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@ARTICLE{Bollack:283059,
      author       = {Bollack, Ariane and Shekari, Mahnaz and Collij, Lyduine E
                      and Luckett, Emma and García, David Valléz and Markiewicz,
                      Pawel and Wolz, Robin and Yaqub, Maqsood and Wink, Alle
                      Meije and Gismondi, Rossella and Stephens, Andrew and
                      Visser, Pieter Jelle and Mett, Anja and Drzezga, Alexander
                      and Buckley, Christopher and Gispert, Juan Domingo and
                      Farrar, Gill and Barkhof, Frederik},
      title        = {{I}mplementing robust amyloid {PET} quantification in
                      multi-center studies: {AMYPAD} approach to address data
                      acquisition, processing, interpretation and data sharing
                      challenges.},
      journal      = {Alzheimer's $\&$ dementia / Translational research $\&$
                      clinical interventions},
      volume       = {11},
      number       = {4},
      issn         = {2352-8737},
      address      = {Hoboken, NJ},
      publisher    = {Wiley},
      reportid     = {DZNE-2025-01466},
      pages        = {e70190},
      year         = {2025},
      abstract     = {Amyloid-positron emission tomography (PET) is pivotal to
                      Alzheimer's management, with the Centiloid standardizing
                      measurements across tracers. AMYPAD trials (Diagnostic and
                      Patient Management Study [DPMS] and Prognostic and Natural
                      History Study [PNHS]) aimed to validate robust
                      quantification in clinical settings. We report our
                      comprehensive approach to amyloid-PET implementation,
                      comprising scan acquisition, harmonization, data storing,
                      and data sharing strategies.Data from 28 scanners were
                      harmonized using Hoffman phantoms. Three quantification
                      workflows were compared: AmyPype (PET-only), IXICO-LEAP, and
                      the standard Centiloid pipeline (magnetic resonance imaging
                      [MRI]-based). Distributions of Centiloids were assessed
                      using Gaussian Mixture Modeling.Binary quantification showed
                      excellent concordance between pipelines (≥ $96\%)$ and
                      compared to visual reads $(>90\%).$ DPMS Centiloids had a
                      bimodal distribution while the PNHS showed a more skewed
                      distribution toward higher Centiloids modeled with three
                      Gaussians (1st Gaussian mean + 2SD = 12 CL, emerging
                      pathology).The harmonization framework, providing strong
                      cross-method correlations in AMYPAD, has been adopted by
                      EARL as the Brain PET/CT accreditation standard and provides
                      a practical approach for other multi-center cohorts to
                      implement similar strategies.We share AMYPAD's end-to-end
                      approach to amyloid positron emission tomography (PET)
                      quantification from data acquisition and handling,
                      harmonization based on Hoffman phantoms, quality control,
                      image processing, to data storage, and data sharing
                      strategies.Centiloid quantification was compared across one
                      PET-only (AmyPype) and two PET-MR pipelines (standard
                      Centiloid and IXIXO-LEAP). Excellent agreement in
                      dichotomized Centiloid valued was observed both between
                      pipelines and when compared to visual reads.Distribution of
                      Centiloid values in the Prognostic and Natural History Study
                      (PNHS) and Diagnostic and Patient Management Study (DPMS)
                      are in line with the initial recruitment strategies of the
                      trials.Harmonization of Amyloid-PET scans framework was
                      adopted by EARL as the Brain PET/CT accreditation standard
                      for multicentre brain PET scans.},
      keywords     = {Alzheimer's (Other) / Centiloid (Other) / PET (Other) /
                      amyloid (Other) / quantification (Other)},
      cin          = {AG Boecker},
      ddc          = {610},
      cid          = {I:(DE-2719)1011202},
      pnm          = {353 - Clinical and Health Care Research (POF4-353)},
      pid          = {G:(DE-HGF)POF4-353},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:41445671},
      pmc          = {pmc:PMC12722600},
      doi          = {10.1002/trc2.70190},
      url          = {https://pub.dzne.de/record/283059},
}