Implementing robust amyloid PET quantification in multi-center studies: AMYPAD approach to address data acquisition, processing, interpretation and data sharing challenges.

INTRODUCTION

Amyloid-positron emission tomography (PET) is pivotal to Alzheimer's management, with the Centiloid standardizing measurements across tracers. AMYPAD trials (Diagnostic and Patient Management Study [DPMS] and Prognostic and Natural History Study [PNHS]) aimed to validate robust quantification in clinical settings. We report our comprehensive approach to amyloid-PET implementation, comprising scan acquisition, harmonization, data storing, and data sharing strategies.

METHODS

Data from 28 scanners were harmonized using Hoffman phantoms. Three quantification workflows were compared: AmyPype (PET-only), IXICO-LEAP, and the standard Centiloid pipeline (magnetic resonance imaging [MRI]-based). Distributions of Centiloids were assessed using Gaussian Mixture Modeling.

RESULTS

Binary quantification showed excellent concordance between pipelines (≥ 96%) and compared to visual reads (>90%). DPMS Centiloids had a bimodal distribution while the PNHS showed a more skewed distribution toward higher Centiloids modeled with three Gaussians (1st Gaussian mean + 2SD = 12 CL, emerging pathology).

DISCUSSION: The harmonization framework, providing strong cross-method correlations in AMYPAD, has been adopted by EARL as the Brain PET/CT accreditation standard and provides a practical approach for other multi-center cohorts to implement similar strategies.

HIGHLIGHTS: We share AMYPAD's end-to-end approach to amyloid positron emission tomography (PET) quantification from data acquisition and handling, harmonization based on Hoffman phantoms, quality control, image processing, to data storage, and data sharing strategies.Centiloid quantification was compared across one PET-only (AmyPype) and two PET-MR pipelines (standard Centiloid and IXIXO-LEAP). Excellent agreement in dichotomized Centiloid valued was observed both between pipelines and when compared to visual reads.Distribution of Centiloid values in the Prognostic and Natural History Study (PNHS) and Diagnostic and Patient Management Study (DPMS) are in line with the initial recruitment strategies of the trials.Harmonization of Amyloid-PET scans framework was adopted by EARL as the Brain PET/CT accreditation standard for multicentre brain PET scans.