模型，一种和两种组织类别，两种和四种速率常数，以及可变血容量项（2kbv; 4kbv）;无模型有和没有规则化的（光谱）分析，包括一个与体素量化;简化的参考组织模型（SRTM）与脑桥作为伪参考区域;并计算注射后约30-60分钟内的修改标准摄取值（mSUV）。重测变化百分比和受试者之间的变异性都进行了评估，重测信度量化组内相关系数（ICC）。结合率估计苍白球：脑桥作为一个指标的方法的能力，以反映结合异质性。SRTM和4kbv模型都没有产生可靠的测量结果，ICC大约为零。用其他方法获得了非常好（> 0.75）或优异（> 0.80）的ICC。最可靠的是频谱分析参数图（各地区平均值±标准差0.83 ± 0.03）、秩成形正则化频谱分析（0.82 ± 0.05）和2kbv模型（0.82 ± 0.09），但mSUV在大多数地区也是可靠的（0.79 ± 0.13）。在五种性能良好的方法中，平均重测变化范围从mSUV的12 ± 10%到2kbv的16%。受试者间变异性较高，平均受试者间变异系数范围为32 ± 13%（mSUV）至45%（2kbv）。mSUV（4.2）、频谱分析衍生的参数图（3.6）和2kbv（3.6）获得了最高的苍白球：脑桥结合率估计值。CB 1受体可用性的定量使用[11 C]MePPEP表现出良好的再现性与几个动力学模型和无模型分析，无论是应用在感兴趣的区域或voxelwise的基础上。简单的mSUV措施也是可靠的，为大多数地区，但不允许完全定量解释。[11 C]MePPEP PET是研究健康和疾病中CB 1受体介导的神经传递的工具。用[11 C]MePPEP-PET评估大麻素受体浓度。顶部，不同量化策略的可靠性（ICC ± SD）：蓝色，房室模型;红色，光谱分析变体;绿色，SRTM;黄色，改良SUV。底部，参数VT图。[11 C]MePPEP是大麻素受体（CB 1 R）的PET示踪剂。在大样本中[11 C]MePPEP数据定量策略的广泛评估我们强调了在感兴趣的区域中定量CB 1 R的成功方法。高度可靠的参数图（ICC 0.83 ± 0.03）允许全脑调查。修改后的标准摄取值也是可靠的，没有动脉输入功能
Endocannabinoids are involved in normal cognition, and dysfunction in cannabinoid-receptor-mediated neurotransmission has been suggested in a variety of neurological and psychiatric pathologies. The type 1 cannabinoid receptor (CB1) is widely expressed in the human central nervous system. The objective of this study was to quantify the test–retest reproducibility of measures of the PET ligand [11C]MePPEP in order to assess the stability of CB1-receptor quantification in humans in vivo. Fifteen healthy subjects (eight females; median age 32 years, range 25 to 65 years) had a 90-minute PET scan on two occasions after injection of a median dose of [11C]MePPEP of 364 MBq. Metabolite-corrected arterial plasma input functions were obtained for all scans. Eight ROIs, reflecting different levels of receptor densities/concentrations, were defined automatically: hippocampus, anterior cingulate gyrus, inferior frontal gyrus, caudate nucleus, globus pallidus, nucleus accumbens, thalamus, and pons. We used seven quantification methods: reversible compartmental models with one and two tissue classes, two and four rate constants, and a variable blood volume term (2kbv; 4kbv); model-free (spectral) analyses with and without regularisation, including one with voxel-wise quantification; the simplified reference tissue model (SRTM) with pons as a pseudo-reference region; and modified standard uptake values (mSUVs) calculated for the period of ~ 30–60 min after injection. Percentage test–retest change and between-subject variability were both assessed, and test–retest reliability was quantified by the intraclass correlation coefficient (ICC). The ratio of binding estimates pallidum:pons served as an indicator of a method's ability to reflect binding heterogeneity. Neither the SRTM nor the 4kbv model produced reliable measures, with ICCs around zero. Very good (> 0.75) or excellent (> 0.80) ICCs were obtained with the other methods. The most reliable were spectral analysis parametric maps (average across regions ± standard deviation 0.83 ± 0.03), rank shaping regularised spectral analysis (0.82 ± 0.05), and the 2kbv model (0.82 ± 0.09), but mSUVs were also reliable for most regions (0.79 ± 0.13). Mean test–retest changes among the five well-performing methods ranged from 12 ± 10% for mSUVs to 16% for 2kbv. Intersubject variability was high, with mean between-subject coefficients of variation ranging from 32 ± 13% for mSUVs to 45% for 2kbv. The highest pallidum:pons ratios of binding estimates were achieved by mSUV (4.2), spectral analysis-derived parametric maps (3.6), and 2kbv (3.6). Quantification of CB1 receptor availability using [11C]MePPEP shows good to excellent reproducibility with several kinetic models and model-free analyses, whether applied on a region-of-interest or voxelwise basis. Simple mSUV measures were also reliable for most regions, but do not allow fully quantitative interpretation. [11C]MePPEP PET is well placed as a tool to investigate CB1-receptor mediated neurotransmission in health and disease. Cannabinoid receptor concentrations assessed with [11C]MePPEP-PET. Top, reliability (ICCs ± SDs) of different quantification strategies: blue, compartmental models; red, spectral analysis variants; green, SRTM; yellow, modified SUVs. Bottom, parametric VT map. [11C]MePPEP is a PET tracer for cannabinoid receptors (CB1R). Extensive evaluation of [11C]MePPEP data quantification strategies in large sample We highlight successful methods to quantify CB1R in regions of interest. Highly reliable parametric maps (ICC 0.83 ± 0.03) allow whole-brain surveys. Modified standard uptake values also reliable, without arterial input functions
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影响因子：
5.7
作者：
Hammers, Alexander;Asselin, Marie-Claude;Koepp, Matthias J.
通讯作者：
Koepp, Matthias J.
影响因子：
3.1
作者：
Allen, EV
通讯作者：
Allen, EV
影响因子：
5.7
作者：
Gunn, RN;Lammertsma, AA;Cunningham, VJ
通讯作者：
Cunningham, VJ
影响因子：
6.3
作者：
CUNNINGHAM, VJ;HUME, SP;JONES, AKP
通讯作者：
JONES, AKP
影响因子：
6.3
作者：
Hammers, Alexander;Panagoda, Prasan;Koepp, Matthias J.
通讯作者：
Koepp, Matthias J.