Longitudinal reproducibility of default-mode network connectivity in healthy elderly participants: A multicentric resting-state fMRI study

Jorge Jovicich (1) , Ludovico Minati (1) , Moira Marizzoni (2) , Rocco Marchitelli (1) , Roser Sala-Llonch (3) , David Bartrés-Faz (4, 3) , Jennifer Arnold (5) , Jens Benninghoff (5) , Ute Fiedler (5) , Luca Roccatagliata (6) , Agnese Picco (7) , Flavio Nobili (8) , Oliver Blin (9) , Stéphanie Bombois (10) , Renaud Lopes (11) , Regis Bordet (12) , Julien Sein (13) , Jean-Philippe Ranjeva (13) , Mira Didic (14) , Helene Gros-Dagnac (15) , Pierre Payoux (15, 16) , Giada Zoccatelli (17) , Franco Alessandrini (17) , Alberto Beltramello (17) , Nuria Bargallo (3) , Antonio Ferretti (18) , Massimo Caulo (18) , Marco Aiello (19) , Carlo Cavaliere (19) , Andrea Soricelli (19) , Lucilla Parnetti (20) , Roberto Tarducci (21) , Piero Floridi (21) , Magda Tsolaki (22) , Manos Constantinidis (23) , Antonios Drevelegas (23) , Paolo Maria Rossini (24) , Camillo Marra (24) , Peter Schoenknecht (25) , Tilman Hensch (25) , Karl-Titus Hoffmann (25) , Joost P. Kuijer (26) , Pieter Jelle Visser (27) , Frederik Barkhof (26) , Giovanni B. Frisoni (2)

1 University of Trento [Trento]
2 IRCCS - Centro San Giovanni di Dio, Fatebenefratelli, Brescia
3 IDIBAPS - Institut d'Investigacions Biomèdiques August Pi i Sunyer
4 Departament de Psiquiatria i Psicobiologia Clinica
5 Universität Duisburg-Essen [Essen]
6 Magnetic Resonance Research Centre on Nervous System Diseases [Genova]
7 UniGe - Università degli studi di Genova = University of Genoa
8 DINOGMI - Dipartimento di Neuroscienze, riabilitazione, oftalmologia, genetica e scienze materno-infantili [Genova]
9 INT - Institut de Neurosciences de la Timone
10 JPArc - Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U837
11 JPL - Jet Propulsion Laboratory
12 TCDV - Troubles cognitifs dégénératifs et vasculaires - U 1171
13 CRMBM - Centre de résonance magnétique biologique et médicale
14 IM2A - Institut de la Mémoire et de la Maladie d'Alzheimer [CHU Pitié-Salpétriêre]
15 ICHN - Imagerie cérébrale et handicaps neurologiques
16 Service de Médecine Nucléaire - Pierre-Paul Riquet [CHU Toulouse]
17 Azienda Ospedaliera Universitaria Integrata of Verona
18 Ud'A - Università degli studi "G. d'Annunzio" Chieti-Pescara [Chieti-Pescara]
19 SDN - Istituto di Ricerca Diagnostica e Nucleare
20 UNIPG - Università degli Studi di Perugia = University of Perugia
21 Perugia General Hospital
22 Aristotle University of Thessaloniki
23 Interbalkan Medical Center of Thessaloniki
24 Fondazione Policlinico Universitario Agostino Gemelli IRCCS
25 University Hospital Leipzig
26 VU University Medical Center [Amsterdam]
27 VU - Vrije Universiteit Amsterdam [Amsterdam]

To date, limited data are available regarding the inter-site consistency of test-retest reproducibility of functional connectivity measurements, in particular with regard to integrity of the Default Mode Network (DMN) in elderly participants. We implemented a harmonized resting-state fMRI protocol on 13 clinical scanners at 3.0 T using vendor-provided sequences. Each site scanned a group of 5 healthy elderly participants twice, at least a week apart. We evaluated inter-site differences and test-retest reproducibility of both temporal signal-to-noise ratio (tSNR) and functional connectivity measurements derived from: i) seed-based analysis (SBA) with seed in the posterior cingulate cortex (PCC), ii) group independent component analysis (ICA) separately for each site (site ICA), and iii) consortium ICA, with group ICA across the whole consortium. Despite protocol harmonization, significant and quantitatively important inter-site differences remained in the tSNR of resting-state fMRI data; these were plausibly driven by hardware and pulse sequence differences across scanners which could not be harmonized. Nevertheless, the tSNR test-retest reproducibility in the consortium was high (ICC = 0.81). The DMN was consistently extracted across all sites and analysis methods. While significant inter-site differences in connectivity scores were found, there were no differences in the associated test-retest error. Overall, ICA measurements were more reliable than PCC-SBA, with site ICA showing higher reproducibility than consortium ICA. Across the DMN nodes, the PCC yielded the most reliable measurements (approximate to 4% test-retest error, ICC = 0.85), the medial frontal cortex the least reliable (approximate to 12%, ICC = 0.82) and the lateral parietal cortices were in between (site ICA). Altogether these findings support usage of harmonized multisite studies of resting-state functional connectivity to characterize longitudinal effects in studies that assess disease progression and treatment response. (C) 2015 Elsevier Inc. All rights reserved.

Keywords: clinical-applications; connectomics; Default Mode Network; disease; Functional connectivity; Functional MRI; human brain; independent component analysis; Multi-center; Multi-site MRI; optimization; physiological noise; Reproducibility; signal-to-noise; test-retest reliability

Domains: Life Sciences [q-bio]; Bioengineering

Jorge Jovicich, Ludovico Minati, Moira Marizzoni, Rocco Marchitelli, Roser Sala-Llonch, et al.. Longitudinal reproducibility of default-mode network connectivity in healthy elderly participants: A multicentric resting-state fMRI study. NeuroImage, 2016, 124, pp.442--454. ⟨10.1016/j.neuroimage.2015.07.010⟩. ⟨hal-01425515⟩