| 1. |
- Alvén, Jennifer, 1989, et al.
(författare)
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A Deep Learning Approach to MR-less Spatial Normalization for Tau PET Images
- 2019
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Ingår i: Medical Image Computing and Computer Assisted Intervention : MICCAI 2019 - 22nd International Conference, Proceedings - MICCAI 2019 - 22nd International Conference, Proceedings. - Cham : Springer International Publishing. - 0302-9743 .- 1611-3349. - 9783030322458 - 9783030322441 ; 11765 LNCS, s. 355-363
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Konferensbidrag (refereegranskat)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.
(författare)
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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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Ingår i: European Neuropsychopharmacology. - : Elsevier BV. - 0924-977X .- 1873-7862. ; 19:12, s. 841-850
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Tidskriftsartikel (refereegranskat)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.
(författare)
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Update on biomarkers for amyloid pathology in Alzheimer's disease
- 2018
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Ingår i: Biomarkers in Medicine. - : Future Medicine Ltd. - 1752-0363 .- 1752-0371. ; 12:7, s. 799-812
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Forskningsöversikt (refereegranskat)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.
(författare)
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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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Ingår i: Hormone and Metabolic Research. - : Georg Thieme Verlag KG. - 0018-5043 .- 1439-4286. ; 50:8
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Tidskriftsartikel (refereegranskat)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.
(författare)
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Serotonin synthesis rate and the tryptophan hydroxylase-2: G-703T polymorphism in social anxiety disorder
- 2016
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Ingår i: Journal of Psychopharmacology. - London, United Kingdom : SAGE Publications. - 0269-8811 .- 1461-7285. ; 30:10, s. 1028-1035
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Tidskriftsartikel (refereegranskat)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.
(författare)
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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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Ingår i: Ejnmmi Research. - : Springer Science and Business Media LLC. - 2191-219X. ; 9
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Tidskriftsartikel (refereegranskat)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-
(författare)
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Characterization of [18F]flutemetamol binding properties : A β-amyloid PET imaging ligand
- 2015
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)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.
(författare)
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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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Ingår i: International Review of Neurobiology. - : Elsevier. - 0074-7742. ; 154, s. 111-130
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Forskningsöversikt (refereegranskat)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.
(författare)
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Imaging β-amyloid using [(18)F]flutemetamol positron emission tomography : from dosimetry to clinical diagnosis
- 2016
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Ingår i: 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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Forskningsöversikt (refereegranskat)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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