New paper published in EJNMMI

A new AMYPAD referenced paper entitled “Visual assessment of [18F]flutemetamol PET images can detect early amyloid pathology and grade its extent” has been published in the European Journal of Nuclear Medicine and Molecular Imaging.


Purpose: To investigate the sensitivity of visual read (VR) to detect early amyloid pathology and the overall utility of regional VR.
Methods: [18F]Flutemetamol PET images of 497 subjects (ALFA+ N = 352; ADC N = 145) were included. Scans were visually assessed according to product guidelines, recording the number of positive regions (0–5) and a final negative/positive classification. Scans were quantified using the standard and regional Centiloid (CL) method. The agreement between VR-based classification and published CL-based cut-offs for early (CL = 12) and established (CL = 30) pathology was determined. An optimal CL cut-off maximizing Youden’s index was derived. Global and regional CL quantification was compared to VR. Finally, 28 post-mortem cases from the [18F]flutemetamol phase III trial were included to assess the percentage agreement between VR and neuropathological classification of neuritic plaque density.
Results: VR showed excellent agreement against CL = 12 (κ = .89, 95.2%) and CL = 30 (κ = .88, 95.4%) cut-offs. ROC analysis resulted in an optimal CL = 17 cut-off against VR (sensitivity = 97.9%, specificity = 97.8%). Each additional positive VR region corresponded to a clear increase in global CL. Regional VR was also associated with regional CL quantification. Compared to mCERADSOT-based classification (i.e., any region mCERADSOT > 1.5), VR was in agreement in 89.3% of cases, with 13 true negatives, 12 true positives, and 3 false positives (FP). Regional sparse-to-moderate neuritic and substantial diffuse Aβ plaque was observed in all FP cases. Regional VR was also associated with regional plaque density.
Conclusion: VR is an appropriate method for assessing early amyloid pathology and that grading the extent of visual amyloid positivity could present clinical value.


Congratulations to the authors: Lyduine E. Collij, Gemma Salvadó, Mahnaz Shekari, Isadora Lopes Alves, Juhan Reimand, Alle Meije Wink, Marissa Zwan, Aida Niñerola-Baizán, Andrés Perissinotti, Philip Scheltens, Milos D. Ikonomovic, Adrian P. L. Smith, Gill Farrar, José Luis Molinuevo, Frederik Barkhof, Christopher J. Buckley, Bart N. M. van Berckel & Juan Domingo Gispert.


Lyduine Collij and Gemma Salvadó have been awarded the Junior Faculty Awards from the organizing committee of the 15th International Conference on Alzheimer’s and Parkinson’s Diseases for this work. Gemma will be presenting this work during the AD/PD™ conference on 12th March 2021. 


This open access article can be found here:

New paper published in EJNMMI
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