The use of Centiloids for applying [¹¹C]PiB classification cutoffs across region‐of‐interest delineation methods

Abstract

Introduction Centiloid standardization was developed to establish a quantitative outcome measure of amyloid burden that could accommodate the integration of different amyloid positron emission tomography radiotracers or different methods of quantifying the same tracer. The goal of this study was to examine the use of Centiloids for establishing amyloid classification cutoffs for differing region-of-interest (ROI) delineation schemes. Methods Using ROIs from hand-drawn delineation in native space as the gold standard, we compared standard uptake value ratios obtained from the 6 hand-drawn ROIs that determine amyloid-positivity classification with standard uptake value ratio obtained from 3 different automated techniques (FreeSurfer, Statistical Parametric Mapping, and superimposed hand-drawn ROIs in Pittsburgh Compound B template space). We tested between-methods reliability using repeated measures models and intraclass correlation coefficients. Results We found high reliability between the hand-drawn standard method and other methods for almost all the regions considered. However, small differences in standard uptake value ratio were found to lead to unreliable classifications when the hand-drawn native space-derived cutoffs were used across other ROI delineation methods. Discussion The use of Centiloid standardization greatly improved the agreement of Pittsburgh Compound B classification across methods and may serve as an alternative method for applying cutoffs across methodologically different outcomes.

Prevalence of Biologically vs Clinically Defined Alzheimer Spectrum Entities Using the National Institute on Aging–Alzheimer’s Association Research Framework

“…Target and reference regions similar to those we used for amyloid PET are widely used throughout the Alzheimer imaging research community, and the approximate cut point we used, centiloid 22, has support in the literature. 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 , 70 , 71 , 72 , 73 Because it is a newer modality, less agreement exists on optimal locations in the brain to measure ligand uptake or on cut points for tau PET. 22 , 26 , 29 , 74 , 75 , 76 , 77 , 78 , 79 , 80 , 81 In sensitivity analyses, we found only minor numeric differences 31 in the prevalence of biological Alzheimer disease (A+T+) when the analyses were done with different tau PET reporter ROIs compared with the primary tau PET meta-ROI (eTable and eFigure 2 in the Supplement ).…”

Centiloid scaling for quantification of brain amyloid with [18F]flutemetamol using multiple processing methods

“…SPM8 was the recommended image processing platform described in the methods of Klunk et al and was selected by us when replicating the process pipeline. More recent versions of SPM have been introduced since, with the use of SPM12 reported by other groups [21]. However, we chose to use SPM8 to ensure we followed the process as accurately as possible.…”

Amyloid accumulation in Down syndrome measured with amyloid load

“…In addition, a majority of DS individuals who were Aβ(+) displayed striatal Aβ retention, 16,22 highlighting the striatum as a target region for early detection in this population 28 . Longitudinal studies in non‐demented DS revealed that participants converting from Aβ(−) to Aβ(+) showed Aβ signal increases of ≈3% to 4% per year, with the striatum showing the earliest and most prominent change 29–31 …”

“…The Alzheimer's Biomarker Consortium—Down Syndrome (ABC‐DS) is an ongoing study to characterize the natural history of AD‐related biomarkers in individuals with DS. Aβ PET scans, using [C‐11]PiB, have been acquired on participants from this study and reported in the literature using longitudinal data from legacy studies 29–31 . The overall aim of this work is to assess and compare longitudinal Aβ change using Aβ L and SUVr in a large DS population.…”