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000274065 1001_ $$aCollij, Lyduine E$$b0
000274065 245__ $$aQuantification Supports Amyloid PET Visual Assessment of Challenging Cases: Results from the AMYPAD Diagnostic and Patient Management Study.
000274065 260__ $$aNew York, NY$$bSoc.$$c2025
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000274065 520__ $$aSeveral 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.
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000274065 650_7 $$2Other$$aAlzheimer
000274065 650_7 $$2Other$$aCentiloid quantification
000274065 650_7 $$2Other$$aamyloid PET
000274065 650_7 $$2Other$$amolecular imaging
000274065 650_7 $$2Other$$aneurology
000274065 650_7 $$2Other$$avisual read
000274065 650_7 $$2NLM Chemicals$$aAmyloid
000274065 650_2 $$2MeSH$$aHumans
000274065 650_2 $$2MeSH$$aPositron-Emission Tomography
000274065 650_2 $$2MeSH$$aMale
000274065 650_2 $$2MeSH$$aFemale
000274065 650_2 $$2MeSH$$aAged
000274065 650_2 $$2MeSH$$aAmyloid: metabolism
000274065 650_2 $$2MeSH$$aRetrospective Studies
000274065 650_2 $$2MeSH$$aAlzheimer Disease: diagnostic imaging
000274065 650_2 $$2MeSH$$aMiddle Aged
000274065 650_2 $$2MeSH$$aImage Processing, Computer-Assisted
000274065 7001_ $$aBischof, Gérard N$$b1
000274065 7001_ $$aAltomare, Daniele$$b2
000274065 7001_ $$aBader, Ilse$$b3
000274065 7001_ $$aBattle, Mark$$b4
000274065 7001_ $$aVállez García, David$$b5
000274065 7001_ $$aLopes Alves, Isadora$$b6
000274065 7001_ $$aWolz, Robin$$b7
000274065 7001_ $$aGismondi, Rossella$$b8
000274065 7001_ $$aStephens, Andrew$$b9
000274065 7001_ $$aWalker, Zuzana$$b10
000274065 7001_ $$aScheltens, Philip$$b11
000274065 7001_ $$aNordberg, Agneta$$b12
000274065 7001_ $$aGispert, Juan Domingo$$b13
000274065 7001_ $$0P:(DE-2719)2811239$$aDrzezga, Alexander$$b14$$udzne
000274065 7001_ $$aPerissinotti, Andrés$$b15
000274065 7001_ $$aMorbelli, Silvia$$b16
000274065 7001_ $$aBuckley, Christopher$$b17
000274065 7001_ $$aGaribotto, Valentina$$b18
000274065 7001_ $$aFrisoni, Giovanni B$$b19
000274065 7001_ $$aFarrar, Gill$$b20
000274065 7001_ $$aBarkhof, Frederik$$b21
000274065 7001_ $$aConsortium, AMYPAD$$b22$$eCollaboration Author
000274065 773__ $$0PERI:(DE-600)2040222-3$$a10.2967/jnumed.124.268119$$gVol. 66, no. 1, p. 110 - 116$$n1$$p110 - 116$$tJournal of nuclear medicine$$v66$$x0097-9058$$y2025
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