UNCORRECTED PROOF 1 Q3 Relationship between simultaneously acquired resting-state regional 2 cerebral glucose metabolism and functional MRI: A PET/MR hybrid 3 scanner study 4 Q4 Marco Aiello a, ⁎, Elena Salvatore b,1 , Arnaud Cachia c,1 , Sabina Pappatà d , Carlo Cavaliere a , Anna Prinster d , 5 Emanuele Nicolai a , Marco Salvatore a , Jean-Claude Baron c,2 , Mario Quarantelli d,2 6 a IRCCS SDN, Istituto di Ricerca Diagnostica e Nucleare, Via E. Gianturco 113, 80143 Naples, Italy 7 b Q5 Department of Neurosciences, Reproductive Sciences and Odontostomatology, Federico II University, via S. Pansini 5-ed. 17, I-80131 Naples, Italy 8 c INSERM U894, Université Paris Descartes, Centre Hospitalier Sainte-Anne, Sorbonne Paris Cité, Paris, France 9 d Biostructure and Bioimaging Institute, National Research Council, Via T. De Amicis 95, 80145 Naples, Italy abstract 10 article info 11 Article history: 12 Received 7 November 2014 13 Accepted 9 March 2015 14 Available online xxxx 15 Keywords: 16 PET/MRI 17 [ 18 F]FDG 18 Functional connectivity 19 Resting-state fMRI 20 Networks 21 Recently introduced hybrid PET/MR scanners provide the opportunity to measure simultaneously, and in direct 22 spatial correspondence, both metabolic demand and functional activity of the brain, hence capturing 23 complementary information on the brain's physiological state. Here we exploited PET/MR simultaneous imaging 24 to explore the relationship between the metabolic information provided by resting-state fluorodeoxyglucose- 25 PET (FDG-PET) and fMRI (rs-fMRI Q6 ) in neurologically healthy subjects. 26 Regional homogeneity (ReHo), fractional amplitude of low frequency fluctuations (fALFF), and degree of 27 centrality (DC) maps were generated from the rs-fMRI data in 23 subjects, and voxel-wise comparison to glucose 28 uptake distribution provided by simultaneously acquired FDG-PET was performed. The mutual relationships 29 among each couple of these four metrics were explored in terms of similarity, both of spatial distribution across 30 the brain and the whole group, and voxel-wise across subjects, taking into account partial volume effects by 31 adjusting for grey matter (GM) volume. Although a significant correlation between the spatial distribution of 32 glucose uptake and rs-fMRI derived metrics was present, only a limited percentage of GM voxels correlated 33 with PET across subjects. Moreover, the correlation between the spatial distributions of PET and RS-fMRI- 34 derived metrics is spatially heterogeneous across both anatomic regions and functional networks, with lowest 35 correlation strength in the limbic network (Spearman rho around -0.11 for DC), and strongest correlation for 36 the default-mode network (up to 0.89 for ReHo and 0.86 for fALFF). Overall, ReHo and fALFF provided significantly 37 higher correlation coefficients with PET (p = 10 -8 and 10 -7 , respectively) as compared to DC, while no 38 significant differences were present between ReHo and fALFF. Local GM volume variations introduced a 39 limited overestimation of the rs-fMRI to FDG correlation between the modalities under investigation 40 through partial volume effects. 41 These novel results provide the basis for future studies of alterations of the coupling between brain metabolism 42 and functional connectivity in pathologic conditions. 43 © 2015 Elsevier Inc. All rights reserved. 44 45 46 47 48 Introduction 49 Resting-state glucose and oxygen metabolism are closely linked 50 ( Q7 Jueptner and Weiller, 1995; Baron et al., 1984) and physiologically 51 related to neural activity. Moreover, both processes are in turn strongly 52 related to resting cerebral blood flow (CBF) that delivers O 2 and glucose 53 to the tissue ( Q8 Attwell and Iadecola, 2002; Baron et al., 1984). The mech- 54 anisms underlying neurovascular coupling and neuronal function are 55 presently incompletely understood and being investigated by a trans- 56 disciplinary research community (Leithner and Royl, 2014). 57 Studying the neurovascular structure is complex due to the need 58 for both neuronal interconnectivity and vascular networks to be intact. NeuroImage xxx (2015) xxx–xxx Abbreviations: AAL,automatedanatomicallabelling;BOLD,blood-oxygen-level-depen- dent; CBF, cerebral blood flow; DC, degree of centrality; DMN, default mode network; fALFF, fractional amplitude of low frequency fluctuations; FC, functional connectivity; FDG, fluorodeoxyglucose; MRI, magnetic resonance imaging; PET, positron emission tomogra- phy; ReHo, regional homogeneity; rGU, relative glucose uptake; rs-fMRI, resting-state func- tional MRI; RSN, resting-state network ⁎ Corresponding author. E-mail address: maiello@sdn-napoli.it (M. Aiello). 1 These two authors share 2nd author position. 2 These two authors share senior authorship. YNIMG-12057; No. of pages: 12; 4C: 4, 6, 7, 8, 9 http://dx.doi.org/10.1016/j.neuroimage.2015.03.017 1053-8119/© 2015 Elsevier Inc. All rights reserved. Contents lists available at ScienceDirect NeuroImage journal homepage: www.elsevier.com/locate/ynimg Please cite this article as: Aiello, M., et al., Relationship between simultaneously acquired resting-state regional cerebral glucose metabolism and functional MRI: A PET/MR hybrid scanner study, NeuroImage (2015), http://dx.doi.org/10.1016/j.neuroimage.2015.03.017