A Visual Interpretation Algorithm for Assessing Brain Tauopathy with [18F]MK6240 Positron Emission Tomography

Abstract

AbstractBackgroundIn vivo characterization of pathologic deposition of tau protein in the human brain by PET imaging is a promising tool in drug development trials in Alzheimer’s disease (AD). [18F]MK‐6240 is a radiotracer with high selectivity and sub‐nanomolar affinity for neurofibrillary tangles. Here, we developed a visual assessment that provides a binary outcome for tau deposition, as well as a semi‐quantitative metric of the extent of regional tau deposition in the brain.MethodData included 214 subjects (AD, HC, MCI, and other disorders) who underwent [18F]MK‐6240 PET scans, which were used to generate 70‐90 min static images. Half of the subjects were reviewed by an expert nuclear medicine physician blind to participants’ diagnosis to identify common patterns of brain uptake. Based on this review, a visual read method was developed for testing in a separate cohort of 102 subjects, which included two additional independent readers. Visual read outcomes were compared with quantitative ROI analysis.ResultReaders demonstrated a high level of concordance for binary regional outcome, with all three‐reader in agreement on 74.3% of scans with a Fleiss’s k=0.912. Readers showed excellent intra‐reader reproducibility, with two readers attaining 10/10 self‐agreement and one reader attaining 9/10 agreement. Relative to clinical diagnosis, readers showed a sensitivity of 76‐81% and specificity of 91‐92%. Mean cortical SUVr was higher in read positive (2.17/0.91) than to negative (1.02/0.18) scans.ConclusionWe developed a read algorithm permitting both binary determination and the regional extent of abnormal tau. These cross‐sectional results demonstrate feasibility, which might allow for further evaluation of progressive tau changes in AD.