Difficult-to-interpret dopamine transporter SPECT with [123I]ioflupane in the diagnosis of parkinsonism

To estimate (i) the rate of difficult-to-interpret cases in dopamine transporter (DAT)-SPECT with [¹²³I]ioflupane and (ii) the diagnostic accuracy of binary visual categorization in difficult-to-interpret DAT-SPECT.The study included 178 control subjects (49% females, 63.7±11.7y) and 178 sex- and age-matched patients with pre-screening clinical diagnosis of Parkinson's disease (PD) from the Parkinson's Progression Markers Initiative (PPMI). SPECT images reconstructed by the PPMI and a local method were visually interpreted twice by 2 independent readers with respect to Parkinson-like reduction of the striatal signal using the following 6-score: -3 = clearly reduced, -2 = probably reduced, -1 = more likely reduced than normal, 1 = more likely normal than reduced, 2 = probably normal, 3 = clearly normal. Cases with 6-score of -1 or 1 were considered "difficult-to-interpret", all other cases were considered "conclusive". To assess diagnostic accuracy relative to the clinical group label (control, PD), the 6-score was binarized using 0 as cutoff.The proportion of difficult-to-interpret cases ranged between 3.4% (95%-CI 1.5-5.2%) and 7.6% (4.8-10.3%) across readers and reconstruction methods. The proportion of cases misclassified by the binarized score ranged between 17.4% (1.9-32.9%) and 50.0% (25.5-74.5%) among the difficult-to-interpret cases, and between 5.1% (2.7-7.4%) and 6.4% (3.8-9.0%) among the conclusive cases.(i) the proportion of difficult-to-interpret cases in DAT-SPECT for the diagnosis of parkinsonism is not larger than 10%, (ii) the diagnostic accuracy of binary decisions is severely reduced in these cases. We therefore recommend reporting difficult-to-interpret cases as "inconclusive", unless in special situations.