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

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.

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 (BP_ND). 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 (CL_NMF), and the amyloid pattern similarity score (AMPSS). These metrics were evaluated using reliability and repeatability in test-retest data, associations with BP_ND and CL, variability of the rate of change and sample size estimates to detect a 25% slowing in Aβ accumulation.

All metrics showed good reliability. Aβ load, Aβ index and CL_NMF were strong associated with the BP_ND. The associations with CL suggest that cross-sectional measures of CL_NMF, Aβ index and Aβ load are robust across studies. Sample size estimates for secondary prevention trial scenarios were the lowest for CL_NMF and Aβ load compared to the CL.

Among the novel data-driven metrics evaluated, the Aβ load, the Aβ index and the CL_NMF can provide comparable performance to more established quantification methods of Aβ PET tracer uptake. The CL_NMF and Aβ load could offer a more precise alternative to CL, although further studies in larger cohorts should be conducted.