Reproducibility of PET Activation Studies: Lessons from a Multi-Center European Experiment EU Concerted Action on Functional Imaging J-B. POLINE, R. V ANDENBERGHE, A. P. HOLMES, K. J. FRISTON, AND R. S. J. FRACKOWIAK 1 The Wellcome Department of Cognitive Neurology, 12 Queen Square, WC1N 3BG, United Kingdom Received April 9, 1996 PET activation studies are performed widely to study human brain function. The question of reproducibility, reliability, and comparability of the results of such experiments has never been addressed on a large scale. Recently, 12 European PET centers performed the same cognitive activation experiment in a Euro- pean Union funded concerted action. The experiment involved a standardized and validated cross-lingual experimental and control task involving verbal flu- ency. Each center contributed at least 6 subjects. In total there were 77 subjects and 247 scans in each of the two conditions, giving 494 scans in total. We have analyzed each center’s dataset and pooled datasets using statistical parametric mapping. We present re- sults that address the consistency of these analyses, discuss the factors that influence their sensitivity, and comment on a number of related methodological is- sues. We used a MANOVAto test for center, condition, and centre by condition effects and found a strong condition and center effect and weaker interactions. The main effect determining reproducibility was the overall sensitivity of the experiment, to which the scanner and number of scans contribute in a major way, with a marked advantage for 3D scanners and a large field of view. An important conclusion is that data from different centers can be pooled to improve the reliability of results, which is of particular importance for studies in patients with rare conditions. r 1996 Academic Press, Inc. INTRODUCTION Over the past decade positron emission tomography (PET) has provided one of the most powerful tools available for studying the relationship between human brain functions and neuroanatomy. Applications in this field are many and PET experiments have brought new insights into the functional anatomy of a number of behaviors. Occasionally, controversies have emerged when different laboratories were unable to replicate results (cf. Petersen et al., 1990; Howard et al., 1992; Price et al., 1994). Generally speaking, differences between PET activation experiments can be divided into those that depend on neurospychological aspects (design of the various tasks, subject selection etc.), those that depend on data acquisition parameters (PET scanner characteristics, reconstruction and correction algorithms, number of subjects scanned, the number of scans per subject etc.), and those that depend on data analysis (including statistical analysis and image post processing). These factors can affect the end result of an experiment to a greater or smaller extent. For these reasons the European concerted action on functional imaging decided to study the reproducibility of PET activation technique across laboratories. While it is relatively easy to analyze the same dataset with different methodologies (method compari- son), it is much more difficult to gather a large number of comparable datasets (same protocol). Because of the great practical difficulties involved in such a project, 1 On behalf of the PET centers in Cologne: K. Herholz, U. Pietrzyk, A. Thiel, Max-Planck-Institut fur Neurologische Forschung. Ger- many. Copenhagen: I. Law, C. Svarer, K. Rune, C. Bonde, O. B. Paulson, Department of Neurology, Rigshopitalet, Denmark. Dussel- dorf: P. Indefrey, Max Planck Institut fu ¨ r Psycholinguistik; R. J. Seitz, Department of Neurology, H. Heine University and Julich: H. Herzog Institute of Medecine Research Centre, Germany. Essen: C. Weiller, S. Kiebel, M. Rijntjes, S. Mu ¨ ller, Neurology Clinic, University of Essen, Germany. London: L. Warburton, FIL, Wellcome Depart- ment of Cognitive Neurology, Queen Square, UK. Groningen: L. A. Stowe, A. M. J. Paans, A. A. Wijers, A. T. M. Willemsen, PET Center, University Hospital Groningen, The Netherlands. Leuven: R. Vanden- berghe, P. Dupont, G. Orban. Department of Brain & Behaviour, Katholieke University Leuven, Belgium. Liege: P. Maquet, E. Salmon, C. Degueldre, CRC Universite de Liege, Belgium. Lyon: I. Faillenot, J. Decety, D. Comar, Hopital Neuro-cardio, Cermep, France. Milano: V. Bettinardi, S. F. Cappa, F. Fazio, M. Gorno-Tempini, F. Grassi, D. Perani, T. Schnur, G. Striano, INB-CNR Universities of Milan and Brescia, Scientific Institute HS Raffaele, Italy. Orsay: B. Mazoyer, N. Tzourio, F. Crivello. SHFJ-DRIPP-DSV, CEA, France. Stockholm: M. Ingvar, K. M. Petersson, G. von Heijne, Cognitive Neurophysiology Department Clinical Neuroscience, Karolinska Hospital, Sweden. NEUROIMAGE 4, 34–54 (1996) ARTICLE NO. 0027 34 1053-8119/96 $18.00 Copyright r 1996 by Academic Press, Inc. All rights of reproduction in any form reserved.