Skip to main content

Advertisement

Log in

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

  • Original Article
  • Published:
European Journal of Nuclear Medicine and Molecular Imaging Aims and scope Submit manuscript

Abstract

Purpose

Positron emission tomography (PET) with 11C-labelled Pittsburgh compound B ([11C]PIB) enables the quantitation of β-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.

Methods

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.

Results

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.

Conclusion

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Klunk WE, Engler H, Nordberg A, Wang Y, Blomqvist G, Holt DP. Imaging brain amyloid in Alzheimer's disease with Pittsburgh Compound-B. Ann Neurol 2004;55:306–19. doi:10.1002/ana.20009.

    Article  PubMed  CAS  Google Scholar 

  2. Kemppainen NM, Aalto S, Wilson IA, Någren K, Helin S, Brück A, et al. Voxel-based analysis of PET amyloid ligand [11C]PIB uptake in Alzheimer disease. Neurology 2006;67:1575–80. doi:10.1212/01.wnl.0000240117.55680.0a.

    Article  PubMed  CAS  Google Scholar 

  3. Edison P, Archer HA, Hinz R, Hammers A, Pavese N, Tai YF, et al. Amyloid, hypometabolism, and cognition in Alzheimer disease: an [11C]PIB and [18F]FDG PET study. Neurology 2007;68:501–8. doi:10.1212/01.wnl.0000244749.20056.d4.

    Article  PubMed  CAS  Google Scholar 

  4. Rowe CC, Ng S, Ackermann U, Gong SJ, Pike K, Savage G, et al. Imaging beta-amyloid burden in aging and dementia. Neurology 2007;68:1718–25. doi:10.1212/01.wnl.0000261919.22630.ea.

    Article  PubMed  CAS  Google Scholar 

  5. Mikhno A, Devanand D, Pelton G, Cuasay K, Gunn R, Upton N, et al. Voxel-based analysis of 11C-PIB scans for diagnosing Alzheimer's disease. J Nucl Med 2008;49:1262–9. doi:10.2967/jnumed.107.049932.

    Article  PubMed  Google Scholar 

  6. Yaqub M, Tolboom N, Boellaard R, Berckel BNM, van Tilburg EW, Luurtsema G, et al. Simplified parametric methods for [11C]PIB studies. Neuroimage 2008;42:76–86. doi:10.1016/j.neuroimage.2008.04.251.

    Article  PubMed  Google Scholar 

  7. Lopresti BJ, Klunk WE, Mathis CA, Hoge JA, Ziolko SK, Lu X, et al. Simplified quantification of Pittsburgh Compound B amyloid imaging PET studies: a comparative analysis. J Nucl Med 2005;46:1959–72.

    PubMed  CAS  Google Scholar 

  8. Price JC, Klunk WE, Lopresti BJ, Lu X, Hoge JA, Ziolko SK, et al. Kinetic modeling of amyloid binding in humans using PET imaging and Pittsburgh Compound-B. J Cereb Blood Flow Metab 2005;25:1528–47. doi:10.1038/sj.jcbfm.9600146.

    Article  PubMed  CAS  Google Scholar 

  9. Kemppainen NM, Aalto S, Wilson IA, Någren K, Helin S, Brück A, et al. PET amyloid ligand [11C]PIB uptake is increased in mild cognitive impairment. Neurology 2007;68:1603–6. doi:10.1212/01.wnl.0000260969.94695.56.

    Article  PubMed  CAS  Google Scholar 

  10. Friston KJ, Worsley KJ, Poline JB, Frith CD, Franckowiak RSJ. Statistical parametric maps in functional brain imaging. A general approach. Hum Brain Mapp 1995;2:189–210. doi:10.1002/hbm.460020402.

    Article  Google Scholar 

  11. Meyer JH, Gunn RN, Myers R, Grasby PM. Assessment of spatial normalization of PET ligand images using ligand-specific templates. Neuroimage 1999;9:545–53. doi:10.1006/nimg.1999.0431.

    Article  PubMed  CAS  Google Scholar 

  12. Ziolko SK, Weissfield LA, Klunk WE, Mathis CA, Hoge JA, Lopresti BJ, et al. Evaluation of voxel-based methods for the statistical analysis of PIB PET amyloid imaging studies in Alzheimer's disease. Neuroimage 2006;33:94–102. doi:10.1016/j.neuroimage.2006.05.063.

    Article  PubMed  Google Scholar 

  13. Brück A, Aalto S, Nurmi E, Bergman J, Rinne JO. Cortical 6-[18F]fluoro-L-dopa uptake and frontal cognitive functions in early Parkinson's disease. Neurobiol Aging 2005;26:891–8. doi:10.1016/j.neurobiolaging.2004.07.014.

    Article  PubMed  Google Scholar 

  14. Kemppainen J, Aalto S, Fujimoto T, Kalliokoski KK, Långsjö J, Oikonen V, et al. High intensity exercise decreases global brain glucose uptake in humans. J Physiol 2005;568:323–32. doi:10.1113/jphysiol.2005.091355.

    Article  PubMed  CAS  Google Scholar 

  15. Salmi E, Aalto S, Hirvonen J, Långsjö JW, Maksimov AT, Oikonen V, et al. Measurement of GABAA receptor binding in vivo with [11C]flumazenil: a test-retest study in healthy subjects. Neuroimage 2008;41:260–9. doi:10.1016/j.neuroimage.2008.02.035.

    Article  PubMed  Google Scholar 

  16. Engler H, Forsberg A, Almkvist O, Blomquist G, Larsson E, Savitcheva I, et al. Two-year follow-up of amyloid deposition in patients with Alzheimer's disease. Brain 2006;129:2856–66. doi:10.1093/brain/awl178.

    Article  PubMed  Google Scholar 

  17. Razifar P, Ringheim A, Engler H, Hall H, Långström B. Masked-volume-wise PCA and "reference Logan" illustrate similar regional differences in kinetic behavior in human brain PET study using [11C]-PIB. BMC Neurol 2009;9:2. doi:10.1186/1471-2377-9-2.

    Article  PubMed  Google Scholar 

  18. Hooper PK, Meikle SR, Eberl S, Fulham MJ. Validation of postinjection transmission measurements for attenuation correction in neurological FDG-PET studies. J Nucl Med 1996;37:128–36.

    PubMed  CAS  Google Scholar 

  19. Blomquist G, Engler H, Nordberg A, Ringheim A, Wall A, Forsberg A, et al. Unidirectional influx and net accumulation of PIB. Open Neuroimaging J 2008;2:114–25. doi:10.2174/1874440000802010114.

    Article  CAS  Google Scholar 

Download references

Acknowledgments

The assistance of the personnel of Turku PET Centre and CRST is gratefully acknowledged. This study was financially supported by grants from the Academy of Finland (project # 205954), the Sigrid Jusélius Foundation and Turku University Hospital (EVO).

Conflicts of Interest

Marita Kailajärvi works currently for Turku Imanet, GE Healthcare. The other authors have no conflicts of interest.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Sargo Aalto.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Aalto, S., Scheinin, N.M., Kemppainen, N.M. et al. Reproducibility of automated simplified voxel-based analysis of PET amyloid ligand [11C]PIB uptake using 30-min scanning data. Eur J Nucl Med Mol Imaging 36, 1651–1660 (2009). https://doi.org/10.1007/s00259-009-1174-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00259-009-1174-1

Keywords

Navigation