Quantitative Amyloid‐PET in Real‐World Practice: Lessons from the Imaging Dementia—Evidence for Amyloid Scanning (IDEAS) study

Abstract

AbstractBackgroundAmyloid‐PET quantification was developed in research settings using highly selected samples, harmonized acquisition protocols, and MRI‐based preprocessing. We aimed to analyze scans from IDEAS, a large‐scale, real‐world study of amyloid‐PET. Major challenges lie in scans being acquired on various PET/PET‐CT/PET‐MR scanners without standardization of acquisition or reconstruction protocols, and without MRI to preprocess data.Method18,295 Medicare beneficiaries with MCI or dementia underwent PET with [18F]florbetapir, [18F]florbetaben, or [18F]flutemetamol at 343 facilities. Sites shared 10,700 raw scans with their visual interpretation (positive or negative) by local radiologists/nuclear medicine physicians. Scans were processed using a PET‐only pipeline, which derives Centiloid based on a cortex‐to‐cerebellum tissue ratio in template space. Processed scans underwent standard visual quality control by 2 raters (Fig 1a‐b), and flagged scans were reviewed in a consensus meeting to discuss troubleshooting options. Injected dose and time between tracer injection and PET acquisition start were obtained from DICOM file header.Result9,963 scans (93%) were successfully pre‐processed with default parameters (Fig 1a) and 403 additional scans (4%) were included after manual intervention (Fig 1c). 339 scans (3%) were excluded because of technical artifacts or major bilateral lesions (Fig 1c). The final sample (n = 10,361) is described in Table 1, with example scans in Fig 1d. Centiloids showed the expected bimodal distribution (Fig 2a) and differentiated visually positive from negative scans (median = ‐2 versus 74 CL; area under the curve = 0.913, Fig 2b). PET acquisition generally followed tracer‐specific FDA recommendations for injected dose and acquisition time, but major variability was observed (Fig 2c). Centiloid values were independent from injected dose but were higher in patients scanned at later time windows for [18F]flutemetamol, resulting from known slow tracer kinetics (Fig 2c).ConclusionMRI‐free, amyloid‐PET quantification in a real‐world setting was feasible, with results conforming to expected distribution of Centiloid values and concordant with visual reads. However, greater standardization of PET acquisition than is currently required by FDA labels will be needed to reliably quantify amyloid PET in clinical practice (e.g., to monitor response to amyloid lowering therapy). The IDEAS dataset will be made available via the Global Alzheimer’s Association Interactive Network in 2023.