1. ¹Department of Nuclear Medicine & PET Research, VU University Medical Centre, Amsterdam, The Netherlands
2. ²Department of Nuclear Medicine & PET Research, Department of Neurology & Alzheimer Centre, VU University Medical Centre, Amsterdam, The Netherlands
3. ³Institute for Research in Extramural Medicine, VU University Medical Centre, Amsterdam, The Netherlands
4. ⁴Department of Neurology & Alzheimer Centre, VU University Medical Centre, Amsterdam, The Netherlands

Correspondence: Dr R Boellaard, Department of Nuclear Medicine & PET Research, VU University Medical Centre, MB Amsterdam 1007, The Netherlands. E-mail: r.boellaard@vumc.nl

Received 19 October 2006; Revised 8 February 2007; Accepted 13 February 2007; Published online 4 April 2007.

Abstract

Inflammation in Alzheimer's disease (AD) may be assessed using (R)-[¹¹C]PK11195 and positron emission tomography. Data can be analyzed using the simplified reference tissue model, provided a suitable reference region is available. This study evaluates various reference regions for analyzing (R)-[¹¹C]PK11195 scans in patients with mild cognitive impairment (MCI) and probable AD. Healthy subjects (n=10, 3010 years and n=10, 706 years) and patients with MCI (n=10, 746 years) and probable AD (n=9, 716 years) were included. Subjects underwent a dynamic three-dimensional (R)-[¹¹C]PK11195 scan including arterial sampling. Gray matter, white matter, total cerebellum and cerebrum, and cluster analysis were evaluated as reference regions. Both plasma input binding potentials of these reference regions (BP^PLASMA) and corresponding reference region input binding potentials of a target region (BP^SRTM) were evaluated. Simulations were performed to assess cluster analysis performance at 5% to 15% coefficient of variation noise levels. Reasonable correlations for BP^PLASMA (R²=0.52 to 0.94) and BP^SRTM (R²=0.59 to 0.76) were observed between results using anatomic regions and cluster analysis. For cerebellum white matter, cerebrum white matter, and total cerebrum a considerable number of unrealistic BP^SRTM values were observed. Cluster analysis did not extract a valid reference region in 10% of the scans. Simulations showed that potentially cluster analysis suffers from negative bias in BP^PLASMA. Most anatomic regions outperformed cluster analysis in terms of absence of both scan rejection and bias. Total cerebellum is the optimal reference region in this patient category.