title: Between-centre variability in transfer function analysis, a widely used method for linear quantification of the dynamic pressure-flow relation: the CARNet study.
abstract: Transfer function analysis (TFA) is a frequently used method to assess dynamic cerebral autoregulation (CA) using spontaneous oscillations in blood pressure (BP) and cerebral blood flow velocity (CBFV). However, controversies and variations exist in how research groups utilise TFA, causing high variability in interpretation. The objective of this study was to evaluate between-centre variability in TFA outcome metrics. 15 centres analysed the same 70 BP and CBFV datasets from healthy subjects (n=50 rest; n=20 during hypercapnia); 10 additional datasets were computer-generated. Each centre used their in-house TFA methods; however, certain parameters were specified to reduce a priori between-centre variability. Hypercapnia was used to assess discriminatory performance and synthetic data to evaluate effects of parameter settings. Results were analysed using the Mann-Whitney test and logistic regression. A large non-homogeneous variation was found in TFA outcome metrics between the centres. Logistic regression demonstrated that 11 centres were able to distinguish between normal and impaired CA with an AUC>0.85. Further analysis identified TFA settings that are associated with large variation in outcome measures. These results indicate the need for standardisation of TFA settings in order to reduce between-centre variability and to allow accurate comparison between studies. Suggestions on optimal signal processing methods are proposed.
authors.affiliation: Radboud University Medical Center, Department of Geriatric Medicine and Donders Institute for Brain, Cognition and Behaviour, The Netherlands.
authors.forename: Aisha S S
authors.initials: AS
authors.lastname: Meel-van den Abeelen
authors.affiliation: Institute of Sound and Vibration Research, University of Southampton, Southampton, UK.
authors.forename: David M
authors.initials: DM
authors.lastname: Simpson
authors.affiliation: Radboud University Medical Center, Department of Geriatric Medicine and Donders Institute for Brain, Cognition and Behaviour, The Netherlands.
authors.forename: Lotte J Y
authors.initials: LJ
authors.lastname: Wang
authors.affiliation: MIRA-Institute for Biomedical Technology and Technical Medicine, Faculty of Science and Technology, University of Twente, The Netherlands.
authors.forename: Cornelis H
authors.initials: CH
authors.lastname: Slump
authors.affiliation: Institute for Exercise and Environmental Medicine, Texas Health Presbyterian Hospital of Dallas and The University of Texas Southwestern Medical Center at Dallas, Dallas, TX, United States.
authors.forename: Rong
authors.initials: R
authors.lastname: Zhang
authors.affiliation: Institute for Exercise and Environmental Medicine, Texas Health Presbyterian Hospital of Dallas and The University of Texas Southwestern Medical Center at Dallas, Dallas, TX, United States.
authors.forename: Takashi
authors.initials: T
authors.lastname: Tarumi
authors.affiliation: Department of Integrative Physiology, University of North Texas Health Science Center, Fort Worth, TX, United States.
authors.forename: Caroline A
authors.initials: CA
authors.lastname: Rickards
authors.affiliation: Institute of Biomedical Engineering, Department of Engineering Science, University of Oxford, Oxford, UK.
authors.forename: Stephen
authors.initials: S
authors.lastname: Payne
authors.affiliation: Department of Electrical and Computer Engineering, University of Cyprus, Cyprus.
authors.forename: Georgios D
authors.initials: GD
authors.lastname: Mitsis
authors.affiliation: Department of Electrical and Computer Engineering, University of Cyprus, Cyprus.
authors.forename: Kyriaki
authors.initials: K
authors.lastname: Kostoglou
authors.affiliation: Department of Biomedical Engineering, University of Southern California, Los Angeles, CA, United States.
authors.forename: Vasilis
authors.initials: V
authors.lastname: Marmarelis
authors.affiliation: Biomedical Simulations Resource, University of Southern California, Los Angeles, CA, United States.
authors.forename: Dae
authors.initials: D
authors.lastname: Shin
authors.affiliation: Cardiovascular Systems Laboratory, Centre for Translational Physiology, University of Otago, Wellington, New Zealand.
authors.forename: Yu-Chieh
authors.initials: YC
authors.lastname: Tzeng
authors.affiliation: School of Health and Exercise Science, University of British Columbia Okanagan, Kelowna, B.C., Canada.
authors.forename: Philip N
authors.initials: PN
authors.lastname: Ainslie
authors.affiliation: Maastricht University Medical Center, Department of Clinical Neurophysiology, The Netherlands.
authors.forename: Erik
authors.initials: E
authors.lastname: Gommer
authors.affiliation: Luzerner Kantonsspital, Zentrum für Neurologie und Neurorehabilitation, Lucerne, Switzerland.
authors.forename: Martin
authors.initials: M
authors.lastname: Müller
authors.affiliation: KU Leuven, Department of Electrical Engineering-ESAT, SCD-SISTA and iMinds Future Health Department, Leuven, Belgium.
authors.forename: Alexander C
authors.initials: AC
authors.lastname: Dorado
authors.affiliation: Academic Neurosurgical Unit, Cambridge University Hospital Trust, UK.
authors.forename: Peter
authors.initials: P
authors.lastname: Smielewski
authors.affiliation: Emergency Department, Clinics Hospital, Universidad de la República, School of Medicine, Montevideo, Uruguay.
authors.forename: Bernardo
authors.initials: B
authors.lastname: Yelicich
authors.affiliation: Emergency Department, Clinics Hospital, Universidad de la República, School of Medicine, Montevideo, Uruguay.
authors.forename: Corina
authors.initials: C
authors.lastname: Puppo
authors.affiliation: Academic Neurosurgical Unit, Cambridge University Hospital Trust, UK.
authors.forename: Xiuyun
authors.initials: X
authors.lastname: Liu
authors.affiliation: Academic Neurosurgical Unit, Cambridge University Hospital Trust, UK.
authors.forename: Marek
authors.initials: M
authors.lastname: Czosnyka
authors.affiliation: Research Center for Adaptive Data Analysis, National Central University, Taiwan.
authors.forename: Cheng-Yen
authors.initials: CY
authors.lastname: Wang
authors.affiliation: Division of Gerontology, Beth Israel Deaconess Medical Center, Boston, MA, United States.
authors.forename: Vera
authors.initials: V
authors.lastname: Novak
authors.affiliation: Leicester NIHR Biomedical Research Unit in Cardiovascular Sciences, Glenfield Hospital, Leicester, UK.
authors.forename: Ronney B
authors.initials: RB
authors.lastname: Panerai
authors.affiliation: Radboud University Medical Center, Department of Geriatric Medicine and Donders Institute for Brain, Cognition and Behaviour, The Netherlands. Electronic address: j.claassen@ger.umcn.nl.
authors.forename: Jurgen A H R
authors.initials: JA
authors.lastname: Claassen
mesh_terms: D001783:Blood Flow Velocity; D001794:Blood Pressure; D002560:Cerebrovascular Circulation; D006706:Homeostasis; D006801:Humans; D006935:Hypercapnia / Q000503:physiopathology; D016014:Linear Models; D008954:Models, Biological; D012815:Signal Processing, Computer-Assisted
keywords: Cerebral autoregulation; Method comparison; Standardisation; Transfer function analysis
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