| 61. |
- Magnusson, Peter, et al.
(författare)
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PET med O-15-vatten påvisade myokardischemi där övrig utredning gick bet.
- 2019
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Ingår i: Läkartidningen. - : Sveriges Läkarförbund. - 0023-7205 .- 1652-7518. ; 116
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Tidskriftsartikel (refereegranskat)abstract
- Elevation of troponin reflects myocardial infarction. The underlying causes should be assessed, as treatment and prognosis may differ widely. Myocardial damage with non-obstructive coronary arteries requires further evaluation including magnetic resonance tomography. We report a case of significant myocardial ischemia which was unnoticed by myocardial scintigraphy but detected by positron emission tomography (PET). The 15O-water tracer allows for quantitative assessment of myocardial perfusion including regional abnormalities and may thus diagnose microvascular dysfunction.
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| 62. |
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| 63. |
- Mitran, Bogdan, et al.
(författare)
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Selection of optimal chelator improves the contrast of GRPR imaging using bombesin analogue RM26.
- 2016
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Ingår i: International journal of oncology. - : Spandidos Publications. - 1791-2423 .- 1019-6439. ; 48:5, s. 2124-2134
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Tidskriftsartikel (refereegranskat)abstract
- Bombesin (BN) analogs bind with high affinity to gastrin-releasing peptide receptors (GRPRs) that are up-regulated in prostate cancer and can be used for the visualization of prostate cancer. The aim of this study was to investigate the influence of radionuclide-chelator complexes on the biodistribution pattern of the 111In-labeled bombesin antagonist PEG2-D-Phe-Gln-Trp-Ala-Val-Gly-His-Sta-Leu-NH2 (PEG2-RM26) and to identify an optimal construct for SPECT imaging. A series of RM26 analogs N-terminally conjugated with NOTA, NODAGA, DOTA and DOTAGA via a PEG2 spacer were radiolabeled with 111In and evaluated both in vitro and in vivo. The conjugates were successfully labeled with 111In with 100% purity and retained binding specificity to GRPR and high stability. The cellular processing of all compounds was characterized by slow internalization. The IC50 values were in the low nanomolar range, with lower IC50 values for positively charged natIn-NOTA-PEG2-RM26 (2.6±0.1 nM) and higher values for negatively charged natIn-DOTAGA-PEG2-RM26 (4.8±0.5 nM). The kinetic binding studies showed KD values in the picomolar range that followed the same pattern as the IC50 data. The biodistribution of all compounds was studied in BALB/c nu/nu mice bearing PC-3 prostate cancer xenografts. Tumor targeting and biodistribution studies displayed rapid clearance of radioactivity from the blood and normal organs via kidney excretion. All conjugates showed similar uptake in tumors at 4 h p.i. The radioactivity accumulation in GRPR-expressing organs was significantly lower for DOTA- and DOTAGA-containing constructs compared to those containing NOTA and NODAGA. 111In-NOTA-PEG2-RM26 with a positively charged complex showed the highest initial uptake and the slowest clearance of radioactivity from the liver. At 4 h p.i., DOTA- and DOTAGA-coupled analogs showed significantly higher tumor-to-organ ratios compared to NOTA- and NODAGA-containing variants. The NODAGA conjugate demonstrated the best retention of radioactivity in tumors, and, at 24 h p.i., had the highest contrast to blood, muscle and bones.
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| 64. |
- Nielsen, Roni, et al.
(författare)
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Cardiovascular Effects of Treatment With the Ketone Body 3-Hydroxybutyrate in Chronic Heart Failure Patients
- 2019
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Ingår i: Circulation. - : LIPPINCOTT WILLIAMS & WILKINS. - 0009-7322 .- 1524-4539. ; 139:18, s. 2129-2141
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Myocardial utilization of 3-hydroxybutyrate (3-OHB) is increased in patients with heart failure and reduced ejection fraction (HFrEF). However, the cardiovascular effects of increased circulating plasma-3-OHB levels in these patients are unknown. Consequently, the authors' aim was to modulate circulating 3-OHB levels in HFrEF patients and evaluate: (1) changes in cardiac output (CO); (2) a potential doseresponse relationship between 3-OHB levels and CO; (3) the impact on myocardial external energy efficiency (MEE) and oxygen consumption (MVO 2); and (4) whether the cardiovascular response differed between HFrEF patients and age-matched volunteers.METHODS: Study 1: 16 chronic HFrEF patients (left ventricular ejection fraction: 37 +/- 3%) were randomized in a crossover design to 3-hour of 3-OHB or placebo infusion. Patients were monitored invasively with a Swan-Ganz catheter and with echocardiography. Study 2: In a doseresponse study, 8 HFrEF patients were examined at increasing 3-OHB infusion rates. Study 3 to 4: 10 HFrEF patients and 10 age-matched volunteers were randomized in a crossover design to 3-hour 3-OHB or placebo infusion. MEE and MVO 2 were evaluated using 11C-acetate positron emission tomography.RESULTS: 3-OHB infusion increased circulating levels of plasma 3-OHB from 0.4 +/- 0.3 to 3.3 +/- 0.4 mM (P< 0.001). CO rose by 2.0 +/- 0.2 L/min (P< 0.001) because of an increase in stroke volume of 20 +/- 2 mL (P< 0.001) and heart rate of 7 +/- 2 beats per minute (bpm) (P< 0.001). Left ventricular ejection fraction increased 8 +/- 1% (P< 0.001) numerically. There was a dose-response relationship with a significant CO increase of 0.3 L/min already at plasma-3-OHB levels of 0.7 mM (P< 0.001). 3-OHB increased MVO 2 without altering MEE. The response to 3-OHB infusion in terms of MEE and CO did not differ between HFrEF patents and age-matched volunteers.CONCLUSIONS: 3-OHB has beneficial hemodynamic effects in HFrEF patients without impairing MEE. These beneficial effects are detectable in the physiological concentration range of circulating 3-OHB levels. The hemodynamic effects of 3-OHB were observed in both HFrEF patients and age-matched volunteers. 3-OHB may potentially constitute a novel treatment principle in HFrEF patients.
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| 65. |
- Nielsen, Roni Ranghøj, et al.
(författare)
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Quantitative estimation of extravascular lung water volume and preload by dynamic 15O-water positron emission tomography
- 2019
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Ingår i: European Heart Journal Cardiovascular Imaging. - : Oxford University Press. - 2047-2404 .- 2047-2412. ; 20:10, s. 1120-1128
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Tidskriftsartikel (refereegranskat)abstract
- AIMS: Left ventricular filling pressure (preload) can be assessed by pulmonary capillary wedge pressure (PCWP) during pulmonary arterial catheterization (PAC). An emerging method [pulse indexed contour cardiac output (PICCO)] can estimate preload by global end-diastolic volume (GEDV) and congestion as extravascular lung water (EVLW) content. However, no reliable quantitative non-invasive methods are available. Hence, in a porcine model of pulmonary congestion, we evaluated EVLW and GEDV by positron emission tomography (PET). The method was applied in 35 heart failure (HF) patients and 9 healthy volunteers.METHODS AND RESULTS: Eight pigs were studied. Pulmonary congestion was induced by a combination of beta-blockers, angiotensin-2 agonist and saline infusion. PAC, PICCO, computerized tomography, and 15O-H2O-PET were performed. EVLW increased from 521 ± 76 to 973 ± 325 mL (P < 0.001) and GEDV from 1068 ± 170 to 1254 ± 85 mL (P < 0.001). 15O-H2O-PET measures of EVLW increased from 566 ± 151 to 797 ± 231 mL (P < 0.001) and GEDV from 364 ± 60 to 524 ± 92 mL (P < 0.001). Both EVLW and GEDV measured with PICCO and 15O-H2O-PET correlated (r2 = 0.40, P < 0.001; r2 = 0.40, P < 0.001, respectively). EVLW correlated with Hounsfield units (HU; PICCO: r2 = 0.36, P < 0.001, PET: r2 = 0.46, P < 0.001) and GEDV with PCWP (PICCO: r2 = 0.20, P = 0.01, PET: r2 = 0.29, P = 0.002). In human subjects, measurements were indexed (I) for body surface area. Neither EVLWI nor HU differed between chronic stable HF patients and healthy volunteers (P = 0.11, P = 0.29) whereas GEDVI was increased in HF patients (336 ± 66 mL/m2 vs. 276 ± 44 mL/m2, P = 0.01).CONCLUSION: The present study demonstrates that 15O-H2O-PET can assess pulmonary congestion and preload quantitatively. Hence, prognostic information from 15O-H2O-PET examinations should be evaluated in clinical trials.
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| 66. |
- Nielsen, Steffen, et al.
(författare)
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Differential gene expression in primary fibroblasts induced by proton and cobalt-60 beam irradiation
- 2017
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Ingår i: Acta Oncologica. - 0284-186X .- 1651-226X. ; 56:11, s. 1406-1412
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Proton beam therapy delivers a more conformal dose distribution than conventional radiotherapy, thus improving normal tissue sparring. Increasing linear energy transfer (LET) along the proton track increases the relative biological effectiveness (RBE) near the distal edge of the Spread-out Bragg peak (SOBP). The severity of normal tissue side effects following photon beam radiotherapy vary considerably between patients.Aim: The dual study aim was to identify gene expression patterns specific to radiation type and proton beam position, and to assess whether individual radiation sensitivity influences gene expression levels in fibroblast cultures irradiated in vitro.Methods: The study includes 30 primary fibroblast cell cultures from patients previously classified as either radiosensitive or radioresistant. Cells were irradiated at three different positions in the proton beam profile: entrance, mid-SOBP and at the SOBP distal edge. Dose was delivered in three fractions × 3.5 Gy(RBE) (RBE 1.1). Cobalt-60 (Co-60) irradiation was used as reference. Real-time qPCR was performed to determine gene expression levels for 17 genes associated with inflammation response, fibrosis and angiogenesis.Results: Differences in median gene expression levels were observed for multiple genes such as IL6, IL8 and CXCL12. Median IL6 expression was 30%, 24% and 47% lower in entrance, mid-SOBP and SOBP distal edge groups than in Co-60 irradiated cells. No genes were found to be oppositely regulated by different radiation qualities. Radiosensitive patient samples had the strongest regulation of gene expression; irrespective of radiation type.Conclusions: Our findings indicate that the increased LET at the SOBP distal edge position did not generally lead to increased transcriptive response in primary fibroblast cultures. Inflammatory factors were generally less extensively upregulated by proton irradiation compared with Co-60 photon irradiation. These effects may possibly influence the development of normal tissue damage in patients treated with proton beam therapy.
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| 67. |
- Nilsson, Karl, et al.
(författare)
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Large-eddy simulations of the Lillgrund wind farm
- 2015
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Ingår i: Wind Energy. - : John Wiley & Sons. - 1095-4244 .- 1099-1824. ; 18:3, s. 449-467
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Tidskriftsartikel (refereegranskat)abstract
- The power production of the Lillgrund wind farm is determined numerically using large-eddy simulations and compared with measurements. In order to simulate realistic atmospheric conditions, pre-generated turbulence and wind shear are imposed in the computational domain. The atmospheric conditions are determined from data extracted from a met mast, which was erected prior to the establishment of the farm. In order to allocate most of the computational power to the simulations of the wake flow, the turbines are modeled using an actuator disc method where the discs are imposed in the computational domain as body forces which for every time step are calculated from tabulated airfoil data. A study of the influence of imposed upstream ambient turbulence is performed and shows that higher levels of turbulence results in slightly increased total power production and that it is of great importance to include ambient turbulence in the simulations. By introducing ambient atmospheric turbulence, the simulations compare very well with measurements at the studied inflow angles. A final study aiming at increasing the farm production by curtailing the power output of the front row turbines and thus letting more kinetic energy pass downstream is performed. The results, however, show that manipulating only the front row turbines has no positive effect on the farm production, and therefore, more complex curtailment strategies are needed to be tested.
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| 68. |
- Nilsson, Karl, et al.
(författare)
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Validation of the actuator line method using near wake measurements of the MEXICO rotor
- 2015
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Ingår i: Wind Energy. - : John Wiley & Sons. - 1095-4244 .- 1099-1824. ; 18:3, s. 499-514
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Tidskriftsartikel (refereegranskat)abstract
- The purpose of the present work is to validate the capability of the actuator line method to compute vortex structures in the near wake behind the MEXICO experimental wind turbine rotor. In the MEXICO project/MexNext Annex, particle image velocimetry measurements have made it possible to determine the exact position of each tip vortex core in a plane parallel to the flow direction. Determining center positions of the vortex cores makes it possible to determine the trajectory of the tip vortices, and thus the wake expansion in space, for the analyzed tip speed ratios. The corresponding cases, in terms of tip speed ratios, have been simulated by large-eddy simulations using a Navier - Stokes code combined with the actuator line method. The flow field is analyzed in terms of wake expansion, vortex core radius, circulation and axial and radial velocity distributions. Generally, the actuator line method generates significantly larger vortex cores than in the experimental cases, but predicts the expansion, the circulation and the velocity distributions with satisfying results. Additionally, the simulation and experimental data are used to test three different techniques to compute the average axial induction in the wake flow. These techniques are based on the helical pitch of the tip vortex structure, 1D momentum theory and wake expansion combined with mass conservation. The results from the different methods vary quite much, especially at high values of λ.
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| 69. |
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| 70. |
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