Medical Research Council Clinical Sciences Centre and Division of Neuroscience, Hammersmith Hospital, Imperial College, London, UK.
Neuroimage. 2012 Apr 15;60(3):1716-23. doi: 10.1016/j.neuroimage.2012.01.099. Epub 2012 Jan 27.
(11)C]PIB is the most widely used PET imaging marker for amyloid in dementia studies. In the majority of studies the cerebellum has been used as a reference region. However, cerebellar amyloid may be present in genetic Alzheimer's (AD), cerebral amyloid angiopathy and prion diseases. Therefore, we investigated whether the pons could be used as an alternative reference region for the analysis of [(11)C]PIB binding in AD. The aims of the study were to: 1) Evaluate the pons as a reference region using arterial plasma input function and Logan graphical analysis of binding. 2) Assess the power of target-to-pons ratios to discriminate controls from AD subjects. 3) Determine the test-retest reliability in AD subjects. 4) Demonstrate the application of target-to-pons ratio in subjects with elevated cerebellar [(11)C]PIB binding.
12 sporadic AD subjects aged 65 ± 4.5 yrs with a mean MMSE 21.4 ± 4 and 10 age-matched control subjects had [(11)C]PIB PET with arterial blood sampling. Three additional subjects (two subjects with pre-symptomatic presenilin-1 mutation carriers and one probable familial AD) were also studied. Object maps were created by segmenting individual MRIs and spatially transforming the gray matter images into standard stereotaxic MNI space and then superimposing a probabilistic atlas. Cortical [(11)C]PIB binding was assessed with an ROI (region of interest) analysis. Parametric maps of the volume of distribution (V(T)) were generated with Logan analysis. Additionally, parametric maps of the 60-90 min target-to-cerebellar ratio (RATIO(CER)) and the 60-90 min target-to-pons ratio (RATIO(PONS)) were computed.
All three approaches were able to differentiate AD from controls (p<0.0001, nonparametric Wilcoxon rank sum test) in the target regions with RATIO(CER) and RATIO(PONS) differences higher than V(T) with use of an arterial input function. All methods had a good reproducibility (intraclass correlation coefficient>0.83); RATIO(CER) performed best closely followed by RATIO(PONS). The two subjects with presenilin-1 mutations and the probable familial AD case showed no significant differences in cortical binding using RATIO(CER), but the RATIO(PONS) approach revealed higher [(11)C]PIB binding in cortex and cerebellum.
This study established 60-90 min target-to-pons RATIOs as a reliable method of analysis in [(11)C]PIB PET studies where cerebellum is not an appropriate reference region.
（11）C]PIB 是用于痴呆研究中淀粉样蛋白的最广泛使用的 PET 成像标志物。在大多数研究中，小脑被用作参考区域。然而，小脑淀粉样蛋白可能存在于遗传性阿尔茨海默病（AD）、脑淀粉样血管病和朊病毒病中。因此，我们研究了桥脑是否可以作为 AD 中[（11）C]PIB 结合分析的替代参考区域。该研究的目的是：1）使用动脉血浆输入函数和绑定的 Logan 图形分析评估桥脑作为参考区域。2）评估目标与桥脑的比值区分对照与 AD 受试者的能力。3）确定 AD 受试者的测试-重测可靠性。4）证明目标与桥脑的比值在小脑[（11）C]PIB 结合升高的受试者中的应用。
12 名年龄在 65±4.5 岁的散发性 AD 受试者，平均 MMSE 为 21.4±4，10 名年龄匹配的对照组受试者进行了[（11）C]PIB PET 与动脉采血。还研究了另外 3 名受试者（两名早发性 presenilin-1 突变携带者和一名可能的家族性 AD 患者）。通过对个体 MRI 进行分割并将灰质图像空间变换到标准立体定向 MNI 空间，然后叠加概率图谱，创建对象图谱。使用 ROI（感兴趣区域）分析评估皮质[（11）C]PIB 结合。使用 Logan 分析生成分布容积（V（T））的参数图。此外，还计算了 60-90 分钟目标与小脑的比值（RATIO（CER））和 60-90 分钟目标与桥脑的比值（RATIO（PONS））的参数图。
所有三种方法都能够使用动脉输入函数区分 AD 与对照组（p<0.0001，非参数 Wilcoxon 秩和检验），差异高于 V（T）的区域包括 RATIO（CER）和 RATIO（PONS）。所有方法的重现性都很好（组内相关系数>0.83）；RATIO（CER）表现最好，其次是 RATIO（PONS）。两名携带早发性 presenilin-1 突变的受试者和一名可能的家族性 AD 病例的皮质结合物使用 RATIO（CER）没有明显差异，但 RATIO（PONS）方法显示皮质和小脑的[（11）C]PIB 结合更高。
本研究确立了 60-90 分钟的目标与桥脑的 RATIO 作为[（11）C]PIB PET 研究中可靠的分析方法，其中小脑不是合适的参考区域。
