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Antoni, Gunnar
Alternative names
Publications (10 of 139) Show all publications
Syvänen, S., Fang, X. T., Hultqvist, G., Falting, J., Antoni, G., Lannfelt, L. & Sehlin, D. (2017). Antibody-based PET radioligands for imaging of amyloid-beta protofibrils. Paper presented at 28th International Symposium on Cerebral Blood Flow, Metabolism and Function / 13th International Conference on Quantification of Brain Function with PET, APR 01-04, 2017, Int Soc Cerebral Blood Flow & Metab, Berlin, GERMANY. Journal of Cerebral Blood Flow and Metabolism, 37, 84-84.
Open this publication in new window or tab >>Antibody-based PET radioligands for imaging of amyloid-beta protofibrils
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2017 (English)In: Journal of Cerebral Blood Flow and Metabolism, ISSN 0271-678X, E-ISSN 1559-7016, Vol. 37, 84-84 p.Article in journal, Meeting abstract (Other academic) Published
Place, publisher, year, edition, pages
Sage Publications, 2017
National Category
Endocrinology and Diabetes Hematology Neurology
Identifiers
urn:nbn:se:uu:diva-331033 (URN)000400157400120 ()
Conference
28th International Symposium on Cerebral Blood Flow, Metabolism and Function / 13th International Conference on Quantification of Brain Function with PET, APR 01-04, 2017, Int Soc Cerebral Blood Flow & Metab, Berlin, GERMANY
Note

Supplement: 1, Meeting Abstract: BPS04-1.

Available from: 2017-10-11 Created: 2017-10-11 Last updated: 2017-10-11
Andersen, T. L., Nordeman, P., Christoffersen, H. F., Audrain, H., Antoni, G. & Skrydstrup, T. (2017). Application of Methyl Bisphosphine-Ligated Palladium Complexes for Low Pressure N-C-11-Acetylation of Peptides. Angewandte Chemie International Edition, 56(16), 4549-4553.
Open this publication in new window or tab >>Application of Methyl Bisphosphine-Ligated Palladium Complexes for Low Pressure N-C-11-Acetylation of Peptides
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2017 (English)In: Angewandte Chemie International Edition, ISSN 1433-7851, E-ISSN 1521-3773, Vol. 56, no 16, 4549-4553 p.Article in journal (Refereed) Published
Abstract [en]

A mild and effective method is described for C-11-labeling of peptides selectively at the N-terminal nitrogen or at internal lysine positions. The presented method relies on the use of specific biphosphine palladium-methyl complexes and their high reactivity towards amino-carbonylation of amine groups in the presence [C-11] carbon monoxide. The protocol facilitates the production of native N-C-11-acetylated peptides, without any structural modifications and has been applied to a selection of bioactive peptides.

Keyword
C-11-labeling, carbonylation, palladium, peptides
National Category
Chemical Sciences
Identifiers
urn:nbn:se:uu:diva-320628 (URN)10.1002/anie.201700446 (DOI)000398154000026 ()28301077 (PubMedID)
Funder
Danish National Research Foundation, DNRF118
Note

De 2 sista författarna delar sistaförfattarskapet.

Available from: 2017-08-14 Created: 2017-08-14 Last updated: 2017-08-14Bibliographically approved
Elgland, M., Nordeman, P., Fyrner, T., Antoni, G., Nilsson, K. P. & Konradsson, P. (2017). beta-Configured clickable [F-18] FDGs as novel F-18-fluoroglycosylation tools for PET. New Journal of Chemistry, 41(18), 10231-10236.
Open this publication in new window or tab >>beta-Configured clickable [F-18] FDGs as novel F-18-fluoroglycosylation tools for PET
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2017 (English)In: New Journal of Chemistry, ISSN 1144-0546, E-ISSN 1369-9261, Vol. 41, no 18, 10231-10236 p.Article in journal (Refereed) Published
Abstract [en]

In oncology and neurology the F-18-radiolabeled glucose analogue 2-deoxy-2-[F-18]fluoro-D-glucose ([F-18]FDG) is by far the most commonly employed metabolic imaging agent for positron emission tomography (PET). Herein, we report a novel synthetic route to beta-configured mannopyranoside precursors and a chemoselective F-18-fluoroglycosylation method that employ two b-configured [F-18]FDG derivatives equipped with either a terminal azide or alkyne aglycon respectively, for use as a CuAAC clickable tool set for PET. The b-configured precursors provided the corresponding [F-18]FDGs in a radiochemical yield of 77-88%. Further, the clickability of these [F-18]FDGs was investigated by click coupling to the suitably functionalized Fmoc-protected amino acids, Fmoc-N-(propargyl)-glycine and Fmoc-3-azido-L-alanine, which provided the F-18-fluoroglycosylated amino acid conjugates in radiochemical yields of 75-83%. The F-18-fluoroglycosylated amino acids presented herein constitute a new and interesting class of metabolic PET radiotracers.

Place, publisher, year, edition, pages
ROYAL SOC CHEMISTRY, 2017
National Category
Chemical Sciences
Identifiers
urn:nbn:se:uu:diva-336822 (URN)10.1039/c7nj00716g (DOI)000411767400073 ()
Funder
Swedish Foundation for Strategic Research Swedish Research Council
Available from: 2017-12-20 Created: 2017-12-20 Last updated: 2017-12-20Bibliographically approved
Tovedal, T., Lubberink, M., Morell, A., Estrada, S., Golla, S. S., Myrdal, G., . . . Lennmyr, F. (2017). Blood Flow Quantitation by Positron Emission Tomography During Selective Antegrade Cerebral Perfusion. Annals of Thoracic Surgery, 103(2), 610-616.
Open this publication in new window or tab >>Blood Flow Quantitation by Positron Emission Tomography During Selective Antegrade Cerebral Perfusion
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2017 (English)In: Annals of Thoracic Surgery, ISSN 0003-4975, E-ISSN 1552-6259, Vol. 103, no 2, 610-616 p.Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Perfusion strategies during aortic surgery usually comprise hypothermic circulatory arrest (HCA), often combined with selective antegrade cerebral perfusion (SACP) or retrograde cerebral perfusion. Cerebral blood flow (CBF) is a fundamental parameter for which the optimal level has not been clearly defined. We sought to determine the CBF at a pump flow level of 6 mL/kg/min, previously shown likely to provide adequate SACP at 20°C in pigs.

METHODS: Repeated positron emission tomography (PET) scans were used to quantify the CBF and glucose metabolism throughout HCA and SACP including cooling and rewarming. Eight pigs on cardiopulmonary bypass were assigned to either HCA alone (n = 4) or HCA+SACP (n = 4). The CBF was measured by repeated [(15)O]water PET scans from baseline to rewarming. The cerebral glucose metabolism was examined by [(18)F]fluorodeoxyglucose PET scans after rewarming to 37°C.

RESULTS: Cooling to 20°C decreased the cortical CBF from 0.31 ± 0.06 at baseline to 0.10 ± 0.02 mL/cm(3)/min (p = 0.008). The CBF was maintained stable by SACP of 6 mL/kg/min during 45 minutes. After rewarming to 37°C, the mean CBF increased to 0.24 ± 0.07 mL/cm(3)/min, without significant differences between the groups at any time-point exclusive of the HCA period. The net cortical uptake (Ki) of [(18)F]fluorodeoxyglucose after rewarming showed no significant difference between the groups.

CONCLUSIONS: Cooling autoregulated the CBF to 0.10 mL/cm(3)/min, and 45 minutes of SACP at 6 mL/kg/min maintained the CBF in the present model. Cerebral glucose metabolism after rewarming was similar in the study groups.

National Category
Basic Medicine Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-302609 (URN)10.1016/j.athoracsur.2016.06.029 (DOI)27592601 (PubMedID)
Available from: 2016-09-07 Created: 2016-09-07 Last updated: 2018-01-10Bibliographically approved
Fang, X. T., Eriksson, J., Antoni, G., Yngve, U., Cato, L., Lannfelt, L., . . . Syvänen, S. (2017). Brain mGluR5 in mice with amyloid beta pathology studied with in vivo [(11)C]ABP688 PET imaging and ex vivo immunoblotting. Neuropharmacology, 113(Pt A), 293-300, Article ID S0028-3908(16)30459-2.
Open this publication in new window or tab >>Brain mGluR5 in mice with amyloid beta pathology studied with in vivo [(11)C]ABP688 PET imaging and ex vivo immunoblotting
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2017 (English)In: Neuropharmacology, ISSN 0028-3908, E-ISSN 1873-7064, Vol. 113, no Pt A, 293-300 p., S0028-3908(16)30459-2Article in journal (Refereed) Published
Abstract [en]

Alzheimer's disease (AD) is characterized by aggregation of amyloid beta (Aβ) into insoluble plaques. Intermediates, Aβ oligomers (Aβo), appear to be the mechanistic cause of disease. The de facto PET AD ligand, [(11)C]PIB, binds and visualizes Aβ plaque load, which does not correlate well with disease severity. Therefore, finding a dynamic target that changes with pathology progression in AD is of great interest. Aβo alter synaptic plasticity, inhibit long-term potentiation, and facilitate long-term depression; key mechanisms involved in memory and learning. In order to convey these neurotoxic effects, Aβo requires interaction with the metabotropic glutamate 5 receptor (mGluR5). The aim was to investigate in vivo mGluR5 changes in an Aβ pathology model using PET. Wild type C57/BL6 (wt) and AβPP transgenic mice (tg-ArcSwe), 4, 8, and 16 months old, were PET scanned with [(11)C]ABP688, which is highly specific to mGluR5, to investigate changes in mGluR5. Mouse brains were extracted postscan and mGluR5 and Aβ protofibril levels were assessed with immunoblotting and ELISA respectively. Receptor-dense brain regions (hippocampus, thalamus, and striatum) displayed higher [(11)C]ABP688 concentrations corresponding to mGluR5 expression pattern. Mice had similar uptake levels of [(11)C]ABP688 regardless of genotype or age. Immunoblotting revealed general decline in mGluR5 expression and elevated levels of mGluR5 in 16 months old tg-ArcSwe compared with wt mice. [(11)C]ABP688 could visualize mGluR5 in the mouse brain. In conclusion, mGluR5 levels were found to decrease with age and tended to be higher in tg-ArcSwe compared with wt mice, however these changes could not be quantified with PET.

Keyword
Alzheimer's disease, PET, [(11)C]ABP688, mGluR5
National Category
Geriatrics Radiology, Nuclear Medicine and Medical Imaging Neurology Pharmacology and Toxicology
Identifiers
urn:nbn:se:uu:diva-317721 (URN)10.1016/j.neuropharm.2016.10.009 (DOI)000390502200028 ()27743932 (PubMedID)
Available from: 2017-03-17 Created: 2017-03-17 Last updated: 2018-01-13Bibliographically approved
Gustafsson, S., Eriksson, J., Syvänen, S., Eriksson, O., Hammarlund-Udenaes, M. & Antoni, G. (2017). Combined PET and microdialysis for in vivo estimation of drug blood-brain barrier transport and brain unbound concentrations. NeuroImage, 155, 177-186.
Open this publication in new window or tab >>Combined PET and microdialysis for in vivo estimation of drug blood-brain barrier transport and brain unbound concentrations
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2017 (English)In: NeuroImage, ISSN 1053-8119, E-ISSN 1095-9572, Vol. 155, 177-186 p.Article in journal (Refereed) Published
Abstract [en]

Methods to investigate blood-brain barrier transport and pharmacologically active drug concentrations in the human brain are limited and data translation between species is challenging. Hence, there is a need to further develop the read-out of techniques like positron emission tomography ( PET) for studying neuropharmacokinetics. PET has a high translational applicability from rodents to man and measures total drug concentrations in vivo. The aim of the present study was to investigate the possibility of translating total drug concentrations, acquired through PET, to unbound concentrations, resembling those measured in the interstitial fluid by microdialysis sampling. Simultaneous PET scanning and brain microdialysis sampling were performed in rats throughout a 60 min infusion of [N-methyl-C-11] oxycodone in combination with a therapeutic dose of oxycodone and during a 60 min follow up period after the end of infusion. The oxycodone concentrations acquired with PET were converted into unbound concentrations by compensating for brain tissue binding and brain intracellular distribution, using the unbound volume of distribution in brain (Vu, brain), and were compared to microdialysis measurements of unbound concentrations. A good congruence between the methods was observed throughout the infusion. However, an accumulating divergence in the acquired PET and microdialysis data was apparent and became more pronounced during the elimination phase, most likely due to the passage of radioactive metabolites into the brain. In conclusion, the study showed that PET can be used to translate non-invasively measured total drug concentrations into unbound concentrations as long as the contribution of radiolabelled metabolites is minor or can be compensated for.

Keyword
Blood-brain barrier, Unbound concentration, Positron emission tomography, Microdialysis, Pharmacokinetics, Oxycodone
National Category
Radiology, Nuclear Medicine and Medical Imaging
Identifiers
urn:nbn:se:uu:diva-332421 (URN)10.1016/j.neuroimage.2017.04.068 (DOI)000405460900015 ()28467891 (PubMedID)
Available from: 2017-11-02 Created: 2017-11-02 Last updated: 2017-11-02Bibliographically approved
Fahlström, M., Lindskog, K., Appel, L., Engström, M., Antoni, G., Kumlien, E., . . . Lubberink, M. (2017). Correlation between regional cerebral blood flow based on simultaneously acquired arterial spin labelling MRI and 15O-water-PET using zero-echo-time-based attenuation correction. Paper presented at Annual Meeting of the Society-of-Nuclear-Medicine-and-Molecular-Imaging (SNMMI), JUN 10-14, 2017, Denver, CO. Journal of Nuclear Medicine, 58(S1), Article ID 362.
Open this publication in new window or tab >>Correlation between regional cerebral blood flow based on simultaneously acquired arterial spin labelling MRI and 15O-water-PET using zero-echo-time-based attenuation correction
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2017 (English)In: Journal of Nuclear Medicine, ISSN 0161-5505, E-ISSN 1535-5667, Vol. 58, no S1, 362Article in journal, Meeting abstract (Other academic) Published
Abstract [en]

Objectives: Arterial spin labelling (ASL) MRI promises clinical value in several common neurological disorders. Its quantitative accuracy and reproducibility, however, need to be further validated, ideally using simultaneously acquired measurements with 15O-water-PET on an integrated PET-MR scanner. However, so far, few studies have attempted this and the inclusion of bone in MR-based attenuation correction for PET has thus far been a challenge, compromising the quantitative accuracy of PET-MR based 15O-water PET data. The aim of the present work was to assess the correlation of ASL- and 15O-water-PET based regional cerebral blood flow (rCBF) values based on simultaneously acquired data, using zero-echo-time (ZTE)-based attenuation correction, as well as to assess the reproducibility of ASL-based rCBF.

Methods: Six subjects underwent 10 min PET scans after automated bolus injection of 400 MBq 15O-water (1 mL/s during 5 s followed by 35 mL saline at 2 mL/s) on a time-of-flight integrated PET-MR scanner (Signa PET-MR, GE Healthcare). Arterial blood radioactivity concentrations were monitored using continuous sampling from the radial artery (Swisstrace Twilite Two). Simultaneously, a 3D FSE pseudo-continuous ASL (3D pCASL) with a spiral read-out as supplied by the scanner manufacturer in the commercial software were acquired using an 8 channel head coil (Invivo Hi-Res Head Coil). In addition, 3D T1-w, ZTE and Dixon fat-water MRI were acquired. The ASL procedure was repeated after 2 h (patients remained in the scanner). Quantifiable ASL-based CBF maps were generated. PET images were reconstructed into 26 frames of increasing durations using time-of-flight OSEM (2 iterations, 28 subsets) and a 5 mm post-filter, with ZTE-based attenuation correction. Blood sampler data were corrected for delay and dispersion and 15O-water-based CBF maps were calculated using a basis function implementation of the single tissue compartment model including a fitted blood volume parameter. CBF maps were co-registered to each patient's T1-w image. 3D T1-w images were segmented and normalised to MNI space using SPM12, and anterior, middle and posterior flow territory volumes of interest (VOIs) were created from a standard template in MNI space and inversely transformed for each patient. In addition, a 45-VOI probabilistic template was applied using PVElab software. Correlations between PET- and ASL-based rCBF values were assessed using regression analysis, and reproducibility of ASL using a paired t-test.

Results: Mean (CI) total brain grey matter CBF values were 67.2 (48.0-86.5) mL/min/100 g for 15O-water-PET and 65.5 (55.7-75.5) mL/min/100 g for ASL. Although correlation and agreement between 15O-water and ASL-based rCBF for individual VOIs in the 45-VOI template were generally poor, significant correlations were found on a grey matter flow territory basis, with R2 ranging from 0.70 in the anterior flow territory to 0.86 in the middle flow territory. rCBF values were significantly reduced between second and first ASL for all flow territories (p<0.01), with a mean decrease of 10%.

Conclusion: A good correlation between regional flow territory CBF values based on ASL and 15O-water-PET was found, using ZTE-based attenuation correction for PET data which takes bone tissue into account. ASL values for regional flow territories may have potential applications in patients with dementia or cerebrovascular diseases affecting blood flow such as moya moya. The decrease of ASL-based rCBF values in the reproducibility study needs to be investigated further to assess whether this is a methodological issue or reflects a true decrease in rCBF. Research Support: Uppsala County Council

National Category
Radiology, Nuclear Medicine and Medical Imaging
Identifiers
urn:nbn:se:uu:diva-333332 (URN)000404949901169 ()
Conference
Annual Meeting of the Society-of-Nuclear-Medicine-and-Molecular-Imaging (SNMMI), JUN 10-14, 2017, Denver, CO
Note

Title in WoS: Correlation between regional cerebral blood flow based on simultaneously acquired arterial spin labelling MRI and O-15-water-PET using zero-echo-time-based attenuation correction

Available from: 2017-11-15 Created: 2017-11-15 Last updated: 2017-11-15Bibliographically approved
Lindström, E., Lindsjö, L., Ilan, E., Sundin, A., Sörensen, J., Danfors, T., . . . Lubberink, M. (2017). Optimisation of penalized likelihood estimation reconstruction (Q.Clear) on a digital time-of-flight PET-CT scanner for four different PET tracers. Paper presented at Annual Meeting of the Society-of-Nuclear-Medicine-and-Molecular-Imaging (SNMMI), JUN 10-14, 2017, Denver, CO. Journal of Nuclear Medicine, 58(S1), Article ID 1355.
Open this publication in new window or tab >>Optimisation of penalized likelihood estimation reconstruction (Q.Clear) on a digital time-of-flight PET-CT scanner for four different PET tracers
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2017 (English)In: Journal of Nuclear Medicine, ISSN 0161-5505, E-ISSN 1535-5667, Vol. 58, no S1, 1355Article in journal, Meeting abstract (Other academic) Published
Abstract [en]

Objectives: The penalized likelihood estimation reconstruction algorithm Q.Clear (GE Healthcare) allows for full convergence and edge preservation through a block sequential regularized expectation maximization technique. In this study the performance of Q.Clear was investigated for different penalization factors (β) with the aim to optimize its clinical use for four different tracers.

Methods: Q.Clear reconstructions with β values of 200, 400, 600 and 800 were compared to time-of-flight ordered subset expectation maximization (TF-OSEM) (3 iterations, 16 subsets and 5 mm Gaussian filter) with point spread function recovery. Clinical whole-body PET/CT (Discovery MI, GE Healthcare) scans with 68Ga-DOTATOC, 18F-FDG, 11C-acetate or 18F-fluoride were analyzed for level of noise in healthy liver tissue, signal to noise ratio (SNR), signal to background ratio (SBR) and maximum standardized uptake value (SUVmax). In addition, acquisition times per bed position and transaxial field of view (FOV) of the reconstructed images were varied. For each tracer, images from 10 patients were included, with a mean of 30 lesions per tracer. A spherical reference volume of interest (VOI) was placed in the liver and lesions were delineated employing a 41% threshold of the maximum voxel.

Results: The lowest levels of noise were reached with the highest beta factor resulting in the highest SNR, but this in turn gave the lowest SBR. Noise equivalence to OSEM was found with β 600 for 68Ga-DOTATOC, 18F-FDG and 18F-fluoride, and β 400 for 11C-acetate with a resulting significant increase of SUVmax (19.4%, 9.7%, 22.5% and 19.0% respectively) (P < 0.0001, paired t-test), SNR (22.1%, 22.6%, 9.5% and 33.6%) and SBR (19.5%, 11.7%, 21.3% and 18.5%) compared to OSEM. SNR decreased while SBR increased for all tracers when extending FOV from 500 to 700 mm, but only significantly for 18F-fluoride. Decreasing image acquisition time gave no statistical difference of SUVmax for 68Ga-DOTATOC, 18F-fluoride (2 to 1.5 min) for any reconstruction method nor for 11C-acetate (3 to 2 min) with β 蠅 400. Decreasing time for 18F-FDG (3 to 2 min) resulted in a change of optimal beta to β 800 in order to reach noise equivalence to OSEM along with maintaining a higher SNR than OSEM.

Conclusion: Images reconstructed by Q.Clear result in a tracer-dependent increase in tumour SUVmax values compared to OSEM at matched levels of noise, and an improved SNR. The optimal penalization factor, both in terms of noise-equivalence to OSEM and in terms of absolute SNR, is tracer dependent.

National Category
Radiology, Nuclear Medicine and Medical Imaging
Identifiers
urn:nbn:se:uu:diva-333337 (URN)000404949906146 ()
Conference
Annual Meeting of the Society-of-Nuclear-Medicine-and-Molecular-Imaging (SNMMI), JUN 10-14, 2017, Denver, CO
Available from: 2017-11-15 Created: 2017-11-15 Last updated: 2017-11-15Bibliographically approved
Nordeman, P., Chow, S. Y., Odell, A. F., Antoni, G. & Odell, L. R. (2017). Palladium-mediated C-11-carbonylations using aryl halides and cyanamide. Organic and biomolecular chemistry, 15(22), 4875-4881.
Open this publication in new window or tab >>Palladium-mediated C-11-carbonylations using aryl halides and cyanamide
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2017 (English)In: Organic and biomolecular chemistry, ISSN 1477-0520, E-ISSN 1477-0539, Vol. 15, no 22, 4875-4881 p.Article in journal (Refereed) Published
Abstract [en]

A robust and high-yielding radiochemical synthesis of C-11-N-cyanobenzamides using a palladium-mediated aminocarbonylation with C-11-CO, aryl halides and cyanamide is described. The bidentate ligand 1,1'-bis(diphenylphosphino)ferrocene provided C-11-N-cyanobenzamides from aryl-iodides, bromides, triflates and even chlorides in 28-79% radiochemical yield after semi-preparative HPLC. To further highlight the utility of this method, novel C-11-N-cyanobenzamide analogs of flufenamic acid, meflanamic acid, dazoxiben and tamibarotene were synthesized in 34-71% radiochemical yields.

National Category
Medicinal Chemistry
Identifiers
urn:nbn:se:uu:diva-327370 (URN)10.1039/c7ob01064h (DOI)000403005500018 ()28537303 (PubMedID)
Available from: 2017-08-11 Created: 2017-08-11 Last updated: 2018-01-13Bibliographically approved
Vedung, F., Antoni, G., Wall, A., Fahlström, M., Larsson, E.-M. & Marklund, N. (2017). Persistent Decrease Of Cerebral Blood Flow In Traumatic Brain Injury And Sports-Related Concussion. Paper presented at 35th Annual National Neurotrauma Symposium, JUL 07-12, 2017, Snowbird, UT. Journal of Neurotrauma, 34(13), A8-A9.
Open this publication in new window or tab >>Persistent Decrease Of Cerebral Blood Flow In Traumatic Brain Injury And Sports-Related Concussion
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2017 (English)In: Journal of Neurotrauma, ISSN 0897-7151, E-ISSN 1557-9042, Vol. 34, no 13, A8-A9 p.Article in journal, Meeting abstract (Other academic) Published
Keyword
Cerebral perfusion, Concussion, ASL, athletes
National Category
Neurology
Identifiers
urn:nbn:se:uu:diva-335815 (URN)10.1089/neu.2017.29011.abstracts (DOI)000404530400021 ()
Conference
35th Annual National Neurotrauma Symposium, JUL 07-12, 2017, Snowbird, UT
Funder
Swedish Research CouncilThe Swedish Brain Foundation
Available from: 2018-01-22 Created: 2018-01-22 Last updated: 2018-01-22Bibliographically approved
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