Benzinger T, Koeppe R, Su Y, Blazey T, Jack C, Thompson P, Saykin A, Correia S, Sperling R, Schofield P.
Reference Tissue Normalization in Autosomal Dominant AD: Comparison of Cerebellar Versus Brainstem Referencing for [11C]PIB in the DIAN Cohort.
Human Amyloid Imaging Abstract. 2012 Jan 1;
Background: The DIAN Study (Dominantly Inherited Alzheimerfs Network) is an international longitudinal study of autosomal dominant Alzheimerfs Disease (ADAD). Imaging studies acquired in this cohort include [11C]PIB, FDG PET and MRI. Mutations represented in this cohort include presenilin and and amyloid precursor protein (PSEN1, PSEN2, APP). [11C]PIB processing for sporadic AD (sAD) has traditionally used a cerebellar region of interest as a reference tissue. However, in ADAD participants may be positive for [11C]PIB in the cerebellum, so an alternative tissue reference may be needed.
Methods:20 participants underwent1C]PIB, FDG PET and MRI. All modalities were transformed and processed in a common atlas space. FreeSurfer parcellation of cortical and subcortical grey and white matter was performed. As there is no standard FreeSurfer region for the pons/brainstem that would reliably be covered by the scans collected in this study, manual pontine/brainstem regions were outlined on each individual scan.
Results/Discussion: Using cerebellar referencing, non-demented carriers were significantly different from the non-carrier cohort in the deep grey matter structures of the caudate, putamen, globus pallidus, and thalamus and in every cortical grey matter structure. Similar analysis using the pointine/brainstem reference is ongoing. The DIAN study represents the largest cohort of families with ADAD studied with imaging to date. It may be helpful to the field to compare approaches for data normalization and processing, especially when traditional reference regions may show elevated signal.