Metabolic and amyloid PET network reorganization in Alzheimer’s disease: differential patterns and partial volume effects

Alzheimer’s disease (AD) is a neurodegenerative disorder, considered a disconnection syndrome with regional molecular pattern abnormalities quantifiable by the aid of PET imaging. Solutions for accurate quantification of network dysfunction are scarce. We evaluate the extent to which PET molecular markers reflect quantifiable network metrics derived through the graph theory framework and how partial volume effects (PVE)-correction (PVEc) affects these PET-derived metrics 75 AD patients and 126 cognitively normal older subjects (CN). Therefore our goal is twofold: 1) to evaluate the differential patterns of [ 18 F]FDG- and [ 18 F]AV45-PET data to depict AD pathology; and ii) to analyse the effects of PVEc on global uptake measures of [ 18 F]FDG- and [ 18 F]AV45-PET data and their derived covariance network reconstructions for differentiating between patients and normal older subjects. Network organization patterns were assessed using graph theory in terms of “degree”, “modularity”, and “efficiency”. PVEc evidenced effects on global uptake measures that are specific to either [ 18 F]FDG- or [ 18 F]AV45-PET, leading to increased statistical differences between the groups. PVEc was further shown to influence the topological characterization of PET-derived covariance brain networks, leading to an optimised characterization of network efficiency and modularisation. Partial-volume effects correction improves the interpretability of PET data in AD and leads to optimised characterization of network properties for organisation or disconnection.

[1]  Jerry L Prince,et al.  Measurement of Radiotracer Concentration in Brain Gray Matter Using Positron Emission Tomography: MRI-Based Correction for Partial Volume Effects , 1992, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[2]  C. Stam Modern network science of neurological disorders , 2014, Nature Reviews Neuroscience.

[3]  C. Gaser,et al.  Partial Volume Segmentation with Adaptive Maximum A Posteriori (MAP) Approach , 2009, NeuroImage.

[4]  Quanzheng Li,et al.  Partial volume correction for PET quantification and its impact on brain network in Alzheimer’s disease , 2017, Scientific Reports.

[5]  Alan C. Evans,et al.  β-Amyloid is associated with aberrant metabolic connectivity in subjects with mild cognitive impairment , 2014, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[6]  John Ashburner,et al.  A fast diffeomorphic image registration algorithm , 2007, NeuroImage.

[7]  J. Petrella,et al.  The Alzheimer structural connectome: changes in cortical network topology with increased amyloid plaque burden. , 2014, Radiology.

[8]  John Seibyl,et al.  Improved longitudinal [18F]-AV45 amyloid PET by white matter reference and VOI-based partial volume effect correction , 2015, NeuroImage.

[9]  Timo Grimmer,et al.  Metabolic connectivity for differential diagnosis of dementing disorders , 2017, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[10]  Sterling C. Johnson,et al.  Associations between white matter microstructure and amyloid burden in preclinical Alzheimer's disease: A multimodal imaging investigation , 2014, NeuroImage: Clinical.

[11]  Zhuangzhi Yan,et al.  Differences in Aβ brain networks in Alzheimer's disease and healthy controls , 2017, Brain Research.

[12]  Michael Weiner,et al.  Breakdown of Brain Connectivity Between Normal Aging and Alzheimer's Disease: A Structural k-Core Network Analysis , 2013, Brain Connect..

[13]  E. Hoffman,et al.  Quantitation in Positron Emission Computed Tomography: 1. Effect of Object Size , 1979, Journal of computer assisted tomography.

[14]  B Horwitz,et al.  Intercorrelations of Glucose Metabolic Rates between Brain Regions: Application to Healthy Males in a State of Reduced Sensory Input , 1984, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[15]  John Seibyl,et al.  Partial-Volume Effect Correction Improves Quantitative Analysis of 18F-Florbetaben β-Amyloid PET Scans , 2016, The Journal of Nuclear Medicine.

[16]  Keith A. Johnson,et al.  Hippocampal hypometabolism in older adults with memory complaints and increased amyloid burden , 2017, Neurology.

[17]  Jagath C. Rajapakse,et al.  Statistical approach to segmentation of single-channel cerebral MR images , 1997, IEEE Transactions on Medical Imaging.

[18]  L. Mosconi,et al.  FDG- and amyloid-PET in Alzheimer's disease: is the whole greater than the sum of the parts? , 2011, The quarterly journal of nuclear medicine and molecular imaging : official publication of the Italian Association of Nuclear Medicine (AIMN) [and] the International Association of Radiopharmacology (IAR), [and] Section of the Society of....

[19]  J. Lorenceau,et al.  Applicability of in vivo staging of regional amyloid burden in a cognitively normal cohort with subjective memory complaints: the INSIGHT-preAD study , 2019, Alzheimer's Research & Therapy.

[20]  O. Sporns,et al.  Network hubs in the human brain , 2013, Trends in Cognitive Sciences.

[21]  Yuan Zhou,et al.  Abnormal Cortical Networks in Mild Cognitive Impairment and Alzheimer's Disease , 2010, PLoS Comput. Biol..

[22]  V Latora,et al.  Efficient behavior of small-world networks. , 2001, Physical review letters.

[23]  A. Díaz-Guilera,et al.  Efficiency of informational transfer in regular and complex networks. , 2004, Physical review. E, Statistical, nonlinear, and soft matter physics.

[24]  Fumiko Hoeft,et al.  GAT: A Graph-Theoretical Analysis Toolbox for Analyzing Between-Group Differences in Large-Scale Structural and Functional Brain Networks , 2012, PloS one.

[25]  C. Jack,et al.  NIA-AA Research Framework: Toward a biological definition of Alzheimer’s disease , 2018, Alzheimer's & Dementia.

[26]  Olaf Sporns,et al.  Complex network measures of brain connectivity: Uses and interpretations , 2010, NeuroImage.

[27]  H. Engler,et al.  Dynamic changes in PET amyloid and FDG imaging at different stages of Alzheimer's disease , 2012, Neurobiology of Aging.

[28]  O. Sporns,et al.  Complex brain networks: graph theoretical analysis of structural and functional systems , 2009, Nature Reviews Neuroscience.

[29]  Jing Li,et al.  Learning brain connectivity of Alzheimer's disease by sparse inverse covariance estimation , 2010, NeuroImage.

[30]  O Almkvist,et al.  Longitudinal changes of tau PET imaging in relation to hypometabolism in prodromal and Alzheimer’s disease dementia , 2018, Molecular Psychiatry.

[31]  J. Brandt,et al.  Regional hypometabolism in Alzheimer's disease as measured by positron emission tomography after correction for effects of partial volume averaging , 1996, Neurology.

[32]  G. Chételat,et al.  Region-Specific Hierarchy between Atrophy, Hypometabolism, and β-Amyloid (Aβ) Load in Alzheimer's Disease Dementia , 2012, The Journal of Neuroscience.

[33]  G. Alexander,et al.  Regional glucose metabolic abnormalities are not the result of atrophy in Alzheimer's disease , 1998, Neurology.

[34]  Henrik Zetterberg,et al.  Earliest accumulation of β-amyloid occurs within the default-mode network and concurrently affects brain connectivity , 2017, Nature Communications.

[35]  Keith A. Johnson,et al.  Partial volume correction in quantitative amyloid imaging , 2015, NeuroImage.

[36]  J. Whitwell,et al.  Alzheimer's disease neuroimaging , 2018, Current opinion in neurology.

[37]  Fernando Maestú,et al.  Network Disruption in the Preclinical Stages of Alzheimer's Disease: From Subjective Cognitive Decline to Mild Cognitive Impairment , 2017, Int. J. Neural Syst..

[38]  Jongbum Seo,et al.  Connectivity analysis of normal and mild cognitive impairment patients based on FDG and PiB-PET images , 2015, Neuroscience Research.

[39]  Daniel R. Schonhaut,et al.  Local and distant relationships between amyloid, tau and neurodegeneration in Alzheimer's Disease , 2017, NeuroImage: Clinical.

[40]  美晴 佐村木,et al.  Partial volume effect-corrected FDG PET and grey matter volume loss in patients with mild Alzheimer's disease , 2007 .

[41]  M. Jorge Cardoso,et al.  Atrophy Rates in Asymptomatic Amyloidosis: Implications for Alzheimer Prevention Trials , 2013, PloS one.

[42]  Z. Ding,et al.  Longitudinal Progression of Cognitive Decline Correlates with Changes in the Spatial Pattern of Brain 18F-FDG PET , 2013, The Journal of Nuclear Medicine.

[43]  D. Selkoe Alzheimer's disease. , 2011, Cold Spring Harbor perspectives in biology.

[44]  J. Morris,et al.  The Cortical Signature of Alzheimer's Disease: Regionally Specific Cortical Thinning Relates to Symptom Severity in Very Mild to Mild AD Dementia and is Detectable in Asymptomatic Amyloid-Positive Individuals , 2008, Cerebral cortex.

[45]  O. Nevalainen,et al.  Evaluation of partial volume effect correction methods for brain positron emission tomography: Quantification and reproducibility , 2007, Journal of medical physics.

[46]  Lisa A. Weissfeld,et al.  Classification of amyloid-positivity in controls: Comparison of visual read and quantitative approaches , 2013, NeuroImage.

[47]  D. Head,et al.  Amyloid Plaques Disrupt Resting State Default Mode Network Connectivity in Cognitively Normal Elderly , 2010, Biological Psychiatry.

[48]  Michael D. Greicius,et al.  Relationships between β-amyloid and functional connectivity in different components of the default mode network in aging. , 2011, Cerebral cortex.

[49]  H. Heinsen,et al.  Longitudinal measures of cholinergic forebrain atrophy in the transition from healthy aging to Alzheimer's disease , 2013, Neurobiology of Aging.

[50]  Jun-Sung Park,et al.  Whole-brain Functional Networks in Cognitively Normal, Mild Cognitive Impairment, and Alzheimer’s Disease , 2013, PloS one.

[51]  J. Sepulcre,et al.  In vivo staging of regional amyloid deposition , 2017, Neurology.

[52]  Massimo Marchiori,et al.  Economic small-world behavior in weighted networks , 2003 .

[53]  Gretel Sanabria-Diaz,et al.  Glucose Metabolism during Resting State Reveals Abnormal Brain Networks Organization in the Alzheimer’s Disease and Mild Cognitive Impairment , 2013, PloS one.

[54]  Claus Svarer,et al.  Covariance statistics and network analysis of brain PET imaging studies , 2019, Scientific Reports.

[55]  Edward T. Bullmore,et al.  Fundamentals of Brain Network Analysis , 2016 .

[56]  Gereon R. Fink,et al.  Impact of tau and amyloid burden on glucose metabolism in Alzheimer's disease , 2016, Annals of clinical and translational neurology.

[57]  H. Matsuda,et al.  Partial volume effect-corrected FDG PET and grey matter volume loss in patients with mild Alzheimer’s disease , 2007, European Journal of Nuclear Medicine and Molecular Imaging.

[58]  I. Buvat,et al.  A review of partial volume correction techniques for emission tomography and their applications in neurology, cardiology and oncology , 2012, Physics in medicine and biology.

[59]  Richard F. Betzel,et al.  Modular Brain Networks. , 2016, Annual review of psychology.

[60]  W. Jagust,et al.  Metabolic brain networks in aging and preclinical Alzheimer's disease , 2017, NeuroImage: Clinical.

[61]  Alexander Hammers,et al.  Three‐dimensional maximum probability atlas of the human brain, with particular reference to the temporal lobe , 2003, Human brain mapping.

[62]  Ralph Buchert,et al.  PETPVE12: an SPM toolbox for Partial Volume Effects correction in brain PET – Application to amyloid imaging with AV45-PET , 2017, NeuroImage.

[63]  M. Modat,et al.  The importance of appropriate partial volume correction for PET quantification in Alzheimer’s disease , 2011, European Journal of Nuclear Medicine and Molecular Imaging.

[64]  Chengjie Xiong,et al.  Quantitative Amyloid Imaging in Autosomal Dominant Alzheimer’s Disease: Results from the DIAN Study Group , 2016, PloS one.

[65]  C. Rowe,et al.  Accelerated cortical atrophy in cognitively normal elderly with high β-amyloid deposition , 2012, Neurology.

[66]  Meritxell Bach Cuadra,et al.  Comparison and validation of tissue modelization and statistical classification methods in T1-weighted MR brain images , 2005, IEEE Transactions on Medical Imaging.

[67]  Sangyun Jeong,et al.  Molecular and Cellular Basis of Neurodegeneration in Alzheimer’s Disease , 2017, Molecules and cells.

[68]  A. Simmons,et al.  Disrupted Network Topology in Patients with Stable and Progressive Mild Cognitive Impairment and Alzheimer's Disease , 2016, Cerebral cortex.

[69]  M. Mintun,et al.  Amyloid deposition, hypometabolism, and longitudinal cognitive decline , 2012, Annals of neurology.

[70]  Alan C. Evans,et al.  Fast and robust parameter estimation for statistical partial volume models in brain MRI , 2004, NeuroImage.

[71]  Y. Jeong,et al.  Glucose Metabolic Brain Networks in Early-Onset vs. Late-Onset Alzheimer's Disease , 2016, Frontiers in Aging Neuroscience.

[72]  Jorge Sepulcre,et al.  Molecular properties underlying regional vulnerability to Alzheimer’s disease pathology , 2018, Brain : a journal of neurology.

[73]  S. Teipel,et al.  Spatial patterns of atrophy, hypometabolism, and amyloid deposition in Alzheimer's disease correspond to dissociable functional brain networks , 2016, Human brain mapping.

[74]  Keith A. Johnson,et al.  Aβ Imaging: feasible, pertinent, and vital to progress in Alzheimer’s disease , 2012, European Journal of Nuclear Medicine and Molecular Imaging.

[75]  D. Perani FDG-PET and amyloid-PET imaging: the diverging paths. , 2014, Current opinion in neurology.

[76]  Yoichi Ishikawa,et al.  A comparison of five partial volume correction methods for Tau and Amyloid PET imaging with [18F]THK5351 and [11C]PIB , 2017, Annals of Nuclear Medicine.

[77]  Marine Fouquet,et al.  Sequential relationships between grey matter and white matter atrophy and brain metabolic abnormalities in early Alzheimer's disease. , 2010, Brain : a journal of neurology.

[78]  M. Kendall,et al.  The Problem of $m$ Rankings , 1939 .

[79]  E. Westman,et al.  Amyloid Network Topology Characterizes the Progression of Alzheimer’s Disease During the Predementia Stages , 2017, Cerebral cortex.