Dataset Information

Early detection of amyloid load using ¹⁸F-florbetaben PET.

ABSTRACT:

Background

A 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 (SUVR_early) and established (SUVR_estab) 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.

Methods

The 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.

Results

SUVR 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.

Conclusions

This 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 registration

Data used in this manuscript belong to clinical trials registered in ClinicalTrials.gov ( NCT00928304 , NCT00750282 , NCT01138111 , NCT02854033 ) and EudraCT (2014-000798-38).

SUBMITTER: Bullich S

PROVIDER: S-EPMC8005243 | biostudies-literature |

REPOSITORIES: biostudies-literature

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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: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:PurposeThe tau tracer [18F]AV1451, also known as flortaucipir, is a promising ligand for imaging tau accumulation in Alzheimer's disease (AD). Most of the previous studies have quantified tau load using standardized uptake value ratios (SUVr) derived from a static [18F]AV1451 scan. SUVr may, however, be flow dependent and, especially for longitudinal studies, should be validated against a fully quantitative approach. The objective of this study was to identify the optimal tracer kinetic model for measuring tau load using [18F]AV1451.ProceduresFollowing intravenous injection of 225 ± 16 MBq [18F]AV1451, 130 min dynamic PET scans were performed in five biomarker confirmed AD patients and five controls. Arterial blood sampling was performed to obtain a metabolite-corrected plasma input function. Next, regional time-activity curves were generated using PVElab software. These curves were analysed using several pharmacokinetic models.ResultsThe reversible single tissue compartment model (1T2k_VB) was the preferred model for all but one control. For AD patients, however, model preference shifted towards a reversible two tissue compartmental model (2T4k_VB). The simplified reference tissue model (SRTM) derived binding potential (BPND) showed good correlation (AD: r 2 = 0.87, slope = 1.06; controls: r 2 = 0.87, slope = 0.86) with indirect plasma input binding (distribution volume ratio-1). Standardized uptake value ratios (80-100 min) correlated well with DVR (r 2 = 0.93, slope = 1.07) and SRTM-derived BPND (r 2 = 0.84, slope = 0.95). In addition, regional differences in tracer binding between subject groups in different tau-specific regions were observed.ConclusionsModel preference of [18F]AV1451 appears to depend on subject status and, in particular, VT. The relationship between model preference and VT suggests that (higher) tau load may be reflected by a second tissue compartment. Nevertheless, consistent results can be obtained using a 2T4k_VB model. In addition, SRTM can be used to derive BPND.

Project description:PurposeCharacteristic features of amyloid-PET (A), tau-PET (T), and FDG-PET (N) can serve for the A/T/N classification of neurodegenerative diseases. Recent studies showed that the early, perfusion-weighted phases of amyloid- or tau-PET recordings serve to detect cerebrometabolic deficits equally to FDG-PET, therefore providing a surrogate of neuronal injury. As such, two channels of diagnostic information can be obtained in the setting of a single PET scan. However, there has hitherto been no comparison of early-phase amyloid- and tau-PET as surrogates for deficits in perfusion/metabolism. Therefore, we undertook to compare [18F]flutemetamol-amyloid-PET and [18F]PI-2620 tau-PET as "one-stop shop" dual purpose tracers for the detection of neurodegenerative disease.MethodsWe obtained early-phase PET recordings with [18F]PI-2620 (0.5-2.5 min p.i.) and [18F]flutemetamol (0-10 min p.i.) in 64 patients with suspected neurodegenerative disease. We contrasted global mean normalized images (SUVr) in the patients with a normal cohort of 15 volunteers without evidence of increased pathology to β-amyloid- and tau-PET examinations. Regional group differences of tracer uptake (z-scores) of 246 Brainnetome volumes of interest were calculated for both tracers, and the correlations of the z-scores were evaluated using Pearson's correlation coefficient. Lobar compartments, regions with significant neuronal injury (z-scores < - 3), and patients with different neurodegenerative disease entities (e.g., Alzheimer's disease or 4R-tauopathies) served for subgroup analysis. Additionally, we used partial regression to correlate regional perfusion alterations with clinical scores in cognition tests.ResultsThe z-scores of perfusion-weighted images of both tracers showed high correlations across the brain, especially in the frontal and parietal lobes, which were the brain regions with pronounced perfusion deficit in the patient group (R = 0.83 ± 0.08; range, 0.61-0.95). Z-scores of individual patients correlated well by region (R = 0.57 ± 0.15; range, 0.16-0.90), notably when significant perfusion deficits were present (R = 0.66 ± 0.15; range, 0.28-0.90).ConclusionThe early perfusion phases of [18F]PI-2620 tau- and [18F]flutemetamol-amyloid-PET are roughly equivalent indices of perfusion defect indicative of regional and lobar neuronal injury in patients with various neurodegenerative diseases. As such, either tracer may serve for two diagnostic channels by assessment of amyloid/tau status and neuronal activity.

Dataset Information

Early detection of amyloid load using ¹⁸F-florbetaben PET.

Background

Methods

Results

Conclusions

Trial registration

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OmicsDI is part of the ELIXIR infrastructure

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Dataset Information

Early detection of amyloid load using 18F-florbetaben PET.

Background

Methods

Results

Conclusions

Trial registration

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Early detection of amyloid load using ¹⁸F-florbetaben PET.