A Fully Automatic Technique for Precise Localization and Quantification of Amyloid-β PET Scans

Tahmi, Mouna; Bou-Zeid, Wassim; Razlighi, Qolamreza R.

doi:10.2967/jnumed.119.228510

Cited by 23 publications

(27 citation statements)

References 38 publications

(55 reference statements)

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“…Dynamic PET frames (4 scans) were aligned to the first frame using rigid-body registration and a static PET image was obtained by averaging the four registered frames. Additional information on the Aβ PET scan processing protocol has been previously published ( 17 ). The standardized uptake value (SUV), defined as the decay-corrected brain radioactivity concentration normalized for injected dose and body weight, was calculated in all regions and each voxel, which subsequently normalized to the SUV in cerebellar gray matter to derive the regional and voxel-wise SUVR.…”

Section: Methodsmentioning

confidence: 99%

Brain Amyloid Burden and Resting-State Functional Connectivity in Late Middle-Aged Hispanics

et al. 2020

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Non-linear relations of brain amyloid beta (Aβ) with task- based functional connectivity (tbFC) measured with functional magnetic resonance imaging (fMRI) have been reported in late middle age. Our objective was to examine the association between brain Aβ and resting-state functional connectivity (rsFC) in late middle-aged adults. Global brain Aβ burden was ascertained with 18 F-Florbetaben Positron Emission Tomography (PET); rsFC was ascertained on 3T Magnetic Resonance Imaging (MRI) among 333 late middle-aged Hispanics adults without dementia in four major brain functional connectivity networks: default mode network (DMN), fronto-parietal control network (FPC), salience network (SAL) and dorsal attention network (DAN). We examined the relationship of global brain Aβ with rsFC using multivariable linear regression adjusted for age, sex, education, and APOE-ε4 genotype. We quantified the non-linear associations both with quadratic terms and by categorizing Aβ into three groups: low Aβ, intermediate Aβ, and positive Aβ. We found no significant linear or non-linear associations between Aβ, measured either continuously or categorically, with rsFC in the examined networks. Our null findings may be explained by the younger age of our participants in whom amyloid burden is relatively low. It is also possible that the recently reported non-linear relationship is exclusive to task fMRI and not rsfMRI.

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Section: Methodsmentioning

confidence: 99%

Brain Amyloid Burden and Resting-State Functional Connectivity in Late Middle-Aged Hispanics

et al. 2020

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“…To process the Aβ and tau PET scans, a fully automatic inhouse developed quantification method was used. This method has already been used in numerous studies and validated using histopathological data [34][35][36][37][38]. Briefly, dynamic PET frames (six frames in tau PET and four frames in Aβ PET) are first aligned to the first frame using rigid-body registration and averaged to generate a static PET image.…”

Section: Quantification Of Molecular Imaging Datamentioning

confidence: 99%

“…The standardized uptake value (SUV), defined as the decay-corrected brain radioactivity concentration normalized for injected dose and body weight, was calculated; it was normalized to cerebellum gray matter to derive the standardized uptake value ratio (SUVR). The FreeSurfer cortical and subcortical regions, as well as vertex-wise surface reconstruction, were used in the native space analysis of the PET data [39]. Finally, all vertex-wise quantification of Aβ, tau, and surface-based probabilistic atlases are generated by FreeSurfer's reconstructed surfaces.…”

Section: Quantification Of Molecular Imaging Datamentioning

confidence: 99%

Distinct and joint effects of low and high levels of Aβ and tau deposition on cortical thickness

Hojjati

Butler

Chiang

et al. 2022

Preprint

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Alzheimer's disease (AD) is defined by the presence of Amyloid-β (Aβ), tau, and neurodegeneration (ATN framework) in the human cerebral cortex. Prior studies have suggested that Aβ deposition can be associated with both cortical thinning and thickening. These contradictory results may be due to small sample sizes, the presence versus absence of tau, and limited detectability in the earliest phase of protein deposition, which may begin in young adulthood and cannot be captured in studies enrolling only older subjects. In this study, we aimed to find the distinct and joint effects of Aβ and tau on neurodegeneration during the progression from normal to abnormal stages of pathologies that remain incompletely understood. We used 18F-MK6240 and 18F-Florbetaben/18F-Florbetapir positron emission tomography (PET) and magnetic resonance imaging (MRI) to quantify tau, Aβ, and cortical thickness in 529 participants ranging in age from 20 to 90. We applied a novel partial volume correction technique based on the absence of proteinopathy in young controls to optimize spatial resolution. Aβ/tau abnormality was defined at 95th percentile of the normal distribution of global Ab/tau observed in young participants. We performed multiple regression analyses to assess the distinct and joint effects of Aβ and tau on cortical thickness. Using 529 participants (83 young, 394 healthy older, 52 MCI) we showed that normal levels of Aβ deposition were significantly associated with increased cortical thickness regardless of the amount of tau (e.g., left entorhinal cortex with t>3.241). The relationship between tau deposition and neurodegeneration was more complex: abnormal levels of tau were associated with cortical thinning in several regions of the brain (e.g., left entorhinal with t<-2.80 and left insula with t<-3.202), as expected based on prior neuroimaging and neuropathological studies. Surprisingly, however, normal levels of tau were found to be associated with cortical thickening. Moreover, at abnormal levels of Aβ and tau, the resonance between them, defined as their correlation throughout the cortex, was associated strongly with cortical thinning when controlling for their additive effect. We confirm prior findings of an association between Aβ deposition and cortical thickening and suggest this may also be the case in the earliest stages of deposition in normal aging. We discuss potential pathophysiologic processes underlying this effect such as inflammation and hyperactivation (excitotoxicity). We also illustrate that resonance between high levels of Aβ and tau uptake is strongly associated with cortical thinning, emphasizing the effects of Aβ/tau synergy in AD pathogenesis.

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“…The structural T1weighted image in FreeSurfer space was registered to the CT/PET fused image using normalized mutual information and six degrees of freedom. A combination of the two transformation matrices obtained from the two rigid-body registrations was used to transfer all Freesurfer regional masks and the cerebellar gray matter from FreeSurfer space to static PET image space using nearest neighbor interpolation [20]. The standardized uptake value (SUV), defined as the decay-corrected brain radioactivity concentration normalized for injected dose and body weight, was calculated in all FreeSurfer regions.…”

Section: Brain Aβmentioning

confidence: 99%

Plasma Amyloid and in vivo Brain Amyloid in Late Middle-Aged Hispanics

Rippon

Palta

Tahmi

et al. 2022

JAD

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Background: Determining amyloid positivity is possible with cerebrospinal fluid and brain imaging of amyloid, but these methods are invasive and expensive. Objective: To relate plasma amyloid-β (Aβ), measured using Single-molecule array (Simoatrademark) assays, to in vivo brain Aβ, measured using positron emission tomography (PET), examine the accuracy of plasma Aβ to predict brain Aβ positivity, and the relation of APOE ɛ4 with plasma Aβ. Methods: We performed a cross-sectional analysis in a cohort of 345 late middle-aged Hispanic men and women (age 64 years, 72% women). Our primary plasma variable was Aβ 42/Aβ 40 ratio measured with Simoa. Brain Aβ burden was measured as global SUVR with 18F-Florbetaben PET examined continuously and categorically. Results: Plasma Aβ 42/Aβ 40 ratio was inversely associated with global Aβ SUVR (β= –0.13, 95% Confidence Interval (CI): –0.23, –0.03; p = 0.013) and Aβ positivity (Odds Ratio: 0.59, 95% CI: 0.38, 0.91; p = 0.016), independent of demographics and APOE ɛ4. ROC curves (AUC = 0.73, 95% CI: 0.64, 0.82; p < 0.0001) showed that the optimal threshold for plasma Aβ 42/Aβ 40 ratio in relation to brain Aβ positivity was 0.060 with a sensitivity of 82.4% and specificity of 62.8% . APOE ɛ4 carriers had lower Aβ 42/Aβ 40 ratio and a higher Aβ positivity determined with the Aβ 42/Aβ 40 ratio threshold of 0.060. Conclusion: Plasma Aβ 42/Aβ 40 ratio assayed using Simoa is weakly correlated with in vivo brain amyloid and has limited accuracy in screening for amyloid positivity and for studying risk factors of brain amyloid burden when in vivo imaging is not feasible.

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A Fully Automatic Technique for Precise Localization and Quantification of Amyloid-β PET Scans

Cited by 23 publications

References 38 publications

Brain Amyloid Burden and Resting-State Functional Connectivity in Late Middle-Aged Hispanics

Brain Amyloid Burden and Resting-State Functional Connectivity in Late Middle-Aged Hispanics

Distinct and joint effects of low and high levels of Aβ and tau deposition on cortical thickness

Plasma Amyloid and in vivo Brain Amyloid in Late Middle-Aged Hispanics

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