This study found that 3–8% of [123I]ioflupane DAT‑SPECT scans are "difficult-to-interpret" using a 6-point visual scale and that binary (normal/abnormal) decisions are much less accurate in these inconclusive cases, which the authors recommend report as "inconclusive".

While not identifying therapeutic targets, the work is clinically valuable for Parkinson's research because it quantifies a nontrivial rate of equivocal DAT-SPECTs that can confound diagnosis, patient selection, and biomarker endpoints in trials and thus helps improve study design and…

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.