Dataset Information

Florbetaben amyloid PET acquisition time: Influence on Centiloids and interpretation.

ABSTRACT:

Introduction

Amyloid positron emission tomography (PET) acquisition timing impacts quantification.

Methods

In florbetaben (FBB) PET scans of 245 adults with and without cognitive impairment, we investigated the impact of post-injection acquisition time on Centiloids (CLs) across five reference regions. CL equations for FBB were derived using standard methods, using FBB data collected between 90 and 110 min with paired Pittsburgh compound B data. Linear mixed models and t-tests evaluated the impact of acquisition time on CL increases.

Results

CL values increased significantly over the scan using the whole cerebellum, cerebellar gray matter, and brainstem as reference regions, particularly in amyloid-positive individuals. In contrast, CLs based on white matter-containing reference regions decreased across the scan.

Discussion

The quantification of CLs in FBB PET imaging is influenced by both the overall scan acquisition time and the choice of reference region. Standardized acquisition protocols or the application of acquisition time-specific CL equations should be implemented in clinical protocols.

Highlights

Acquisition timing affects florbetaben positron emission tomography (PET) scan quantification, especially in amyloid-positive participants. The impact of acquisition timing on quantification varies across common reference regions. Consistent acquisitions and/or appropriate post-injection adjustments are needed to ensure comparability of PET data.

SUBMITTER: Johns E

PROVIDER: S-EPMC11350032 | biostudies-literature | 2024 Aug

REPOSITORIES: biostudies-literature

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Publications

Florbetaben amyloid PET acquisition time: Influence on Centiloids and interpretation.

Johns Emily E Vossler Hillary A HA Young Christina B CB Carlson Mackenzie L ML Winer Joseph R JR Younes Kyan K Park Jennifer J Rathmann-Bloch Julia J Smith Viktorija V Harrison Theresa M TM Landau Susan S Henderson Victor V Wagner Anthony A Sha Sharon J SJ Zeineh Michael M Zaharchuk Greg G Poston Kathleen L KL Davidzon Guido A GA Mormino Elizabeth C EC

Alzheimer's & dementia : the journal of the Alzheimer's Association 20240704 8

<h4>Introduction</h4>Amyloid positron emission tomography (PET) acquisition timing impacts quantification.<h4>Methods</h4>In florbetaben (FBB) PET scans of 245 adults with and without cognitive impairment, we investigated the impact of post-injection acquisition time on Centiloids (CLs) across five reference regions. CL equations for FBB were derived using standard methods, using FBB data collected between 90 and 110 min with paired Pittsburgh compound B data. Linear mixed models and t-tests eva ...[more]

PMID: 38962867

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Project description:BackgroundA low amount and extent of Aβ deposition at early stages of Alzheimer's disease (AD) may limit the use of previously developed pathology-proven composite SUVR cutoffs. This study aims to characterize the population with earliest abnormal Aβ accumulation using 18F-florbetaben PET. Quantitative thresholds for the early (SUVRearly) and established (SUVRestab) Aβ deposition were developed, and the topography of early Aβ deposition was assessed. Subsequently, Aβ accumulation over time, progression from mild cognitive impairment (MCI) to AD dementia, and tau deposition were assessed in subjects with early and established Aβ deposition.MethodsThe study population consisted of 686 subjects (n = 287 (cognitively normal healthy controls), n = 166 (subjects with subjective cognitive decline (SCD)), n = 129 (subjects with MCI), and n = 101 (subjects with AD dementia)). Three categories in the Aβ-deposition continuum were defined based on the developed SUVR cutoffs: Aβ-negative subjects, subjects with early Aβ deposition ("gray zone"), and subjects with established Aβ pathology.ResultsSUVR using the whole cerebellum as the reference region and centiloid (CL) cutoffs for early and established amyloid pathology were 1.10 (13.5 CL) and 1.24 (35.7 CL), respectively. Cingulate cortices and precuneus, frontal, and inferior lateral temporal cortices were the regions showing the initial pathological tracer retention. Subjects in the "gray zone" or with established Aβ pathology accumulated more amyloid over time than Aβ-negative subjects. After a 4-year clinical follow-up, none of the Aβ-negative or the gray zone subjects progressed to AD dementia while 91% of the MCI subjects with established Aβ pathology progressed. Tau deposition was infrequent in those subjects without established Aβ pathology.ConclusionsThis study supports the utility of using two cutoffs for amyloid PET abnormality defining a "gray zone": a lower cutoff of 13.5 CL indicating emerging Aβ pathology and a higher cutoff of 35.7 CL where amyloid burden levels correspond to established neuropathology findings. These cutoffs define a subset of subjects characterized by pre-AD dementia levels of amyloid burden that precede other biomarkers such as tau deposition or clinical symptoms and accelerated amyloid accumulation. The determination of different amyloid loads, particularly low amyloid levels, is useful in determining who will eventually progress to dementia. Quantitation of amyloid provides a sensitive measure in these low-load cases and may help to identify a group of subjects most likely to benefit from intervention.Trial registrationData used in this manuscript belong to clinical trials registered in ClinicalTrials.gov ( NCT00928304 , NCT00750282 , NCT01138111 , NCT02854033 ) and EudraCT (2014-000798-38).

Project description:BackgroundFlorbetaben, a 18F-labeled stilbene derivative (Neuraceq®, formerly known as BAY-949172), is a diagnostic radiopharmaceutical developed to visualize β-amyloid plaques in the brain. Here, we report a pilot study evaluating patients with suspected cardiac amyloidosis for systemic extent of disease.MethodsWe prospectively enrolled nine patients, 61-86 year old (mean ± SD 69.4 ± 8.6), referred from the cardiac amyloid clinic. First, dynamic imaging of the heart was acquired immediately after injection of 222-318.2 MBq (mean ± SD 270.1 ± 33.3) of 18F-florbetaben using the GE SIGNA PET/MRI. This was followed by a whole-body PET/MRI scan 60-146.4 min (mean ± SD 98 ± 33.4) after injection. Cardiac MRI sequences included ECG-triggered cine SSFP, T2-weighted, and late gadolinium-enhanced imaging. Whole-body MRI sequences included MRAC and axial T1-weighted imaging.ResultsHigh early uptake and delayed high uptake in the left ventricle correlated with amyloid deposition in five patients, while low uptake on early and delayed cardiac imaging was noted in four patients. Cardiac function measurements were successfully obtained in all participants. Areas of increased abnormal 18F-florbetaben accumulation were noted on delayed whole-body imaging in the bone marrow (seven patients), stomach (diffuse in five patients and focal in one patient), brain (five patients), salivary glands (three patients), tongue (three patients), spleen (three patients), skeletal muscles (three patients), ocular muscles (two patients), thyroid (two patients), pleura (two patients), kidneys (two patients), and lungs (two patients).ConclusionsWhole-body 18F-florbetaben PET/MRI is promising for localization of systemic amyloid deposition. This technique may provide important structural and functional information regarding the organs involved by disease, with potential to guide biopsy and evaluate response to treatment.Trial registrationClinicaltrials.gov registration: NCT03119558 .

Project description:BACKGROUND:A long dynamic scanning protocol may be required to accurately measure longitudinal changes in amyloid load. However, such a protocol results in a lower patient comfort and scanning efficiency compared to static scans. A compromise can be achieved by implementing dual-time-window protocols. This study aimed to optimize these protocols for quantitative [18F]flutemetamol and [18F]florbetaben studies. METHODS:Rate constants for subjects across the Alzheimer's disease spectrum (i.e., non-displaceable binding potential (BPND) in the range 0.02-0.77 and 0.02-1.04 for [18F]flutemetamol and [18F]florbetaben, respectively) were established based on clinical [18F]flutemetamol (N = 6) and [18F]florbetaben (N = 20) data, and used to simulate tissue time-activity curves (TACs) of 110 min using a reference tissue and plasma input model. Next, noise was added (N = 50) and data points corresponding to different intervals were removed from the TACs, ranging from 0 (i.e., 90-90 = full-kinetic curve) to 80 (i.e., 10-90) minutes, creating a dual-time-window. Resulting TACs were fitted using the simplified reference tissue method (SRTM) to estimate the BPND, outliers (≥ 1.5 × BPND max) were removed and the bias was assessed using the distribution volume ratio (DVR = BPND + 1). To this end, acceptability curves, which display the fraction of data below a certain bias threshold, were generated and the area under those curves were calculated. RESULTS:[18F]Flutemetamol and [18F]florbetaben data demonstrated an increased bias in amyloid estimate for larger intervals and higher noise levels. An acceptable bias (≤ 3.1%) in DVR could be obtained with all except the 10-90 and 20-90-min intervals. Furthermore, a reduced fraction of acceptable data and most outliers were present for these two largest intervals (maximum percentage outliers 48 and 32 for [18F]flutemetamol and [18F]florbetaben, respectively). CONCLUSIONS:The length of the interval inversely correlates with the accuracy of the BPND estimates. Consequently, a dual-time-window protocol of 0-30 and 90-110 min (=maximum of 60 min interval) allows for accurate estimation of BPND values for both tracers. [18F]flutemetamol: EudraCT 2007-000784-19, registered 8 February 2007, [18F]florbetaben: EudraCT 2006-003882-15, registered 2006.

Project description:Purpose To reduce radiotracer requirements for amyloid PET/MRI without sacrificing diagnostic quality by using deep learning methods. Materials and Methods Forty data sets from 39 patients (mean age ± standard deviation [SD], 67 years ± 8), including 16 male patients and 23 female patients (mean age, 66 years ± 6 and 68 years ± 9, respectively), who underwent simultaneous amyloid (fluorine 18 [18F]-florbetaben) PET/MRI examinations were acquired from March 2016 through October 2017 and retrospectively analyzed. One hundredth of the raw list-mode PET data were randomly chosen to simulate a low-dose (1%) acquisition. Convolutional neural networks were implemented with low-dose PET and multiple MR images (PET-plus-MR model) or with low-dose PET alone (PET-only) as inputs to predict full-dose PET images. Quality of the synthesized images was evaluated while Bland-Altman plots assessed the agreement of regional standard uptake value ratios (SUVRs) between image types. Two readers scored image quality on a five-point scale (5 = excellent) and determined amyloid status (positive or negative). Statistical analyses were carried out to assess the difference of image quality metrics and reader agreement and to determine confidence intervals (CIs) for reading results. Results The synthesized images (especially from the PET-plus-MR model) showed marked improvement on all quality metrics compared with the low-dose image. All PET-plus-MR images scored 3 or higher, with proportions of images rated greater than 3 similar to those for the full-dose images (-10% difference [eight of 80 readings], 95% CI: -15%, -5%). Accuracy for amyloid status was high (71 of 80 readings [89%]) and similar to intrareader reproducibility of full-dose images (73 of 80 [91%]). The PET-plus-MR model also had the smallest mean and variance for SUVR difference to full-dose images. Conclusion Simultaneously acquired MRI and ultra-low-dose PET data can be used to synthesize full-dose-like amyloid PET images. © RSNA, 2018 Online supplemental material is available for this article. See also the editorial by Catana in this issue.

Project description:Background18F-Florbetaben amyloid positron emission tomography (PET) scan is crucial for diagnosing Alzheimer's disease, typically involving a 20 min acquisition. However, maintaining such prolonged scans can be challenging in some cases. This study explores the diagnostic impact and feasibility of reducing scan durations by comparing quantitative measures between shortened and standard scans. Additionally, we identified the optimal Centiloid threshold to distinguish between positive and negative amyloid results.ResultsWe analyzed 307 PET scans from our memory clinic, each followed up for a minimum of two years. The scans, conducted 90 to 110 min after approximately 300 MBq of 18F-Florbetaben injection, were categorized into four sets of 5 min durations: 5, 10, 15, and 20 min. Nuclear medicine physicians validated and rated each scan as either amyloid-positive or negative. For quantitative assessments, we employed the standardized uptake value ratio (SUVR) and Centiloid scales, comparing total SUVR and Centiloid values across five subregions (global, frontal, posterior cingulate-precuneus, lateral temporal, and parietal) using Bland-Altman analysis. Receiver operator characteristic (ROC) curves were utilized to develop optimal Centiloid thresholds. Comparing the images at 5, 10, 15, and 20 min images, SUVR and Centiloid values gradually increased with prolonged scan times. The mean SUVR difference between 5 and 20 min was 0.03 for the amyloid-positive and 0.01 for the amyloid-negative groups; Centiloid differences were 4.60 and 2.38, respectively. Additionally, no significant variation was observed in total SUVR and Centiloid values among the durations across all subregions in positive and negative groups (all p > 0.1). ROC analysis indicated that a Centiloid threshold of 21.86 at 5 min provided optimal agreement with visual assessments (AUC = 0.985, sensitivity = 0.950, specificity = 0.972), especially using the global area.ConclusionsThis study demonstrated that 5 min image scans with an optimal threshold of CL = 21.86 exhibited minimal bias in SUVR and Centiloid values compared to longer scans (10, 15, and 20 min). Our findings suggest that shorter scan times are a viable and effective option for brain amyloid PET imaging in clinical settings.

Dataset Information

Florbetaben amyloid PET acquisition time: Influence on Centiloids and interpretation.

Introduction

Methods

Results

Discussion

Highlights

Publications

Florbetaben amyloid PET acquisition time: Influence on Centiloids and interpretation.

Similar Datasets

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