Visual assessment of [18F]flutemetamol PET images can detect early amyloid pathology and grade its extent.

Abstract

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.

• 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, ALFA study, AMYPAD consortium
• Journal: European journal of nuclear medicine and molecular imaging (Eur J Nucl Med Mol Imaging) Vol. 48 Issue 7 Pg. 2169-2182 (07 2021) ISSN: 1619-7089 [Electronic] Germany
• PMID: 33615397 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Amyloid
• Amyloid beta-Peptides
• Aniline Compounds
• Benzothiazoles
• flutemetamol

Topics

• Alzheimer Disease (diagnostic imaging)
• Amyloid (metabolism)
• Amyloid beta-Peptides (metabolism)
• Aniline Compounds
• Benzothiazoles
• Brain (metabolism)
• Humans
• Positron-Emission Tomography