Assessing Amyloid Pathology in Cognitively Normal Subjects Using 18F-Flutemetamol PET: Comparing Visual Reads and Quantitative Methods

Our objective was to determine the optimal approach for assessing amyloid disease in a cognitively normal elderly population. Methods: Dynamic F-18-flutemetamol PET scans were acquired using a coffee-break protocol (a 0- to 30-min scan and a 90- to 110-min scan) on 190 cognitively normal elderly individuals (mean age, 70.4 y; 60% female). Parametric images were generated from SUV ratio (SUVr) and non-displaceable binding potential (BPND) methods, with cerebellar gray matter as a reference region, and were visually assessed by 3 trained readers. Interreader agreement was calculated using kappa-statistics, and semiquantitative values were obtained. Global cutoffs were calculated for both SUVr and BPND using a receiver-operating-characteristic analysis and the Youden index. Visual assessment was related to semiquantitative classifications. Results: Interreader agreement in visual assessment was moderate for SUVr (kappa = 0.57) and good for BPND images (kappa = 0.77). There was discordance between readers for 35 cases (18%) using SUVr and for 15 cases (8%) using BPND, with 9 overlapping cases. For the total cohort, the mean (+/- SD) SUVr and BPND were 1.33 (+/- 0.21) and 0.16 (+/- 0.12), respectively. Most of the 35 cases (91%) for which SUVr image assessment was discordant between readers were classified as negative based on semiquantitative measurements. Conclusion: The use of parametric BPND images for visual assessment of F-18-flutemetamol in a population with low amyloid burden improves interreader agreement. Implementing semi-quantification in addition to visual assessment of SUVr images can reduce false-positive classification in this population.