Comparison of 18F‐Flortaucipir visual assessment, SUVR quantification and CSF pTau for defining T‐status in the AT(N) framework: Neuroimaging / Multi‐modal comparisons. (7th December 2020) - Provost, Karine
Abstract: Background: Tau‐PET is included in the AT(N) research framework to define T‐status. However, no consensus exists as to how to classify patients as T+ or T‐ with this modality. We aim to compare T‐status derived from 18 F‐Flortaucipir (FTP) PET visual assessment, 18 F‐FTP SUVR quantification, and CSF pTau. Methods: 278 subjects who underwent 18 F‐FTP PET and CSF analysis within 1 year were included from UCSF and ADNI. The cohort consisted of a continuum from cognitively normal controls (CN) to Alzheimer's disease dementia (AD), and non‐Alzheimer's disorders (clinical diagnoses, Table 1). T‐status was derived from: (1) 18 F‐FTP consensus between two readers performing blinded visual assessment based on a priori criteria (Figure 1, inter‐rater k=0.68, 95%CI 0.59‐0.76; Provost et al, HAI Conference, 2020); (2) 18 F‐FTP SUVR quantification of from a temporal meta‐ROI using a previously validated threshold (SUVR >1.27, Ossenkoppele et al. 2018); (3) Elecsys® Phospho‐Tau (181P) CSF (Roche Diagnostics) applying a ROC‐based threshold derived from an external ADNI cohort comparing amyloid‐positive AD vs. healthy controls (pTau >24.5 pg/mL). Results: T+ was assigned in a higher proportion of AD, MCI and amyloid‐positive CN with 18 F‐FTP visual assessment compared to 18 F‐FTP SUVR and CSF pTau (Table 2). However, visual ratings also yielded the highest proportion of T+ in amyloid‐negative CN and MCI. Contrasting amyloid‐positive AD/MCI with other groups, sensitivity was highest for 18 F‐FTP visual assessment, while specificity was highest for 18 F‐FTP SUVR (Table 3). In a subset of patients with autopsy (n=11), T‐status derived from 18 F‐FTP visual assessment had an accuracy of 100%, compared to 82% for SUVR quantification and 64% for CSF pTau. Overall agreement between the 3 classification criteria ranged from 68% to 76% in the whole cohort (Figure 2) and was highest in patients with AD (94%). Patients with concordant T‐status across all three modalities were significantly younger, had higher CSF pTau, higher 18 F‐FTP SUVR (Figure 3), and were more likely to be amyloid positive. Conclusions: Concordance of T‐status derived from 18 F‐FTP visual assessment, SUVR quantification and CSF pTau varies across disease stage, being highest in AD. 18 F‐FTP visual assessment offers highest sensitivity, while SUVR threshold maximizes specificity.