Evaluation of novel data-driven metrics of amyloid β deposition for longitudinal PET studies

Purpose: Positron emission tomography (PET) provides in vivo quantification of amyloid-β (Aβ) pathology. Established methods for assessing Aβ burden can be affected by physiological and technical factors. Novel, data-driven metrics have been developed to account for these sources of variability. We...

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Main Authors: Ariane Bollack, Pawel J Markiewicz, Alle Meije Wink, Lloyd Prosser, Johan Lilja, Pierrick Bourgeat, Jonathan M Schott, William Coath, Lyduine E Collij, Hugh G Pemberton, Gill Farrar, Frederik Barkhof, David M Cash
Format: Article
Language:English
Published: Elsevier 2023-10-01
Series:NeuroImage
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S1053811923004640
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author Ariane Bollack
Pawel J Markiewicz
Alle Meije Wink
Lloyd Prosser
Johan Lilja
Pierrick Bourgeat
Jonathan M Schott
William Coath
Lyduine E Collij
Hugh G Pemberton
Gill Farrar
Frederik Barkhof
David M Cash
author_facet Ariane Bollack
Pawel J Markiewicz
Alle Meije Wink
Lloyd Prosser
Johan Lilja
Pierrick Bourgeat
Jonathan M Schott
William Coath
Lyduine E Collij
Hugh G Pemberton
Gill Farrar
Frederik Barkhof
David M Cash
author_sort Ariane Bollack
collection DOAJ
description Purpose: Positron emission tomography (PET) provides in vivo quantification of amyloid-β (Aβ) pathology. Established methods for assessing Aβ burden can be affected by physiological and technical factors. Novel, data-driven metrics have been developed to account for these sources of variability. We aimed to evaluate the performance of four of these amyloid PET metrics against conventional techniques, using a common set of criteria. Methods: Three cohorts were used for evaluation: Insight 46 (N=464, [18F]florbetapir), AIBL (N=277, [18F]flutemetamol), and an independent test-retest data (N=10, [18F]flutemetamol). Established metrics of amyloid tracer uptake included the Centiloid (CL) and where dynamic data was available, the non-displaceable binding potential (BPND). The four data-driven metrics computed were the amyloid load (Aβ load), the Aβ-PET pathology accumulation index (Aβ index), the Centiloid derived from non-negative matrix factorisation (CLNMF), and the amyloid pattern similarity score (AMPSS). These metrics were evaluated using reliability and repeatability in test-retest data, associations with BPND and CL, variability of the rate of change and sample size estimates to detect a 25% slowing in Aβ accumulation. Results: All metrics showed good reliability. Aβ load, Aβ index and CLNMF were strong associated with the BPND. The associations with CL suggest that cross-sectional measures of CLNMF, Aβ index and Aβ load are robust across studies. Sample size estimates for secondary prevention trial scenarios were the lowest for CLNMF and Aβ load compared to the CL. Conclusion: Among the novel data-driven metrics evaluated, the Aβ load, the Aβ index and the CLNMF can provide comparable performance to more established quantification methods of Aβ PET tracer uptake. The CLNMF and Aβ load could offer a more precise alternative to CL, although further studies in larger cohorts should be conducted.
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spelling doaj.art-31a4b313a057412299854b162b868a652023-09-16T05:28:55ZengElsevierNeuroImage1095-95722023-10-01280120313Evaluation of novel data-driven metrics of amyloid β deposition for longitudinal PET studiesAriane Bollack0Pawel J Markiewicz1Alle Meije Wink2Lloyd Prosser3Johan Lilja4Pierrick Bourgeat5Jonathan M Schott6William Coath7Lyduine E Collij8Hugh G Pemberton9Gill Farrar10Frederik Barkhof11David M Cash12Centre for Medical Image Computing, Department of Medical Physics and Biomedical Engineering, UCL, London, UK; Corresponding author.Centre for Medical Image Computing, Department of Medical Physics and Biomedical Engineering, UCL, London, UKAmsterdam UMC, location VUmc, Department of Radiology and Nuclear Medicine, Amsterdam, the NetherlandsDementia Research Centre, UCL Queen Square Institute of Neurology, London, UKHermes Medical Solutions, Stockholm, SwedenThe Australian e-Health Research Centre, CSIRO, Brisbane, AustraliaDementia Research Centre, UCL Queen Square Institute of Neurology, London, UKDementia Research Centre, UCL Queen Square Institute of Neurology, London, UKAmsterdam UMC, location VUmc, Department of Radiology and Nuclear Medicine, Amsterdam, the Netherlands; Clinical Memory Research Unit, Department of Clinical Sciences, Lund University, Malmö, SwedenCentre for Medical Image Computing, Department of Medical Physics and Biomedical Engineering, UCL, London, UK; GE HealthCare, Amersham, UK; Queen Square Institute of Neurology, University College London, UKGE HealthCare, Amersham, UKCentre for Medical Image Computing, Department of Medical Physics and Biomedical Engineering, UCL, London, UK; Amsterdam UMC, location VUmc, Department of Radiology and Nuclear Medicine, Amsterdam, the Netherlands; Queen Square Institute of Neurology, University College London, UKQueen Square Institute of Neurology, University College London, UK; UK Dementia Research Institute at University College London, London, UKPurpose: Positron emission tomography (PET) provides in vivo quantification of amyloid-β (Aβ) pathology. Established methods for assessing Aβ burden can be affected by physiological and technical factors. Novel, data-driven metrics have been developed to account for these sources of variability. We aimed to evaluate the performance of four of these amyloid PET metrics against conventional techniques, using a common set of criteria. Methods: Three cohorts were used for evaluation: Insight 46 (N=464, [18F]florbetapir), AIBL (N=277, [18F]flutemetamol), and an independent test-retest data (N=10, [18F]flutemetamol). Established metrics of amyloid tracer uptake included the Centiloid (CL) and where dynamic data was available, the non-displaceable binding potential (BPND). The four data-driven metrics computed were the amyloid load (Aβ load), the Aβ-PET pathology accumulation index (Aβ index), the Centiloid derived from non-negative matrix factorisation (CLNMF), and the amyloid pattern similarity score (AMPSS). These metrics were evaluated using reliability and repeatability in test-retest data, associations with BPND and CL, variability of the rate of change and sample size estimates to detect a 25% slowing in Aβ accumulation. Results: All metrics showed good reliability. Aβ load, Aβ index and CLNMF were strong associated with the BPND. The associations with CL suggest that cross-sectional measures of CLNMF, Aβ index and Aβ load are robust across studies. Sample size estimates for secondary prevention trial scenarios were the lowest for CLNMF and Aβ load compared to the CL. Conclusion: Among the novel data-driven metrics evaluated, the Aβ load, the Aβ index and the CLNMF can provide comparable performance to more established quantification methods of Aβ PET tracer uptake. The CLNMF and Aβ load could offer a more precise alternative to CL, although further studies in larger cohorts should be conducted.http://www.sciencedirect.com/science/article/pii/S1053811923004640QuantificationLongitudinalMachine learningAmyloidPETAlzheimer's
spellingShingle Ariane Bollack
Pawel J Markiewicz
Alle Meije Wink
Lloyd Prosser
Johan Lilja
Pierrick Bourgeat
Jonathan M Schott
William Coath
Lyduine E Collij
Hugh G Pemberton
Gill Farrar
Frederik Barkhof
David M Cash
Evaluation of novel data-driven metrics of amyloid β deposition for longitudinal PET studies
NeuroImage
Quantification
Longitudinal
Machine learning
Amyloid
PET
Alzheimer's
title Evaluation of novel data-driven metrics of amyloid β deposition for longitudinal PET studies
title_full Evaluation of novel data-driven metrics of amyloid β deposition for longitudinal PET studies
title_fullStr Evaluation of novel data-driven metrics of amyloid β deposition for longitudinal PET studies
title_full_unstemmed Evaluation of novel data-driven metrics of amyloid β deposition for longitudinal PET studies
title_short Evaluation of novel data-driven metrics of amyloid β deposition for longitudinal PET studies
title_sort evaluation of novel data driven metrics of amyloid β deposition for longitudinal pet studies
topic Quantification
Longitudinal
Machine learning
Amyloid
PET
Alzheimer's
url http://www.sciencedirect.com/science/article/pii/S1053811923004640
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