Standardization of amyloid quantitation with florbetapir standardized uptake value ratios to the Centiloid scale

Navitsky, Michael; Joshi, Abhinay D.; Kennedy, Ian; Klunk, William E.; Rowe, Christopher C.; Wong, Dean F.; Pontecorvo, Michael J.; Mintun, Mark A.; Devous, Michael D.

doi:10.1016/j.jalz.2018.06.1353

Cited by 126 publications

(151 citation statements)

References 20 publications

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“…Eq. 5) derived based on raw SUVrs without RSF PVC was similar to the published equations from a recent paper [16]. The difference is attributable to variation in image acquisition protocols and quantification procedures.…”

Section: Resultssupporting

confidence: 68%

“…Previously, Laudau et al [31] compared these two tracers using florbetapir data collected approximately 1.5 years after PiB imaging and found a correlation between 0.86 and 0.95 depending on the quantification method used. More recently, Navitsky et al [16] reported a florbetapir‐to‐PiB SUVr correlation of approximately 0.95. These results are in agreement with ours.…”

Section: Discussionmentioning

confidence: 99%

“…The variance of amyloid burden measurements in young controls was SD = 3.7 for [ 18 F]‐NAV4694 and SD = 6.81 for [ 18 F]‐florbetaben [14,15]. Recently, Navitsky et al [16] reported an SD = 12.07 for florbetapir, and here, we observed an SD = 14.2 for the raw florbetapir SUVr‐derived Centiloid measurements; however, when the RSF PVC technique was used in the quantification procedure, the variance was substantially reduced (SD = 5.4). This suggests that the variability in a pathologically free cohort may primarily be related to nonspecific uptake in the white matter, and PVC can reduce this effect.…”

Section: Discussionmentioning

confidence: 99%

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Comparison of Pittsburgh compound B and florbetapir in cross‐sectional and longitudinal studies

Su¹,

Flores

Wang

et al. 2019

Alz & Dem Diag Ass & Dis Mo

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101

124

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Introduction Quantitative in vivo measurement of brain amyloid burden is important for both research and clinical purposes. However, the existence of multiple imaging tracers presents challenges to the interpretation of such measurements. This study presents a direct comparison of Pittsburgh compound B–based and florbetapir-based amyloid imaging in the same participants from two independent cohorts using a crossover design. Methods Pittsburgh compound B and florbetapir amyloid PET imaging data from three different cohorts were analyzed using previously established pipelines to obtain global amyloid burden measurements. These measurements were converted to the Centiloid scale to allow fair comparison between the two tracers. The mean and inter-individual variability of the two tracers were compared using multivariate linear models both cross-sectionally and longitudinally. Results Global amyloid burden measured using the two tracers were strongly correlated in both cohorts. However, higher variability was observed when florbetapir was used as the imaging tracer. The variability may be partially caused by white matter signal as partial volume correction reduces the variability and improves the correlations between the two tracers. Amyloid burden measured using both tracers was found to be in association with clinical and psychometric measurements. Longitudinal comparison of the two tracers was also performed in similar but separate cohorts whose baseline amyloid load was considered elevated (i.e., amyloid positive). No significant difference was detected in the average annualized rate of change measurements made with these two tracers. Discussion Although the amyloid burden measurements were quite similar using these two tracers as expected, difference was observable even after conversion into the Centiloid scale. Further investigation is warranted to identify optimal strategies to harmonize amyloid imaging data acquired using different tracers.

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Section: Resultssupporting

confidence: 68%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Comparison of Pittsburgh compound B and florbetapir in cross‐sectional and longitudinal studies

Su¹,

Flores

Wang

et al. 2019

Alz & Dem Diag Ass & Dis Mo

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101

124

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“…CL results below this threshold should provide reassurance that patients are unlikely to have Alzheimer's disease. This is reasonably concordant with the findings of Navitsky and colleagues, who determined a threshold of 24.1 CL with florbetapir for CERAD amyloid plaque classification of moderate or frequent vs sparse or none, in 59 individuals [21]. This is also concordant with the Centiloid analysis by Dore and colleagues of a florbetaban phase III post-mortem study in 66 individuals, which yielded a threshold of 19 CL for the same categorisation [22].…”

Section: Fig 1 Centiloid Results and "High" Vs "Low" C Score Categoriessupporting

confidence: 89%

Comparison of amyloid PET measured in Centiloid units with neuropathological findings in Alzheimer’s Disease

Amadoru

Doré

McLean

et al. 2019

Preprint

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Background: We aimed to determine the Centiloid unit (CL) thresholds for sparse and moderate density neuritic plaques. Methods: Amyloid PET results in CL for 49 subjects were compared with post-mortem neuritic plaque density, visual read, and final clinicopathological diagnosis. A Youden Index was used to determine the optimal CL thresholds from receiver operator characteristic (ROC) curves. Results: A threshold of 20.1 CL yielded highest accuracy in detecting moderate or frequent plaque density (ROC AUC 0.97). A threshold of 9.5 CL was optimal for detecting sparse, moderate or frequent plaques (ROC AUC 0.96). Those cases with a final clinicopathological diagnosis of Alzheimer’s disease yielded a median CL result of 87.7 (IQR ±42.2) with 94% > 45 CL. Positive visual read agreed highly with results >26 CL. Conclusions: In this cohort, values <9.5 CL accurately reflected the absence of any neuritic plaques, and >20.1 CL indicated the presence of at least moderate plaque density. Clinicopathological diagnosis of AD was rare with CL <45.

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“…All YC subjects were younger than 45 years of age (mean ± SD: 27 ± 4.3 y), the sample had equal gender distribution (M/F: 6/7), and low APOE4 positivity prevalence (9 negative, 1 positive, 3 unknown). The data was originally acquired to serve as a YC reference data set for scaling of global Florbetapir-PET signal to the standardized Centiloid scale (Navitsky et al, 2018a) and is freely available on the Global Alzheimer Association Interactive Network website (GAAIN; http://www.gaain.org/centiloid-project). As reported previously (Grothe et al, 2017;Navitsky et al, 2018a), written informed consent was obtained for all study participants and/or authorized representatives, and data collection and sharing were performed in accordance with the ethical standards of the institutional and/or national research committees (http://adni.…”

Section: Participantsmentioning

confidence: 99%

Longitudinal validity of PET‐based staging of regional amyloid deposition

Jelistratova

Teipel

Grothe

2020

Human Brain Mapping

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Positron emission tomography (PET)‐based staging of regional amyloid deposition has recently emerged as a promising tool for sensitive detection and stratification of pathology progression in Alzheimer's Disease (AD). Here we present an updated methodological framework for PET‐based amyloid staging using region–specific amyloid‐positivity thresholds and assess its longitudinal validity using serial PET acquisitions. We defined region‐specific thresholds of amyloid‐positivity based on Florbetapir‐PET data of 13 young healthy individuals (age ≤ 45y), applied these thresholds to Florbetapir‐PET data of 179 cognitively normal older individuals to estimate a regional amyloid staging model, and tested this model in a larger sample of patients with mild cognitive impairment (N = 403) and AD dementia (N = 85). 2‐year follow‐up Florbetapir‐PET scans from a subset of this sample (N = 436) were used to assess the longitudinal validity of the cross‐sectional model based on individual stage transitions and data‐driven longitudinal trajectory modeling. Results show a remarkable congruence between cross‐sectionally estimated and longitudinally modeled trajectories of amyloid accumulation, beginning in anterior temporal areas, followed by frontal and medial parietal areas, the remaining associative neocortex, and finally primary sensory‐motor areas and subcortical regions. Over 98% of individual amyloid deposition profiles and longitudinal stage transitions adhered to this staging scheme of regional pathology progression, which was further supported by corresponding changes in cerebrospinal fluid biomarkers. In conclusion, we provide a methodological refinement and longitudinal validation of PET‐based staging of regional amyloid accumulation, which may help improving early detection and in‐vivo stratification of pathologic disease progression in AD.

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Standardization of amyloid quantitation with florbetapir standardized uptake value ratios to the Centiloid scale

Abstract: These findings may allow improved tracer-independent amyloid quantitation.

Cited by 126 publications

References 20 publications

Comparison of Pittsburgh compound B and florbetapir in cross‐sectional and longitudinal studies

Comparison of Pittsburgh compound B and florbetapir in cross‐sectional and longitudinal studies

Comparison of amyloid PET measured in Centiloid units with neuropathological findings in Alzheimer’s Disease

Longitudinal validity of PET‐based staging of regional amyloid deposition

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