Publications
1046 results found
Hansen AK, Damholdt MF, Fedorova TD, et al., 2017, In Vivo Cortical Tau in Parkinson's Disease Using 18F-AV-1451 Positron Emission Tomography, MOVEMENT DISORDERS, Vol: 32, Pages: 921-927, ISSN: 0885-3185
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- Citations: 33
Parbo P, Ismail R, Hansen KV, et al., 2017, Brain inflammation accompanies amyloid in the majority of mild cognitive impairment cases due to Alzheimer's disease, BRAIN, Vol: 140, Pages: 2002-2011, ISSN: 0006-8950
Borghammer P, Knudsen K, Fedorova TD, et al., 2017, Imaging Parkinson's disease below the neck, NPJ PARKINSONS DISEASE, Vol: 3
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- Citations: 12
Firbank MJ, Yarnall AJ, Lawson RA, et al., 2017, Cerebral glucose metabolism and cognition in newly diagnosed Parkinson's disease: ICICLE-PD study, JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY, Vol: 88, Pages: 310-316, ISSN: 0022-3050
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- Citations: 62
Fan Z, Brooks DJ, Okello A, et al., 2017, An early and late peak in microglial activation in Alzheimer's disease trajectory, Brain, Vol: 140, Pages: 792-803, ISSN: 0006-8950
search inputSearchAn early and late peak in microglial activation in Alzheimer’s disease trajectoryZhen Fan, David J. Brooks, Aren Okello, Paul EdisonBrain, Volume 140, Issue 3, March 2017, Pages 792–803, https://doi.org/10.1093/brain/aww349Published:24 January 2017Article historyReceived:20 June 2016Revision received:31 October 2016Accepted:18 November 2016Published:24 January 2017 pdfPDF Split View Cite Permissions Icon Permissions ShareAbstractAmyloid-β deposition, neuroinflammation and tau tangle formation all play a significant role in Alzheimer’s disease. We hypothesized that there is microglial activation early on in Alzheimer’s disease trajectory, where in the initial phase, microglia may be trying to repair the damage, while later on in the disease these microglia could be ineffective and produce proinflammatory cytokines leading to progressive neuronal damage. In this longitudinal study, we have evaluated the temporal profile of microglial activation and its relationship between fibrillar amyloid load at baseline and follow-up in subjects with mild cognitive impairment, and this was compared with subjects with Alzheimer’s disease. Thirty subjects (eight mild cognitive impairment, eight Alzheimer’s disease and 14 controls) aged between 54 and 77 years underwent 11C-(R)PK11195, 11C-PIB positron emission tomography and magnetic resonance imaging scans. Patients were followed-up after 14 ± 4 months. Region of interest and Statistical Parametric Mapping analysis were used to determine longitudinal alterations. Single subject analysis was performed to evaluate the individualized pathological changes over time. Correlations between levels of microglial activation and amyloid deposition at a voxel level were assessed using Biological Parametric Mapping. We demonstrated that both baseline and follow-up microglial activation in the mild cognitive impairment cohort compared to controls were increased by 4
Buckley CJ, Sherwin PF, Smith APL, et al., 2017, Validation of an electronic image reader training programme for interpretation of [<SUP>18</SUP>F]flutemetamol β- amyloid PET brain images, NUCLEAR MEDICINE COMMUNICATIONS, Vol: 38, Pages: 234-241, ISSN: 0143-3636
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- Citations: 50
Peraza LR, Nesbitt D, Lawson RA, et al., 2017, Intra-and Inter-Network Functional Alterations in Parkinson's Disease with Mild Cognitive Impairment, HUMAN BRAIN MAPPING, Vol: 38, Pages: 1702-1715, ISSN: 1065-9471
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- Citations: 38
Fedorova TD, Seidelin LB, Knudsen K, et al., 2017, Decreased intestinal acetylcholinesterase in early Parkinson disease, NEUROLOGY, Vol: 88, Pages: 775-781, ISSN: 0028-3878
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- Citations: 60
Brooks DJ, 2017, In Vivo Cortical Tau in Parkinson’s Disease Using 18F-AV-1451 Positron Emission Tomography, Movement Disorders, ISSN: 1531-8257
Pagano G, Molloy S, Bain P, et al., 2016, Sleep problems and hypothalamic dopamine D3 receptor availability in Parkinson's disease, Neurology, Vol: 87, Pages: 2451-2456, ISSN: 0028-3878
Objective: To investigate the relationship between hypothalamic D3 dopamine receptor availability and severity of sleep problems in Parkinson disease (PD).Methods: Twelve patients were assessed with PET and the high-affinity dopamine D3 receptor radioligand [11C]-propyl-hexahydro-naphtho-oxazin ([11C]-PHNO). Severity of sleep problems was rated with appropriate subitems of the Unified Parkinson's Disease Rating Scale part I (patient questionnaire) and the Epworth Sleepiness Scale.Results: We found that lower dopamine D3 receptor availability measured with [11C]-PHNO PET was associated with greater severity of excessive daytime sleepiness but not with problems of falling asleep or insomnia.Conclusion: In our cohort of patients with PD, the occurrence of excessive daytime sleepiness was linked to reductions in hypothalamic dopamine D3 receptor availability. If these preliminary findings are confirmed in larger cohorts of patients with polysomnographic characterization, selective pharmacologic modulation of the dopaminergic D3 system could be used to increase daytime alertness in patients with PD.
Pagano G, Molloy S, Bain PG, et al., 2016, Sleep Problems and Hypothalamic Dopamine D3 Receptor Availability in Parkinson's Disease, Neurology
Leistedt B, Peiris HV, Elsner F, et al., 2016, MAPPING AND SIMULATING SYSTEMATICS DUE TO SPATIALLY VARYING OBSERVING CONDITIONS IN DES SCIENCE VERIFICATION DATA, ASTROPHYSICAL JOURNAL SUPPLEMENT SERIES, Vol: 226, ISSN: 0067-0049
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- Citations: 42
Rozo E, Rykoff ES, Abate A, et al., 2016, redMaGiC: selecting luminous red galaxies from the DES Science Verification data, MONTHLY NOTICES OF THE ROYAL ASTRONOMICAL SOCIETY, Vol: 461, Pages: 1431-1450, ISSN: 0035-8711
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- Citations: 126
Brooks DJ, 2016, Molecular imaging of dopamine transporters, AGEING RESEARCH REVIEWS, Vol: 30, Pages: 114-121, ISSN: 1568-1637
Bonnett C, Troxel MA, Hartley W, et al., 2016, Redshift distributions of galaxies in the dark energy survey science verification shear catalogue and implications for weak lensing, Physical Review D: Particles, Fields, Gravitation and Cosmology, Vol: 94, Pages: 042005 – 1-042005 – 26, ISSN: 1550-2368
We present photometric redshift estimates for galaxies used in the weak lensing analysis of the Dark Energy Survey Science Verification (DES SV) data. Four model- or machine learning-based photometric redshift methods—annz2, bpz calibrated against BCC-Ufig simulations, skynet, and tpz—are analyzed. For training, calibration, and testing of these methods, we construct a catalogue of spectroscopically confirmed galaxies matched against DES SV data. The performance of the methods is evaluated against the matched spectroscopic catalogue, focusing on metrics relevant for weak lensing analyses, with additional validation against COSMOS photo-z’s. From the galaxies in the DES SV shear catalogue, which have mean redshift 0.72±0.01 over the range 0.3<z<1.3, we construct three tomographic bins with means of z={0.45,0.67,1.00}. These bins each have systematic uncertainties δz≲0.05 in the mean of the fiducial skynet photo-z n(z). We propagate the errors in the redshift distributions through to their impact on cosmological parameters estimated with cosmic shear, and find that they cause shifts in the value of σ8 of approximately 3%. This shift is within the one sigma statistical errors on σ8 for the DES SV shear catalogue. We further study the potential impact of systematic differences on the critical surface density, Σcrit, finding levels of bias safely less than the statistical power of DES SV data. We recommend a final Gaussian prior for the photo-z bias in the mean of n(z) of width 0.05 for each of the three tomographic bins, and show that this is a sufficient bias model for the corresponding cosmology analysis.
Calsolaro V, Ashraf A, Fan Z, et al., 2016, Increased [11C](R)PK11195-PET and attenuated cerebral glucose metabolism: a common theme in neurodegenerative diseases?, Alzheimer's and Dementia, Vol: 12, Pages: P1085-P1085, ISSN: 1552-5260
Fan Z, Brooks D, Okello A, et al., 2016, An early and late peak in microglial activation in Alzheimer’s disease trajectory: a longitudinal PET study, Alzheimer's and Dementia, Vol: 12, Pages: P527-P528, ISSN: 1552-5260
Fan Z, Edison P, Atkinson R, et al., 2016, Flutriciclamide ([18F]GE180) PET: first in human PET study of novel in vivo marker of human translator protein, Alzheimer's and Dementia, Vol: 12, Pages: P397-P397, ISSN: 1552-5260
Femminella G, Dani M, Fan Z, et al., 2016, Does neuroinflammation predate amyloid formation in subjects at risk for Alzheimer’s disease?, Alzheimer's and Dementia, Vol: 12, Pages: P283-P283, ISSN: 1552-5260
Brooks DJ, 2016, Imaging of genetic and degenerative disorders primarily causing Parkinsonism., Handbook of Clinical Neurology, Vol: 135, Pages: 493-505, ISSN: 0072-9752
In this chapter the structural and functional imaging changes associated with both genetic causes of Parkinson's disease and the sporadic condition are reviewed. The role of imaging for supporting diagnosis and detecting subclinical disease is discussed and the potential use and drawbacks of using imaging biomarkers for monitoring disease progression are debated. Additionally, the use of imaging for differentiating atypical parkinsonian syndromes from Parkinson's disease is presented.
Becker MR, Troxel MA, MacCrann N, et al., 2016, Cosmic shear measurements with Dark Energy Survey Science Verification data, Physical Review D: Particles, Fields, Gravitation and Cosmology, Vol: 94, Pages: 022002 – 1-022002 – 24, ISSN: 1550-2368
We present measurements of weak gravitational lensing cosmic shear two-point statistics using Dark Energy Survey Science Verification data. We demonstrate that our results are robust to the choice of shear measurement pipeline, either ngmix or im3shape, and robust to the choice of two-point statistic, including both real and Fourier-space statistics. Our results pass a suite of null tests including tests for B-mode contamination and direct tests for any dependence of the two-point functions on a set of 16 observing conditions and galaxy properties, such as seeing, airmass, galaxy color, galaxy magnitude, etc. We furthermore use a large suite of simulations to compute the covariance matrix of the cosmic shear measurements and assign statistical significance to our null tests. We find that our covariance matrix is consistent with the halo model prediction, indicating that it has the appropriate level of halo sample variance. We compare the same jackknife procedure applied to the data and the simulations in order to search for additional sources of noise not captured by the simulations. We find no statistically significant extra sources of noise in the data. The overall detection significance with tomography for our highest source density catalog is 9.7σ. Cosmological constraints from the measurements in this work are presented in a companion paper [DES et al., Phys. Rev. D 94, 022001 (2016).].
Abbott T, Abdalla FB, Allam S, et al., 2016, Cosmology from cosmic shear with Dark Energy Survey Science Verification data, Physical Review D: Particles, Fields, Gravitation and Cosmology, Vol: 94, Pages: 022001 – 1-022001 – 22, ISSN: 1550-2368
We present the first constraints on cosmology from the Dark Energy Survey (DES), using weak lensing measurements from the preliminary Science Verification (SV) data. We use 139 square degrees of SV data, which is less than 3% of the full DES survey area. Using cosmic shear 2-point measurements over three redshift bins we find σ8(Ωm/0.3)0.5=0.81±0.06 (68% confidence), after marginalizing over 7 systematics parameters and 3 other cosmological parameters. We examine the robustness of our results to the choice of data vector and systematics assumed, and find them to be stable. About 20% of our error bar comes from marginalizing over shear and photometric redshift calibration uncertainties. The current state-of-the-art cosmic shear measurements from CFHTLenS are mildly discrepant with the cosmological constraints from Planck CMB data; our results are consistent with both data sets. Our uncertainties are ∼30% larger than those from CFHTLenS when we carry out a comparable analysis of the two data sets, which we attribute largely to the lower number density of our shear catalogue. We investigate constraints on dark energy and find that, with this small fraction of the full survey, the DES SV constraints make negligible impact on the Planck constraints. The moderate disagreement between the CFHTLenS and Planck values of σ8(Ωm/0.3)0.5 is present regardless of the value of w.
Lou HC, Rosenstand A, Brooks DJ, et al., 2016, Exogenous dopamine reduces GABA receptor availability in the human brain, BRAIN AND BEHAVIOR, Vol: 6, ISSN: 2162-3279
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- Citations: 8
Feeney C, Scott G, Raffel J, et al., 2016, Kinetic analysis of the translocator protein positron emission tomography ligand [18F]GE-180 in the human brain, European Journal of Nuclear Medicine and Molecular Imaging, Vol: 43, Pages: 2201-2210, ISSN: 1619-7089
PURPOSE: PET can image neuroinflammation by targeting the translocator protein (TSPO), which is upregulated in activated microglia. The high nonspecific binding of the first-generation TSPO radioligand [(11)C]PK-11195 limits accurate quantification. [(18)F]GE-180, a novel TSPO ligand, displays superior binding to [(11)C]PK-11195 in vitro. Our objectives were to: (1) evaluate tracer characteristics of [(18)F]GE-180 in the brains of healthy human subjects; and (2) investigate whether the TSPO Ala147Thr polymorphism influences outcome measures. METHODS: Ten volunteers (five high-affinity binders, HABs, and five mixed-affinity binders, MABs) underwent a dynamic PET scan with arterial sampling after injection of [(18)F]GE-180. Kinetic modelling of time-activity curves with one-tissue and two-tissue compartment models and Logan graphical analysis was applied to the data. The primary outcome measure was the total volume of distribution (V T) across various regions of interest (ROIs). Secondary outcome measures were the standardized uptake values (SUV), the distribution volume and SUV ratios estimated using a pseudoreference region. RESULTS: The two-tissue compartment model was the best model. The average regional delivery rate constant (K 1) was 0.01 mL cm(-3) min(-1) indicating low extraction across the blood-brain barrier (1 %). The estimated median V T across all ROIs was also low, ranging from 0.16 mL cm(-3) in the striatum to 0.38 mL cm(-3) in the thalamus. There were no significant differences in V T between HABs and MABs across all ROIs. CONCLUSION: A reversible two-tissue compartment model fitted the data well and determined that the tracer has a low first-pass extraction (approximately 1 %) and low V T estimates in healthy individuals. There was no observable dependency on the rs6971 polymorphism as compared to other second-generation TSPO PET tracers. Investigation of [(18)F]GE-180 in populations with neuroinflammatory disease is nee
Fan Z, Calsolaro V, Atkinson R, et al., 2016, Flutriciclamide (18F-GE180) PET: first in human PET study of novel 3rd generation in vivo marker of human translator protein., Journal of Nuclear Medicine, Vol: 57, Pages: 1753-1759, ISSN: 1535-5667
Neuroinflammation is associated with neurodegenerative disease. PET (positron emission tomography) radioligands targeting the 18 kDa translocator protein (TSPO) has been used as in vivo markers of neuroinflammation, but there is an urgent need for novel probes with improved signal-to-noise ratio. Flutriciclamide ((18)F-GE180) is a recently developed third generation TSPO ligand. In this first study, we evaluated the optimum scan duration and kinetic modelling strategies for (18)F-GE180 PET in (older) healthy controls (HC). METHODS: Ten HC, six TSPO high affinity binders (HABs) and four mixed affinity binders (MABs), were recruited. All subjects had detailed neuropsychological tests, MRI and a 210 min (18)F-GE180 dynamic PET/CT scan using metabolite corrected arterial plasma input function. We evaluated five different kinetic models: irreversible and reversible two-tissue compartment models, a reversible one-tissue model and two models with an extra irreversible vascular compartment. The optimum scan length was investigated based on 210 min scan data. The feasibility of generating parametric maps was also investigated using graphical analysis. RESULTS: (18)F-GE180 concentration was higher in plasma than in whole blood during the entire scan duration. Using the kinetic model, the volume of distribution (VT) was 0.17 in HABs and 0.12 in MABs. The model that best represented brain (18)F-GE180 kinetics across regions was the reversible two-tissue compartment model (2TCM4k) and 90 min resulted as the optimum scan length required to obtain stable estimates. Logan graphical analysis with arterial input function gave a VT highly consistent with VT in kinetic model, which could be used for voxel-wise analysis. CONCLUSION: We report for the first time the kinetic properties of the novel third generation TSPO PET ligand, (18)F-GE180, in humans: 2TCM4k is the optimal method to quantify the brain uptake, 90 min is the optimal scan length and Logan approach could be used to genera
Hansen AK, Knudsen K, Lillethorup TP, et al., 2016, In vivo imaging of neuromelanin in Parkinson's disease using 18F-AV-1451 PET., Brain, Vol: 139, Pages: 2039-2049, ISSN: 1460-2156
The tau tangle ligand (18)F-AV-1451 ((18)F-T807) binds to neuromelanin in the midbrain, and may therefore be a measure of the pigmented dopaminergic neuronal count in the substantia nigra. Parkinson's disease is characterized by progressive loss of dopaminergic neurons. Extrapolation of post-mortem data predicts that a ∼30% decline of nigral dopamine neurons is necessary to cause motor symptoms in Parkinson's disease. Putamen dopamine terminal loss at disease onset most likely exceeds that of the nigral cell bodies and has been estimated to be of the order of 50-70%. We investigated the utility of (18)F-AV-1451 positron emission tomography to visualize the concentration of nigral neuromelanin in Parkinson's disease and correlated the findings to dopamine transporter density, measured by (123)I-FP-CIT single photon emission computed tomography. A total of 17 patients with idiopathic Parkinson's disease and 16 age- and sex-matched control subjects had (18)F-AV-1451 positron emission tomography using a Siemens high-resolution research tomograph. Twelve patients with Parkinson's disease also received a standardized (123)I-FP-CIT single photon emission computed tomography scan at our imaging facility. Many of the patients with Parkinson's disease displayed visually apparent decreased (18)F-AV-1451 signal in the midbrain. On quantitation, patients showed a 30% mean decrease in total nigral (18)F-AV-1451 volume of distribution compared with controls (P = 0.004), but there was an overlap of the individual ranges. We saw no significant correlation between symptom dominant side and contralateral nigral volume of distribution. There was no correlation between nigral (18)F-AV-1451 volume of distribution and age or time since diagnosis. In the subset of 12 patients, who also had a (123)I-FP-CIT scan, the mean total striatal dopamine transporter signal was decreased by 45% and the mean total (18)F-AV-1451 substantia nigra volume of distribution was decreased by 33% after medi
Femminella GD, Ninan S, Atkinson R, et al., 2016, Does Microglial Activation Influence Hippocampal Volume and Neuronal Function in Alzheimer's Disease and Parkinson's Disease Dementia?, Journal of Alzheimers Disease, Vol: 51, Pages: 1275-1289, ISSN: 1875-8908
Background:The influence of neuroinflammation on neuronal function and hippocampal atrophy in Alzheimer’s disease (AD) and Parkinson’s disease dementia (PDD) is still unclear.Objectives:Here we investigated whether microglial activation measured by [11C]PK11195 PET is associated with neuronal function measured by cerebral glucose metabolic rate (rCMRGlc) using FDG-PET and hippocampal volume measurements.Methods:We enrolled 25 subjects (9 PDD, 8 AD, and 8 controls) who underwent PET scans with [11C](R)PK11195, [18F]FDG, and volumetric MRI scanning.Results:SPM correlation analysis in AD and PDD showed a negative correlation between hippocampal volume and microglial activation within hippocampus or parahippocampus and with cortical and subcortical areas of projections from hippocampus, while there was a positive correlation between rCMRGlc in cortical and subcortical areas of projections from hippocampus and hippocampal volume. Hippocampal volume was significantly reduced in AD compared to controls but not in PDD.Conclusions:These findings indicate that microglial activation inversely correlated with hippocampal volume and hippocampal rCMRGlc in neurodegenerative diseases with dementia, providing further evidence for the central role of microglial activation in neurodegenerative diseases.
Borghammer P, Knudsen K, Brooks DJ, 2016, Imaging Systemic Dysfunction in Parkinson’s Disease, Current Neurology and Neuroscience Reports, Vol: 16, ISSN: 1534-6293
Breen DP, Nombela C, Vuono R, et al., 2016, Hypothalamic volume loss is associated with reduced melatonin output in Parkinson's disease, Movement Disorders, Vol: 31, Pages: 1062-1066, ISSN: 1531-8257
BACKGROUND: Recent studies have suggested that melatonin-a hormone produced by the pineal gland under circadian control-contributes to PD-related sleep dysfunction. We hypothesized that degenerative changes to the neural structures controlling pineal function (especially the suprachiasmatic nuclei of the anterior hypothalamus) may be responsible for reduced melatonin output in these patients. We compared hypothalamic volumes in PD patients with matched controls and determined whether volume loss correlated with reduced melatonin output in the PD group. METHODS: A total of 12 PD patients and 12 matched controls underwent magnetic resonance imaging to determine hypothalamic volume. In addition, PD patients underwent 24-hour blood sampling in a controlled environment to determine serum melatonin concentrations using enzyme-linked immunosorbent assays. RESULTS: PD patients had significantly reduced hypothalamic gray matter volume when compared with matched controls. Melatonin levels were significantly associated with hypothalamic gray matter volume and disease severity in PD patients. CONCLUSION: Melatonin levels are associated with hypothalamic gray matter volume loss and disease severity in PD patients. This provides anatomical and physiological support for an intrinsic sleep and circadian phenotype in PD. © 2016 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.
Scott GPT, Ramlackhansingh A, Edison P, et al., 2016, Amyloid pathology and axonal injury after brain trauma, Neurology, Vol: 86, Pages: 821-828, ISSN: 0028-3878
Objective: To image amyloid-β (Aβ) plaque burden in long-term survivors of traumatic brain injury (TBI), test whether traumatic axonal injury and Aβ are correlated, and compare the spatial distribution of Aβ to Alzheimer’s disease.Methods: Patients 11 months to 17 years after moderate-severe TBI had 11C-Pittsburgh compound-B (PIB) PET, structural and diffusion MRI and neuropsychological examination. Healthy aged controls and AD patients had PET and structural MRI. Binding potential (BPND) images of 11C-PIB, which index Aβ plaque density, were computed using an automatic reference region extraction procedure. Voxelwise and regional differences in BPND were assessed. In TBI, a measure of white matter integrity, fractional anisotropy (FA), was estimated and correlated with 11C-PIB BPND.Results: 28 participants (9 TBI, 9 controls, 10 AD) were assessed. Increased 11C-PIB BPND was found in TBI versus controls in the posterior cingulate cortex (PCC) and cerebellum. Binding in the PCC increased with decreasing FA of associated white matter tracts, and increased with time since injury. Compared to AD, binding after TBI was lower in neocortical regions, but increased in the cerebellum. Conclusions: Increased Aβ burden was observed in TBI. The distribution overlaps with, but is distinct from, that of AD. This suggests a mechanistic link between TBI and the development of neuropathological features of dementia, which may relate to axonal damage produced by the injury.
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