Impact of off‐target signal on longitudinal FTP quantification

Abstract

AbstractBackgroundDespite off‐target signal, Flortaucipir (FTP) PET is useful for measuring tau in vivo. We previously showed in a cross‐sectional cohort of cognitively unimpaired (CU) amyloid negative (Aβ‐) individuals that the global cortical SUVR is highly correlated to putamen and thalamus SUVR, suggesting that there is substantial off‐target signal in the cortex. Here we explore the impact on off‐target signal on longitudinal FTP quantification.MethodsA group of CUAβ‐ subjects scanned through ADNI and Lawrence Berkeley National Laboratory (LBNL) were used to define corrections for off‐target signal (derivation cohort) which were then applied to a separate longitudinal cohort of CUAβ‐, CUAβ+, and cognitively impaired (CI) Aβ+ subjects (Table 1). SUVRs were calculated using two possible reference regions (inferior cerebellar gray and supratentorial white matter) with or without partial volume correction (PVC). The relationship of off‐target signal between thalamus and cortex was estimated as the regression between thalamus and Braak IV‐VI in CUAβ‐ (figure 1) and then applied in the longitiduinal cohort to temporal meta and Braak ROIs to regress out the influence of the thalamic signal (figure 2). Hedges’ effect size was calculated between diagnosis groups with and without regressing out thalamic signal in the LBNL longitudinal cohort to examine effects in a smaller cohort.ResultsThere was a significant correlation in cross‐sectional CUAβ‐ subjects between thalamus and Braak IV‐VI regardless of reference region and PVC (Figure 1). This correlation increased when comparing annual change between thalamus and Braak IV‐VI in longitudinal CUAβ‐ subjects (Figure 3). There was no significant difference across diagnosis groups in the longitudinal cohort between either baseline thalamus or annual change in thalamus. Correlation between annual change in thalamus and entorhinal cortex or meta temporal ROI were often significant (12/12 for inferior cerebellar gray reference region, 8/12 for white matter reference region, Figure 4). Effect size between diagnosis groups increased as a result of regressing out thalamic signal for all temporal meta ROI comparisons and for CUAβ+>CUAβ‐ and CIAβ+>CUAβ‐ in the entorhinal cortex (Figure 5).ConclusionWhen taking into account off‐target signal, it is possible to improve effect size of longitudinal FTP by ∼12%.