Browsing by Author "Bedell, BJ"

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    Hierarchical multivariate covariance analysis of metabolic connectivity
    (SAGE Publications, 2014-10-08) Carbonell, F; Charil, A; Zijdenbos, AP; Evans, AC; Bedell, BJ
    Conventional brain connectivity analysis is typically based on the assessment of interregional correlations. Given that correlation coefficients are derived from both covariance and variance, group differences in covariance may be obscured by differences in the variance terms. To facilitate a comprehensive assessment of connectivity, we propose a unified statistical framework that interrogates the individual terms of the correlation coefficient. We have evaluated the utility of this method for metabolic connectivity analysis using [18F]2-fluoro-2-deoxyglucose (FDG) positron emission tomography (PET) data from the Alzheimer's Disease Neuroimaging Initiative (ADNI) study. As an illustrative example of the utility of this approach, we examined metabolic connectivity in angular gyrus and precuneus seed regions of mild cognitive impairment (MCI) subjects with low and high β-amyloid burdens. This new multivariate method allowed us to identify alterations in the metabolic connectome, which would not have been detected using classic seed-based correlation analysis. Ultimately, this novel approach should be extensible to brain network analysis and broadly applicable to other imaging modalities, such as functional magnetic resonance imaging (MRI).© 2014,SAGE Publications
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    Optimal target region for subject classification on the basis of amyloid PET images
    (Society of Nuclear Medicine and Molecular Imaging, 2015-09-01) Carbonell, F; Zijdenbos, AP; Charil, A; Grand’Maison, MG; Bedell, BJ
    Classification of subjects on the basis of amyloid PET scans is increasingly being used in research studies and clinical practice. Although qualitative, visual assessment is currently the gold standard approach, automated classification techniques are inherently more reproducible and efficient. The objective of this work was to develop a statistical approach for the automated classification of subjects with different levels of cognitive impairment into a group with low amyloid levels (AβL) and a group with high amyloid levels (AβH) through the use of amyloid PET data from the Alzheimer Disease Neuroimaging Initiative study. Methods: In our framework, an iterative, voxelwise, regularized discriminant analysis is combined with a receiver operating characteristic approach that optimizes the selection of a region of interest (ROI) and a cutoff value for the automated classification of subjects into the AβL and AβH groups. The robustness, spatial stability, and generalization of the resulting target ROIs were evaluated by use of the standardized uptake value ratio for 18F-florbetapir PET images from subjects who served as healthy controls, subjects who had mild cognitive impairment, and subjects who had Alzheimer disease and were participating in the Alzheimer Disease Neuroimaging Initiative study. Results: We determined that several iterations of the discriminant analysis improved the classification of subjects into the AβL and AβH groups. We found that an ROI consisting of the posterior cingulate cortex/precuneus and the medial frontal cortex yielded optimal group separation and showed good stability across different reference regions and cognitive cohorts. A key step in this process was the automated determination of the cutoff value for group separation, which was dependent on the reference region used for the standardized uptake value ratio calculation and which was shown to have a relatively narrow range across subject groups. Conclusion: We developed a data-driven approach for the determination of an optimal target ROI and an associated cutoff value for the separation of subjects into the AβL and AβH groups. Future work should include the application of this process to other datasets to facilitate the determination of the translatability of the optimal ROI obtained in this study to other populations. Ideally, the accuracy of our target ROI and cutoff value could be further validated with PET-autopsy data from large-scale studies. It is anticipated that this approach will be extremely useful for the enrichment of study populations in clinical trials involving putative disease-modifying therapeutic agents for Alzheimer disease. © 2015, by the Society of Nuclear Medicine and Molecular Imaging, Inc.
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    β-Amyloid is associated with aberrant metabolic connectivity in subjects with mild cognitive impairment
    (SAGE Journals, 2014-04-16) Carbonell, F; Charil, A; Zijdenbos, AP; Evans, AC; Bedell, BJ
    Positron emission tomography (PET) studies using [18F]2-fluoro-2-deoxyglucose (FDG) have identified a well-defined pattern of glucose hypometabolism in Alzheimer's disease (AD). The assessment of the metabolic relationship among brain regions has the potential to provide unique information regarding the disease process. Previous studies of metabolic correlation patterns have demonstrated alterations in AD subjects relative to age-matched, healthy control subjects. The objective of this study was to examine the associations between β-amyloid, apolipoprotein E ɛ4 (APOE ɛ4) genotype, and metabolic correlations patterns in subjects diagnosed with mild cognitive impairment (MCI). Mild cognitive impairment subjects from the Alzheimer's Disease Neuroimaging Initiative (ADNI) study were categorized into β-amyloid-low and β-amyloid-high groups, based on quantitative analysis of [18F]florbetapir PET scans, and APOE ɛ4 non-carriers and carriers based on genotyping. We generated voxel-wise metabolic correlation strength maps across the entire cerebral cortex for each group, and, subsequently, performed a seed-based analysis. We found that the APOE ɛ4 genotype was closely related to regional glucose hypometabolism, while elevated, fibrillar β-amyloid burden was associated with specific derangements of the metabolic correlation patterns. © 2014 International Society for Cerebral Blood Flow & Metabolism, Inc. This work is licensed under a Creative Commons Attribution 3.0