Reproducibility of automated simplified voxel-based analysis of PET amyloid ligand [(11)C]PIB uptake using 30-min scanning data

Turku PET Centre, University of Turku and Turku University Hospital, Turku, Finland.
European Journal of Nuclear Medicine (Impact Factor: 5.38). 07/2009; 36(10):1651-60. DOI: 10.1007/s00259-009-1174-1
Source: PubMed


Positron emission tomography (PET) with 11C-labelled Pittsburgh compound B ([11C]PIB) enables the quantitation of beta-amyloid accumulation in the brain of patients with Alzheimer's disease (AD). Voxel-based image analysis techniques conducted in a standard brain space provide an objective, rapid and fully automated method to analyze [11C]PIB PET data. The purpose of this study was to evaluate both region- and voxel-level reproducibility of automated and simplified [11C]PIB quantitation when using only 30 min of imaging data.
Six AD patients and four healthy controls were scanned twice with an average interval of 6 weeks. To evaluate the feasibility of short scanning (convenient for AD patients), [11C]PIB uptake was quantitated using 30 min of imaging data (60 to 90 min after tracer injection) for region-to-cerebellum ratio calculations. To evaluate the reproducibility, a test-retest design was used to derive absolute variability (VAR) estimates and intraclass correlation coefficients at both region-of-interest (ROI) and voxel level.
The reproducibility both at the region level (VAR 0.9-5.5%) and at the voxel level (VAR 4.2-6.4%) was good to excellent. Based on the variability estimates obtained, power calculations indicated that 90% power to obtain statistically significant difference can be achieved using a sample size of five subjects per group when a 15% change from baseline (increase or decrease) in [11C]PIB accumulation in the frontal cortex is anticipated in one group compared to no change in another group.
Our results showed that an automated analysis method based on an efficient scanning protocol provides reproducible results for [11C]PIB uptake and appears suitable for PET studies aiming at the quantitation of amyloid accumulation in the brain of AD patients for the evaluation of progression and treatment effects.

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    • "From a methodological perspective, the analysis of the [11C]PIB data was restricted to static retention ratios, which are more practical for multicentre studies than parameters derived from full kinetic analysis. Static retention values provide a robust and sensitive parameter [43] that is highly correlated with other kinetically derived parameters [44]. The standardized automated procedure that was developed robustly determined regional [11C]PIB retention, demonstrating its feasibility for efficient image processing in multicentre studies. "
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    ABSTRACT: Purpose: Amyloid PET tracers have been developed for in vivo detection of brain fibrillar amyloid deposition in Alzheimer's disease (AD). To serve as an early biomarker in AD the amyloid PET tracers need to be analysed in multicentre clinical studies. Methods: In this study 238 [(11)C]Pittsburgh compound-B (PIB) datasets from five different European centres were pooled. Of these 238 datasets, 18 were excluded, leaving [(11)C]PIB datasets from 97 patients with clinically diagnosed AD (mean age 69 ± 8 years), 72 patients with mild cognitive impairment (MCI; mean age 67.5 ± 8 years) and 51 healthy controls (mean age 67.4 ± 6 years) available for analysis. Of the MCI patients, 64 were longitudinally followed for 28 ± 15 months. Most participants (175 out of 220) were also tested for apolipoprotein E (ApoE) genotype. Results: [(11)C]PIB retention in the neocortical and subcortical brain regions was significantly higher in AD patients than in age-matched controls. Intermediate [(11)C]PIB retention was observed in MCI patients, with a bimodal distribution (64 % MCI PIB-positive and 36 % MCI PIB-negative), which was significantly different the pattern in both the AD patients and controls. Higher [(11)C]PIB retention was observed in MCI ApoE ε4 carriers compared to non-ApoE ε4 carriers (p < 0.005). Of the MCI PIB-positive patients, 67 % had converted to AD at follow-up while none of the MCI PIB-negative patients converted. Conclusion: This study demonstrated the robustness of [(11)C]PIB PET as a marker of neocortical fibrillar amyloid deposition in brain when assessed in a multicentre setting. MCI PIB-positive patients showed more severe memory impairment than MCI PIB-negative patients and progressed to AD at an estimated rate of 25 % per year. None of the MCI PIB-negative patients converted to AD, and thus PIB negativity had a 100 % negative predictive value for progression to AD. This supports the notion that PIB-positive scans in MCI patients are an indicator of prodromal AD.
    European Journal of Nuclear Medicine 01/2013; 40(1):104-114. DOI:10.1007/s00259-012-2237-2 · 5.38 Impact Factor
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    • "Our two subjects with presenilin-1 mutations, in the absence of memory loss, both had higher RATIO PONS in the cortex and the cerebellum than the mean control values whereas RATIO CER underestimated the [ 11 C]PIB binding differences (Table 4). Studies have examined the reproducibility of [ 11 C]PIB using different methods of analysis (Aalto et al., 2009; Edison et al., 2009; Engler et al., 2006; Lopresti et al., 2005; Price et al., 2005) and have shown that reference tissue methods perform better than the arterial input method of analysis for discrimination of AD from healthy normals, while the target-to-cerebellum ratio performed better than the other simplified methods of analysis in terms of sensitivity and reproducibility (Yaqub et al., 2008). Here, the target-to-pons ratio demonstrated high sensitivity for detecting AD and gave comparable test–retest reproducibility to RATIO CER . "
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    ABSTRACT: 11C]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 [11C]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 [11C]PIB binding.
    NeuroImage 01/2012; 60(3):1716-23. DOI:10.1016/j.neuroimage.2012.01.099 · 6.36 Impact Factor
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    Alzheimer's and Dementia 07/2009; 5(4). DOI:10.1016/j.jalz.2009.05.006 · 12.41 Impact Factor
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