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Considerations for Performing Level-2 Centiloid Transformations for Amyloid PET SUVR values.

ABSTRACT: The Centiloid Project describes a post-hoc data transformation to standardize amyloid PET measurements to enable direct data comparisons across sites and studies using differing acquisition/analysis methods. It uses linear regression that transforms values using different measurement scales to match those from a standard Centiloid unit scale. Our group's measurement method differs from the Centiloid's standard method in both acquisition and analysis methods. In this work we examine multiple variations for performing these transformations and compare several approaches. We hypothesized that using Deming regression, which accounts for error on both axes, would produce a more optimal transformation than the recommended standard linear regression. We also examined the effects of performing separate regressions for differences in acquisition and analysis methods, rather than a direct single-regression approach. Our results found that all transformation approaches had very similar performance and were within the recommended tolerance thresholds.

SUBMITTER: Schwarz CG

PROVIDER: S-EPMC5943521 | biostudies-literature | 2018 May

REPOSITORIES: biostudies-literature

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Considerations for Performing Level-2 Centiloid Transformations for Amyloid PET SUVR values.

Schwarz Christopher G CG Tosakulwong Nirubol N Senjem Matthew L ML Gunter Jeffrey L JL Therneau Terry M TM Vemuri Prashanthi P Lowe Val J VJ Jack Clifford R CR

Scientific reports 20180509 1

The Centiloid Project describes a post-hoc data transformation to standardize amyloid PET measurements to enable direct data comparisons across sites and studies using differing acquisition/analysis methods. It uses linear regression that transforms values using different measurement scales to match those from a standard Centiloid unit scale. Our group's measurement method differs from the Centiloid's standard method in both acquisition and analysis methods. In this work we examine multiple vari ...[more]

PMID: 29743601

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Project description:BACKGROUND:The Centiloid scale has been developed to standardize measurements of amyloid PET imaging. Reference cut-off values of this continuous measurement enable the consistent operationalization of decision-making for multicentre research studies and clinical trials. In this study, we aimed at deriving reference Centiloid thresholds that maximize the agreement against core Alzheimer's disease (AD) cerebrospinal fluid (CSF) biomarkers in two large independent cohorts. METHODS:A total of 516 participants of the ALFA+ Study (N = 205) and ADNI (N = 311) underwent amyloid PET imaging ([18F]flutemetamol and [18F]florbetapir, respectively) and core AD CSF biomarker determination using Elecsys® tests. Tracer uptake was quantified in Centiloid units (CL). Optimal Centiloid cut-offs were sought that maximize the agreement between PET and dichotomous determinations based on CSF levels of Aβ42, tTau, pTau, and their ratios, using pre-established reference cut-off values. To this end, a receiver operating characteristic analysis (ROC) was conducted, and Centiloid cut-offs were calculated as those that maximized the Youden's J Index or the overall percentage agreement recorded. RESULTS:All Centiloid cut-offs fell within the range of 25-35, except for CSF Aβ42 that rendered an optimal cut-off value of 12 CL. As expected, the agreement of tau/Aβ42 ratios was higher than that of CSF Aβ42. Centiloid cut-off robustness was confirmed even when established in an independent cohort and against variations of CSF cut-offs. CONCLUSIONS:A cut-off of 12 CL matches previously reported values derived against postmortem measures of AD neuropathology. Together with these previous findings, our results flag two relevant inflection points that would serve as boundary of different stages of amyloid pathology: one around 12 CL that marks the transition from the absence of pathology to subtle pathology and another one around 30 CL indicating the presence of established pathology. The derivation of robust and generalizable cut-offs for core AD biomarkers requires cohorts with adequate representation of intermediate levels. TRIAL REGISTRATION:ALFA+ Study, NCT02485730 ALFA PET Sub-study, NCT02685969.

Project description:BackgroundThe standard Centiloid (CL) method was proposed to harmonize and quantify global 18F-labeled amyloid beta (Aβ) PET ligands using MRI as an anatomical reference. However, there is need for harmonizing and quantifying regional Aβ uptakes between ligands using CT as an anatomical reference. In the present study, we developed and validated a CT-based regional direct comparison of 18F-florbetaben (FBB) and 18F-flutemetamol (FMM) Centiloid (rdcCL).MethodsFor development of MRI-based or CT-based rdcCLs, the cohort consisted of 63 subjects (20 young controls (YC) and 18 old controls (OC), and 25 participants with Alzheimer's disease dementia (ADD)). We performed a direct comparison of the FMM-FBB rdcCL method using MRI and CT images to define a common target region and the six regional VOIs of frontal, temporal, parietal, posterior cingulate, occipital, and striatal regions. Global and regional rdcCL scales were compared between MRI-based and CT-based methods. For clinical validation, the cohort consisted of 2245 subjects (627 CN, 933 MCI, and 685 ADD).ResultsBoth MRI-based and CT-based rdcCL scales showed that FMM and FBB were highly correlated with each other, globally and regionally (R2 = 0.96~0.99). Both FMM and FBB showed that CT-based rdcCL scales were highly correlated with MRI-based rdcCL scales (R2 = 0.97~0.99). Regarding the absolute difference of rdcCLs between FMM and FBB, the CT-based method was not different from the MRI-based method, globally or regionally (p value = 0.07~0.95). In our clinical validation study, the global negative group showed that the regional positive subgroup had worse neuropsychological performance than the regional negative subgroup (p < 0.05). The global positive group also showed that the striatal positive subgroup had worse neuropsychological performance than the striatal negative subgroup (p < 0.05).ConclusionsOur findings suggest that it is feasible to convert regional FMM or FBB rdcSUVR values into rdcCL scales without additional MRI scans. This allows a more easily accessible method for researchers that can be applicable to a variety of different conditions.

Dataset Information

Considerations for Performing Level-2 Centiloid Transformations for Amyloid PET SUVR values.

Publications

Considerations for Performing Level-2 Centiloid Transformations for Amyloid PET SUVR values.

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