SPECT Dopamine Transporters, Consensus QIBA Profile

Parkinsonism is a major health problem. Distinguishing neurodegenerative causes of parkinsonism from non-degenerative movement disorders that can mimic Parkinson’s disease (PD) has important implications for prognosis and clinical management. The goal of this QIBA Profile is to optimize the performance of Iodine-123 (123I) ioflupane single photon emission computed tomography (SPECT) for quantifying the concentration of regional cerebral dopamine transporters (DaT) in patients with movement disorders. The Claim (Section 2): This profile claims that conformance with its specifications will provide test-retest technical variance of less than 15% COV. In clinical use this might permit the ability to distinguish true biological change from measurement noise in clinical trials of participants who will be studied cross— sectionally, to aid accurate cohort recruitment and longitudinally with 123I-ioflupane. The claim is founded on observations that neurodegenerative disorders, such as idiopathic PD and Diffuse Lewy Body Dementia (DLBD), are associated with dopaminergic neuronal degeneration, which can be particularly pronounced in the substantia nigra. The degeneration of the axonal projections from the substania nigra to the basal ganglia is manifested as a loss of DaT activity. In most clinical imaging contexts where the question is about a neurodegenerative disorder, the loss is first observed in the most posterior aspect of the putamen, and then seems to march anteriorly, with left and right sides showing asymmetric changes. As a result, quantifying DaT can distinguish normal and abnormal states. The Activities (Section 3) describe what needs to be done to make measurements that reliably distinguish patients from controls with confidence. Requirements are placed on the Actors who participate in those activities as necessary to achieve the Claim. The Assessment Procedures (Section 4) for evaluating specific requirements are defined as needed. This QIBA Profile, “Quantifying Dopamine Transporters with 123Iodine Labeled Ioflupane in Neurodegenerative Disease”, addresses quantitative SPECT imaging, which is often used as a diagnostic, as well as a longitudinal biomarker of disease progression or response to treatment. It places requirements on Acquisition Devices, Technologists, Radiologists, Reconstruction Software and Image Analysis Tools involved in Subject Handling, Image Data Acquisition, Image Data Reconstruction, Image QA and Image Analysis. The requirements are focused on achieving sufficient accuracy and avoiding technical variability of the DaT measurements to distinguish neurodegenerative causes of parkinsonism from non-degenerative causes. The clinical performance target is to achieve a 95% confidence interval for the striatal binding ratio with both a reproducibility and a repeatability of +/- 15%. This document is intended to help clinicians basing decisions on this biomarker, imaging staff generating this biomarker, vendor staff developing related products, purchasers of such products, and investigators designing trials with imaging endpoints. Note that this document only states requirements to achieve the claim, not “requirements on standard of care”. Conformance to this Profile is secondary to properly caring for the patient. This QIBA Profile, and others like it addressing CT, MRI, PET and ultrasound can be found at www.qibawiki.rsna.org.