Biological parametric mapping with robust and non-parametric statistics

Yang, Xue; Beason‐Held, Lori L.; Resnick, Susan M.; Landman, Bennett A.

doi:10.1016/j.neuroimage.2011.04.046

Cited by 31 publications

(34 citation statements)

References 24 publications

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“…We used Robust Biological Parametric Mapping (BPM), version 2.1(26, 27), to determine voxel-wise DVR-CBF and DVR-R 1 relationships. Robust BPM is based on BPM, which allows voxel-wise regression of data from two imaging modalities using least-squares regression.…”

Section: Methodsmentioning

confidence: 99%

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Voxelwise Relationships Between Distribution Volume Ratio and Cerebral Blood Flow: Implications for Analysis of β-Amyloid Images

et al. 2015

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Quantification of β-amyloid (Aβ) in vivo is often accomplished using the distribution volume ratio (DVR), based on a simplified reference tissue model. We investigated the local relationships between DVR and cerebral blood flow (CBF), as well as relative blood flow (R1), in nondemented older adults. Methods Fifty-five nondemented participants (mean age 78.5 years) in the Baltimore Longitudinal Study of Aging underwent 15O-H2O PET CBF and dynamic 11C-PiB-PET. 15O-H2O PET images were normalized and smoothed using SPM. A simplified reference tissue model with linear regression and spatial constraints was used to generate parametric DVR images. The DVR images were regressed on CBF images on a voxel-by-voxel basis using robust Biological Parametric Mapping, adjusting for age and sex (FDR p=0.05, k=50). DVR images were also regressed on R1 images, a measure of the transport rate constant from vascular space to tissue. All analyses were performed in the entire sample, and in high and low tertiles of mean cortical DVR. Results Voxel-based analyses showed that increased DVR is associated with increased CBF in frontal, parietal, temporal, and occipital cortices. However, this association appears to spare regions that typically show early β-amyloid (Aβ) deposition. A more robust relationship between DVR and CBF was observed in the lowest tertile of DVR, i.e., negligible cortical Aβ load, compared to the highest tertile of cortical DVR and Aβ load. Spatial distributions of the DVR-CBF and DVR-R1 correlations showed similar patterns. No reliable negative voxel-wise relationships between DVR and CBF or R1 were observed. Conclusion Robust associations between DVR and CBF at negligible Aβ levels, together with similar spatial distributions of DVR-CBF and DVR-R1 correlations, suggest that regional distribution of DVR reflects blood flow and tracer influx rather than pattern of Aβ deposition in those with minimal Aβ load. DVR-CBF associations in individuals with higher DVR are more likely to reflect true associations between patterns of Aβ deposition and CBF or neural activity. These findings have important implications for analysis and interpretation of voxel-wise correlations with external variables in individuals with varying amounts of Aβ load.

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Section: Methodsmentioning

confidence: 99%

“…Robust BPM is based on BPM, which allows voxel-wise regression of data from two imaging modalities using least-squares regression. (28) Robust BPM extends this approach by using robust regression (M-estimation) (29) to account for outliers in the imaging data (26). …”

Section: Methodsmentioning

confidence: 99%

Voxelwise Relationships Between Distribution Volume Ratio and Cerebral Blood Flow: Implications for Analysis of β-Amyloid Images

et al. 2015

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“…Also, the integration of complementary information through a multimodal approach will be very useful to overcome the shortcomings of each single protocol, requiring advanced analysis tools which are able to integrate information from different protocols into the same processing pipeline. Similar approaches are likely to aid in better discrimination and staging of AD [8,[246][247][248]. In this context, information from different modalities may be simultaneously combined using the support of machine learning algorithms enabling the classification of a single subject into a predefined group while dealing with any type of input features (e.g.…”

Section: Functional Mri Markersmentioning

confidence: 99%

Perspective on future role of biological markers in clinical therapy trials of Alzheimer's disease: A long-range point of view beyond 2020

Hampel

Lista

Teipel

et al. 2014

Biochemical Pharmacology

105

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Recent advances in understanding the molecular mechanisms underlying various paths toward the pathogenesis of Alzheimer's disease (AD) has begun to provide new insight for interventions to modify disease progression. The evolving knowledge gained from multidisciplinary basic research has begun to identify new concepts for treatments and distinct classes of therapeutic targets; as well as putative disease-modifying compounds that are now being tested in clinical trials. There is a mounting consensus that such disease modifying compounds and/or interventions are more likely to be effectively administered as early as possible in the cascade of pathogenic processes preceding and underlying the clinical expression of AD. The budding sentiment is that "treatments" need to be applied before various molecular mechanisms converge into an irreversible pathway leading to morphological, metabolic and functional alterations that characterize the pathophysiology of AD. In light of this, biological indicators of pathophysiological mechanisms are desired to chart and detect AD throughout the asymptomatic early molecular stages into the prodromal and early dementia phase. A major conceptual development in the clinical AD research field was the recent proposal of new diagnostic criteria, which specifically incorporate the use of biomarkers as defining criteria for preclinical stages of AD. This paradigm shift in AD definition, conceptualization, operationalization, detection and diagnosis represents novel fundamental opportunities for the modification of interventional trial designs. This perspective summarizes not only present knowledge regarding biological markers but also unresolved questions on the status of surrogate indicators for detection of the disease in asymptomatic people and diagnosis of AD

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“…In order to assess the influence of gray matter atrophy on the results, we used the voxel-wise regression routine available in the robust Biological Parametric Mapping toolbox (Yang et al, 2011). This routine allows to enter an imaging dependent variable, while regressing out the effect of several imaging and non-imaging regressors in a voxel-by-voxel analysis.…”

Section: Influence Of Gray Matter Atrophy On Age Effects: Bpm Analysesmentioning

confidence: 99%

Age effect on the default mode network, inner thoughts, and cognitive abilities

Mevel

Landeau

Fouquet

et al. 2013

Neurobiology of Aging

114

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Age-related effects on the Default Mode Network (DMN) connectivity as measured at rest using functional MRI (fMRI) are now well described. Little is known however about the relationships between these changes and age-related effects on cognition or on the unconstrained thoughts occurring during the resting-state scan, called as inner experience.Brain resting-state activity, inner experience and cognitive ability measurements were obtained in 70 participants aged 19 to 80 years. The anterior-posterior disruption of DMN activity with age reported in previous studies was recovered here. A significant effect of age was also found on cognitive abilities but not on inner experience. Finally, age-related changes in DMN connectivity were found to correlate with cognitive abilities, and more specifically with autobiographical memory performance. These findings provide new information to fuel the debate on the role of the brain default mode and more specifically on the impact of agerelated changes in resting-state activity as measured with fMRI.

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Biological parametric mapping with robust and non-parametric statistics

Cited by 31 publications

References 24 publications

Voxelwise Relationships Between Distribution Volume Ratio and Cerebral Blood Flow: Implications for Analysis of β-Amyloid Images

Voxelwise Relationships Between Distribution Volume Ratio and Cerebral Blood Flow: Implications for Analysis of β-Amyloid Images

Perspective on future role of biological markers in clinical therapy trials of Alzheimer's disease: A long-range point of view beyond 2020

Age effect on the default mode network, inner thoughts, and cognitive abilities

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