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Published online before print September 13, 2006, doi:10.1212/01.wnl.0000240117.55680.0a)
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Received December 22, 2005
Accepted June 15, 2006

Voxel-based analysis of PET amyloid ligand [11C]PIB uptake in Alzheimer disease

N. M. Kemppainen MD, PhD, S. Aalto MSc, I. A. Wilson PhD, K. NÅgren PhD, S. Helin MSc, A Brück MD, PhD, V. Oikonen MSc, M. Kailajärvi MD, PhD, M. Scheinin MD, PhD, M. Viitanen MD, PhD, R. Parkkola MD, PhD, and J. O. Rinne MD, PhD*

From the Turku PET Centre (N.M.K., S.A., K.N., S.H., A.B., V.O., J.O.R.) and Department of Pharmacology and Clinical Research Services Turku (CRST) (M.K., M.S.), University of Turku, Department of Psychology (S.A.), Åbo Akademi University, Turku City Hospital (M.V.), Department of Clinical Radiology, Turku University Hospital (R.P.), Turku Imanet Ltd (J.O.R.), Turku, Finland; GE Healthcare Medical Diagnostics (I.A.W.), UK; and Clinical Geriatrics (M.V.), Karolinska Institutet, Stockholm, Sweden.


* To whom correspondence should be addressed. E-mail: juha.rinne{at}tyks.fi.

Abstract-- Background: PET studies with N-methyl-[11C]2-(4'-methylaminophenyl)-6-hydroxybenzothiazole ([11C]PIB) have revealed an increased tracer uptake in several brain regions in Alzheimer disease (AD). Objective: To employ voxel-based analysis method to identify brain regions with significant increases in [11C]PIB uptake in AD vs healthy control subjects, indicative of increased amyloid accumulation in these regions. Methods: We studied 17 patients with AD and 11 control subjects with PET using [11C]PIB as tracer. Parametric images were computed by calculating a region-to-cerebellum ratio over 60 to 90 minutes in each voxel. Group differences in [11C]PIB uptake were analyzed with statistical parametric mapping (SPM) and automated region-of-interest (ROI) analysis. Results: SPM showed increased uptake (p < 0.001) in the frontal, parietal, and lateral temporal cortices as well as in the posterior cingulate and the striatum. No significant differences in uptake were found in the primary sensory and motor cortices, primary visual cortex, thalamus, and medial temporal lobe. These results were supported by automated ROI analysis, with most prominent increases in AD subjects in the frontal cortex ([11C]PIB uptake 163% of the control mean) and posterior cingulate (146%) followed by the parietal (146%) and temporal (145%) cortices and striatum (133%), as well as small increases in the occipital cortex (117%) and thalamus (115%). Conclusions: Voxel-based analysis revealed widespread distribution of increased [11C]PIB uptake in Alzheimer disease (AD). These findings are in accordance with the distribution and phases of amyloid pathology in AD, previously documented in postmortem studies.




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