Quantification supports visual assessment of challenging amyloid‐PET images
Authors: Collij Lyduine E. , Bischof Gerard N , Altomare Daniele , García David Vállez , Alves Isadora Lopes , Battle Mark R , Hegde Manoj , Wolz Robin , Gismondi Rossella , Stephens Andrew W. , Walker Zuzana , Scheltens Philip , Nordberg Agneta K , Gispert Juan Domingo , Farrar Gill , Drzezga Alexander , Perissinotti Andrés , Morbelli Silvia , Buckley Christopher , Garibotto Valentina , Frisoni Giovanni B , Barkhof Frederik ,   the AMYPAD consortium
Published: December 2023

Background

In clinical practice, amyloid‐PET images are visually assessed to determine the presence or absence of amyloid pathology. The expected arrival of disease‐modifying treatments warrants the need for objective quantification of amyloid burden to further support treatment decisions. Here, we investigated whether quantification increases reader confidence and influences visual read (VR) classification in patients with challenging or ambiguous amyloid information sampled across the clinical continuum.

Methods

From the AMYPAD‐DPMS trial (N = 840), we selected a subsample of 85 amyloid‐PET scans ([18F]flutemetamol, N = 48/[18F]florbetaben, N = 53), for which 1) visual assessment was discordant with amyloid status based on Centiloid (CL) (cut‐off = 21) and/or 2) were assessed with a low confidence (i.e. ≤3 on a 5‐point scale) by the local reader. In addition, concordant negative and positive (N = 8/8) scans across tracers were included to balance the dataset (N = 101, Table‐1). PET images were processed using GEHCs AMYPYPE PET‐only pipeline, providing global CL and regional z‐scores for 7 cortical ROIs. VR classification and corresponding confidence was assessed for 3 independent certified assessors before and after disclosure of the quantification results. In addition, readers stated whether CL quantification and/or the regional z‐scores supported their assessment. Reader agreement was assessed using Fleiss Kappa. Changes in reader confidence after disclosure was assessed using paired t‐test.

Results

Overall, readers reported global CL and regional z‐score quantification to be VR‐supportive in 76.2% and 49.7% of assessments, respectively. After disclosure of quantitative results, concordance between readers (Kbaseline= 0.60; Kpost‐disclosure= 0.79), concordance between majority‐VR and CL‐status (agreementbaseline = 75.2%; agreementpost‐disclosure = 81.2%), and reader confidence (Mbaseline= 4.0 vs. Mpost‐disclosure= 4.37, t = ‐5.8, p<0.001) significantly improved. Classification changed for 26 (8.6%) assessments, with 8 (30.8%) changing to VR‐ and 18 (69.2%) to VR+. In these cases, CL was considered supportive in 16 (61.5%) cases, regional z‐scores were considered supportive for 8/10 remaining cases, and most often for the posterior cingulate/precuneus region. The 2 remaining cases had a low confidence at both time‐points. Example cases are shown in Figure 1.

Conclusion

In a dataset enriched with challenging amyloid‐PET scans for visual assessment, quantification resulted in a significantly increased agreement and confidence across readers. We further aim to determine in which cases quantification was considered most supportive.