| 1. |
- Alvén, Jennifer, 1989, et al.
(author)
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A Deep Learning Approach to MR-less Spatial Normalization for Tau PET Images
- 2019
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In: Medical Image Computing and Computer Assisted Intervention : MICCAI 2019 - 22nd International Conference, Proceedings - MICCAI 2019 - 22nd International Conference, Proceedings. - Cham : Springer International Publishing. - 1611-3349 .- 0302-9743. - 9783030322458 - 9783030322441 ; 11765 LNCS, s. 355-363
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Conference paper (peer-reviewed)abstract
- The procedure of aligning a positron emission tomography (PET) image with a common coordinate system, spatial normalization, typically demands a corresponding structural magnetic resonance (MR) image. However, MR imaging is not always available or feasible for the subject, which calls for enabling spatial normalization without MR, MR-less spatial normalization. In this work, we propose a template-free approach to MR-less spatial normalization for [18F]flortaucipir tau PET images. We use a deep neural network that estimates an aligning transformation from the PET input image, and outputs the spatially normalized image as well as the parameterized transformation. In order to do so, the proposed network iteratively estimates a set of rigid and affine transformations by means of convolutional neural network regressors as well as spatial transformer layers. The network is trained and validated on 199 tau PET volumes with corresponding ground truth transformations, and tested on two different datasets. The proposed method shows competitive performance in terms of registration accuracy as well as speed, and compares favourably to previously published results.
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| 2. |
- Appel, Lieuwe, et al.
(author)
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BL-1020, a novel antipsychotic candidate with GABA-enhancing effects : D2 receptor occupancy study in humans
- 2009
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In: European Neuropsychopharmacology. - : Elsevier BV. - 0924-977X .- 1873-7862. ; 19:12, s. 841-850
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Journal article (peer-reviewed)abstract
- BL-1020 is a potentially novel antipsychotic, which comprises the typical antipsychotic perphenazine linked by an ester bound to gamma-aminobutyric acid (GABA), intending a simultaneous dopamine-2 (D(2)) receptor blockade and GABA facilitation in the brain. This positron emission tomography (PET) study, using [(11)C]raclopride, assessed the extent and duration of D(2) receptor occupancy (D(2) RO) and safety for single doses of BL-1020 in healthy male subjects. Overall, this study did not raise any safety concern. Single doses of 16-32 mg BL-1020 caused a dose dependent striatal D(2) RO. The 32 mg dose of BL-1020 resulted in an average D(2) RO of 44% at 4-6 h post dosing (pd), which declined to 33% at 24 h pd. Equimolar doses of BL-1020 and perphenazine resulted in similar D(2) RO at 24 h pd. Pharmacokinetic-pharmacodynamic analysis predicted that oral once daily administration of 32 mg BL-1020 would result in D(2) ROs ranging from 52 to 66% at a steady state.
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| 3. |
- Ashton, Nicholas J., et al.
(author)
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Update on biomarkers for amyloid pathology in Alzheimer's disease
- 2018
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In: Biomarkers in Medicine. - : Future Medicine Ltd. - 1752-0363 .- 1752-0371. ; 12:7, s. 799-812
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Research review (peer-reviewed)abstract
- At the center of Alzheimer's disease pathogenesis is the aberrant aggregation of amyloid-β (Aβ) into oligomers, fibrils and plaques. Effective monitoring of Aβ deposition directly in patients is essential to assist anti-Aβ therapeutics in target engagement and participant selection. In the advent of approved anti-Aβ therapeutics, biomarkers will become of fundamental importance in initiating treatments having disease modifying effects at the earliest stage. Two well-established Aβ biomarkers are widely utilized: Aβ-binding ligands for positron emission tomography and immunoassays to measure Aβ42 in cerebrospinal fluid. In this review, we will discuss the current clinical, diagnostic and research state of biomarkers for Aβ pathology. Furthermore, we will explore the current application of blood-based markers to assess Aβ pathology.
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| 4. |
- Boersma, Greta J., et al.
(author)
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Altered Glucose Uptake in Muscle, Visceral Adipose Tissue, and Brain Predict Whole-Body Insulin Resistance and may Contribute to the Development of Type 2 Diabetes: A Combined PET/MR Study
- 2018
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In: Hormone and Metabolic Research. - : Georg Thieme Verlag KG. - 0018-5043 .- 1439-4286. ; 50:8
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Journal article (peer-reviewed)abstract
- We assessed glucose uptake in different tissues in type 2 diabetes (T2D), prediabetes, and control subjects to elucidate its impact in the development of whole-body insulin resistance and T2D. Thirteen T2D, 12 prediabetes, and 10 control subjects, matched for age and BMI, underwent OGTT and abdominal subcutaneous adipose tissue (SAT) biopsies. Integrated whole-body 18F-FDG PET and MRI were performed during a hyperinsulinemic euglycemic clamp to asses glucose uptake rate (MRglu) in several tissues. MRglu in skeletal muscle, SAT, visceral adipose tissue (VAT), and liver was significantly reduced in T2D subjects and correlated positively with M-values (r = 0.884, r = 0.574, r = 0.707 and r = 0.403, respectively). Brain MRglu was significantly higher in T2D and prediabetes subjects and had a significant inverse correlation with M-values (r = -0.616). Myocardial MRglu did not differ between groups and did not correlate with the M-values. A multivariate model including skeletal muscle, brain and VAT MRglu best predicted the M-values (adjusted r2 = 0.85). In addition, SAT MRglu correlated with SAT glucose uptake ex vivo (r = 0.491). In different stages of the development of T2D, glucose uptake during hyperinsulinemia is elevated in the brain in parallel with an impairment in peripheral organs. Impaired glucose uptake in skeletal muscle and VAT together with elevated glucose uptake in brain were independently associated with whole-body insulin resistance, and these tissue-specific alterations may contribute to T2D development.
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| 5. |
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| 6. |
- Furmark, Tomas, et al.
(author)
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Serotonin synthesis rate and the tryptophan hydroxylase-2: G-703T polymorphism in social anxiety disorder
- 2016
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In: Journal of Psychopharmacology. - London, United Kingdom : SAGE Publications. - 0269-8811 .- 1461-7285. ; 30:10, s. 1028-1035
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Journal article (peer-reviewed)abstract
- It is disputed whether anxiety disorders, like social anxiety disorder, are characterized by serotonin over- or underactivity. Here, we evaluated whether our recent finding of elevated neural serotonin synthesis rate in patients with social anxiety disorder could be reproduced in a separate cohort, and whether allelic variation in the tryptophan hydroxylase-2 (TPH2) G-703T polymorphism relates to differences in serotonin synthesis assessed with positron emission tomography. Eighteen social anxiety disorder patients and six healthy controls were scanned during 60 minutes in a resting state using positron emission tomography and 5-hydroxy-L-[ -C-11]tryptophan, [C-11]5-HTP, a substrate of the second enzymatic step in serotonin synthesis. Parametric images were generated, using the reference Patlak method, and analysed using Statistical Parametric Mapping (SPM8). Blood samples for genotyping of the TPH2 G-703T polymorphism were obtained from 16 social anxiety disorder patients (T carriers: n=5, GG carriers: n=11). A significantly elevated [C-11]5-HTP accumulation rate, indicative of enhanced decarboxylase activity and thereby serotonin synthesis capacity, was detected in social anxiety disorder patients compared with controls in the hippocampus and basal ganglia nuclei and, at a more lenient (uncorrected) statistical threshold, in the amygdala and anterior cingulate cortex. In patients, the serotonin synthesis rate in the amygdala and anterior cingulate cortex was significantly elevated in TPH2 T carriers in comparison with GG homozygotes. Our results support that social anxiety disorder entails an overactive presynaptic serotonergic system that, in turn, seems functionally influenced by the TPH2 G-703T polymorphism in emotionally relevant brain regions.
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| 7. |
- Heeman, F., et al.
(author)
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Optimized dual-time-window protocols for quantitative F-18 flutemetamol and F-18 florbetaben PET studies
- 2019
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In: Ejnmmi Research. - : Springer Science and Business Media LLC. - 2191-219X. ; 9
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Journal article (peer-reviewed)abstract
- BackgroundA long dynamic scanning protocol may be required to accurately measure longitudinal changes in amyloid load. However, such a protocol results in a lower patient comfort and scanning efficiency compared to static scans. A compromise can be achieved by implementing dual-time-window protocols. This study aimed to optimize these protocols for quantitative [F-18]flutemetamol and [F-18]florbetaben studies.MethodsRate constants for subjects across the Alzheimer's disease spectrum (i.e., non-displaceable binding potential (BPND) in the range 0.02-0.77 and 0.02-1.04 for [F-18]flutemetamol and [F-18]florbetaben, respectively) were established based on clinical [F-18]flutemetamol (N=6) and [F-18]florbetaben (N=20) data, and used to simulate tissue time-activity curves (TACs) of 110min using a reference tissue and plasma input model. Next, noise was added (N=50) and data points corresponding to different intervals were removed from the TACs, ranging from 0 (i.e., 90-90=full-kinetic curve) to 80 (i.e., 10-90) minutes, creating a dual-time-window. Resulting TACs were fitted using the simplified reference tissue method (SRTM) to estimate the BPND, outliers (1.5xBP(ND) max) were removed and the bias was assessed using the distribution volume ratio (DVR=BPND+1). To this end, acceptability curves, which display the fraction of data below a certain bias threshold, were generated and the area under those curves were calculated.Results[F-18]Flutemetamol and [F-18]florbetaben data demonstrated an increased bias in amyloid estimate for larger intervals and higher noise levels. An acceptable bias (3.1%) in DVR could be obtained with all except the 10-90 and 20-90-min intervals. Furthermore, a reduced fraction of acceptable data and most outliers were present for these two largest intervals (maximum percentage outliers 48 and 32 for [F-18]flutemetamol and [F-18]florbetaben, respectively).ConclusionsThe length of the interval inversely correlates with the accuracy of the BPND estimates. Consequently, a dual-time-window protocol of 0-30 and 90-110min (=maximum of 60min interval) allows for accurate estimation of BPND values for both tracers.[F-18]flutemetamol: EudraCT 2007-000784-19, registered 8 February 2007, [F-18]florbetaben: EudraCT 2006-003882-15, registered 2006.
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| 8. |
- Heurling, Kerstin, 1982-
(author)
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Characterization of [18F]flutemetamol binding properties : A β-amyloid PET imaging ligand
- 2015
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Doctoral thesis (other academic/artistic)abstract
- The criteria for diagnosing Alzheimer’s disease (AD) have recently been revised to include the use of biomarkers for the in vivo presence of β-amyloid, one of the neuropathological hallmarks of AD. Examples of such biomarkers are positron emission tomography (PET) β-amyloid specific ligands, including [18F]flutemetamol. The aim of this thesis was to characterize the binding properties of [18F]flutemetamol from a tracer kinetic perspective as well as by validating binding measures through comparison with tissue pathology assessments. The applicability of previously developed kinetic models of tracer binding for voxel-based analysis was examined and compared to arterial input compartment modelling, the “gold standard” for PET quantification. Several voxel-based methods were found to exhibit high correlations with compartment modelling, including the semi-quantitative standardized uptake value ratio (SUVR). The kinetic components of [18F]flutemetamol uptake were also investigated without model assumptions using the data driven method spectral analysis, with binding to β-amyloid shown to relate to a slow kinetic component. The same component was also found to predominate in the uptake of white matter, known to be free of β-amyloid accumulation. White matter uptake was however possible to separate from β-amyloid binding based on the relative contribution of the slow component to the total volume of distribution. Uptake of [18F]flutemetamol as quantified using SUVR or assessed visually was found to correlate well with tissue pathology assessments. Classifying the brains of 68 deceased subjects who had undergone [18F]flutemetamol PET scanning ante mortem, based on the spatial distribution of β-amyloid according to pre-defined phases, revealed that abnormal uptake patterns of [18F]flutemetamol were only certain to be found in the last phase of β-amyloid accumulation. In the same cohort however, [18F]flutemetamol was also shown to accurately distinguish between subjects with AD and non-AD dementia. While this supports the use of [18F]flutemetamol in clinical settings for ruling out AD, the association of abnormal [18F]flutemetamol uptake to late phases of β-amyloid accumulation may limit the detection of early accumulation and pre-clinical stages of AD. It remains to be investigated whether application of voxel-based methods and slow component filtering may increase sensitivity, particularly in the context of clinical trials.
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| 9. |
- Heurling, Kerstin, et al.
(author)
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Disturbances in brain energy metabolism in insulin resistance and diabetes and Alzheimer's disease — Learnings from brain imaging biomarkers
- 2020
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In: International Review of Neurobiology. - : Elsevier. - 0074-7742. ; 154, s. 111-130
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Research review (peer-reviewed)abstract
- Medical imaging techniques, such as structural and functional magnetic resonance imaging and positron emission tomography, have been used to gain a better understanding of the alterations of the metabolic processes in the brain relating to type 2 diabetes melltius, insulin resistance and Alzheimer's disease. These studies have shown that there are several similarities in the effects that these seemingly disparate diseases have on the brain, and that some of the abnormalities are reversed by metabolic interventions. This review provides an overview of the overlap between these diseases using medical imaging, focusing on glucose metabolism, mitochondrial function and lipid metabolism.
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| 10. |
- Heurling, Kerstin, et al.
(author)
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Imaging β-amyloid using [(18)F]flutemetamol positron emission tomography : from dosimetry to clinical diagnosis
- 2016
-
In: European Journal of Nuclear Medicine and Molecular Imaging. - : Springer Science and Business Media LLC. - 1619-7070 .- 1619-7089. ; 43:2, s. 362-373
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Research review (peer-reviewed)abstract
- In Alzheimer's disease (AD), the deposition of β-amyloid (Aβ) is hypothesized to result in a series of secondary neurodegenerative processes, leading ultimately to synaptic dysfunction and neuronal loss. Since the advent of the first Aβ-specific positron emission tomography (PET) ligand, (11)C-Pittsburgh compound B ([(11)C]PIB), several (18)F ligands have been developed that circumvent the limitations of [(11)C]PIB tied to its short half-life. To date, three such compounds have been approved for clinical use by the US and European regulatory bodies, including [(18)F]AV-45 ([(18)F]florbetapir; Amyvid™), [(18)F]-BAY94-9172 ([(18)F]florbetaben; Neuraceq™) and [(18)F]3'-F-PIB ([(18)F]flutemetamol; Vizamyl™). The present review aims to summarize and discuss the currently available knowledge on [(18)F]flutemetamol PET. As the (18)F analogue of [(11)C]PIB, [(18)F]flutemetamol may be of use in the differentiation of AD from related neurodegenerative disorders and may help with subject selection and measurement of target engagement in the context of clinical trials testing anti-amyloid therapeutics. We will also discuss its potential use in non-AD amyloidopathies.
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| 11. |
- Heurling, Kerstin, 1982-, et al.
(author)
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Parametric imaging and quantitative analysis of the PET amyloid ligand [(18)F]flutemetamol.
- 2015
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In: NeuroImage. - : Elsevier BV. - 1053-8119 .- 1095-9572. ; 121, s. 184-192
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Journal article (peer-reviewed)abstract
- OBJECTIVES: The amyloid imaging PET tracer [(18)F]flutemetamol was recently approved by regulatory authorities in the US and EU for estimation of β-amyloid neuritic plaque density in cognitively impaired patients. While the clinical assessment in line with the label is a qualitative visual assessment of 20min summation images, the aim of this work was to assess the performance of various parametric analysis methods and standardized uptake value ratio (SUVR), in comparison with arterial input based compartment modeling.METHODS: The cerebellar cortex was used as reference region in the generation of parametric images of binding potential (BPND) using multilinear reference tissue methods (MRTMo, MRTM, MRTM2), basis function implementations of the simplified reference tissue model (here called RPM) and the two-parameter version of SRTM (here called RPM2) and reference region based Logan graphical analysis. Regionally averaged values of parametric results were compared with the BPND of corresponding regions from arterial input compartment modeling. Dynamic PET data were also pre-filtered using a 3D Gaussian smoothing of 5mm FWHM and the effect of the filtering on the correlation was investigated. In addition, the use of SUVR images was evaluated. The accuracy of several kinetic models were also assessed through simulations of time-activity curves based on clinical data for low and high binding adding different levels of statistical noise representing regions and individual voxels.RESULTS: The highest correlation was observed for pre-filtered reference Logan, with correction for individual reference region efflux rate constant k2' (R(2)=0.98), or using a cohort mean k2' (R(2)=0.97). Pre-processing filtered MRTM2, unfiltered SUVR over the scanning window 70-90min and unfiltered RPM also demonstrated high correlations with arterial input compartment modeling (MRTM2 R(2)=0.97, RPM R(2)=0.96 and SUVR R(2)=0.95) Poorest agreement was seen with MRTM without pre-filtering (R(2)=0.68).CONCLUSIONS: Parametric imaging allows for quantification without introducing bias due to selection of anatomical regions, and thus enables objective statistical voxel-based comparisons of tracer binding. Several parametric modeling approaches perform well, especially after Gaussian pre-filtering of the dynamic data. However, the semi-quantitative use of SUVR between 70 and 90min has comparable agreement with full kinetic modeling, thus supporting its use as a simplified method for quantitative assessment of tracer uptake.
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| 12. |
- Heurling, Kerstin, et al.
(author)
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Quantitative positron emission tomography in brain research
- 2017
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In: Brain Research. - : Elsevier BV. - 0006-8993 .- 1872-6240. ; 1670, s. 220-234
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Journal article (peer-reviewed)abstract
- The application of positron emission tomography (PET) in brain research has increased substantially during the past 20 years, and is still growing. PET provides a unique insight into physiological and pathological processes in vivo. In this article we introduce the fundamentals of PET, and the methods available for acquiring quantitative estimates of the parameters of interest. A short introduction to different areas of application is also given, including basic research of brain function and in neurology, psychiatry, drug receptor occupancy studies, and its application in diagnostics of neurodegenerative disorders such as Alzheimer's disease and Parkinson's disease. Our aim is to inform the unfamiliar reader of the underlying basics and potential applications of PET, hoping to inspire the reader into considering how the technique could be of benefit for his or her own research. (C) 2017 Elsevier B.V. All rights reserved.
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| 13. |
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| 14. |
- Heurling, Kerstin, et al.
(author)
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Regional times to equilibria and their impact on semi-quantification of [18F]AV-1451 uptake
- 2019
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In: Journal of Cerebral Blood Flow and Metabolism. - 0271-678X .- 1559-7016. ; 39:11, s. 2223-2232
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Journal article (peer-reviewed)abstract
- The semi-quantitative estimate standardised uptake value ratios (SUVR) correlate well with specific binding of the tracer expressed as distribution volume ratios (DVR) for the tau positron emission tomography tracer [18F]AV-1451 uptake and are therefore widely used as proxy for tracer binding. With regard to tracer kinetic modelling, there exists a time point when SUVR deviates minimally from DVR, occurring when the specific binding reaches a transient equilibrium. Here, we have investigated whether the time to equilibrium affects the agreement between SUVR and DVR across different brain regions. We show that the time required to reach equilibrium differs across brain regions, resulting in region-specific biases. However, even though the 80–100 min post-injection time window did not show the smallest bias numerically, the disagreement between SUVR and DVR varied least between regions during this time. In conclusion, our findings suggest a regional component to the bias of SUVR related to the time to transient equilibrium of the specific binding. [18F]AV-1451 uptake should consequently be interpreted with some caution when compared across brain regions using this method of quantification. The commonly used time window 80–100 min post-injection shows the most consistent bias across regions and is recommended for semi-quantification of [18F]AV-1451.
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| 15. |
- Heurling, Kerstin, et al.
(author)
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Separation of β-amyloid binding and white matter uptake of (18)F-flutemetamol using spectral analysis.
- 2015
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In: American journal of nuclear medicine and molecular imaging. - 2160-8407. ; 5:5
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Journal article (peer-reviewed)abstract
- The kinetic components of the β-amyloid ligand (18)F-flutemetamol binding in grey and white matter were investigated through spectral analysis, and a method developed for creation of parametric images separating grey and white matter uptake. Tracer uptake in grey and white matter and cerebellar cortex was analyzed through spectral analysis in six subjects, with (n=4) or without (n=2) apparent β-amyloid deposition, having undergone dynamic (18)F-flutemetamol scanning with arterial blood sampling. The spectra were divided into three components: slow, intermediate and fast basis function rates. The contribution of each of the components to total volume of distribution (VT) was assessed for different tissue types. The slow component dominated in white matter (average 90%), had a higher contribution to grey matter VT in subjects with β-amyloid deposition (average 44%) than without (average 6%) and was absent in cerebellar cortex, attributing the slow component of (18)F-flutemetamol uptake in grey matter to β-amyloid binding. Parametric images of voxel-based spectral analysis were created for VT, the slow component and images segmented based on the slow component contribution; confirming that grey matter and white matter uptake can be discriminated on voxel-level using a threshold for the contribution from the slow component to VT.
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| 16. |
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| 17. |
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| 18. |
- Heurling, Kerstin, et al.
(author)
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Synaptic vesicle protein 2A as a potential biomarker in synaptopathies
- 2019
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In: Molecular and Cellular Neuroscience. - : Elsevier. - 1044-7431 .- 1095-9327. ; 97, s. 34-42
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Journal article (peer-reviewed)abstract
- Measuring synaptic density in vivo using positron emission tomography (PET) imaging-based biomarkers targeting the synaptic vesicle protein 2A (SV2A) has received much attention recently due to its potential research and clinical applications in synaptopathies, including neurodegenerative and psychiatric diseases. Fluid-based biomarkers in proteinopathies have previously been suggested to provide information on pathology and disease status that is complementary to PET-based measures, and the same can be hypothesized with respect to SV2A. This review provides an overview of the current state of SV2A PET imaging as a biomarker of synaptic density, the potential role of fluid-based biomarkers for SV2A, and related future perspectives.
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| 19. |
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| 20. |
- Ikonomovic, Milos D, et al.
(author)
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Post-mortem histopathology underlying β-amyloid PET imaging following flutemetamol F 18 injection
- 2016
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In: Acta neuropathologica communications. - : Springer Science and Business Media LLC. - 2051-5960. ; 4
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Journal article (peer-reviewed)abstract
- In vivo imaging of fibrillar β-amyloid deposits may assist clinical diagnosis of Alzheimer's disease (AD), aid treatment selection for patients, assist clinical trials of therapeutic drugs through subject selection, and be used as an outcome measure. A recent phase III trial of [(18)F]flutemetamol positron emission tomography (PET) imaging in 106 end-of-life subjects demonstrated the ability to identify fibrillar β-amyloid by comparing in vivo PET to post-mortem histopathology. Post-mortem analyses demonstrated a broad and continuous spectrum of β-amyloid pathology in AD and other dementing and non-dementing disease groups. The GE067-026 trial demonstrated 91% sensitivity and 90% specificity of [(18)F]flutemetamol PET by majority read for the presence of moderate or frequent plaques. The probability of an abnormal [(18)F]flutemetamol scan increased with neocortical plaque density and AD diagnosis. All dementia cases with non-AD neurodegenerative diseases and those without histopathological features of β-amyloid deposits were [(18)F]flutemetamol negative. Majority PET assessments accurately reflected the amyloid plaque burden in 90% of cases. However, ten cases demonstrated a mismatch between PET image interpretations and post-mortem findings. Although tracer retention was best associated with amyloid in neuritic plaques, amyloid in diffuse plaques and cerebral amyloid angiopathy best explain three [(18)F]flutemetamol positive cases with mismatched (sparse) neuritic plaque burden. Advanced cortical atrophy was associated with the seven false negative [(18)F]flutemetamol images. The interpretation of images from pathologically equivocal cases was associated with low reader confidence and inter-reader agreement. Our results support that amyloid in neuritic plaque burden is the primary form of β-amyloid pathology detectable with [(18)F]flutemetamol PET imaging.
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| 21. |
- Johansson, Emil, et al.
(author)
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Whole-Body Imaging of Tissue-specific Insulin Sensitivity and Body Composition by Using an Integrated PET/MR System: A Feasibility Study
- 2018
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In: Radiology. - : Radiological Society of North America (RSNA). - 0033-8419 .- 1527-1315. ; 286:1, s. 271-278
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Journal article (peer-reviewed)abstract
- Purpose: To develop, evaluate, and demonstrate the feasibility of a whole-body protocol for simultaneous assessment of tissue-specific insulin-mediated fluorine 18 (F-18) fluorodeoxyglucose (FDG) influx rates, tissue depots, and whole-body insulin sensitivity (referred to as the M value). Materials and Methods: An integrated positron emission tomography (PET)/magnetic resonance (MR) imaging system combined with hyperinsulinemic euglycemic clamp (HEC) was used. Dynamic whole-body PET imaging was used to determine the insulin-mediated F-18-FDG tissue influx rate (K-i) in the whole-body region by using the Patlak method. M value was determined with the HEC method at PET imaging. Tissue depots were quantified by using water-fat separated MR imaging and manual segmentations. Feasibility of the imaging protocol was demonstrated by using five healthy control participants and five patients with type 2 diabetes. Associations between M value and K-i were studied in multiple tissues by using the Pearson correlation. Results: Positive correlations were found between M value and K-i in multiple tissues: the gluteus muscle (r = 0.875; P = .001), thigh muscle (r = 0.903; P < .001), calf muscle (r = 0.825; P = .003), and abdominal visceral adipose tissue (r = 0.820; P = .004). A negative correlation was found in the brain (r = 0.798; P = .006). The MR imaging-based method for quantification of tissue depots was feasible for determining adipose tissue volumes and fat fractions. Conclusion: This PET/MR imaging protocol may be feasible for simultaneous assessment of tissue-specific insulin-mediated F-18-FDG influx rates, tissue depots, and M value. (C) RSNA, 2017
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| 22. |
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| 23. |
- Leinonen, Ville, et al.
(author)
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Diagnostic effectiveness of quantitative [¹⁸F]flutemetamol PET imaging for detection of fibrillar amyloid β using cortical biopsy histopathology as the standard of truth in subjects with idiopathic normal pressure hydrocephalus.
- 2014
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In: Acta neuropathologica communications. - : Springer Science and Business Media LLC. - 2051-5960. ; 2, s. 46-
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Journal article (peer-reviewed)abstract
- INTRODUCTION: PET imaging of amyloid-β (Aβ) in vivo holds promise for aiding in earlier diagnosis and intervention in Alzheimer's disease (AD) and mild cognitive impairment. AD-like Aβ pathology is a common comorbidity in patients with idiopathic normal pressure hydrocephalus (iNPH). Fifty patients with iNPH needing ventriculo-peritoneal shunting or intracranial pressure monitoring underwent [18F]flutemetamol PET before (N = 28) or after (N = 22) surgery. Cortical uptake of [18F]flutemetamol was assessed visually by blinded reviewers, and also quantitatively via standard uptake value ratio (SUVR) in specific neocortical regions in relation to either cerebellum or pons reference region: the cerebral cortex of (prospective studies) or surrounding (retrospective studies) the biopsy site, the contralateral homolog, and a calculated composite brain measure. Aβ pathology in the biopsy specimen (standard of truth [SoT]) was measured using Bielschowsky silver and thioflavin S plaque scores, percentage area of grey matter positive for monoclonal antibody to Aβ (4G8), and overall pathology impression. We set out to find (1) which pair(s) of PET SUVR and pathology SoT endpoints matched best, (2) whether quantitative measures of [18F]flutemetamol PET were better for predicting the pathology outcome than blinded image examination (BIE), and (3) whether there was a better match between PET image findings in retrospective vs. prospective studies.RESULTS: Of the 24 possible endpoint/SoT combinations, the one with composite-cerebellum SUVR and SoT based on overall pathology had the highest Youden index (1.000), receiver operating characteristic area under the curve (1.000), sensitivity (1.000), specificity (1.000), and sum of sensitivity and specificity for the pooled data as well as for the retrospective and prospective studies separately (2.00, for all 3). The BIE sum of sensitivity and specificity, comparable to that for quantitation, was highest using Bielschowsky silver as SoT for all SUVRs (ipsilateral, contralateral, and composite, for both reference regions). The composite SUVR had a 100% positive predictive value (both reference regions) for the overall pathology diagnosis. All SUVRs had a 100% negative predictive value for the Bielschowsky silver result.CONCLUSION: Bielschowsky silver stain and overall pathology judgment showed the strongest associations with imaging results.
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| 24. |
- Leinonen, V, et al.
(author)
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Positron emission tomography with [18F]flutemetamol and [11C]PiB for in vivo detection of cerebral cortical amyloid in normal pressure hydrocephalus patients.
- 2013
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In: European Journal of Neurology. - : Wiley. - 1351-5101 .- 1468-1331. ; 20:7, s. 1043-52
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Journal article (peer-reviewed)abstract
- BACKGROUND AND PURPOSE: This study determined the correlation between uptake of the amyloid positron emission tomography (PET) imaging agent [(18) F]flutemetamol and amyloid-β measured by immunohistochemical and histochemical staining in a frontal cortical biopsy.METHODS: Fifteen patients with possible normal pressure hydrocephalus (NPH) and previous brain biopsy obtained during intracranial pressure monitoring underwent [18F]flutemetamol PET. Seven of these patients also underwent [11C] Pittsburgh compound B (PiB) PET. [18F]Flutemetamol and [11C]PiB uptake was quantified using standardized uptake value ratio (SUVR) with the cerebellar cortex as a reference region. Tissue amyloid-β was evaluated using the monoclonal antibody 4G8, Thioflavin-S and Bielschowsky silver stain.RESULTS: [18F]Flutemetamol and [11C]PiB SUVRs correlated with biopsy specimen amyloid-β levels contralateral (r = 0.86, P < 0.0001; r = 0.96, P = 0.0008) and ipsilateral (r = 0.82, P = 0.0002; r = 0.87, P = 0.01) to the biopsy site. Association between cortical composite [(18) F]flutemetamol SUVRs and [11C]PiB SUVRs was highly significant (r = 0.97, P = 0.0003).CONCLUSIONS: [18F]Flutemetamol detects brain amyloid-β in vivo with moderate to high sensitivity and high specificity. This agent, therefore, represents a valuable new tool to study and verify the presence of amyloid-β pathology, both in patients with possible NPH and among the wider population.
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| 25. |
- Leuzy, Antoine, et al.
(author)
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In vivo Detection of Alzheimer's Disease.
- 2018
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In: The Yale journal of biology and medicine. - 1551-4056 .- 0044-0086. ; 91:3, s. 291-300
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Research review (peer-reviewed)abstract
- Recent revisions to the diagnostic criteria for Alzheimer's disease (AD) incorporated conceptual advances in the field. Specifically, AD is now recognized to encompass a continuum, spanning from preclinical (accruing brain pathology in the absence of symptoms) through symptomatic predementia (prodromal AD, mild cognitive impairment) and dementia phases. The role of biological markers (biomarkers) of both the underlying molecular pathologies and related neurodegenerative changes has also been acknowledged. In this abridged review, we provide an overview of fluid (cerebrospinal fluid and blood) and molecular imaging-based biomarkers used within the field and discuss the potential role of computer driven artificial intelligence approaches for both the early and accurate identification of AD and as a tool for population enrichment in clinical trials testing candidate disease modifying therapies.
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| 26. |
- Leuzy, Antoine, et al.
(author)
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Use of amyloid PET across the spectrum of Alzheimer's disease : clinical utility and associated ethical issues
- 2014
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In: Amyloid. - : Informa UK Limited. - 1350-6129 .- 1744-2818. ; 21:3, s. 143-148
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Research review (peer-reviewed)abstract
- Recent advances have made possible the in vivo detection of beta-amyloid (Ab) pathology using positron emission tomography. While the gold standard for amyloid imaging, carbon-11 labeled Pittsburgh compound B is increasingly being replaced by fluorine-18 labeled radiopharmaceuticals, with three already approved for clinical use by US and European regulatory bodies. Appropriate use criteria proposed by an amyloid imaging taskforce convened by the Alzheimer's Association and the Society of Nuclear Medicine and Molecular Imaging recommend restricting use of this technology to the evaluation of patients with mild cognitive impairment or atypical dementia syndromes. While use among asymptomatic individuals is currently viewed as inappropriate due prognostic uncertainty, elevated levels of brain Ab among asymptomatic individuals may represent preclinical Alzheimer's disease. Amyloid imaging is likewise expected to play a role in the design of clinical trials. Though preliminary results suggest amyloid imaging to possess clinical utility and cost-effectiveness, both domains have yet to be assessed systematically. As the field moves toward adoption of a pro-disclosure stance for amyloid imaging findings, it is imperative that a broad range of stakeholders be involved to ensure the appropriateness of emerging policies and protocols.
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| 27. |
- Leuzy, Antoine, et al.
(author)
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Validation of a spatial normalization method using a principal component derived adaptive template for [18F]florbetaben PET
- 2020
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In: American Journal of Nuclear Medicine and Molecular Imaging. - : E-CENTURY PUBLISHING CORP. - 2160-8407. ; 10:4, s. 161-167
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Journal article (peer-reviewed)abstract
- Quantification may help in the context of amyloid-beta positron emission tomography (PET). Quantification typically requires that PET images be spatially normalized, a process that can be subject to bias. We herein aimed to test whether a principal component approach (PCA) previously applied to [F-18]flutemetamol PET extends to [F-18] florbetaben. PCA was applied to [F-18]florbetaben PET data for 132 subjects (70 Alzheimer dementia, 62 controls) and used to generate an adaptive synthetic template. Spatial normalization of [F-18]florbetaben data using this approach was compared to that achieved using SPM12's magnetic resonance (MR) imaging driven algorithm. The two registration methods showed high agreement and minimal difference in standardized uptake value ratios (SUVR) (R-2 = 0.997 using cerebellum as reference region and 0.996 using the pons). Our method allows for robust and accurate registration of [F-18]florbetaben images to template space, without the need for an MR image, and may prove of value in clinical and research settings.
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| 28. |
- Miki, Takami, et al.
(author)
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Brain uptake and safety of Flutemetamol F 18 injection in Japanese subjects with probable Alzheimer's disease, subjects with amnestic mild cognitive impairment and healthy volunteers
- 2017
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In: Annals of Nuclear Medicine. - : Springer Science and Business Media LLC. - 0914-7187 .- 1864-6433. ; 31:3, s. 260-272
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Journal article (peer-reviewed)abstract
- Objective This Phase 2 study assessed the performance of positron emission tomography (PET) brain images made with Flutemetamol F 18 Injection in detecting beta-amyloid neuritic plaques in Japanese subjects. Methods Seventy subjects (25 with probable Alzheimer's disease (pAD), 20 with amnestic mild cognitive impairment (aMCI), and 25 cognitively normal healthy volunteers[HVs]) underwent PET brain imaging after intravenous Flutemetamol F 18 Injection (185 MBq). Images were interpreted as normal or abnormal for neuritic plaque density by each of five non-Japanese and five Japanese readers who were blinded to clinical data. The primary efficacy analysis (based on HV and pAD data) was the agreement of the non-Japanese readers' image interpretations with the clinical diagnosis, resulting in estimates of positive percent agreement (PPA; based on AD subjects; similar to sensitivity) and negative percent agreement (NPA; based on HVs; similar to specificity). Secondary analyses included PPA and NPA for the Japanese readers; inter-reader agreement (IRA); intra-reader reproducibility (IRR); quantitative image interpretations (standardized uptake value ratios [SUVRs]) by diagnostic subgroup; test-retest variability in five pAD subjects; and safety. Results PPA was 92% for all non-Japanese readers and ranged from 88 to 92% for the Japanese readers. NPA ranged from 96 to 100% for both the non-Japanese readers and the Japanese readers. The majority image interpretations (the interpretations made independently by ae3 of 5 readers) resulted in PPA values of 92 and 92% and NPA values of 100 and 96% for the non-Japanese and Japanese readers, respectively. IRA and IRR were strong. Composite SUVR values (mean of multiple regional values) allowed clear differentiation between pAD subjects and HVs. Test-retest variability ranged from 1.14 to 2.27%, and test-retest agreement of the blinded visual interpretations was 100% for all readers. Flutemetamol F 18 Injection was generally well tolerated. Conclusion The detection of brain neuritic plaques in Japanese subjects using [F-18]Flutemetamol PET images gave results highly consistent with clinical diagnosis, with non-Japanese and Japanese readers giving similar results. Inter-reader agreement and intra-reader reproducibility were high for both sets of readers. Visual delineation of abnormal and normal scans was corroborated by quantitative assessment, with low test-retest variability.
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| 29. |
- Oldgren, Jonas, 1964-, et al.
(author)
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Effects of 6 weeks of treatment with dapagliflozin, a sodium-glucose co-transporter-2 inhibitor, on myocardial function and metabolism in patients with type 2 diabetes : A randomized, placebo-controlled, exploratory study
- 2021
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In: Diabetes, obesity and metabolism. - : John Wiley & Sons. - 1462-8902 .- 1463-1326. ; 23:7, s. 1505-1517
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Journal article (peer-reviewed)abstract
- Aim To explore the early effects of dapagliflozin on myocardial function and metabolism in patients with type 2 diabetes without heart failure. Materials and Methods Patients with type 2 diabetes on metformin treatment were randomized to double-blind, 6-week placebo or dapagliflozin 10 mg daily treatment. Investigations included cardiac function and structure with myocardial resonance imaging; cardiac oxygen consumption, perfusion and efficiency with [C-11]-acetate positron emission tomography (PET); and cardiac and hepatic fatty acid uptake with [F-18]-6-thia-heptadecanoic acid PET, analysed by ANCOVA as least square means with 95% confidence intervals. Results Evaluable patients (placebo: n = 24, dapagliflozin: n = 25; 53% males) had a mean age of 64.4 years, a body mass index of 30.2 kg/m(2) and an HbA1c of 6.7%. Body weight and HbA1c were significantly decreased by dapagliflozin versus placebo. Dapagliflozin had no effect on myocardial efficiency, but external left ventricular (LV) work (-0.095 [-0.145, -0.043] J/g/min) and LV oxygen consumption were significantly reduced (-0.30 [-0.49, -0.12] J/g/min) by dapagliflozin, although the changes were not statistically significant versus changes in the placebo group. Change in left atrial maximal volume with dapagliflozin versus placebo was -3.19 (-6.32, -0.07) mL/m(2) (p = .056). Peak global radial strain decreased with dapagliflozin versus placebo (-3.92% [-7.57%, -0.28%]; p = .035), while peak global longitudinal and circumferential strains were unchanged. Hepatic fatty acid uptake was increased by dapagliflozin versus placebo (0.024 [0.004, 0.044] mu mol/g/min; p = .018), while cardiac uptake was unchanged. Conclusions This exploratory study indicates reduced heart work but limited effects on myocardial function, efficiency and cardiac fatty acid uptake, while hepatic fatty acid uptake increased, after 6 weeks of treatment with dapagliflozin.
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| 30. |
- Rosqvist, Fredrik, 1985-, et al.
(author)
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Overeating saturated fat promotes fatty liver and ceramides compared to polyunsaturated fat : a randomized trial
- 2019
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In: Journal of Clinical Endocrinology and Metabolism. - : Oxford University Press. - 0021-972X .- 1945-7197. ; 104:12, s. 6207-6219
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Journal article (peer-reviewed)abstract
- CONTEXT: Saturated fat (SFA) versus polyunsaturated fat (PUFA) may promote non-alcoholic fatty liver disease (NAFLD) by yet unclear mechanisms.OBJECTIVE: To investigate if overeating SFA- and PUFA-enriched diets lead to differential liver fat accumulation in overweight and obese humans.DESIGN: Double-blind randomized trial (LIPOGAIN-2). Overfeeding SFA vs PUFA for 8 weeks, followed by 4 weeks of caloric restriction.SETTING: General community.Participants: n=61 overweight or obese men and women.INTERVENTION: Muffins high in either palm (SFA)- or sunflower oil (PUFA) were added to the habitual diet.MAIN OUTCOME MEASURE: Lean tissue mass (not reported here). Secondary and exploratory outcomes included liver and ectopic fat depots.RESULTS: By design, body weight gain was similar in SFA (2.31±1.38 kg) and PUFA (2.01±1.90 kg) groups, P=0.50. SFA markedly induced liver fat content (50% relative increase) along with liver enzymes and atherogenic serum lipids. In contrast, despite similar weight gain, PUFA did not increase liver fat or liver enzymes or cause any adverse effects on blood lipids. SFA had no differential effect on the accumulation of visceral fat, pancreas fat or total body fat compared with PUFA. SFA consistently increased, while PUFA reduced circulating ceramides; changes that were moderately associated with liver fat changes and proposed markers of hepatic lipogenesis. The adverse metabolic effects of SFA were reversed by calorie restriction.CONCLUSIONS: Saturated fat markedly induces liver fat and serum ceramides whereas dietary polyunsaturated fat prevent liver fat accumulation, reduce ceramides and hyperlipidemia during excess energy intake and weight gain in overweight individuals.
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| 31. |
- Senda, Michio, et al.
(author)
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An exploratory efficacy study of the amyloid imaging agent [F-18]flutemetamol in Japanese Subjects
- 2015
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In: Annals of Nuclear Medicine. - : Springer Science and Business Media LLC. - 0914-7187 .- 1864-6433. ; 29:5, s. 391-399
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Journal article (peer-reviewed)abstract
- The aim of the study presented was to investigate the brain uptake properties of the amyloid PET agent [F-18]flutemetamol in Japanese healthy controls and clinically probable Alzheimer's disease (AD) patients, and to make a comparison with the results of a previously performed study on Caucasian subjects. [F-18]flutemetamol was recently approved by the American Food and Drug Administration and the European Medicines Agency for visualization of amyloid in vivo. Since the first clinical study of [F-18]flutemetamol-an F-18 derivative of the PET tracer 11C-Pittsburgh Compound B targeting beta-amyloid--took place, several clinical studies have been performed, but few focusing on a Japanese population. In the Step A, three elderly healthy volunteers and three AD subjects underwent dynamic PET scanning 0-30 and 60-150 min after injection of 185 MBq [F-18]flutemetamol. The brain volume of distribution (V-T) was quantified using Logan's linear graphical analysis and as standardized uptake value ratios (SUVR) with a cerebellar reference. The optimal acquisition window was determined from brain time activity curves for Step B. In the Step B, 5 AD and 5 elderly healthy volunteers were scanned from 80 to 140 min after intravenous injection of [F-18]flutemetamol. The data from the two parts were pooled for estimation of overall efficacy. [F-18]Flutemetamol injection was shown to be safe-no serious adverse events were reported during this study. A simplified SUVR estimate of the uptake of [F-18]flutemetamol using a time window of 85-115 min post injection successfully discriminated AD cases from healthy volunteers. AD subjects showed an elevated tracer uptake in prefrontal cortex, the lateral temporal cortex and precuneus amongst other regions. No significant [F-18]flutemetamol PET differences could be seen between the Japanese AD cases in this study and those from an earlier Caucasian study, or between control subjects in Japanese and Caucasian studies. This study supports the use of [F-18]flutemetamol PET in Japanese population as a marker of the presence of fibrillar beta-amyloid. The lack of differences between the Japanese cohort and those from a previous Caucasian cohort supports the extrapolation of results from other Caucasian [F-18]flutemetamol PET studies to the Japanese population.
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| 32. |
- Thal, Dietmar Rudolf, et al.
(author)
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[(18)F]flutemetamol amyloid positron emission tomography in preclinical and symptomatic Alzheimer's disease : Specific detection of advanced phases of amyloid-β pathology.
- 2015
-
In: Alzheimer's & Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 11:8, s. 975-85
-
Journal article (peer-reviewed)abstract
- BACKGROUND: Amyloid positron emission tomography (PET) has become an important tool to identify amyloid-β (Aβ) pathology in Alzheimer's disease (AD) patients. Here, we determined the diagnostic value of the amyloid PET tracer [(18)F]flutemetamol in relation to Aβ pathology at autopsy.METHODS: [(18)F]flutemetamol PET was carried out in a cohort of 68 patients included in a [(18)F]flutemetamol amyloid PET imaging end-of-life study (GE067-007). At autopsy, AD pathology was determined and Aβ plaque pathology was classified into phases of its regional distribution (0-5).RESULTS: [(18)F]flutemetamol PET was universally positive in cases with advanced stage postmortem Aβ pathology (Aβ phases 4 and 5). Negative amyloid PET was universally observed in nondemented or non-AD dementia cases with initial Aβ phases 1 and 2, whereas 33.3% of the phase 3 cases were positive.CONCLUSIONS: [(18)F]flutemetamol amyloid PET detects primarily advanced stages of Aβ pathology in preclinical and symptomatic AD cases.
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| 33. |
- Thal, D. R., et al.
(author)
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Different aspects of Alzheimer's disease-related amyloid beta-peptide pathology and their relationship to amyloid positron emission tomography imaging and dementia
- 2019
-
In: Acta Neuropathologica Communications. - : Springer Science and Business Media LLC. - 2051-5960. ; 7:1
-
Journal article (peer-reviewed)abstract
- Alzheimer's disease (AD)-related amyloid beta-peptide (A beta) pathology in the form of amyloid plaques and cerebral amyloid angiopathy (CAA) spreads in its topographical distribution, increases in quantity, and undergoes qualitative changes in its composition of modified A beta species throughout the pathogenesis of AD. It is not clear which of these aspects of A beta pathology contribute to AD progression and to what extent amyloid positron emission tomography (PET) reflects each of these aspects. To address these questions three cohorts of human autopsy cases (in total n = 271) were neuropathologically and biochemically examined for the topographical distribution of A beta pathology (plaques and CAA), its quantity and its composition. These parameters were compared with neurofibrillary tangle (NFT) and neuritic plaque pathology, the degree of dementia and the results from [F-18]flutemetamol amyloid PET imaging in cohort 3. All three aspects of A beta pathology correlated with one another, the estimation of A beta pathology by [F-18]flutemetamol PET, AD-related NFT pathology, neuritic plaques, and with the degree of dementia. These results show that one aspect of A beta pathology can be used to predict the other two, and correlates well with the development of dementia, advancing NFT and neuritic plaque pathology. Moreover, amyloid PET estimates all three aspects of A beta pathology in-vivo. Accordingly, amyloid PET-based estimates for staging of amyloid pathology indicate the progression status of amyloid pathology in general and, in doing so, also of AD pathology. Only 7.75% of our cases deviated from this general association.
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| 34. |
- Thal, D. R., et al.
(author)
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Estimation of amyloid distribution by F-18 flutemetamol PET predicts the neuropathological phase of amyloid beta-protein deposition
- 2018
-
In: Acta Neuropathologica. - : Springer Science and Business Media LLC. - 0001-6322 .- 1432-0533. ; 136:4, s. 557-567
-
Journal article (peer-reviewed)abstract
- The deposition of the amyloid β-protein (Aβ) in senile plaques is one of the histopathological hallmarks of Alzheimer’s disease (AD). Aβ-plaques arise first in neocortical areas and, then, expand into further brain regions in a process described by 5 phases. Since it is possible to identify amyloid pathology with radioactive-labeled tracers by positron emission tomography (PET) the question arises whether it is possible to distinguish the neuropathological Aβ-phases with amyloid PET imaging. To address this question we reassessed 97 cases of the end-of-life study cohort of the phase 3 [18F]flutemetamol trial (ClinicalTrials.gov identifiers NCT01165554, and NCT02090855) by combining the standardized uptake value ratios (SUVRs) with pons as reference region for cortical and caudate nucleus-related [18F]flutemetamol-retention. We tested them for their prediction of the neuropathological pattern found at autopsy. By defining threshold levels for cortical and caudate nucleus SUVRs we could distinguish different levels of [18F]flutemetamol uptake termed PET-Aβ phase estimates. When comparing these PET-Aβ phase estimates with the neuropathological Aβ-phases we found that PET-Aβ phase estimate 0 corresponded with Aβ-phases 0-2, 1 with Aβ-phase 3, 2 with Aβ-phase 4, and 3 with Aβ-phase 5. Classification using the PET-Aβ phase estimates predicted the correct Aβ-phase in 72.16% of the cases studied here. Bootstrap analysis was used to confirm the robustness of the estimates around this association. When allowing a range of±1 phase for a given Aβ-phase correct classification was given in 96.91% of the cases. In doing so, we provide a novel method to convert SUVR-levels into PET-Aβ phase estimates that can be easily translated into neuropathological phases of Aβ-deposition. This method allows direct conclusions about the pathological distribution of amyloid plaques (Aβ-phases) in vivo. Accordingly, this method may be ideally suited to detect early preclinical AD-patients, to follow them with disease progression, and to provide a more precise prognosis for them based on the knowledge about the underlying pathological phase of the disease.
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| 35. |
- Tjörnstrand, Axel, et al.
(author)
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Lower 68 Ga-DOTATOC Uptake in Non-Functioning Pituitary Neuroendocrine Tumors Compared to Normal Pituitary Gland - a Proof-of-Concept Study.
- 2020
-
In: Clinical Endocrinology. - : Wiley. - 0300-0664 .- 1365-2265. ; 92:3, s. 222-231
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Journal article (peer-reviewed)abstract
- OBJECTIVES: 68 Ga-DOTATOC PET targets somatostatin receptors (SSTRs) and is well established for the detection of SSTR-expressing tumors, such as gastrointestinal neuroendocrine tumors. Pituitary adenomas, recently designated as pituitary neuroendocrine tumors (PitNETs), also express SSTRs, but there has been no previous evaluations of 68 Ga-DOTATOC PET in PitNET patients. The aim of this pilot study was to evaluate the diagnostic properties of 68 Ga-DOTATOC PET in the most common PitNET, i.e. non-functioning (NF)-PitNET.DESIGN/METHODS: NF-PitNET patients (n = 9) and controls (n = 13) were examined preoperatively with 68 Ga-DOTATOC PET for 45 min after tracer injection in dynamic list mode. Tumor specimens were collected during surgery in patients. MRI and PET images were co-registered using PMOD software. The maximum standard uptake value (SUVmax ) was analyzed in manually outlined regions of interest (ROC) around the tumor in patients and around the pituitary gland in controls. Immunohistochemical analyses were conducted on tumor specimens for assessment of tumor cell type and SSTR expression.RESULTS: Median SUVmax (IQR) was lower in patients than in controls (3.9 [3.4-8.5] vs 14.1 [12.5-15.9]; P < .01]. In ROC analysis, the area under the curve was 0.87 (P < .01) for SUVmax , with 78% sensitivity and 92% specificity. Immunohistochemical analysis showed NF-PitNETs were of gonadotroph (n = 7) and corticotroph (n = 2) origin. SSTR expression was high for SSTR3, low-to-moderate for SSTR2, and low for SSTR1 and SSTR5.CONCLUSIONS: This proof-of-concept study shows that 68 Ga-DOTATOC PET can be used to differentiate between normal pituitary tissue and NF-PitNET.
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| 36. |
- Tjörnstrand, Axel, et al.
(author)
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Pre- and postoperative Ga-68-DOTATOC positron emission tomography for hormone-secreting pituitary neuroendocrine tumours
- 2021
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In: Clinical Endocrinology. - : John Wiley & Sons. - 0300-0664 .- 1365-2265. ; 94:6, s. 956-967
-
Journal article (peer-reviewed)abstract
- Objectives Somatostatin receptors (SSTRs) are potential targets for detecting pituitary neuroendocrine tumours (PitNETs) that can be visualized effectively with Ga-68-labelled PET tracers. With this study, we have evaluated the diagnostic properties of such a tracer, Ga-68-DOTATOC, in patients with hormone-producing PitNETs before and after surgery. Design/Methods This prospective case-control study presents preoperative positron emission tomography (PET) and histopathological data in 18 patients with somatotroph (n = 8), corticotroph (n = 7) and thyrotroph (n = 3) PitNETs. Patients were scanned pre- and postoperatively with Ga-68-DOTATOC PET. For the postoperative part of the study, patients with gonadotroph tumours (n = 7) were also included. Fifteen pituitary healthy controls underwent the same protocol once. The maximum standard uptake value (SUVmax) was analysed in manually outlined regions around the tumour in patients and around the pituitary gland in controls. specimens were collected during surgery in subjects for assessment of adenohypophyseal tumour cell type and the SSTR expression. Results Thyrotroph tumours showed higher uptake (median SUVmax 41.1; IQR 37.4-60.0) and corticotroph tumours lower uptake (SUVmax 6.8; 2.6-9.3) than normal pituitary gland (SUVmax 13.8; 12.1-15.5). The uptake in somatotroph tumours (SUVmax 15.9; 11.6-19.7) was similar to the uptake in the pituitary gland. There was a strong correlation between SUVmax and SSTR2 expression (r = .75 (P < .01)). In the postoperative evaluation, PET was able to correlate tracer uptake with biochemical cure and noncure in patients with an abnormal postoperative magnetic resonance image and a preoperative tumour uptake SUVmax > 13.8. Conclusions Ga-68-DOTATOC PET can be used to detect thyrotroph tumours in the pre- and postoperative imaging assessment. Corticotroph tumours had a significantly lower uptake compared to the pituitary gland but without a distinct increased tumour uptake the clinical postoperative value is limited.
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| 37. |
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