Dataset Information

Dual-phase ¹⁸F-florbetaben PET provides cerebral perfusion proxy along with beta-amyloid burden in Alzheimer's disease.

ABSTRACT:

Background

This study investigated changes in brain perfusion and Aβ burden according to the progression of Alzheimer's disease (AD) by using a dual-phase ¹⁸F-florbetaben (FBB) PET protocol.

Methods

Sixty subjects, including 12 with Aβ-negative normal cognition (Aβ^-NC), 32 with Aβ-positive mild cognitive impairment (Aβ⁺MCI), and 16 with Aβ-positive AD (Aβ⁺AD), were enrolled. A dynamic PET scan was obtained in the early phase (0-10 min, eFBB) and delayed phase (90-110 min, dFBB), which were then averaged into a single frame, respectively. In addition to the averaged eFBB, an R1 parametric map was calculated from the eFBB scan based on a simplified reference tissue model (SRTM). Between-group regional and voxel-wise analyses of the images were performed. The associations between cognitive profiles and PET-derived parameters were investigated.

Results

Both the R1 and eFBB perfusion reductions in the cortical regions were not significantly different between the Aβ^-NC and Aβ⁺MCI groups, while they were significantly reduced from the Aβ⁺MCI to Aβ⁺AD groups in regional and voxel-wise analyses. However, cortical Aβ depositions on dFBB were not significantly different between the Aβ⁺MCI and Aβ⁺AD groups. There were strong positive correlations between the R1 and eFBB images in regional and voxel-wise analyses. Both perfusion components showed significant correlations with general and specific cognitive profiles.

Conclusion

The results of this study demonstrated the feasibility of dual-phase ¹⁸F-FBB PET to evaluate different trajectories of dual biomarkers for neurodegeneration and Aβ burden over the course of AD. In addition, both eFBB and SRTM-based R1 can provide robust indices of brain perfusion.

SUBMITTER: Yoon HJ

PROVIDER: S-EPMC8346681 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

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Publications

Dual-phase <sup>18</sup>F-florbetaben PET provides cerebral perfusion proxy along with beta-amyloid burden in Alzheimer's disease.

Yoon Hai-Jeon HJ Kim Bom Sahn BS Jeong Jee Hyang JH Kim Geon Ha GH Park Hee Kyung HK Chun Min Young MY Ha Seunggyun S

NeuroImage. Clinical 20210724

<h4>Background</h4>This study investigated changes in brain perfusion and Aβ burden according to the progression of Alzheimer's disease (AD) by using a dual-phase <sup>18</sup>F-florbetaben (FBB) PET protocol.<h4>Methods</h4>Sixty subjects, including 12 with Aβ-negative normal cognition (Aβ<sup>-</sup>NC), 32 with Aβ-positive mild cognitive impairment (Aβ<sup>+</sup>MCI), and 16 with Aβ-positive AD (Aβ<sup>+</sup>AD), were enrolled. A dynamic PET scan was obtained in the early phase (0-10 min, e ...[more]

PMID: 34339946

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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: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: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.

Project description:BackgroundKinetic modeling of 18F-florbetaben provides important quantification of brain amyloid deposition in research and clinical settings but its use is limited by the requirement of arterial blood data for quantitative PET. The total-body EXPLORER PET scanner supports the dynamic acquisition of a full human body simultaneously and permits noninvasive image-derived input functions (IDIFs) as an alternative to arterial blood sampling. This study quantified brain amyloid burden with kinetic modeling, leveraging dynamic 18F-florbetaben PET in aorta IDIFs and the brain in an elderly cohort.Methods18F-florbetaben dynamic PET imaging was performed on the EXPLORER system with tracer injection (300 MBq) in 3 individuals with Alzheimer's disease (AD), 3 with mild cognitive impairment, and 9 healthy controls. Image-derived input functions were extracted from the descending aorta with manual regions of interest based on the first 30 s after injection. Dynamic time-activity curves (TACs) for 110 min were fitted to the two-tissue compartment model (2TCM) using population-based metabolite corrected IDIFs to calculate total and specific distribution volumes (VT, Vs) in key brain regions with early amyloid accumulation. Non-displaceable binding potential ([Formula: see text] was also calculated from the multi-reference tissue model (MRTM).ResultsAmyloid-positive (AD) patients showed the highest VT and VS in anterior cingulate, posterior cingulate, and precuneus, consistent with [Formula: see text] analysis. [Formula: see text]and VT from kinetic models were correlated (r² = 0.46, P < 2[Formula: see text] with a stronger positive correlation observed in amyloid-positive participants, indicating reliable model fits with the IDIFs. VT from 2TCM was highly correlated ([Formula: see text]= 0.65, P < 2[Formula: see text]) with Logan graphical VT estimation.ConclusionNon-invasive quantification of amyloid binding from total-body 18F-florbetaben PET data is feasible using aorta IDIFs with high agreement between kinetic distribution volume parameters compared to [Formula: see text]in amyloid-positive and amyloid-negative older individuals.

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

Dual-phase ¹⁸F-florbetaben PET provides cerebral perfusion proxy along with beta-amyloid burden in Alzheimer's disease.

Background

Methods

Results

Conclusion

Publications

Dual-phase <sup>18</sup>F-florbetaben PET provides cerebral perfusion proxy along with beta-amyloid burden in Alzheimer's disease.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Dataset Information

Dual-phase 18F-florbetaben PET provides cerebral perfusion proxy along with beta-amyloid burden in Alzheimer's disease.

Background

Methods

Results

Conclusion

Publications

Dual-phase <sup>18</sup>F-florbetaben PET provides cerebral perfusion proxy along with beta-amyloid burden in Alzheimer's disease.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Dual-phase ¹⁸F-florbetaben PET provides cerebral perfusion proxy along with beta-amyloid burden in Alzheimer's disease.