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@ARTICLE{Collij:274065,
      author       = {Collij, Lyduine E and Bischof, Gérard N and Altomare,
                      Daniele and Bader, Ilse and Battle, Mark and Vállez
                      García, David and Lopes Alves, Isadora and Wolz, Robin and
                      Gismondi, Rossella and Stephens, Andrew and Walker, Zuzana
                      and Scheltens, Philip and Nordberg, Agneta and Gispert, Juan
                      Domingo and Drzezga, Alexander and Perissinotti, Andrés and
                      Morbelli, Silvia and Buckley, Christopher and Garibotto,
                      Valentina and Frisoni, Giovanni B and Farrar, Gill and
                      Barkhof, Frederik},
      collaboration = {Consortium, AMYPAD},
      title        = {{Q}uantification {S}upports {A}myloid {PET} {V}isual
                      {A}ssessment of {C}hallenging {C}ases: {R}esults from the
                      {AMYPAD} {D}iagnostic and {P}atient {M}anagement {S}tudy.},
      journal      = {Journal of nuclear medicine},
      volume       = {66},
      number       = {1},
      issn         = {0097-9058},
      address      = {New York, NY},
      publisher    = {Soc.},
      reportid     = {DZNE-2025-00046},
      pages        = {110 - 116},
      year         = {2025},
      abstract     = {Several studies have demonstrated strong agreement between
                      routine clinical visual assessment and quantification,
                      suggesting that quantification approaches could support
                      assessment by less experienced readers or in challenging
                      cases. However, all studies to date have implemented a
                      retrospective case collection, and challenging cases were
                      generally underrepresented. Methods: We included all
                      participants (n = 741) from the AMYPAD diagnostic and
                      patient management study with available baseline amyloid PET
                      quantification. Quantification was done with the PET-only
                      AmyPype pipeline, providing global Centiloid and regional z
                      scores. Visual assessment was performed by local readers for
                      the entire cohort. From the total cohort, we selected a
                      subsample of 85 cases for which the amyloid status based on
                      the local reader's visual assessment and the Centiloid
                      classification (cutoff = 21) was discordant or that were
                      assessed with low confidence (i.e., ≤3 on a 5-point scale)
                      by the local reader. In addition, concordant negative (n =
                      8) and positive (n = 8) scans across tracers were selected.
                      In this sample (n = 101 cases; [18F]flutemetamol, n = 48;
                      [18F]florbetaben, n = 53), the visual assessments and
                      corresponding confidence by 5 certified independent central
                      readers were captured before and after disclosure of the
                      quantification results. Results: For the whole AMYPAD
                      diagnostic and patient management study cohort, overall
                      assessment by local readers highly agreed with Centiloid
                      status (κ = 0.85, $92.3\%$ agreement). This was
                      consistently observed within disease stages (subjective
                      cognitive decline-plus, κ = 0.82, $92.3\%$ agreement; mild
                      cognitive impairment, κ = 0.80, $89.8\%$ agreement;
                      dementia, κ = 0.87, $94.6\%$ agreement). Across all central
                      reader assessments in the challenging subsample,
                      quantification of global Centiloid and regional z scores was
                      considered supportive of visual reads in $70.3\%$ and
                      $49.3\%$ of assessments, respectively. After disclosure of
                      the quantitative results, we observed improvement in
                      concordance across the 5 readers (baseline κ = 0.65,
                      $65.3\%$ agreement; κ after disclosure = 0.74, $73.3\%$
                      agreement) and a significant increase in reader confidence
                      (baseline mean (M) = 4.0 vs. M after disclosure = 4.34,
                      Wilcoxon statistic (W) = 101,056, P < 0.001). Conclusion: In
                      this clinical study enriched for challenging amyloid PET
                      cases, we demonstrate the value of quantification to support
                      visual assessment. After disclosure, both interreader
                      agreement and confidence showed significant improvement.
                      These results are important considering the arrival of
                      antiamyloid therapies, which used the Centiloid metric for
                      trial inclusion and target engagement. Moreover,
                      quantification could support determination of amyloid-β
                      status with high certainty, an important factor for
                      treatment initiation.},
      keywords     = {Humans / Positron-Emission Tomography / Male / Female /
                      Aged / Amyloid: metabolism / Retrospective Studies /
                      Alzheimer Disease: diagnostic imaging / Middle Aged / Image
                      Processing, Computer-Assisted / Alzheimer (Other) /
                      Centiloid quantification (Other) / amyloid PET (Other) /
                      molecular imaging (Other) / neurology (Other) / visual read
                      (Other) / Amyloid (NLM Chemicals)},
      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:39542700},
      pmc          = {pmc:PMC11705786},
      doi          = {10.2967/jnumed.124.268119},
      url          = {https://pub.dzne.de/record/274065},
}