title: A multi-centre evaluation of eleven clinically feasible brain PET/MRI attenuation correction techniques using a large cohort of patients.
abstract: To accurately quantify the radioactivity concentration measured by PET, emission data need to be corrected for photon attenuation; however, the MRI signal cannot easily be converted into attenuation values, making attenuation correction (AC) in PET/MRI challenging. In order to further improve the current vendor-implemented MR-AC methods for absolute quantification, a number of prototype methods have been proposed in the literature. These can be categorized into three types: template/atlas-based, segmentation-based, and reconstruction-based. These proposed methods in general demonstrated improvements compared to vendor-implemented AC, and many studies report deviations in PET uptake after AC of only a few percent from a gold standard CT-AC. Using a unified quantitative evaluation with identical metrics, subject cohort, and common CT-based reference, the aims of this study were to evaluate a selection of novel methods proposed in the literature, and identify the ones suitable for clinical use.
  
  
  
  In total, 11 AC methods were evaluated: two vendor-implemented (MR-ACDIXONand MR-ACUTE), five based on template/atlas information (MR-ACSEGBONE(Koesters et al., 2016), MR-ACONTARIO(Anazodo et al., 2014), MR-ACBOSTON(Izquierdo-Garcia et al., 2014), MR-ACUCL(Burgos et al., 2014), and MR-ACMAXPROB(Merida et al., 2015)), one based on simultaneous reconstruction of attenuation and emission (MR-ACMLAA(Benoit et al., 2015)), and three based on image-segmentation (MR-ACMUNICH(Cabello et al., 2015), MR-ACCAR-RiDR(Juttukonda et al., 2015), and MR-ACRESOLUTE(Ladefoged et al., 2015)). We selected 359 subjects who were scanned using one of the following radiotracers: [18F]FDG (210), [11C]PiB (51), and [18F]florbetapir (98). The comparison to AC with a gold standard CT was performed both globally and regionally, with a special focus on robustness and outlier analysis.
  
  
  
  The average performance in PET tracer uptake was within ±5% of CT for all of the proposed methods, with the average±SD global percentage bias in PET FDG uptake for each method being: MR-ACDIXON(-11.3±3.5)%, MR-ACUTE(-5.7±2.0)%, MR-ACONTARIO(-4.3±3.6)%, MR-ACMUNICH(3.7±2.1)%, MR-ACMLAA(-1.9±2.6)%, MR-ACSEGBONE(-1.7±3.6)%, MR-ACUCL(0.8±1.2)%, MR-ACCAR-RiDR(-0.4±1.9)%, MR-ACMAXPROB(-0.4±1.6)%, MR-ACBOSTON(-0.3±1.8)%, and MR-ACRESOLUTE(0.3±1.7)%, ordered by average bias. The overall best performing methods (MR-ACBOSTON, MR-ACMAXPROB, MR-ACRESOLUTEand MR-ACUCL, ordered alphabetically) showed regional average errors within ±3% of PET with CT-AC in all regions of the brain with FDG, and the same four methods, as well as MR-ACCAR-RiDR, showed that for 95% of the patients, 95% of brain voxels had an uptake that deviated by less than 15% from the reference. Comparable performance was obtained with PiB and florbetapir.
  
  
  
  All of the proposed novel methods have an average global performance within likely acceptable limits (±5% of CT-based reference), and the main difference among the methods was found in the robustness, outlier analysis, and clinical feasibility. Overall, the best performing methods were MR-ACBOSTON, MR-ACMAXPROB, MR-ACRESOLUTE and MR-ACUCL, ordered alphabetically. These methods all minimized the number of outliers, standard deviation, and average global and local error. The methods MR-ACMUNICH and MR-ACCAR-RiDR were both within acceptable quantitative limits, so these methods should be considered if processing time is a factor. The method MR-ACSEGBONE also demonstrates promising results, and performs well within the likely acceptable quantitative limits. For clinical routine scans where processing time can be a key factor, this vendor-provided solution currently outperforms most methods. With the performance of the methods presented here, it may be concluded that the challenge of improving the accuracy of MR-AC in adult brains with normal anatomy has been solved to a quantitatively acceptable degree, which is smaller than the quantification reproducibility in PET imaging.
authors.affiliation: Department of Clinical Physiology, Nuclear Medicine and PET, Rigshospitalet Copenhagen, Denmark.
authors.forename: Claes N
authors.initials: CN
authors.lastname: Ladefoged
authors.affiliation: Department of Clinical Physiology, Nuclear Medicine and PET, Rigshospitalet Copenhagen, Denmark.
authors.forename: Ian
authors.initials: I
authors.lastname: Law
authors.affiliation: Lawson Health Research Institute, London, ON, Canada.
authors.forename: Udunna
authors.initials: U
authors.lastname: Anazodo
authors.affiliation: Lawson Health Research Institute, London, ON, Canada.
authors.forename: Keith
authors.initials: K
authors.lastname: St Lawrence
authors.affiliation: Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA, USA.
authors.forename: David
authors.initials: D
authors.lastname: Izquierdo-Garcia
authors.affiliation: Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA, USA.
authors.forename: Ciprian
authors.initials: C
authors.lastname: Catana
authors.affiliation: Translational Imaging Group, Centre for Medical Image Computing, University College London, NW1 2HE, London, UK.
authors.forename: Ninon
authors.initials: N
authors.lastname: Burgos
authors.affiliation: Translational Imaging Group, Centre for Medical Image Computing, University College London, NW1 2HE, London, UK; Dementia Research Centre, Institute of Neurology, University College London, WC1N 3AR, London, UK.
authors.forename: M Jorge
authors.initials: MJ
authors.lastname: Cardoso
authors.affiliation: Translational Imaging Group, Centre for Medical Image Computing, University College London, NW1 2HE, London, UK; Dementia Research Centre, Institute of Neurology, University College London, WC1N 3AR, London, UK.
authors.forename: Sebastien
authors.initials: S
authors.lastname: Ourselin
authors.affiliation: Institute of Nuclear Medicine, University College London, London, UK.
authors.forename: Brian
authors.initials: B
authors.lastname: Hutton
authors.affiliation: LILI-EQUIPEX - Lyon Integrated Life Imaging: hybrid MR-PET, CERMEP Imaging Centre, Lyon, France; Siemens Healthcare France SAS, Saint-Denis, France.
authors.forename: Inés
authors.initials: I
authors.lastname: Mérida
authors.affiliation: LILI-EQUIPEX - Lyon Integrated Life Imaging: hybrid MR-PET, CERMEP Imaging Centre, Lyon, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Costes
authors.affiliation: LILI-EQUIPEX - Lyon Integrated Life Imaging: hybrid MR-PET, CERMEP Imaging Centre, Lyon, France; King's College London & Guy's and St Thomas' PET Centre, Division of Imaging Sciences and Biomedical Engineering, King's College London, London, UK.
authors.forename: Alexander
authors.initials: A
authors.lastname: Hammers
authors.affiliation: Department of Clinical Physiology, Nuclear Medicine and PET, Rigshospitalet Copenhagen, Denmark.
authors.forename: Didier
authors.initials: D
authors.lastname: Benoit
authors.affiliation: Department of Clinical Physiology, Nuclear Medicine and PET, Rigshospitalet Copenhagen, Denmark.
authors.forename: Søren
authors.initials: S
authors.lastname: Holm
authors.affiliation: Joint Department of Biomedical Engineering, The University of North Carolina at Chapel Hill and North Carolina State University, Chapel Hill, NC 27599, USA.
authors.forename: Meher
authors.initials: M
authors.lastname: Juttukonda
authors.affiliation: Joint Department of Biomedical Engineering, The University of North Carolina at Chapel Hill and North Carolina State University, Chapel Hill, NC 27599, USA.
authors.forename: Hongyu
authors.initials: H
authors.lastname: An
authors.affiliation: Nuklearmedizinische Klinik und Poliklinik, Klinikum rechts der Isar, Technische Universitaet Muenchen, Munich, Germany.
authors.forename: Jorge
authors.initials: J
authors.lastname: Cabello
authors.affiliation: Nuklearmedizinische Klinik und Poliklinik, Klinikum rechts der Isar, Technische Universitaet Muenchen, Munich, Germany.
authors.forename: Mathias
authors.initials: M
authors.lastname: Lukas
authors.affiliation: Nuklearmedizinische Klinik und Poliklinik, Klinikum rechts der Isar, Technische Universitaet Muenchen, Munich, Germany.
authors.forename: Stephan
authors.initials: S
authors.lastname: Nekolla
authors.affiliation: Nuklearmedizinische Klinik und Poliklinik, Klinikum rechts der Isar, Technische Universitaet Muenchen, Munich, Germany.
authors.forename: Sibylle
authors.initials: S
authors.lastname: Ziegler
authors.affiliation: Siemens Healthcare GmbH, Erlangen, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Fenchel
authors.affiliation: Siemens Healthcare GmbH, Erlangen, Germany; University of Surrey, Guildford, Surrey, UK.
authors.forename: Bjoern
authors.initials: B
authors.lastname: Jakoby
authors.affiliation: Siemens Medical Solutions USA, Inc., Knoxville, TN, USA.
authors.forename: Michael E
authors.initials: ME
authors.lastname: Casey
authors.affiliation: Mallinckrodt Institute of Radiology, Washington University, St. Louis, MO 63130, USA.
authors.forename: Tammie
authors.initials: T
authors.lastname: Benzinger
authors.affiliation: Department of Clinical Physiology, Nuclear Medicine and PET, Rigshospitalet Copenhagen, Denmark.
authors.forename: Liselotte
authors.initials: L
authors.lastname: Højgaard
authors.affiliation: Department of Clinical Physiology, Nuclear Medicine and PET, Rigshospitalet Copenhagen, Denmark.
authors.forename: Adam E
authors.initials: AE
authors.lastname: Hansen
authors.affiliation: Department of Clinical Physiology, Nuclear Medicine and PET, Rigshospitalet Copenhagen, Denmark. Electronic address: fling@rh.dk.
authors.forename: Flemming L
authors.initials: FL
authors.lastname: Andersen
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001921:Brain / Q000000981:diagnostic imaging*; D060825:Cognitive Dysfunction / Q000000981:diagnostic imaging*; D015331:Cohort Studies; D003704:Dementia / Q000000981:diagnostic imaging*; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted / Q000379:methods* / Q000592:standards; D008279:Magnetic Resonance Imaging / Q000379:methods* / Q000592:standards; D008297:Male; D008875:Middle Aged; D049268:Positron-Emission Tomography / Q000379:methods* / Q000592:standards; D019275:Radiopharmaceuticals; D055815:Young Adult
chemical_list: D019275:Radiopharmaceuticals
keywords: Attenuation correction; Brain; PET/MRI