Publications Repository - Helmholtz-Zentrum Dresden-Rossendorf
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42029 Publications
Increased FDG uptake on late-treatment PET in non-tumour-affected oesophagus is prognostic for pathological complete response and disease recurrence in patients undergoing neoadjuvant radiochemotherapy
Zschaeck, S.; Hofheinz, F.; Zöphel, K.; Bütof, R.; Jentsch, C.; Schmollack, J.; Löck, S.; Kotzerke, J.; Baretton, G.; Weitz, J.; Baumann, M.; Krause, M.
Abstract
Purpose
Early side effects including oesophagitis are potential prognostic factors in patients undergoing radiochemotherapy (RCT) for locally advanced oesophageal cancer (LAEC). We assessed the prognostic value of 18F-fluorodeoxyglucose (FDG) uptake within irradiated non-tumour-affected oesophagus (NTO) during restaging positron emission tomography (PET) as a surrogate for inflammation/oesophagitis.
Methods
This retrospective evaluation included 64 patients with LAEC who had completed neoadjuvant RCT and had successful oncological resection. All patients underwent FDG PET/CT before and after RCT. In the restaging PET scan maximum and mean standardized uptake values (SUVmax, SUVmean) were determined in the tumour and NTO. Univariate Cox regression with respect to overall survival, local control, distant metastases and treatment failure was performed. Independence of clinically relevant parameters was tested in a multivariate Cox regression analysis.
Results
Increased FDG uptake, measured in terms of SUVmean in NTO during restaging was significantly associated with complete pathological remission (p = 0.002) and did not show a high correlation with FDG response of the tumour (rho < 0.3). In the univariate analysis, increased SUVmax and SUVmean in NTO was associated with improved overall survival (p = 0.011, p = 0.004), better local control (p = 0.051, p = 0.044), a lower rate of treatment failure (p < 0.001 for both) and development of distant metastases (p = 0.012, p = 0.001). In the multivariate analysis, SUVmax and SUVmean in NTO remained a significant prognostic factor for treatment failure (p < 0.001, p = 0.004) and distant metastases (p = 0.040, p = 0.011).
Conclusions
FDG uptake in irradiated normal tissues measured on restaging PET has significant prognostic value in patients undergoing neoadjuvant RCT for LAEC. This effect may potentially be of use in treatment personalization.
Keywords: Oesophageal cancer Radiochemotherapy Side effects Inflammation FDG pet
Involved research facilities
- PET-Center
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European Journal of Nuclear Medicine and Molecular Imaging 44(2017)11, 1813-1822
DOI: 10.1007/s00259-017-3742-0
Cited 12 times in Scopus
Permalink: https://www.hzdr.de/publications/Publ-25857
Nonmodal and nonlinear dynamics of helical magnetorotational instability
Mamatsashvili, G.; Stefani, F.
Abstract
The helical magnetorotational instability (HMRI), a relative of standard MRI (SMRI), has become a subject of active research in recent years in connection with the experiments on magnetized cylindrical Taylor-Couette (TC) flows. It occurs in the presence of helical magnetic field, consisting of azimuthal and axial components and, like SMRI with only axial magnetic field, taps into the rotational energy of the flow. However, a main advantage of HMRI is that, being governed by the Reynolds (Re) and Hartmann (Ha) numbers, it persists even at very small magnetic Prandtl numbers typical to liquid metals, in contrast to SMRI. The linear development of HMRI has been widely studied theoretically using both classical modal and more recently by nonmodal stability analysis, where a fundamental connection between nonmodal dynamics and dissipation-induced (double-diffusive) modal instabilities, such as HMRI, has been demonstrated. A series of specially designed liquid metal TC experiments provided the first experimental evidence of HMRI and reproduced the main results of the linear theory, such as the stability threshold and propagation speed (frequency) of HMRI-wave. More importantly, these experiments revealed much richer dynamics of HMRI as a function of system parameters (Re, Ha, etc.) than that obtained from the linear analysis only. These results prompted further theoretical studies of the nonlinear development of HMRI, but detailed physics of its saturation and sustenance still remains missing, especially when comparison with the experiment is concerned.
Motivated by the existing experimental results, we investigate the evolution of HMRI, from its linear growth to nonlinear saturation using numerical simulations.
We show that depending on the Reynolds number, two regimes of saturation can be realized. At Re below a certain critical value (but higher than the instability threshold), the saturation energy linearly depends on Re and the corresponding energy spectrum is dominated by the most unstable mode and its multiple wavenumbers, while at larger Re, the energy increases with Re, but not linearly, and the related spectrum looks like turbulent spectrum, being much smoother over wavenumbers. The nonlinear state remains markedly axisymmetric (m = 0)
and at high Re can be viewed as a 2D turbulence, whose (spectral) properties are further examined.
Keywords: MHD; turbulence; nonmodal growth; instabilities; numerical simulations
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Lecture (Conference)
2nd Conference on Natural Dynamos, 25.06.-01.07.2017, Valtice Castle, Czech Republic
Permalink: https://www.hzdr.de/publications/Publ-25856
Kinetic Modeling of the New σ1 Receptor Ligand (-)-[18F]Fluspidine in the Human Brain
Becker, G. A. F.; Meyer, P.; Patt, M.; Hesse, S.; Luthardt, J.; Patt, J.; Rullmann, M.; Fischer, S.; Kluge, A.; Steinbach, J.; Wünsch, B.; Brust, P.; Sabri, O.
Abstract
Objectives:
The σ1 receptor, a transmembrane protein located at the endoplasmatic reticulum is involved in a variety of neuropsychiatric diseases, e.g. depression, schizophrenia and drug addiction. The newly developed PET tracer (-)-[18F]Fluspidine was successfully applied to quantify σ1 receptors in the porcine brain [1]. Here we present the first PET quantification of σ1 receptors with (-)-[18F] Fluspidine in humans.
Methods:
After intravenous administration of 269.6±13.3 MBq (-)-[18F]Fluspidine PET brain imaging was performed in 10 healthy subjects (age 36.6±14.8 years; gender 5F/5M) using an ECAT EXACT HR+ system in 3D-acquisition mode. 26 frames were acquired from 0-210 min post injection and motion corrected with SPM2. Kinetic modeling using 1- and 2-tissue compartment models (1TCM, 2TCM) with metabolite corrected arterial input-function was applied to the volume of interest (VOI) based tissue time-activity curves (TACs) in 43 brain regions (anatomically defined via MRI co-registration). Time ranges from 0 to 90 and 0 to 210 min were investigated. Model-based receptor parameter was the total distribution volume VT (ml/cm-3), a linear function of receptor density.
Results:
TACs of all 43 regions could be described with the 1- and 2TCM. VT in all cortical regions could be reliably estimated from 90 min PET data already. In white matter longer measurements can be necessary. The distribution volume was highest in the cerebellar cortex (31.4±6.1), low in the centrum semiovale (17.7±7.1) and ranged in cortical structures between 20.9±3.9 in the orbitofrontal and 24.9±5.7 in the posterior cingulate cortex (pcc) (2TCM, 90 min). The distribution volumes computed from 210 min data were comparable to 90 min results, e.g. in pcc 25.7±5.9 (2TCM) and 25.7±6.0 (1TCM).
Conclusions:
σ1 receptor parameters in cortical structures can be estimated with a 1- or 2TCM from 90 min (-)-[18F]Fluspidine TACs. If a model derived receptor parameter is used in a classification problem, e.g., distinguishing patients with depression from healthy controls, the final model decision should be made on the basis of the PET data of both groups.
References:
P. Brust, ..., O. Sabri, Journal of Nuclear Medicine 2014, 55, 1730-1736
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Abstract in refereed journal
Journal of Labelled Compounds and Radiopharmaceuticals 60(2017)S1, S383
DOI: 10.1002/jlcr.3508
Cited 3 times in Scopus
Permalink: https://www.hzdr.de/publications/Publ-25855
Development of (S)-[18F]T1 as first PET tracer for imaging the α3β4 nicotinic acetylcholine receptor
Sarasamkan, J.; Fischer, S.; Deuther-Conrad, W.; Scheunemann, M.; Ludwig, F.-A.; Vajragupta, O.; Brust, P.
Abstract
Objectives:
Neuronal nicotinic acetylcholine receptors (nAChRs) are composed of diverse subtypes which have different functional properties, distributions and pharmacological profiles. The α7, α3β4 and α4β2 nAChRs are well recognized as drug targets implicated in cognitive disorders and addiction. Therefore, to image nAChRs in vivo, subtype-selective radiotracers need to be developed.
Methods:
A novel PET radiotracer for imaging nAChRs was developed based on the design and synthesis of six racemates (T1-T6) and its enantiomers based on the structure of triazole-quinuclidine QND8. All R enantiomers were found to be selective to α7 nAChR while their S counterparts were selective to α3β4 nAChR. (S)-T1 binds selectively to α3β4 nAChR (Ki 3.09 nM) with very modest off-target binding to α1 receptor, dopamine receptors and serotonin receptors. Radiosynthesis of (S)-[18F]T1 was achieved by two-step reaction, starting with the preparation of 18F-alkyne synthon (1-ethynyl-4-[18F]fluorobenzene; [18F]2), followed by the click reaction between [18F]2 and (S)-azidoquinuclidine.
Results:
The radiosynthesis of (S)-[18F]T1 was achieved in 130 min with the overall isolated radiochemical yield of 4.3±1.3%, radiochemical purity > 99%, and molar radioactivity > 158 GBq/µmol at end of synthesis. The brain uptake and brain-to-blood ratio of this tracer in mice at 30 min after injection were 6.06% ID/g and 6.1, respectively. The tracer remained intact > 99% in brain homogenates. Only one major radiometabolite was detected in plasma and urine samples. In vitro autoradiography on pig brain slices revealed high binding of (S)-[18F]T1 to brain regions consistent with the α3β4 nAChR distribution. Selective binding of (S)-[18F]T1 was evidenced by (i) the reduction of percent labeling of this tracer in the presence of a selective α3β4 nAChR partial agonist, AT-1001 and (ii) the retention of the tracer in the presence of α7 nAChR-specific SSR180711.
Conclusions:
These findings suggest the potential of (S)-[18F]T1 for imaging the α3β4 nAChR in the brain as a promising tool for both diagnosis and therapy monitoring of neurodegenerative diseases and addiction.
Acknowledgement:
This work was supported by Thailand Research Fund (TRF) through the Royal Golden Jubilee Ph.D. Program (grant no. PHD/0272/2552) to J.S. and O.V.
References:
[1] K. Arunrungvichian, V. V. Fokin, O. Vajragupta, P. Taylor. ACS Chem Neurosci. 2015, 6, 1317-1330.
[2] J. Sarasamkan, M. Scheunemann, N. Apaijai, S. Palee, W. Parichatikanond, K. Arunrungvichian, et al. ACS Med. Chem. Lett. 2016, 7, 890- 895.
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Abstract in refereed journal
Journal of Labelled Compounds and Radiopharmaceuticals 60(2017)S1, S50
DOI: 10.1002/jlcr.3507
Permalink: https://www.hzdr.de/publications/Publ-25854
ElectroHydroDynamic emitters developments for improving Focused Ion Beam machines
Gierak, J.; Bischoff, L.; Mazarov, P.; Bruchhaus, L.; Blanchard-Desce, M.; Vaultier, M.; Lozano, P.
Abstract
The patterning of samples using Focused Ion Beams (FIB) is very popular, widely used both for industrial [1] and emerging nanoscience prototyping applications [2]. This FIB technique allows 3D and direct patterning of target materials using a finely focused pencil of ions having speeds of several hundreds of km/seconds at impact with a penetration range of a few tens of nanometres. Thanks to this, local information and/or modifications can be obtained at the target surface. In what the ion nature is concerned, apart that many elements can be used in FIB technology as pure elements or in the form of alloys, gallium (Ga+ ions) is often preferred.
Traditionally for several decades FIB technology has been mainly based on gallium Liquid Metal Ion Sources (LMIS). LMIS are also known as electrohydrodynamically (EHD) driven ion emitters operating in a cone-jet mode. The very high brightness, long lifespan, small source size, and easy handling of this emitter remain its chief and most decisive advantages. On the other hand, some weaknesses are also well known that inhibit the resolution of EHD/LMIS-based FIBs. Therefore progress on ion sources operational characteristics still remains very desirable.
In this presentation we will first summarize our work aiming at understanding, optimizing and evaluating gallium LMIS “needle type” performances. In particular stable operation at lowest possible emission currents will be detailed. The gains in terms of patterning resolution and beam selectivity [3], we will evaluate, are firm evidence that progresses can still be expected from this mature technology.
We will then review and detail the advantages of Liquid Metal Alloy Ion Sources (LMAIS) that represent a promising alternative to expand the already remarkable application field and potential of FIB machines in the field of nanosciences. Indeed selecting the best suited elements transported in a focused ion beam can open new nanofabrication routes. In this presentation we will explain that nearly half of the elements of the periodic table can already be made available to the FIB technology as a result of a continuous research effort in this area [4] and how, in our opinion, nanofabrication shall now take benefit of these capabilities. Finally we will introduce our new addition to the arsenal of EHD driven devices: The Ionic Liquid Ion Sources (ILIS). ILIS are capable to produce ion beams through field-evaporation, also in the cone-jet mode, but from room temperature molten-salts [5]. The possibility of extracting both positive and negative ions at
emission current several orders of magnitude below LMIS standards is already a very appealing perspective in terms of source virtual source size and brightness. Then we will show that ILIS allows to access new ionic species thanks to the almost limitless chemical engineering latitude of molten salts. Moreover subsequent tuning can be achieved via selecting the tip polarity, the ion emission current and the ion landing energy. We will show the possibility to achieve a new kind of FIB patterning using a beam of chemically reactive ion radicals native in the transported beam. This represents a formidable perspective for FIB technology.
In conclusion we will summarize our vision on the future of FIB technology based on electrohydrodynamically (EHD) driven emitters operating in the conejet mode, both in terms of performances, versatility and on the science frontiers these might help to push.
[1] J. Orloff, Scientific American Oct. 1994, pp.74-79
[2] J. Gierak Nanofabrication 2014; Volume 1: pp. 35–52
[3] J. Gierak and R. Jede, Patent US8546768 B2, WO2010029270A1; Sept 2008
[4] L. Bischoff, P. Mazarov, L. Bruchhaus, and J. Gierak, Appl. Phys. Rev. 2016; 3: pp. 021101
[5] C. Perez-Martinez, J. Gierak, and P. C. Lozano, P106 (Invited), EIPBN Conference, May 31-
June 3, 2016, Pittsburgh, PA
Keywords: Focused Ion Beam; Liquid Metal Alloy Ion Source; Ionic Liquid Ion Source; FIB patterning
Involved research facilities
- Ion Beam Center DOI: 10.17815/jlsrf-3-159
Related publications
- DOI: 10.17815/jlsrf-3-159 is cited by this (Id 25853) publication
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Lecture (Conference)
Conference on ultracold ion and electron beams, 10.-12.07.2017, Eindhoven, The Netherlands -
Lecture (Conference)
61th International Conference on Electron, Ion, and Photon Beam Technology and Nanofabrication EIPBN-2017, 30.05.-02.06.2017, Orlando, USA
Permalink: https://www.hzdr.de/publications/Publ-25853
Ion-Beam-Induced Atomic Mixing in Ge, Si, and SiGe, Studied by Means of Isotope Multilayer Structures
Bracht, H.; Radek, M.; Posselt, M.; Liedke, B.; Schmidt, B.; Voelskow, M.; Bischoff, L.; Böttger, R.; Prucnal, S.; Hansen, J. L.; Larsen, A. N.; Bougeard, D.
Abstract
Crystalline and preamorphized isotope multilayers are utilized to investigate the dependence of ion beam mixing in silicon (Si), germanium (Ge), and silicon germanium (SiGe) on the atomic structure of the sample, temperature, ion flux, and electrical doping by the implanted ions. The magnitude of mixing is determined by secondary ion mass spectrometry. Rutherford backscattering spectrometry in channeling geometry, Raman spectroscopy, and transmission electron microscopy provide information about the structural state after ion irradiation. Different temperature regimes with characteristic mixing properties are identified. A disparity in atomic mixing of Si and Ge becomes evident while SiGe shows an intermediate behavior. Overall, atomic mixing increases with temperature, and it is stronger in the amorphous than in the crystalline state. Ion-beam-induced mixing in Ge shows no dependence on doping by the implanted ions. In contrast, a doping effect is found in Si at higher temperature. Molecular dynamics simulations clearly show that ion beam mixing in Ge is mainly determined by the thermal spike mechanism. In the case of Si thermal spike, mixing prevails at low temperature whereas ion beam-induced enhanced self-diffusion dominates the atomic mixing at high temperature. The latter process is attributed to highly mobile Si di-interstitials formed under irradiation and during damage annealing.
Keywords: silicon; germanium; ion beam; atomic mixing; thermal spike; radiation enhanced diffusion; amorphization; recrystallization; molecular dynamics
Involved research facilities
- Ion Beam Center DOI: 10.17815/jlsrf-3-159
Related publications
- DOI: 10.17815/jlsrf-3-159 is cited by this (Id 25852) publication
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Materials 10(2017), 813
DOI: 10.3390/ma10070813
ISSN: 1996-1944
Cited 8 times in Scopus
Permalink: https://www.hzdr.de/publications/Publ-25852
Modeling tumor control probability for spatially inhomogeneous risk of failure based on clinical outcome data
Lühr, A.; Löck, S.; Jakobi, A.; Stützer, K.; Bandurska-Luque, A.; Vogelius, I. R.; Enghardt, W.; Baumann, M.; Krause, M.
Abstract
Purpose
Objectives of this work are (1) to derive a general clinically relevant approach to model tumor control probability (TCP) for spatially variable risk of failure and (2) to demonstrate its applicability by estimating TCP for patients planned for photon and proton irradiation.
Methods and Materials
The approach divides the target volume into sub-volumes according to retrospectively observed spatial failure patterns. The product of all sub-volume TCPi values reproduces the observed TCP for the total tumor. The derived formalism provides for each target sub-volume i the tumor control dose (D50,i) and slope (γ50,i) parameters at 50% TCPi. For a simultaneous integrated boost (SIB) prescription for 45 advanced head and neck cancer patients, TCP values for photon and proton irradiation were calculated and compared. The target volume was divided into gross tumor volume (GTV), surrounding clinical target volume (CTV), and elective CTV (CTVE). The risk of a local failure in each of these sub-volumes was taken from the literature.
Results
Convenient expressions for D50,i and γ50,i were provided for the Poisson and the logistic model. Comparable TCP estimates were obtained for photon and proton plans of the 45 patients using the sub-volume model, despite notably higher dose levels (on average +4.9%) in the low-risk CTVE for photon irradiation. In contrast, assuming a homogeneous dose response in the entire target volume resulted in TCP estimates contradicting clinical experience (the highest failure rate in the low-risk CTVE) and differing substantially between photon and proton irradiation.
Conclusions
The presented method is of practical value for three reasons: It (a) is based on empirical clinical outcome data; (b) can be applied to non-uniform dose prescriptions as well as different tumor entities and dose-response models; and (c) is provided in a convenient compact form. The approach may be utilized to target spatial patterns of local failures observed in patient cohorts by prescribing different doses to different target regions. Its predictive power depends on the uncertainty of the employed established TCP parameters D50 and γ50 and to a smaller extent on that of the clinically observed pattern of failure risk.
Keywords: Radiotherapy; Dose–response modeling; TCP; Inhomogeneous dose; Head and neck cancer; Proton therapy
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Zeitschrift für Medizinische Physik 27(2017), 285-299
DOI: 10.1016/j.zemedi.2017.06.003
Cited 6 times in Scopus
Downloads
- Final Draft PDF 1023 kB Secondary publication
Permalink: https://www.hzdr.de/publications/Publ-25851
Superconducting Ferromagnetic Nanodiamond
Zhang, G.; Samuely, T.; Xu, Z.; Jochum, J. K.; Volodin, A.; Zhou, S.; May, P. W.; Onufriienko, O.; Kačmarčík, J.; Steele, J. A.; Li, J.; Vanacken, J.; Vacík, J.; Szabó, P.; Yuan, H.; Roeffaers, M. B. J.; Cerbu, D.; Samuely, P.; Hofkens, J.; Moshchalkov, V. V.
Abstract
Superconductivity and ferromagnetism are two mutually antagonistic states in condensed matter. Research on the interplay between these two competing orderings sheds light not only on the cause of various quantum phenomena in strongly correlated systems but also on the general mechanism of superconductivity. Here we report on the observation of the electronic entanglement between superconducting and ferromagnetic states in hydrogenated boron-doped nanodiamond films, which have a superconducting transition temperature Tc ∼ 3 K and a Curie temperature TCurie > 400 K. In spite of the high TCurie, our nanodiamond films demonstrate a decrease in the temperature dependence of magnetization below 100 K, in correspondence to an increase in the temperature dependence of resistivity. These anomalous magnetic and electrical transport properties reveal the presence of an intriguing precursor phase, in which spin fluctuations intervene as a result of the interplay between the two antagonistic states. Furthermore, the observations of high-temperature ferromagnetism, giant positive magnetoresistance, and anomalous Hall effect bring attention to the potential applications of our superconducting ferromagnetic nanodiamond films in magnetoelectronics, spintronics, and magnetic field sensing.
Keywords: anomalous Hall effect; giant positive magnetoresistance; nanodiamond; spin fluctuations; superconductivity and ferromagnetism
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ACS Nano 11(2017), 5358-5366
DOI: 10.1021/acsnano.7b01688
Cited 29 times in Scopus
Downloads
- Final Draft PDF 7,3 MB Secondary publication
Permalink: https://www.hzdr.de/publications/Publ-25850
Structural and optical properties of Gd implanted GaN with various crystallographic orientations
Macková, A.; Malinský, P.; Jagerová, A.; Sofer, Z.; Klímová, K.; Sedmidubský, D.; Pristovsek, M.; Mikulics, M.; Lorinčík, J.; Böttger, R.; Akhmadaliev, S.
Abstract
Structure, morphology, and optical properties of Gd implanted GaN epitaxial layers were studied for (0001), (11 − 20), and (11 − 22) orientations. The GaN layers grown by MOVPE on sapphire were subsequently implanted with 200 keV Gd+ ions using fluences of 5 × 1015 and 5 × 1016 cm− 2. Dopant depth profiling was accomplished by Rutherford Back-Scattering spectrometry (RBS). Structural and optical changes during subsequent annealing were characterized by RBS, Raman spectroscopy, and photoluminescence measurements. Post-implantation annealing induced a structural reorganization of GaN structure in the buried layer depending on the introduced disorder level, i.e. depending on the implantation fluence and on crystallographic orientation. The defect density depth distribution was evaluated by RBS. The surface morphology and optical properties depend on particular crystallographic orientation.
Keywords: GaN implantation; RBS channelling; Optical properties of Gd implanted GaN
Involved research facilities
- Ion Beam Center DOI: 10.17815/jlsrf-3-159
Related publications
- DOI: 10.17815/jlsrf-3-159 is cited by this (Id 25849) publication
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Thin Solid Films 638(2017), 63
DOI: 10.1016/j.tsf.2017.07.036
Cited 13 times in Scopus
Permalink: https://www.hzdr.de/publications/Publ-25849
Interplay between magnetic domain patterning and anisotropic magnetoresistance probed by magnetooptics
Osten, J.; Lenz, K.; Schultheiss, H.; Lindner, J.; McCord, J.; Fassbender, J.
Abstract
We study the correlation between the magnetic reversal and the anisotropic magnetoresistance (AMR) response in magnetic hybrid structures that were created by local modification of magnetic properties induced by ion implantation. The stripe pattern have been investigated simultaneously by dual-wavelength Kerr microscopy and magnetoresistance measurements. We observe that the switching of the stripe pattern introduces an additional AMR maximum. The domain wall in between the stripes provides a positive resistance contribution, whereas domains at the stripe edges lead to an asymmetric AMR response. A method for calculating the AMR response from the quantitative Kerr micrographs is demonstrated that allows the reconstruction of the AMR value within a region of interest only.
Keywords: anisotropic magnetoresistance; magnetic domain
Involved research facilities
- Ion Beam Center DOI: 10.17815/jlsrf-3-159
Related publications
- DOI: 10.17815/jlsrf-3-159 is cited by this (Id 25848) publication
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Physical Review B 97(2018), 014415
DOI: 10.1103/PhysRevB.97.014415
Cited 4 times in Scopus
Downloads
- Final Draft PDF 3,5 MB Secondary publication
Permalink: https://www.hzdr.de/publications/Publ-25848
Experimental and Numerical Modeling of Fluid Flow Processes in Continuous Casting: Results from the LIMMCAST-Project
Timmel, K.; Kratzsch, C.; Asad, A.; Schurmann, D.; Schwarze, R.; Eckert, S.
Abstract
The present paper reports about numerical simulations and model experiments concerned with the fluid flow in the continuous casting process of steel. This work was carried out in the LIMMCAST project in the framework of the Helmholtz alliance LIMTECH. A brief description of the LIMMCAST facilities used for the experimental modeling at HZDR is given here. Ultrasonic and inductive techniques and the X-ray radioscopy were employed for flow measurements or visualizations of two-phase flow regimes occurring in the submerged entry nozzle and the mold. Corresponding numerical simulations were performed at TUBAF taking into account the dimensions and properties of the model experiments. Numerical models were successfully validated using the experimental data base. The reasonable and in many cases excellent agreement of numerical with experimental data allows to extrapolate the models to real casting configurations. Exemplary results will be presented here showing the effect of electromagnetic brakes or electromagnetic stirrers on the flow in the mold or illustrating the properties of two-phase flows resulting from an Ar injection through the stopper rod.
Keywords: LIMTECH-alliance; Continuous Casting; numerical modeling; experimental modeling; liquid metal models; electromagnetic actuators; two-phase flow
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IOP Conference Series: Materials Science and Engineering 228(2017)1, 012019
DOI: 10.1088/1757-899X/228/1/012019
ISSN: 1757-899X
Cited 19 times in Scopus
Permalink: https://www.hzdr.de/publications/Publ-25847
Arterial spin labeling spatial coefficient of variation predicts carotid occlusion side
Mutsaerts, H. J.; Petr, J.; Bokkers, R.; Hendrikse, J.; Lazar, R.; Marshall, R.; Asllani, I.
Abstract
Collateral perfusion has been shown to be of key prognostic importance in carotid steno‐occlusive disease as it prevents irreversible ischemia1, 2. Arterial spin labeling ﴾ASL﴿ may provide a biomarker of collateral perfusion by measuring arterial transit time ﴾ATT﴿ in addition to cerebral blood flow ﴾CBF﴿. However, this leads to longer scanning times, lower signal‐to‐noise ratio3 and higher motion sensitivity4. We have developed a method to estimate the ATT from a single post‐labeling delay ﴾PLD﴿ ASL image using the spatial coefficient of variance ﴾CoV﴿5. Here, we investigate whether the spatial CoV lateralization through collateral perfusion can predict the side of carotid occlusion.
Involved research facilities
- PET-Center
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Lecture (Conference)
34th Annual Scientific Meeting of European Society for Magnetic Resonance in Medicine and Biology, 19.10.2017, Barcelona, Spain -
Abstract in refereed journal
Magnetic Resonance Materials in Physics, Biology and Medicine 30(2017)Suppl 1, 198
DOI: 10.1007/s10334-017-0633-0
ISSN: 1352-8661
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Permalink: https://www.hzdr.de/publications/Publ-25846
ExploreASL: image processing toolbox for multi-center arterial spin labeling population analyses
Mutsaerts, H.; Petr, J.; Lysvik, E.; Schrantee, A.; Shirzadi, Z.; Zelaya, F.; Groote, I.; O'Daly, O.; Kuijer, J.; de Bresser, J.; Richard, E.; Caan, M.; van Osch, M.; Golay, X.; Reneman, L.; Macintosh, B.; Masellis, M.; Hendrikse, J.; Barkhof, F.; Bjørnerud, A.; Nederveen, A.; Asllani, I.; Groot, P.
Abstract
Arterial spin labeling (ASL) perfusion MRI1 is rapidly maturing as a research tool, potential future biomarker2 and pharmacological monitoring agent3 for many diseases including neurodegeneration. There is thus a growing need for standardization of ASL image processing and quality control (QC) for voxel-based (VBA) and region-of-interest (ROI)-based analyses. Here, we present ExploreASL, a non-commercial software package that aims to harmonize image processing for ASL perfusion images for single- and multi-center studies4, 5. In addition, ExploreASL combines key structural image processing tools from recent literature to differentiate perfusion from structural effects.
Initiated through the EU-funded COST-action "ASL In Dementia", ExploreASL is a collaborative framework of researchers and clinical investigators. It was already used to process ~4000 ASL images from all major MRI vendors and ASL sequences, and a large variety of patient populations. The ultimate goal is to combine data from a large number of studies and identify common and different perfusion patterns to enhance knowledge of ASL image analysis and of the role of perfusion and structural changes in neurodegenerative pathophysiology.
Involved research facilities
- PET-Center
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Lecture (Conference)
34th Annual Scientific Meeting of European Society for Magnetic Resonance in Medicine and Biology, 19.10.2017, Barcelona, Spain
Permalink: https://www.hzdr.de/publications/Publ-25845
Perfusion changes following elective surgery in the elderly
Mutsaerts, H. J.; Kant, I.; Petr, J.; Winterer, G.; Spies, C.; Pischon, T.; Asllani, I.; Slooter, A.; Hendrikse, J.
Abstract
Purpose / Introduction
As society ages and medical technology advances, more and more elderly undergo elective surgery. However, older patients have an
increased risk of postoperative cognitive dysfunction, leading to impaired quality of life and an increased chance of becoming dependent 1.
The pathophysiology of these long‐term side effects is poorly understood. New imaging biomarkers may be used to study the postoperative
changes and evaluate the efficacy between different surgical or anesthetic strategies 1. In this study we explore the cerebral
blood flow ﴾CBF﴿ changes following elective surgery using arterial spin labeling ﴾ASL﴿ perfusion MRI.
Subjects and Methods
Data were drawn from the Biomarker Development for Postoperative Cognitive Impairment in the Elderly ﴾BioCog﴿ study. Sixty‐five elderly
﴾71.7 ± 5.2 yrs, 73.9% M﴿ were scanned before and approximately 3 months after various types of elective surgery, excluding brain surgery
and history of dementia. A background suppressed 2D EPI pseudo‐continuous ASL scan was performed, with labeling duration 1650 ms
and post‐labeling delay slice‐range 1525‐2225 ms. CBF maps were processed2 and transformed into standard space3 using ExploreASL4.
We investigated global CBF changes, cognitive decline regions and the spatial coefficient of variation ﴾CoV﴿5.
Results
CBF decreased with 11.4% in the white matter ﴾WM, p=0.004﴿ and with 7.6% in the gray matter ﴾GM, p=0.017﴿ ﴾Table 1﴿. We did not
identify regional CBF changes ﴾data not shown﴿, suggesting that CBF decreased to a similar degree across the brain. The 8.8% WB CBF
decrease was correlated with baseline WB CBF ﴾r=0.63, p<0.001﴿.
The spatial CoV did not change ﴾p=0.179﴿, implying that there were no major macro‐vascular changes. Visually, the CBF decrease was
subtle and slightly asymmetrical ﴾Figure 1﴿. Figure 2 shows that CBF decreased in the majority of the individuals. This effect seems to be
stronger for higher baseline CBF values, whereas for lower CBF baseline values there were also patients whose CBF increased.
Discussion / Conclusion
We identified global CBF decreases across the brain after elective surgery, which was related with baseline CBF. Future studies are
encouraged to confirm these explorative findings in larger samples, investigate the apparent perfusion asymmetry and whether subgroups
can be defined with different degrees of CBF changes. Such an analysis may differentiate to what extent our findings are related to the type
or duration of surgery or anesthetics. Furthermore, the clinical relevance of these changes should be investigated by studying long‐term
adverse outcomes after surgery such as postoperative cognitive dysfunction1.
Involved research facilities
- PET-Center
-
Lecture (Conference)
34th Annual Scientific Meeting of European Society for Magnetic Resonance in Medicine and Biology, 19.10.2017, Barcelona, Spain -
Abstract in refereed journal
Magnetic Resonance Materials in Physics, Biology and Medicine 30(2017)Suppl 1, 372
DOI: 10.1007/s10334-017-0633-0
ISSN: 1352-8661
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Permalink: https://www.hzdr.de/publications/Publ-25844
Comparison of two methods for atrophy-correction in perfusion imaging: Partial-volume correction versus gray matter volume covariate
Petr, J.; Mutsaerts, H. J.; Hofheinz, F.; Steketee, R. M.; Smits, M.; Nederveen, A. J.; van den Hoff, J.; Asllani, I.
Abstract
Purpose / Introduction
Partial volume (PV) effects, caused by the mixing of different tissue signals within a voxel, are a well-recognized confounder in arterial spin labeling (ASL) imaging1,2, and are especially relevant in populations with atrophy3,4. Although several PV-correction algorithms exist5,6,7, many investigators continue to account for PV by using gray matter volume (GM-vol) as a covariate in the analysis of PV-uncorrected cerebral blood flow (CBF) images. To gain insight into this issue, we compared the performance of PV-correction5 vs GM-vol covariate using data based on acquired images that were simulated to reflect decreases in GM-vol and CBF.
Subjects and Methods
A total of 88 3D T1w images with 1x1x1mm3 resolution were acquired on twenty-two healthy volunteers8 (22.6±2.1 years, 9 men) who were scanned twice on two 3T scanners (GE Discovery and Philips Intera). T1w images were segmented, and CBF images were simulated to reflect GM-vol and CBF decrease with age, which was randomly and uniformly assigned to each subject (range 40-80 years). Sixteen different combinations of linear GM-volume and CBF decrease of 0, 0.25, 0.5 and 1% per year were simulated. The GM-vol decrease was simulated as cortical thinning using the high-resolution PV maps (Figure 1). The PV maps were then downsampled to the 3x3x7mm3 resolution. CBF images were simulated assuming baseline GM-CBF of 80±4 mL/min/100g and age-independent GM/WM-CBF ratio of 3. Additionally, pixelwise Gaussian noise (s.d. ±4 mL/min/100g) was added to the simulated CBF images11 (Figure 2). The mean CBF in voxels with GM content above 70% was analyzed with the two methods using a multivariate linear regression with age as fixed effect. The estimated slope of CBF change with age was compared with the simulated (ground truth) value.
Results
The PV-correction outperformed the GM-covariate method in all cases, and the PV-correction relative error was under 0.5% (Table 1). The error of the GM-covariate method increased with increasing atrophy and reached a maximum value of 10%.
Discussion / Conclusion
In the presence of atrophy, PV correction allowed for detection of CBF changes relatively independent of atrophy and with higher accuracy than the GM-volume covariate method. The reason is probably that the underestimation of PV-uncorrected CBF in the presence of atrophy does not perfectly correlate with the GM-vol decrease as it depends on additional factors such as cortical thickness. Further studies should evaluate the effect of global and local segmentation errors, and focal atrophy on the efficacy of both methods.
Involved research facilities
- PET-Center
-
Poster
34th Annual Scientific Meeting of European Society for Magnetic Resonance in Medicine and Biology, 19.10.2017, Barcelona, Spain -
Abstract in refereed journal
Magnetic Resonance Materials in Physics, Biology and Medicine 30(2017)Suppl 1, 395
DOI: 10.1007/s10334-017-0633-0
ISSN: 1352-8661
Downloads
Permalink: https://www.hzdr.de/publications/Publ-25843
Theranostic mercury 197(m)Hg: comparing different Hg/Au separation methods
Wang, C.; Červenák, J.; Walther, M.; Lebeda, O.; Preusche, S.; Pietzsch, H. J.; Steinbach, J.
Abstract
Objectives: The access to no-carrier-added 197(m)Hg for imaging and therapy research based on proton or deuteron irradiation of gold was recently reported1,2. The development of a rapid, reliable method for Hg/Au separation represents an important prerequisite for increasing yields. Ideally would be, a reversible interaction at least of one of the two metal ions, allowing for the product elution into a small volume. Besides the liquid-liquid extraction with methyl isobutyl keton (MIBK)1, the solid phase extraction using LN resin (LaNthanides) containing di(2-ethylhexyl)orthophosphoric acid as extractant was examined for this application2.
Methods: The gold target was irradiated for 120 minutes with a 25 µA beam current of 10 MeV protons resulting in 200 MBq of 197(m)Hg or with 15.6 MeV deuteron beam at 7.8 µA beam current for 180 min resulting in ca 800 MBq of of 197(m)Hg (EOB). The irradiated gold foil was dissolved after 1 h in 700 µl of aqua regia (freshly prepared 1 h before EOB from 525 µl 30% HCl + 175 µl 65% HNO3) at room temperature. The column preparation was carried out directly before use by loading 3.6 g LN resin slurried with 10 ml of 6M HCl onto the column and rinsing with additional 30 ml of 6M HCl. After dilution of the 700 µl product solution with 300 µl 6M HCl, this mixture was loaded onto the column and eluted with 6M HCl in 1 ml aliquots.
Results: Comparing with the previously described liquid-liquid extraction1, the solid phase extraction using the LN resin showed shorter performance time. After loading the mixture of chloroauric acid and n.c.a. mercury chloride, the colored gold solution was observed to rapidly distribute in the upper part of the column and then slowly proceeds down during the stepwise elution with 6M HCl. After the addition of 5–6 ml of HCl, the yellow chloroauric acid extended roughly two thirds down the column and almost stopped to move, while over 90% of n.c.a. radiomercury chloride (higher than 60-80% extracted with 4×500 µl MIBK) eluted in the following 2 ml of HCl. The separated 197(m)Hg has excellent radionuclidic purity with no detectable traces of 198Au. It is massively produced in the deuteron activation of gold and acts as a very sensitive tracer of the separation process efficiency.
Conclusions: In contrast to the liquid-liquid extraction, LN resin based method is significantly more efficient and provides product of high radionuclidic purity. Another major advantages compared to the liquid-liquid extraction are obviously 1) better handling and easy automation that shorten the separation time and minimize radiation burden, 2) negligible product losses 3) open possibility to collect and recycle the target material.
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Poster
22nd International Symposium on Radiopharmaceutical Sciences, 14.-19.05.2017, Dresden, Deutschland
Permalink: https://www.hzdr.de/publications/Publ-25842
Liquid metal batteries - materials selection and fluid dynamics
Weier, T.; Bund, A.; El-Mofid, W.; Horstmann, G.; Lalau, C.-C.; Landgraf, S.; Nimtz, M.; Starace, M.; Stefani, F.; Weber, N.
Abstract
Liquid metal batteries are possible candidates for massive and economically feasible large-scale stationary storage and as such could be key components of future energy systems based mainly or exclusively on intermittent renewable electricity sources. The completely liquid interior of liquid metal batteries and the high current densities give rise to a multitude of fluid flow phenomena that will primarily influence the operation of future large cells, but might be important for today’s smaller cells as well. The paper at hand starts with a discussion of the relative merits of using molten salts or ionic liquids as electrolytes for liquid metal cells and touches the choice of electrode materials. This excursus into electrochemistry is followed by an overview of investigations on magnetohydrodynamic instabilities in liquid metal batteries, namely the Tayler instability and electromagnetically excited gravity waves. A section on electro-vortex flows complements the discussion of flow phenomena. Focus of the flow related investigations lies on the integrity of the electrolyte layer and related critical parameters.
Keywords: liquid metal batteries; Tayler instability; metal pad role instability; electro-vortex flows
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IOP Conference Series: Materials Science and Engineering 228(2017), 012013
DOI: 10.1088/1757-899X/228/1/012013
Cited 34 times in Scopus
Permalink: https://www.hzdr.de/publications/Publ-25841
Numerical simulations of convection in the titanium reduction reactor
Teimurazov, A.; Frick, P.; Weber, N.; Stefani, F.
Abstract
We introduce a hydrodynamic model of convective flows in a titanium reduction reactor. The reactor retort is a cylindrical vessel with a radius of 0.75 m and a height up to 4m, filled with liquid magnesium at a temperature of 850°C. The exothermic chemical reaction on the metal surface, cooling of the side wall and heating of the lower part of the retort cause strong temperature gradients in the reactor during the process. These temperature gradients cause intensive convective flows inside the reactor. As a result of the reaction, a block of titanium sponge grows at the retort bottom and the magnesium salt, whose density is close to the density of magnesium, settles down. The process of magnesium salt settling in a titanium reduction reactor was numerically studied in a two-dimensional (full size model) and three-dimensional (30% size of the real model) non-stationary formulation. A detailed analysis was performed for configurations with and without presence of convective flow due to work of furnace heaters. It has been established that magnesium salt is settling in drops with sizes from ~3 cm to ~10 cm. It was shown that convective flow can entrain the drop and carry it with the vortex.
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Journal of Physics: Conference Series 891(2017)1, 012076
DOI: 10.1088/1742-6596/891/1/012076
Cited 8 times in Scopus
Permalink: https://www.hzdr.de/publications/Publ-25840
A fluorescence anisotropy-based assay to characterize the GTP-binding site of tissue transglutaminase
Hauser, C.; Kasprzyk, R.; Wodtke, R.; Jemielity, J.; Löser, R.; Pietsch, M.
Abstract
High activity of tissue transglutaminase (TGase 2) in various tumors is associated with both their increased metastatic and invasive potential and their resistance towards chemotherapy and radiation. This renders TGase 2 an attractive target for the development of agents that are capable of targeting the tumor-associated TGase 2 for both imaging and therapeutic approaches [1]. TGase 2 exists in two different conformations, with the closed one being the major intracellular form. It functions as a GTP-binding protein (Gh protein) at low Ca2+ levels, whereas transition to the open conformation (initiated by an increase in Ca2+ concentration) allows for the transamidase activity leading to protein-protein crosslinking [2].
Characterization of the GTP-binding activity of TGase 2 was done by means of a new fluorescence anisotropy assay using the literature known BODIPY FL-GTPγS [3]. This compound, internally quenched by an intramolecular stacking of the BODIPY and the guanosin moieties, is commonly used in fluorescence-based assays that make use of the unfolding and thereby dequenching of the fluorophore upon binding, leading to an increase in fluorescence. [3] Such behavior, however, interferes with the analysis of fluorescence anisotropy as the measured data have to be corrected [4].
To optimize the new assay, we investigated a small series of newly developed GTP- and GDP-analogues labeled with fluorescein for TGase affinity and change in fluorescence upon protein binding. All compounds show a significantly smaller increase in fluorescence intensity compared to the BODIPY FL-labeled nucleotide and – in some cases – an up to ten-fold superior binding affinity towards TGase 2. The fluorescence anisotropy assay was then validated for inhibition studies by investigation of GTP and GTPγS, which both show IC50 values (64 nM and 109 nM, respectively) that are in agreement with literature data [5,6].
Further investigations included titration of the GTP/TGase 2 interaction with CaCl2 to determine the Ca2+ concentration needed to shift TGase 2 to the extended conformation and inhibition studies with GDP and ATP as well as compounds targeting the acyltransferase domain of TGase 2.
References:
[1] Pietsch, M. et al. Bioorg. Med. Chem. Lett. 2013, 23, 6528.
[2] Kerr, C. et al. Oncogene 2016, doi: 10.1038/onc.2016.452.
[3] McEwen, D. P. et al. Methods Enzymol. 2002, 344, 403.
[4] Jameson, D. M. & Mocz, G. Methods Mol. Biol. 2005, 305, 301-322.
[5] Datta, S. et al. Biochemistry 2007, 46, 14819.
[6] Schaertl, S. et al. J. Biomol. Screen. 2010, 15, 478.
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Poster
Debrecen University Symposium 2017 - Transglutaminases in Medicine, 03.-05.08.2017, Debrecen, Ungarn
Permalink: https://www.hzdr.de/publications/Publ-25839
Radiosynthesis and in vitro characterisation of a potent 18F-fluorinated Nε-acryloyllysine as activity-based probe for transglutaminase 2
Wodtke, R.; Bauer, D.; Pufe, J.; Hauser, S.; Hauser, C.; Pietsch, M.; Pietzsch, J.; Löser, R.
Abstract
Transglutaminase 2 (TGase 2) represents an interesting target for the development of PET tracers for functional imaging of tumours. Among the TGase 2 inhibitors described in the literature, Nα-phenylacetyl-Nε-acryloyl-L-lysine-4-(6-methylpyridin-2-yl)piperazide (1) [1] seems to be most suitable for radiotracer development as this compound exhibits both strong inhibitory potential and selectivity towards human (h) TGase 2. Extensive structure-activity relationship studies by our group revealed some potent fluorinated analogues of 1, of which compound 3 (methyl group is substituted by fluorine) is a potential candidate for PET tracer development due to its great inhibitory potency and promising pharmacokinetic properties.
For the radiosyntheses of [18F]3, 6-nitro (2a) and 6-trimethylammonio-pyridines (2b) were envisaged as precursors for direct 18F-fluorination. The fluorination reactions using [18F]fluoride were performed under various conditions. Labelling of 2a by [18F]fluoride resulted in only moderate radiochemical yields (≈20%) accompanied by the formation of two 18F-labelled side products. In contrast to this, 18F-fluorination of 2b yielded exclusively [18F]3 in high radiochemical yields (≈70%). Therefore, precursor 2b was chosen for further radiosyntheses. In vitro characterisation of [18F]3 with regards to its reactivity towards hTGase 2 as well as its selectivity and specificity was done by radio-TLC and radio-SDS-PAGE. Kinetic investigations by radio-TLC provided values for kinact/KI that are in good agreement with values obtained by fluorimetric activity assays. Incubation of whole cell lysates of different human tumour cell lines exhibiting a high expression of TGase 2 with [18F]3, followed by SDS-PAGE and measurement of the 18F activity revealed essentially a single band around the molecular mass of hTGase 2 (≈77 kDa). Accordingly, no band was observed for those tumour cells which do not express TGase 2. Further experiments with [18F]3 will include cell uptake studies in living tumour cells as well as stability, biodistribution and PET studies in mice.
[1] J. Wityak et al. ACS Med. Chem. Lett. 2012, 3, 1024-1028
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Lecture (Conference)
Deberecen University Symposium 2017 - Transglutaminases in Medicine, 03.-05.08.2017, Debrecen, Ungarn
Permalink: https://www.hzdr.de/publications/Publ-25838
Magnetic field dynamos and magnetically triggered flow instabilities
Stefani, F.; Albrecht, T.; Arlt, R.; Christen, M.; Gailitis, A.; Gellert, M.; Giesecke, A.; Goepfert, O.; Herault, J.; Kirillov, O.; Mamatsashvili, G.; Priede, J.; Rüdiger, G.; Seilmayer, M.; Tilgner, A.; Vogt, T.
Abstract
The project A2 of the LIMTECH Alliance aimed at a better understanding of those magnetohydrodynamic instabilities that are relevant for the generation and the action of cosmic magnetic fields. These comprise the hydromagnetic dynamo effect and various magnetically triggered flow instabilities, such as the magnetorotational instability and the Tayler instability. The project was intended to support the experimental capabilities to become available in the framework of the DREsden Sodium facility for DYNamo and thermohydraulic studies (DRESDYN). An associated starting grant was focused on the dimensioning of a liquid metal experiment on the newly found magnetic destabilization of rotating flows with positive shear. In this survey paper, the main results of these two projects are summarized.
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IOP Conference Series: Materials Science and Engineering 228(2017), 012002
DOI: 10.1088/1757-899X/228/1/012002
Cited 3 times in Scopus
Permalink: https://www.hzdr.de/publications/Publ-25837
Strategies for the radiosynthesis of potent fluorinated Nε-acryloyllysines as potential PET tracers for transglutaminase 2
Wodtke, R.; Jäckel, E.; Bauer, D.; Lohse, M.; Wong, A.; Pufe, J.; Ruiz-Gómez, G.; Hauser, C.; Hauser, S.; Steinbach, J.; Teresa Pisabarro, M. T.; Pietsch, M.; Pietzsch, J.; Löser, R.
Abstract
Objectives: Various kinds of tumour entities are characterised by increased activity of transglutaminase 2 (TGase 2), which contributes to enhanced invasive potential of the tumour cells and their resistance to chemo- and radiotherapy. Therefore, this enzyme represents an interesting target for the development of PET tracers for functional imaging of tumours. Among the TGase 2 inhibitors described in the literature, Nε-acryloyllysine 1 [1] seems to be most suitable for radiotracer development as this compound exhibits both strong inhibitory potential and selectivity towards human TGase 2. Extensive structure-activity relationship studies by our group revealed some potent fluorinated analogues of 1, of which compounds 2 and 4 were identified as potential candidates for PET tracer development due to their great inhibitory potencies and promising pharmacokinetic properties.
Methods: Reference compounds 2 and 4 as well as the precursor 3 were synthesised in a modular synthetic route. For the radiosynthesis of [18F]2, thienyl and anisyl iodonium salts were envisaged as precursors for prosthetic labelling groups, which were synthesised starting from iodophenylacetates. The fluorination reactions using [18F]F- were performed under various conditions to maximise the radiochemical yield (RCY).
Results: Although a wide range of conditions for radiolabelling of the phenylacetic acid-derived iodonium salts were applied, no incorporation of [18F]F- could be observed. To identify possible reasons for this, the two other regioisomeric phenylacetic acid-derived iodonium salts were synthesised and subjected to labelling with [18F]F-. As a result of these efforts, the CH acidity of the benzylic methylene group was supposed to have a detrimental effect on the labelling reaction. In contrast to this, labelling of precursor 3 was successful with RCYs (non-isolated crude product) of up to 15%. Due to the difficult separation of 3 and [18F]4, the nitro group was reduced to the respective amino group by tin(II) chloride prior to purification by RP-HPLC.
Conclusions: After identifying fluorinated Nε-acryloyllysines as potential PET tracer candidates, strategies for their radiosynthesis were developed. While attempts for the incorporation of fluorine-18 at the non-activated phenylacetic acid moiety revealed inherent structural limitations, labelling at the 2-nitropyridine-derived precursor led to a promising PET tracer candidate.
References:
[1] J. Wityak et al. ACS Med. Chem. Lett. 2012, 3, 1024-1028
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Abstract in refereed journal
Journal of Labelled Compounds and Radiopharmaceuticals 60(2017)S1, S419-S419
DOI: 10.1002/jlcr.3508
Cited 3 times in Scopus
Permalink: https://www.hzdr.de/publications/Publ-25836
Improving Stability of Cathepsin B Endopeptidase Substrates as Potential Cleavage Sites in Activatable Cell-Penetrating Peptides
Kuhne, K.; Behring, L.; Birgit Belter, B.; Wodtke, R.; Steinbach, J.; Pietzsch, J.; Löser, R.
Abstract
Objectives: The cysteine protease cathepsin B, whose expression in tumors correlates with increased metastasis, therapy resistance, and a generally poor prognosis, represents an excellent target for molecular imaging using radiotracers [1]. We aim to develop a cathepsin B specific, substrate-based radiotracer derived from poly-d-arginine-based activatable cell penetrating peptides [2]. With in vivo application of peptides being often limited by short biological half-life, stabilization against proteolytic degradation is a key aspect in the development of this agent.
Methods: Octapeptide substrates containing the FRET pair aminobenzoyl/dinitrophenyl (Abz/Dnp) were synthesized by solid phase peptide synthesis in high purities and good yields, using non-proteinogenic and N-methylated amino acids (AA) for stabilization. All substrates were evaluated for cleavage efficiency by cathepsin B in orientation to [3]. In vitro stability studies were performed in human serum, with analysis by UPLC-ESI-MS, using the UV absorbance of Dnp (λ = 365 nm) for quantification and subsequent ESI-MS analysis for identification of degradation products.
Results: Rapid degradation has been observed for the endopeptidase substrate Abz-Gly-Ile-Val-Arg-Ala-Lys(Dnp)-Gly-Ser-NH2 in the in vitro serum stability assay (T1/2 = 3.7 min), which was due to cleavage at the P1-P1’ cleavage site (Arg-Ala) as indicated by LC-MS analysis. In a first step, arginine was substituted by citrulline to decrease susceptibility to trypsin-like serum proteases, which increased serum stability (T1/2 = 8.9 min). The non-proteinogenic AA homoarginine, homocitrulline and O-carboxybenzylserine are being tested as further potential substitutes for arginine. Secondary cleavage sites, identified at P4-P3 (Gly-Ile) and P2’-P3’ (Lys-Gly), were suppressed by insertion of Nα-methyl-isoleucine and Nα-methyl-glycine.
Conclusions: After the optimization of the endopeptidase substrate with regards to cathepsin B-specific cleavage, substrate stabilization against other proteases is a crucial step to a peptide-based radiotracer. We have demonstrated the potential for stabilization by introduction of citrulline, with further stabilization by insertion of N-methylated and non-proteinogenic amino acids ongoing, which will pave the way to the envisaged substrate-based imaging probes.
References:
1. Löser & Pietzsch, Front. Chem. 2015, 3, 37
2. Jiang et al., PNAS 2004, 101, 17867
3. Cotrin et al., Anal. Biochem. 2004, 335, 244
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Abstract in refereed journal
Journal of Labelled Compounds and Radiopharmaceuticals 60(2017)S1, S221-S221
DOI: 10.1002/jlcr.3508
Cited 3 times in Scopus
Permalink: https://www.hzdr.de/publications/Publ-25835
Brain volume and perfusion changes in healthy tissue of glioblastoma patients treated with radiochemotherapy
Petr, J.
Abstract
Brain volume and perfusion changes in healthy tissue of glioblastoma
patients treated with radiochemotherapy
Involved research facilities
- PET-Center
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Invited lecture (Conferences)
Invited talk at Leiden University Medical Center, 17.01.2017, Leiden, Netherlands
Permalink: https://www.hzdr.de/publications/Publ-25834
Resolution and deformation issues of the partial volume correction of ASL data
Petr, J.; Mutsaerts, H.; de Vita, E.; Maus, J.; van den Hoff, J.; Asllani, I.
Involved research facilities
- PET-Center
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Invited lecture (Conferences)
Invited lecture at UCL Institute of Neurology, 15.03.2016, London, United Kingdom
Permalink: https://www.hzdr.de/publications/Publ-25833
Thermal convection of liquid metal in the titanium reduction reactor
Teimurazov, A.; Frick, P.; Stefani, F.
Abstract
The structure of the convective flow of molten magnesium in a metallothermic titanium reduction reactor has been studied numerically in a three-dimensional non-stationary formulation with conjugated heat transfer between liquid magnesium and solids (steel walls of the cavity and titanium block). A nonuniform computational mesh with a total of 3.7 million grid points was used. The Large Eddy Simulation technique was applied to take into account the turbulence in the liquid phase. The instantaneous and average characteristics of the process and the velocity and temperature pulsation fields are analyzed. The simulations have been performed for three specific heating regimes: with furnace heaters operating at full power, with furnace heaters switched on at the bottom of the vessel only, and with switched-off furnace heaters. It is shown that the localization of the cooling zone can completely reorganize the structure of the large-scale flow. Therefore, by changing heating regimes, it is possible to influence the flow structure for the purpose of creating the most favorable conditions for the reaction. It is also shown that the presence of the titanium block strongly affects the flow structure.
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IOP Conference Series: Materials Science and Engineering 208(2017), 012041
DOI: 10.1088/1757-899X/208/1/012041
Cited 13 times in Scopus
Permalink: https://www.hzdr.de/publications/Publ-25832
Stability of MR Brain Perfusion Measurement Using Arterial Spin Labeling
Petr, J.; Hofheinz, F.; Platzek, I.; Schramm, G.; van den Hoff, J.
Abstract
Reproducibility of ASL perfusion measurements.
Involved research facilities
- PET-Center
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Lecture (Conference)
Meeting of the ASL COST Action, 03.02.2015, Les Diablerets, Switzerland
Permalink: https://www.hzdr.de/publications/Publ-25831
Transitions in a magnetized quasi-laminar spherical Couette flow
Kasprzyk, C.; Kaplan, E.; Seilmayer, M.; Stefani, F.
Abstract
First results of a new spherical Couette experiment are presented. The liquid metal flow in a spherical shell is exposed to a homogeneous axial magnetic field. For a Reynolds number Re=1000, we study the effect of increasing Hartmann number Ha. The resulting flow structures are inspected by ultrasound Doppler velocimetry. With a weak applied magnetic field, we observe an equatorially antisymmetric jet instability with the azimuthal wave number m=3. As the magnetic field strength increases, this instability vanishes. When the field is increased further, an equatorially symmetric return flow instability arises. Our observations are shown to be in good agreement with linear stability analysis and non-linear flow simulations.
- Magnetohydrodynamics 53(2017)2, 393-401
Downloads
- Final Draft PDF 1,8 MB Secondary publication
Permalink: https://www.hzdr.de/publications/Publ-25830
Comparison of MLAA-derived attenuation maps with and without utilisation of time-of-flight information in the attenuation estimation step
Nikulin, P.; Lougovski, A.; Hofheinz, F.; Maus, J.; van den Hoff, J.
Abstract
INTRODUCTION
As is well known, quantitative combined PET/MR imaging depends on accurate MR-based attenuation correction (MRAC). While a mostly satisfactory state of affairs has been reached today, problems persist regarding segmentation
errors including unsatisfactory bone identification and residual systematic differences in comparison to PET/CT. Alternative or complementary strategies for attenuation correction (AC), therefore, are of considerable relevance. In this context, Maximum Likelihood reconstruction of Attenuation and Activity (MLAA) is one of the most promising approaches. As A. Rezaei et al. have shown [1], Time-Of-Flight (TOF) image reconstruction is required to eliminate possible ”crosstalk” between the estimated activity and attenuation distribution. On the other hand, it is widely believed that use of the TOF information during attenuation estimation does not result in image quality improvement and thus is unnecessary, see for example ref. [2]. However, so far this assumption has never been thoroughly tested. We address this issue in the present investigation. To this end, we have compared TOF and non-TOF versions of the attenuation estimation algorithm as part of MLAA within the framework of our previously developed Tube of response High resolution OSEM Reconstruction (THOR), see ref [3].
METHODS
MLAA is an image reconstruction algorithm, which maximizes the Likelihood function by alternately updating activity distribution and attenuation map. Maximum-Likelihood Estimation-Maximization (MLEM) is normally used for the
activity estimation and Maximum-Likelihood Transmission Reconstruction (MLTR) for the attenuation estimation. In order to investigate the potential impact of using TOF-MLTR instead of nonTOF-MLTR in the MLAA workflow both of them were implemented as a part of our THOR application. List-mode MLEM algorithm was used for activity reconstruction and accelerated by utilizing ordered subsets. For scatter correction (SC), the time-of-flight extension of the Single Scatter Simulation algorithm (SSS) was used, see ref [4]. Attenuation map reconstruction was performed by ordered subsets accelerated list-mode version of MLTR, which is equivalent to the standard sinograms based MLTR in the non-TOF case. For the initial attenuation map estimate the MR-derived outline of the scanned object was uniformly filled with the attenuation coefficient of water. During reconstruction, attenuation map estimates were augmented by a pre-computed template of the patient bed. The main difference between TOF- and nonTOF-MLTR is the way how scatter and randoms corrections are handled. TOF information allows to individually compute this correction for each event (or TOF-bin) depending on event position along the LOR, while this correction is assumed to be the same for all the events within the LOR in the non-TOF algorithm. Consequently, any differences between both MLTR versions should be most pronounced for high contrast objects as is the case, e.g., if the bladder is within the field-of-view. Therefore, two different configurations of the whole body phantom L981602 were used. The phantom in configuration A has two cylindrical air-filled inserts and one cylindrical bone-like insert. This phantom allows to assess accuracy of the attenuation map estimate under low-contrast conditions. The phantom in configuration B comprises a large spherical ”bladder” insert with high target-to-background contrast and a small ”lesion” insert with lower contrast. The attenuation map is uniform in this case, which facilitates detection of scatter-related artifacts in the MLAA reconstructed attenuation image. Transmission scans of the phantoms with the Siemens HR+ scanner were performed and used as ground-truth for the attenuation maps.
RESULTS
The whole body phantom in both configurations was scanned with the Time-Of-Flight capable Philips Ingenuity-TF PET/MR scanner (TOF resolution (FWHM): ∼600 ps). Acquired data were reconstructed with THOR MLAA and TOF-MLTR and nonTOF-MLTR, respectively. In the case of configuration A (low activity contrast, high attenuation contrast) TOF-MLTR does not improve attenuation coefficients estimate significantly. Reconstructed attenuation values differ by less than 1% for bone and less than 15% for air. The situation is different for configuration B (high activity contrast, homogeneous attenuation). Due to presence of the large hot object in the field-of-view a massive artifact appears in the transaxial plane of the reconstructed attenuation map containing the ”bladder” insert. In the coronal view this artifact appears as a rather large area of apparently reduced attenuation in the middle of the phantom. The difference between the attenuation coefficient of the water background in the central and the peripheral zones depends on the reconstruction method used. Specifically, the use of TOF-MLTR instead of nonTOF-MLTR yields twofold decrease of the artifact. On the other hand, the attenuation coefficient inside the ”bladder” is about 12% higher than the reference value with TOF-MLTR compared to a 6% overestimate with nonTOF-MLTR (where this reduced deviation probably is due to the influence of the mentioned attenuation artifact).
CONCLUSION
Our preliminary results indicate that the use of TOF-MLTR within the MLAA framework provides only small improvements in terms of attenuation map accuracy if activity contrasts are modest. However, it can distinctly decrease scatter related artifacts in the presence of high activity contrast such as is frequently observed in the pelvis region. We hypothesize the advantages of TOF-MLTR will become even more apparent with increasing TOF resolution. A more detailed investigation of the benefits of TOF-MLTR usage within the MLAA workflow is under way.
REFERENCES
[1] A. Rezaei, M. Defrise, G. Bal, C. Michel, M. Conti, C. Watson, and J. Nuyts, “Simultaneous reconstruction of activity and attenuation in time-of-flight PET.” IEEE transactions on Medical Imaging, vol. 31, no. 12, pp. 2224–33, dec 2012.
[2] A. Rezaei and J. Nuyts, “Simultaneous reconstruction of the activity image and registration of the CT image in TOF-PET,” IEEE Nuclear Science Symposium Conference Record, vol. 1852, p. 1852, 2016.
[3] A. Lougovski, F. Hofheinz, J. Maus, G. Schramm, E. Will, J. van den Hoff, and J. van den Hoff, “A volume of intersection approach for on-the-fly system matrix calculation in 3D PET image reconstruction,” Physics in Medicine and Biology, vol. 59, no. 3, pp. 561–577, feb 2014.
[4] C. C. Watson, “Extension of Single Scatter Simulation to Scatter Correction of Time-of-Flight PET,” IEEE Transactions on Nuclear Science, vol. 54, no. 5, pp. 1679–1686, 2007.
Keywords: PET; TOF-PET; PET/MR; MLAA; MRAC; Attenuation Correction
Involved research facilities
- PET-Center
-
Poster
PSMR 2017 - 6th Conference on PET-MRI and SPECT-MRI, 29.-31.05.2017, Lisbon, Portugal
Permalink: https://www.hzdr.de/publications/Publ-25829
Sun - Batteries - Sun
Stefani, F.; Galindo, V.; Giesecke, A.; Weber, N.; Weier, T.
Abstract
Liquid metal batteries (LMBs) are presently discussed as cheap means for the storage of wind and solar energy. Among other drivers of undesired fluid motion that could destroy the three-fluids stratification, the Tayler instability (TI) sets some upper limit for the upscalability of LMBs. We present the principles of the TI, its possible effects on LMBs, and some simple ways to suppress it. We focus on the peculiar saturation mechanism of the TI at low magnetic Prandtl numbers, which relies on the change of the hydrodynamic base state. We discuss the recently found helicity oscillations of the m=1 velocity field of the TI which, in turn, might have consequences for stellar dynamo models for which the TI had originally been discussed. We show that these helicity oscillations can be resonantly excited by certain m=2 perturbations which would result, e.g., from planetary tidal forces. It is this high sensitivity of the helicity oscillations that could empower those very weak tidal forces to synchronize the entire solar dynamo.
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Lecture (Conference)
International workshop on liquid metal battery fluid dynamics (LMBFD 2017), 16.-17.05.2017, Dresden, Germany
Permalink: https://www.hzdr.de/publications/Publ-25828
The DRESDYN project: planned experiments and present status
Stefani, F.; Eckert, S.; Gerbeth, G.; Giesecke, A.; Gundrum, T.; Räbiger, D.; Seilmayer, M.; Weier, T.
Abstract
The Dresden sodium facility for dynamo and thermohydraulic studies (DRESDYN) is a platform for large-scale liquid sodium experiments devoted to fundamental geo- and astrophysical questions as well as to various applied problems related to the conversion and storage of energy. Its most ambitious part is a precession driven dynamo experiment, comprising 8 tons of liquid sodium supposed to rotate with up to 10 Hz and to precess with up to 1 Hz. Another large-scale set-up is a Tayler-Couette experiment with a gap width of 0.2 m and a height of 2 m, whose inner cylinder rotates with up to 20 Hz. Equipped with a coil system for the generation of an axial field of up to 120 mT and two different axial currents through the center and the liquid sodium, this experiment aims at studying various versions of the magnetorotational instability and their combinations with the Tayler instability. We discuss the physical background of these two experiments and delineate the present status of their technical realization. Other installations, such as a sodium loop and a test stand for In-Service-Inspection experiments, will also be sketched.
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Lecture (Conference)
88th GAMM Annual Meeting, 06.-10.03.2017, Weimar, Germany
Permalink: https://www.hzdr.de/publications/Publ-25827
Ultrasound propagation in bond frustrated HgCr2S4 spinel in magnetic fields
Felea, V.; Prodan, L.; Stefanet, E.; Cong, P. T.; Zherlitsyn, S.; Tsurkan, V.
Abstract
Ultrasound and magnetization studies of bond frustrated spinel HgCr2S4 are performed as a function of temperature in static magnetic fields. Beside the anharmonic effect, the sound velocity shows pronounced anomaly at the antiferromagnetic (AFM) transition at TN = 23 K with an additional significant increase of the order of 0.5 % indicating a strong spin-lattice coupling. External magnetic fields enhance the ferromagnetic (FM) correlations and shift the anomalies to lower temperatures concomitantly with the reduction of the Néel temperature. The constructed H–T Phase diagram beside the long-range AFM states reveals the state with induced FM order and regimes with short-range AFM and FM correlations as well.
Involved research facilities
- High Magnetic Field Laboratory (HLD)
-
Low Temperature Physics 43(2017), 559-563
DOI: 10.1063/1.4985206
ISSN: 1063-777X
Cited 2 times in Scopus
Permalink: https://www.hzdr.de/publications/Publ-25826
Comparison of arterial spin labeling registration strategies in the multi-center GENetic frontotemporal dementia initiative (GENFI)
Mutsaerts, H. J. M. M.; Petr, J.; Thomas, D. L.; de Vita, E.; Cash, D. M.; van Osch, M. J. P.; Golay, X.; Groot, P. F. C.; Ourselin, S.; van Swieten, J.; Laforce, R.; Tagliavini, F.; Borroni, B.; Galimberti, D.; Rowe, J. B.; Graff, C.; D. Pizzini, F. B.; Finger, E.; Sorbi, S.; Castelo Branco, M.; Rohrer, J. D.; Masellis, M.; Macintosh, B. J.
Abstract
Purpose: To compare registration strategies to align arterial spin labeling (ASL) with 3D T1-weighted (T1w) images, with the goal of reducing the between-subject variability of cerebral blood flow (CBF) images.
Materials and Methods: Multi-center 3T ASL data were collected at eight sites with four different sequences in the multi-center GENetic Frontotemporal dementia Initiative (GENFI) study. In a total of 48 healthy controls, we compared the following image registration options: (I) which images to use for registration (perfusion-weighted images [PWI] to the segmented gray matter (GM) probability map (pGM) (CBF-pGM) or M0 to T1w (M0-T1w); (II) which transformation to use (rigid-body or non-rigid); and (III) whether to mask or not (no masking, M0-based FMRIB software library Brain Extraction Tool [BET] masking). In addition to visual comparison, we quantified image similarity using the Pearson correlation coefficient (CC), and used the Mann-Whitney U rank sum test.Results: CBF-pGM outperformed M0-T1w (CC improvement 47.2% 6 22.0%; P < 0.001), and the non-rigid transformation outperformed rigid-body (20.6% 6 5.3%; P < 0.001). Masking only improved the M0-T1w rigid-body registration (14.5% 6 15.5%; P 5 0.007).
Conclusion: The choice of image registration strategy impacts ASL group analyses. The non-rigid transformation is promising but requires validation. CBF-pGM rigid-body registration without masking can be used as a default strategy.
In patients with expansive perfusion deficits, M0-T1w may outperform CBF-pGM in sequences with high effective spatial resolution. BET-masking only improves M0-T1w registration when the M0 image has sufficient contrast.
Involved research facilities
- PET-Center
-
Journal of Magnetic Resonance Imaging 47(2018)1, 131-140
Online First (2017) DOI: 10.1002/jmri.25751
Cited 37 times in Scopus
Downloads
- Final Draft PDF 1,2 MB Secondary publication
Permalink: https://www.hzdr.de/publications/Publ-25825
Scatter correction in TOF and non-TOF PET image reconstruction in THOR
Nikulin, P.; Lougovski, A.; Hofheinz, F.; Maus, J.; van den Hoff, J.
Abstract
INTRODUCTION
As is well known, quantitative combined PET/MR imaging depends on accurate MR-based attenuation correction (MRAC). While a mostly satisfactory state of affairs has been reached today, problems persist regarding segmentation errors including unsatisfactory bone identification and residual systematic differences in comparison to PET/CT. Alternative or complementary strategies for attenuation correction (AC), therefore, are of considerable relevance. In this context, Maximum Likelihood reconstruction of Attenuation and Activity (MLAA) is one of the most promising approaches but, as A. Rezaei et al. have shown [1], Time-Of-Flight (TOF) image reconstruction is then required to eliminate possible ”crosstalks” between the estimated activity and attenuation distribution. We are aiming at implementation of MLAA for the Philips Ingenuity-TF PET/MR scanner as part of our previously developed Tube of response High resolution OSEM Reconstruction (THOR), see ref [2]. As a prerequisite we are currently modifying THOR to make full use of the available TOF information. The most critical point in this context is accurate and computational efficient TOF Scatter Correction (TOF-SC). Here, we report on our approach to solving this issue and compare TOF-SC techniques with conventional non-TOF SC method.
METHODS
One possible implementation of TOF-SC uses a straight forward extension of Watson’s well-known Single Scatter Simulation (SSS) algorithm [3] but this approach results in about an order of magnitude increase of computational burden compared to standard SSS. Alternatively, one can use standard SSS to estimate the number of scattered events in each Line Of Response (LOR) and use an additional algorithm to estimate the shape of the time distribution of scattered events within each LOR (scatter mask). To integrate TOF-SC into our THOR reconstruction, four different approaches to scatter mask calculation have been investigated:
A. Simple scatter scaling
This approach assumes that scattered and unscattered events have identical time distribution within each single LOR.
B. Attenuation based SC
In this approach the object is modeled as a set of “scatter points” which are generated by SSS. Each scatter point is then also assumed to be a scatter source. For each detector pair and scatter point the geometric path difference from scatter source to both detectors is calculated and an effective position of the scattered event within the corresponding LOR is determined. By repeating this procedure for a large number of scatter points and post-processing the results by smoothing or using a TOF-binning technique one can compute the required scatter mask.
C. Attenuation and activity based SC
While approach B allows to properly handle the shape of the attenuating object it does not take into account the given activity distribution. To fix this issue scatter sources and scatter points should be separated. To do this in a simple and fast way we introduce a small set of “emission points” for approximation of the given activity distribution. The activity distribution/object is then described as superposition of suitable 3D Gaussian distributions around these emission
points. Calculation of the scatter masks is similar to the previous approach, but now scatter sources are determined as projections of emission points onto straight lines connecting selected scatter point and detectors. In this approach the intensity of each source is proportional to the intensity of corresponding emission point and decreases according to a Gaussian as a function of the distance between them.
D. TOF-SSS Time-Of-Flight extension of Single Scatter Simulation by Watson.
RESULTS
All four approaches have been integrated into THOR and tested in dedicated phantom and patient studies. Approach A does not yield quantitatively correct scatter distributions for big objects. Approach B is superior to A but notable artifacts remain in the presence of high-contrast. Approach C is able to eliminate part of these artifacts but requires more computation time. Approach D is the most accurate and computationally most expensive.
CONCLUSION
Our preliminary results indicate that attenuation based SC might be the best compromise between computation time and image quality for a wide range of applications.
REFERENCES
[1] A. Rezaei, M. Defrise, G. Bal, C. Michel, M. Conti, C. Watson, and J. Nuyts, “Simultaneous reconstruction of activity and attenuation in time-of-flight PET.” IEEE transactions on Medical Imaging, vol. 31, no. 12, pp. 2224–33, dec 2012.
[2] A. Lougovski, F. Hofheinz, J. Maus, G. Schramm, E. Will, J. van den Hoff, and J. van den Hoff, “A volume of intersection approach for on-the-fly system matrix calculation in 3D PET image reconstruction,” Physics in Medicine and Biology, vol. 59, no. 3, pp. 561–577, feb 2014.
[3] C. C. Watson, “Extension of Single Scatter Simulation to Scatter Correction of Time-of-Flight PET,” IEEE Transations on Nuclear Science, vol. 54, no. 5, pp. 1679–1686, 2007.
Keywords: PET; TOF-PET; Scatter Correction; TOF-SC; Single Scatter Simulation; SSS
Involved research facilities
- PET-Center
-
Lecture (Conference)
Seminar on PET image reconstruction, 28.-30.09.2016, Leuven, Belgium
Permalink: https://www.hzdr.de/publications/Publ-25824
Effect of Brain Extraction of Low Resolution Arterial Spin Labeling (ASL) Fmri Images on Realignment and Coregistration
Liao, J.; Petr, J.; Lazar, R. M.; Marshall, R. S.; Asllani, I.
Abstract
ASL is an fMRI method that maps cerebral blood (CBF), which is a key parameter of brain physiology. In ASL, flow-weighted images are computed by subtracting a “labeled” image from a contiguously acquired unlabeled control image. The difference is then converted to a CBF image using partial volume (PV) maps obtained from the segmentation of the anatomical T1w image. It follows that the quality of ASL data is dependent on the quality of motion correction and coregistration of the high-resolution T1w image to the low-resolution ASL. We tested whether applying brain-extraction on the low-resolution ASL would improve both these processes. The test was performed on 8 patients with carotid occlusive disease. Improvement in motion realignment was defined as % change averaged over the 6 degrees of freedom and across patients; improvement in coregistration was assessed as a difference in the mutual information (MI) value between the T1w and extracted and original ASL, respectively. There was a noticeable effect of brain extraction on both realignment and coregistration.
Keywords: MR neuroimaging; Brain image analysis; Rigid-body image registration; ASL
Involved research facilities
- PET-Center
-
Contribution to proceedings
39th Annual International Conference of the IEEE Engineering in Medicine and Biology Society, 11.-15.07.2017, Jeju Island, Korea -
Poster
39th Annual International Conference of the IEEE Engineering in Medicine and Biology Society, 11.07.2017, Jeju Island, Korea
Permalink: https://www.hzdr.de/publications/Publ-25823
SUR: a superior alternative to SUV as a surrogate of tumor glucose metabolism
van den Hoff, J.
Involved research facilities
- PET-Center
-
Invited lecture (Conferences)
Symposium Nuclear Medicine & Molecular Imaging, Katholieke Universiteit Leuven, 10.01.2017, Leuven, Belgien
Permalink: https://www.hzdr.de/publications/Publ-25822
Standardised Uptake Ratio (SUR): die robuste Variante des SUV
van den Hoff, J.
Involved research facilities
- PET-Center
-
Invited lecture (Conferences)
Jahrestagung der Bayrischen Gesellschft für Nuklearmedizin, 01.07.2016, Regensburg, Deutschland
Permalink: https://www.hzdr.de/publications/Publ-25821
Magnetohydrodynamic instabilities in liquid metal batteries
Stefani, F.
Abstract
The increasing deployment of strongly fluctuating renewable energies requires a corresponding large-scale expansion of electricity storage. Liquid metal batteries (LMBs) are presently discussed as a possible route of economical grid-scale energy storage. They consist of two liquid metal electrodes and a molten salt ionic conductor sandwiched between them. The density ratios allow for a stable stratification of the three layers. In the talk, we concentrate on the magnetohydrodynamic aspects of this cell type, with special focus on electro-vortex flows, the sloshing instability, and possible effects of the Tayler instability.
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Lecture (Conference)
XXth Winter School on Continuous Media Mechanics, 13.-16.02.2017, Perm, Russia
Permalink: https://www.hzdr.de/publications/Publ-25820
Upconverting Nanophosphors for bioimaging: Preparation Strategies for hydrophilic colloidal Stable Particles
Nsubuga, A.; Sgarzi, M.; Joshi, T.; Stephan, H.
Abstract
Currently, there is a widespread interest to use neodymium containing upconverting nanophosphors (UCNPs) for bioimaging applications. The infatuation of these nanoparticles derives from their capacity for excitation in the biologically transparent window (700-1000 nm), exceptional ability to convert near infrared radiation into visible light (upconversion), which prevents autofluorescence and over-heating effect of biological tissues and capability for deep tissue, high contrast imaging related to minimum autofluorescence in this spectral range [1]. Despite the fast progress in lanthanide-doped upconversion nanoparticles, the preparation of ultrasmall, monodisperse and hydrophilic UCNPs that display intense luminescence is still a challenging issue. Only a few examples of ultrasmall and hydrophilic UCNPs have been reported [2-3]. Here, we report the elaboration, synthesis and surface modification of sub-10 nm UCNPs with an excitation wavelength of 795 nm, which are composed of a host lattice of crystalline NaYF4 doped with Nd3+ and Yb3+ as sensitizers, and Er3+,Ho3+ or Tm3+ as emitter ions. Established strategies for synthesizing UCNPs yield mainly hydrophobic particles[1]. We report the conversion of these into hydrophilic, colloidally-stable, and biocompatible by using mainly ligand exchange strategies, and the influence of the coating on the UCNPs’ photophysical properties. This study will also allow establishing information about biodistribution, pharmacokinetics and formation of protein corona for ultrasmall UCNPs.
Keywords: Upconversion; lanthanide; Sub 10 nm particles; surface functionalization; Bio imaging
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Lecture (Conference)
NANOTECH France 2017, 28.-30.06.2017, Paris, France
Permalink: https://www.hzdr.de/publications/Publ-25819
Time efficient scatter correction in Time-Of-Flight PET image reconstruction
Nikulin, P.; Lougovski, A.; Hofheinz, F.; Maus, J.; van den Hoff, J.
Abstract
Aim
We are currently modifying our previously developed Tube of response High resolution OSEM Reconstruction (THOR), see ref [1], to make full use of the available Time-of-Flight (TOF) information. The most critical point in this context is accurate and computational efficient TOF Scatter Correction (TOF-SC). Here, we report on our approach to solving this issue.
Methods
Four different, partly newly developed approaches to estimation of scatter time distribution have been investigated: A. Simple scatter scaling: this approach assumes that scattered and unscattered events have identical time distribution within each single LOR. B. Attenuation based SC (new approach): in this approach the object is modeled as a set of “scatter points”. Each scatter point is also assumed to be a scatter source. C. Attenuation and activity based SC (new approach): in this approach a small set of “emission points” for approximation of the given activity distribution is introduced. Calculations are similar to B except that scatter sources are determined as projections of emission points onto straight lines connecting selected scatter point and detectors. D. TOF-SSS Time-Of-Flight extension of Single Scatter Simulation by Watson.
Results
All four approaches have been integrated into THOR and tested in dedicated phantom and patient studies. Approach A does not yield quantitatively correct scatter distributions for big objects. Approach B is superior to A but notable artifacts remain in the presence of high-contrast. Approach C is able to eliminate part of these artifacts but requires more computation time. Approach D is the most accurate and computationally most expensive.
Conclusion
Our preliminary results indicate that attenuation based SC might be the best compromise between computation time and image quality for a wide range of applications.
Literature
[1] A. Lougovski, F. Hofheinz, J. Maus, et al., Physics in Medicine
and Biology 59(3), 561 (2014)
Keywords: PET; TOF-PET; Scatter Correction; TOF-SC
Involved research facilities
- PET-Center
-
Poster
NuklearMedizin 2017, 26.-29.04.2017, Dresden, Germany
Permalink: https://www.hzdr.de/publications/Publ-25818
Liquid metal experiments on hydromagnetic dynamos and magnetically triggered flow instabilities
Stefani, F.
Abstract
The magnetic fields of planets, stars and galaxies are generated by self-excitation in moving electrically conducting fluids. Magnetic fields play, in turn, an active role in cosmic structure formation by destabilizing rotational flows that would be otherwise hydrodynamically stable. For a long time, both effects had been the subject of purely theoretical investigations. The lecture gives an overview about the recent liquid metal experiments on dynamo action and magnetically triggered instabilities. An outlook on future experiments, including a precession driven dynamo and a large-scale Tayler-Couette experiment to be set-up in the framework of the DRESDYN project, is also given.
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Invited lecture (Conferences)
XXth Winter School on Continuous Media Mechanics, 13.-16.02.2017, Perm, Russia
Permalink: https://www.hzdr.de/publications/Publ-25817
Time efficient scatter correction in Time-Of-Flight PET image reconstruction
Nikulin, P.; Lougovski, A.; Hofheinz, F.; Maus, J.; van den Hoff, J.
Abstract
INTRODUCTION
As is well known, quantitative combined PET/MR imaging depends on accurate MR-based attenuation correction (MRAC). While a mostly satisfactory state of affairs has been reached today, problems persist regarding segmentation errors including unsatisfactory bone identification and residual systematic differences in comparison to PET/CT. Alternative or complementary strategies for attenuation correction (AC), therefore, are of considerable relevance. In this context, Maximum Likelihood reconstruction of Attenuation and Activity (MLAA) is one of the most promising approaches but, as A. Rezaei et al. have shown [1], Time-Of-Flight (TOF) image reconstruction is then required to eliminate possible ”crosstalks” between the estimated activity and attenuation distribution. We are aiming at implementation of MLAA for the Philips Ingenuity-TF PET/MR scanner as part of our previously developed Tube of response High resolution OSEM Reconstruction (THOR), see ref [2]. As a prerequisite we are currently modifying THOR to make full use of the available TOF information. The most critical point in this context is accurate and computational efficient TOF Scatter Correction (TOF-SC). Here, we report on our approach to solving this issue.
METHODS
One possible implementation of TOF-SC uses a straight forward extension of Watson’s well-known Single Scatter Simulation (SSS) algorithm [3] but this approach results in about an order of magnitude increase of computational burden compared to standard SSS. Alternatively, one can use standard SSS to estimate the number of scattered events in each Line Of Response (LOR) and use an additional algorithm to estimate the shape of the time distribution of scattered events within each LOR (scatter mask). To integrate TOF-SC into our THOR reconstruction, three different approaches to scatter mask calculation have been investigated which are modifications/improvements of key ideas from article [4]:
A. Simple scatter scaling
This approach assumes that scattered and unscattered events have identical time distribution within each single LOR.
B. Attenuation based SC
In this approach the object is modeled as a set of “scatter points” which are generated by SSS. Each scatter point is then also assumed to be a scatter source. For each detector pair and scatter point the geometric path difference from scatter source to both detectors is calculated and an effective position of the scattered event within the corresponding LOR is determined. By repeating this procedure for a large number of scatter points and post-processing the results by smoothing or using a TOF-binning technique one can compute the required scatter mask.
C. Attenuation and activity based SC
While approach B allows to properly handle the shape of the attenuating object it does not take into account the given activity distribution. To fix this issue scatter sources and scatter points should be separated. To do this in a simple and fast way we introduce a small set of “emission points” for approximation of the given activity distribution. The activity distribution/object is then described as superposition of suitable 3D Gaussian distributions around these emission
points. Calculation of the scatter masks is similar to the previous approach, but now scatter sources are determined as projections of emission points onto straight lines connecting selected scatter point and detectors. In this approach the intensity of each source is proportional to the intensity of corresponding emission point and decreases according to a Gaussian as a function of the distance between them.
RESULTS
All three approaches have been integrated into our THOR reconstruction and tested in phantom and patient studies. Simple scatter scaling (approach A) does not yield quantitatively correct scatter distributions for big objects such as whole body phantoms. Attenuation based SC (approach B) does not have this problem due to proper handling of the object shape, but notable artifacts appear in the presence of high-contrast such as in the pelvis/bladder region. The combined attenuation and activity based algorithm (approach C) is able to eliminate part of the latter artifacts but requires more computation time.
CONCLUSION
Our preliminary results indicate that attenuation based SC might be the best compromise between computation time and image quality for a wide range of applications. A more detailed investigation of the efficiency and accuracy of the implemented TOF-SC methods is currently in progress.
REFERENCES
[1] A. Rezaei, M. Defrise, G. Bal, C. Michel, M. Conti, C. Watson, and J. Nuyts, “Simultaneous reconstruction of activity and attenuation in time-of-flight PET.” IEEE transactions on Medical Imaging, vol. 31, no. 12, pp. 2224–33, dec 2012.
[2] A. Lougovski, F. Hofheinz, J. Maus, G. Schramm, E. Will, J. van den Hoff, and J. van den Hoff, “A volume of intersection approach for on-the-fly system matrix calculation in 3D PET image reconstruction,” Physics in Medicine and Biology, vol. 59, no. 3, pp. 561–577, feb 2014.
[3] C. C. Watson, “Extension of Single Scatter Simulation to Scatter Correction of Time-of-Flight PET,” IEEE Transations on Nuclear Science, vol. 54, no. 5, pp. 1679–1686, 2007.
[4] M. Conti, B. Bendriem, M. Casey, M. Chen, F. Kehren, C. Michel, and V. Panin, “First experimental results of time-of-flight reconstruction on an LSO PET scanner.” Physics in medicine and biology, vol. 50, no. 19, pp. 4507–4526, oct 2005.
Keywords: PET; TOF-PET; Scatter Correction; TOF-SC
Involved research facilities
- PET-Center
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Lecture (Conference)
PSMR 2016 - 5th Conference on PET/MR and SPECT/MR, 23.-25.05.2016, Cologne, Germany
Permalink: https://www.hzdr.de/publications/Publ-25816
DRESDYN: Liquid metal experiments on dynamo action and magnetorotational instability
Gundrum, T.; Eckert, S.; Gerbeth, G.; Stefani, F.; Steglich, C.
Abstract
We report on two large-scale liquid sodium experiments on precession-driven dynamo action and magnetorotational instability that are planned in the framework of the DRESDYN project.
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Poster
Nuclear Astrophysics at the Dresden Felsenkeller, 26.-28.06.2017, Dresden, Germany
Permalink: https://www.hzdr.de/publications/Publ-25815
Can planetary tides synchronize the solar dynamo?
Stefani, F.; Galindo, V.; Giesecke, A.; Weber, N.; Weier, T.
Abstract
While the traditional explanation of the Hale cycle of the solar magnetic field relies on intrinsic features of the solar dynamo, we presently witness an increased interest in the question of whether gravitational forces of planets could influence the length and intensity of the cycle. Although tidal forces are usually considered as much too weak to play any role, one should note the large gravitational acceleration at the tachocline that amounts to 500 m/s². This translates the apparently tiny tidal heights of the order of 1 mm to equivalent velocities of 1 m/s. Such velocities, when allowed to coherently develop in the quiet regions of the tachocline, might indeed be relevant for the dynamo.
In our quest for a viable physical mechanism that could link the weak planetary force with solar dynamo action, we focus on the helicity oscillations that were recently found in simulations of the current-driven, kink-type Tayler instability that is characterized by an m=1 azimuthal dependence. We show how these helicity oscillations can be resonantly excited by m=2 perturbations that reflect tidal oscillations. Specifically, we speculate that the 11.07 years tidal oscillation induced by the tidally dominant Venus--Earth--Jupiter system may lead to a 1:1 resonant excitation of the oscillation of the associated alpha-effect. In the framework of a reduced, zero-dimensional alpha-Omega dynamo model, including a weak non-oscillatory and a resonantly excited oscillatory part of alpha, we recover the 22.14-year cycle of the solar dynamo. We finally show that the synchronization model can produce the correct orientation of the butterfly diagram even in case that the product of the non-oscillatory part of alpha with Omega is positive.
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Poster
2nd Conference on Natural Dynamos, 25.06.-01.07.2017, Valtice, Czech Republic
Permalink: https://www.hzdr.de/publications/Publ-25814
Spectroscopic and microscopic approach of U(VI) sorption on Acidovorax facilis for remediation purpose
Krawczyk-Bärsch, E.; Gerber, U.; Steudtner, R.; Müller, K.; Moll, H.; Rossberg, A.; Merroun, M. L.
Abstract
The Gram-negative betaproteobacterium Acidovorax facilis is a suitable candidate for in situ bioremediation of contaminated waste waters and environments [1]. For spectroscopic and microscopic studies kinetic U(VI) sorption experiments were performed under aerobic conditions at 30°C by adjusting an initial U(VI) concentration to 0.1 mM at a neutral pH range by adding UO2(NO3)2 to the batch culture.
A high-resolution image of the cellular localization of U by A. facilis was achieved by using electron microscopy (STEM/HAADF). The elemental distribution analysis of phosphorus and uranium clearly indicates that U is entirely present in the cell membrane. By cryo-Time-resolved laser-induced fluorescence spectroscopy (cryo-TRLFS) studies the spectra deconvolution indicates a fast binding of U(VI) on phosphorylic functionality groups during the first hour with a subsequent formation of Uranyl-carboxylic species in addition to the Uranyl-phosphorylic species. Compared to emission spectra of the Uranyl-lipopolysaccharide [2] we suggest an interaction of UO22+ with cell membrane components of the outer membrane of A. facilis cells, whereas lipopolysaccharide will form the most stable complex. These results support those obtained by Extended X-ray absorption fine structure spectroscopy (EXAFS), where a relative short average U-Oeq bond length of 2.35 Å were observed for the U(VI) interaction with lipopolysaccharide indicating a binding of the U(VI) via organic phosphate groups in a monodentate fashion. The strong interaction of U(VI) with phosphorylic and carboxylic groups was reinforced by in-situ attenuated total reflection Fourier-transform (ATR FT-IR) spectroscopic studies due to the presence of characteristic phosphoryl vibrations. Most of the bound U(VI) presumably remained on the cells, more precisely on the phosphorylic functionalities at the cell membrane.
[1] Gerber et al. (2016). J. Hazard. Mater. 317, 127–134.
[2] Barkleit et al. (2008). Appl. Spectrosc. 62(7), 798-802.
Keywords: Uranium; Acidovorax facilis; TRLFS; EXAFS; ATR FT-IR; STEM/HAADF
Involved research facilities
- Rossendorf Beamline at ESRF DOI: 10.1107/S1600577520014265
Related publications
- DOI: 10.1107/S1600577520014265 is cited by this (Id 25813) publication
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Lecture (Conference)
Goldschmidt2017, 13.-18.08.2017, Paris, France
Permalink: https://www.hzdr.de/publications/Publ-25813
Laboratory experiments on dynamo action and magnetically triggered flow instabilities
Stefani, F.
Abstract
Magnetic fields of planets, stars and galaxies are known to be generated by the homogeneous dynamo effect in moving electrically conducting fluids, such as liquid metals or plasmas. Once generated, magnetic fields can foster cosmic structure formation by destabilizing, via the magnetorotational instability (MRI) or the Tayler instability (TI), those rotating flows that would be otherwise hydrodynamically stable. The mutual reinforcement of dynamo action and magnetic instabilities leads to interesting concepts such as the MRI-dynamo or the Tayler-Spruit-dynamo.
For a long time, all these topics had been the subject of purely theoretical and numerical research. This situation changed in 1999 when the threshold of magnetic-field self-excitation was exceeded in the two liquid sodium experiments in Riga and Karlsruhe. Since 2006, the VKS dynamo experiment in Cadarache has successfully reproduced many features of geophysical interest such as reversals and excursions. Further liquid metal experiments in Grenoble, Madison, Maryland, Perm, Princeton, Perm, and Socorro have contributed important findings related to the alpha, beta and Omega effects as well as to various wave phenomena in magnetized rotating fluids. MRI-related research was partly successful with the observation of the helical MRI and the azimuthal MRI at the PROMISE facility at Helmholtz-Zentrum Dresden-Rossendorf (HZDR). First evidence of the current-driven Tayler instability in a liquid metal was also obtained.
The lecture gives an overview about liquid metal experiments on dynamo action and magnetically triggered flow instabilities. It concludes with an overview about future experiments, with special focus on the precession driven liquid sodium experiment and the large-scale Tayler-Couette experiment that are under construction in the framework of the DRESDYN project at HZDR.The prospects for experimental validation of the recently discussed magnetic destabilization of flows with positive shear are also discussed.
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Invited lecture (Conferences)
2nd Conference on Natural Dynamos, 25.06.-01.07.2017, Valtice, Czech Republic
Permalink: https://www.hzdr.de/publications/Publ-25812
Evaluation of hemodynamic impairments in healthy elderly participants and patients with high-grade unilateral carotid artery stenosis
Kaczmarz, S.; Göttler, J.; Griese, V.; Petr, J.; van de Ven, K.; Helle, M.; Kooijman, H.; Kluge, A.; Karampinos, D.; Zimmer, C.; Sorg, C.; Preibisch, C.
Abstract
Internal carotid-artery stenosis (ICAS) causes complex and not yet well understood physiological impairments. We present preliminary data from an ongoing clinical study in ICAS patients and healthy, age-matched participants. The major aims were to evaluate the reliability of a multimodal MRI-protocol and investigate physiological changes. For ICAS patients, regionally impaired vascular-reactivity as well as hypo-perfusion were found. In accordance with literature, we did not find ICAS-induced changes in oxygen extraction on group level. The presented preliminary results thus imply successful application of multimodal MRI methods and are highly promising with respect to gaining a deeper insight into ICAS-related physiological changes.
Keywords: stenosis; ASL; perfusion; MRI
Involved research facilities
- PET-Center
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Contribution to proceedings
25th Scientific Meeting and Exhibition of International Society for Magnetic Resonance in Medicine, 22.-27.04.2017, Honolulu, Hawaii, USA
Proceedings of the 25th Scientific Meeting and Exhibition of International Society for Magnetic Resonance in Medicine -
Lecture (Conference)
25th Scientific Meeting and Exhibition of International Society for Magnetic Resonance in Medicine, 22.04.2017, Honolulu, Hawaii, USA
Permalink: https://www.hzdr.de/publications/Publ-25811
Perfusion decrease during radiochemotherapy is not fully explained by volumetric gray matter changes
Petr, J.; Mutsaerts, H.; Hofheinz, F.; Asllani, I.; van Osch, M.; Platzek, I.; Seidlitz, A.; Krause, M.; van den Hoff, J.
Abstract
Radiochemotherapy in brain-tumor patients was shown to cause gray matter (GM) volume and cerebral blood flow (CBF) changes. The interaction of these two effects, however, remains unclear. Here, we investigated GM volume and ASL CBF changes and their interaction in the healthy hemisphere of 38 glioblastoma patients undergoing radiochemotherapy with Temozolomide. We found a statistically significant CBF decrease with dependence on the RT-dose. PV-corrected results indicated that, while to a certain extent the apparent CBF decrease measured by ASL is caused by GM atrophy, there still remain significant CBF changes that cannot be explained by structural changes alone.
Keywords: ASL; perfusion; glioblastoma; radiochemotherapy; atrophy; partial volume
Involved research facilities
- PET-Center
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Contribution to proceedings
25th Scientific Meeting and Exhibition of International Society for Magnetic Resonance in Medicine, 22.-27.04.2017, Honolulu, Hawaii, USA
Proceedings of the 25th Scientific Meeting and Exhibition of International Society for Magnetic Resonance in Medicine -
Poster
25th Scientific Meeting and Exhibition of International Society for Magnetic Resonance in Medicine, 22.04.2017, Honolulu, Hawaii, USA
Permalink: https://www.hzdr.de/publications/Publ-25810
Brain volume loss in glioblastoma patients following photon and proton radiochemotherapy
Petr, J.; Hofheinz, F.; Gommlich, A.; Raschke, F.; Troost, E.; Beuthien-Baumann, B.; Seidlitz, A.; Platzek, I.; Baumann, M.; Krause, M.; van den Hoff, J.
Abstract
Gray matter (GM) atrophy in healthy brain tissue following radiochemotherapy was shown in brain-tumor patients in several studies. Here, we aimed to study GM and white matter (WM) changes in glioblastoma patients undergoing photon (n=43) and proton (n=12) radiochemotherapy. In photon-therapy patients, a statistically significant decrease of both GM (~2%) and WM (1.3-2.3%) volume was found with a positive influence of the RT-dose on the GM volume loss. In proton-therapy patients, no significant changes in GM and WM volumes were observed after therapy. This indicates that the proton-therapy has the potential to reduce structural GM changes in healthy tissue.
Keywords: radiochemotherapy; proton therapy; atrophy; morphometrics
Involved research facilities
- PET-Center
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Contribution to proceedings
25th Scientific Meeting and Exhibition of International Society for Magnetic Resonance in Medicine, 22.-27.04.2017, Honolulu, Hawaii, USA
Brain volume loss in glioblastoma patients following photon and proton radiochemotherapy -
Lecture (Conference)
25th Scientific Meeting and Exhibition of International Society for Magnetic Resonance in Medicine, 22.04.2017, Honolulu, Hawaii
Permalink: https://www.hzdr.de/publications/Publ-25809
Kinetic Modeling
van den Hoff, J.
Abstract
A mathematical description of the time-dependent tissue uptake and tissue clearance after injection of contrast agents or radioactively labeled tracers with suitable models (kinetic modeling) allows a detailed analysis of transport processes and metabolism in vivo. Such an analysis can provide at once quantitative information for several interesting parame- ters such as local blood volume, blood flow, distribution volumes, metabolic rates, binding potentials, and so forth. While the mathematical techniques are – with some reservations – in principle suited for data analysis in other tomographic modalities as well (notably CT and MRI), the broadest field of application is found in PET. We will focus especially on small animal PET in the following.
Keywords: PET; Kinetic Modeling; Small Animal Imaging
Involved research facilities
- PET-Center
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Book chapter
Fabian Kiessling, Bernd J. Pichler, Peter Hauff: Small Animal Imaging: Basics and Practical Guide, Heidelberg: Springer International Publishing, 2017, 978-3-319-42200-8, 559-580
DOI: 10.1007/978-3-319-42202-2_21
Permalink: https://www.hzdr.de/publications/Publ-25808
Steering magnons by non-collinear spin textures
Schultheiss, K.; Wagner, K.; Kákay, A.; Schultheiss, H.
Abstract
One of the grand challenges in cutting edge quantum and condensed matter physics is to harness the spin degree of electrons for information technologies. While spintronics, based on charge transport by spin polarized electrons, made its leap in data storage by providing extremely sensitive detectors in magnetic hard-drives [1], it turned out to be challenging to transport spin information without great losses [2]. With magnonics a visionary concept inspired researchers worldwide: Utilize spin waves - the collective excitation quanta of the spin system in magnetically ordered materials - as carriers for information [3-8]. Spin waves, which are also called magnons, are waves of the electrons’ spin precessional motion. They propagate without charge transport and its associated Ohmic losses, paving the way for a substantial reduction of energy consumption in computers.
While macroscopic prototypes of magnonic logic gates have been demonstrated [9,10], the full potential of magnonics lies in the combination of magnons with nano-sized spin textures. Both magnons and spin textures share a common ground set by the interplay of dipolar, spin-orbit and exchange energies rendering them perfect interaction partners. Magnons are fast, sensitive to the spins’ directions and easily driven far from equilibrium. Spin textures are robust, non-volatile and still reprogrammable on ultra short timescales. The vast possibilities offered by combining these magnetic phenomena, add value to both magnonics and the fundamental understanding of complex spin textures.
The scope of this chapter is about experimental studies on magnon transport in metallic ferromagnetic microstructures with focus on actively controlling the magnon propagation. Two inherent characteristics of magnons enable for lateral steering: the anisotropy of the magnon dispersion and its sensitivity to changes in the internal magnetic field distribution. We intend to give an idea of how these magnon features can be utilized towards realizing functionalized magnonic networks.
Keywords: spin waves; magnonics; spintronics; magneto-optics; spin textures; domain walls
Involved research facilities
- Ion Beam Center DOI: 10.17815/jlsrf-3-159
Related publications
- DOI: 10.17815/jlsrf-3-159 is cited by this (Id 25807) publication
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Book chapter
Sergej Demokritov: Spin Wave Confinement: Propagating Waves (2nd Edition), Singapore: Pan Stanford Publishing Pte. Ltd., 2017, 9789814774352
Permalink: https://www.hzdr.de/publications/Publ-25807
EXILL - a high efficiency, high resolution setup for γ-spectroscopy at an intense cold neutron beam
Jentschel, M.; Blanca, A.; de France, G.; Köster, U.; Leoni, S.; Mutti, P.; Simpson, G.; Soldner, T.; Ur, C.; Urban, W.; Ahmed, S.; Astieri, A.; Augey, L.; Back, T.; Baczyk, P.; Bajoga, A.; Balabanski, D.; Belgya, T.; Benzoni, G.; Bernards, C.; Biswas, D.; Bocchi, G.; Bottoni, S.; Britton, R.; Bruyneel, B.; Burnett, J.; Cakirli, R. B.; Carroll, R.; Catford, W.; Cederwall, B.; Celikovic, I.; Cieplicka, N.; Clement, E.; Cooper, N.; Crespic, F.; Csatlos, M.; Czerwinski, M.; Danu, L.; Davies, A.; Didierjean, F.; Drouet, F.; Duchene, G.; Ducoin, C.; Eberhardt, K.; Erturk, S.; Fraile, L. M.; Gottardo, A.; Grente, L.; Grocutt, L.; Guerrero, C.; Guinet, D.; Hartig, A.-L.; Henrich, C.; Ignatov, A.; Ilieva, S.; Ivanova, D.; John, B.; John, R.; Jolie, J.; Kisyov, S.; Konstantinopoulos, T.; Korgul, A.; Krasznahorkay, A.; Kröll, T.; Kurpeta, J.; Kutiu, I.; Lalkovski, S.; Larijani, C.; Leguillon, R.; Lica, R.; Litaize, O.; Magron, C.; Mancuso, C.; Ruiz Martinez, E.; Massarczyk, R.; Mazzocchi, C.; Melon, B.; Mengoni, D.; Million, B.; Mokry, C.; Mukhopadhyay, S.; Mulholland, K.; Nannini, A.; Napoli, D. R.; Olaizola, B.; Orlandi, R.; Patel, Z.; Paziy, V.; Petrache, C.; Pfeiffer, M.; Podolyak, Z.; Ramdhane, M.; Redon, N.; Regan, P.; Regis, J. M.; Regnier, D.; Oliver, R. J.; Rudigier, M.; Runke, J.; Rzaca-Urban, T.; Saed-Samii, N.; Salsacq, M. D.; Scheck, M.; Schwengner, R.; Sengele, L.; Simpson, G.; Singh, P.; Smith, J.; Stezowski, O.; Szpak, B.; Thomas, T.; Thürauf, M.; Timaru, J.; Toml, A.; Tomandl, I.; Tornyi, T.; Townsley, C.; Tuerler, A.; Valenta, S.; Vancraeyenest, A.; Vandone, V.; Vanhoy, J.; Vedia, V.; Warr, N.; Werner, V.; Wilmsen, D.; Wilson, E.; Zerrouki, T.; Zielinska, M.
Abstract
In the EXILL campaign a highly efficient array of HPGe detectors was operated at the cold neutron beam instrument PF1B of the Institut Laue-Langevin to carry out nuclear structure studies, via measurements of -rays following neutron-induced capture and fission reactions. The setup consisted of a collimation system producing a pencil beam with a thermal capture equivalent
flux of about 108 s-1 cm-2 at the target position and negligible neutron halo. The target was surrounded by an array of eight to ten anti-Compton shielded EXOGAM clover detectors, four to six
anti-Compton shielded large coaxial GASP detectors and two smaller clover detectors. The detectors were arranged in an array of rhombicuboctahedron geometry, providing the possibility to carry out very precise angular correlation and directional-polarization correlation measurements. The trigger-less acquisition system allowed an event collection rate of up to 6 × 105 Hz. From triggerless collected data it was possible to construct decay schemes and in combination with the FATIMA array of LaBr3 detectors to analyze half-lives of excited levels in the pico- to micro-second range. Precise energy and efficiency calibrations of EXILL were performed using 27Al(n,γ)28Al and 35Cl(n,γ)36Cl reactions in the energy range from 30 keV up to 10 MeV.
Keywords: neutron-induced fission; 235U; 241Pu; (n,γ)-reactions; Ge detectors; angular correlations; multiple-γ coincidences
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Journal of Instrumentation 12(2017), P11003
DOI: 10.1088/1748-0221/12/11/P11003
Cited 34 times in Scopus
Permalink: https://www.hzdr.de/publications/Publ-25806
Nuclear-Physics Experiments at the Bremsstrahlung Facility γELBE
Schwengner, R.; Wagner, A.
Abstract
The γELBE facility at HZDR is described.
Keywords: electron accelerator; bremsstrahlung; HPGE detectors
Involved research facilities
- Radiation Source ELBE DOI: 10.17815/jlsrf-2-58
- γ-ELBE DOI: 10.58065/24020
Related publications
- DOI: 10.17815/jlsrf-2-58 is cited by this (Id 25805) publication
- DOI: 10.58065/24020 is cited by this (Id 25805) publication
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Nuclear Physics News 27(2017)4, 23-26
DOI: 10.1080/10619127.2017.1388699
Cited 1 times in Scopus
Permalink: https://www.hzdr.de/publications/Publ-25805
Modified ultrasmall nanoparticles as multimodal imaging agents for biomedical applications
Singh, G.; Licciardello, N.; Hunoldt, S.; Bergmann, R.; Zarschler, K.; Faramus, A.; de Cola, L.; Stephan, H.
Abstract
Objectives
The synthesis of multimodal imaging agents is a growing research field and a lot of work is currently being done in this area because of its wide biomedical applications. The idea behind the use of nuclear and optical dual labelled imaging probes is the possibility to synergistically exploit the advantages of positron emission tomography (PET) and optical imaging. The dual labelled imaging agents combat the limitations of sensitivity, spatial and temporal resolution and also tissue penetrability [1]. The combination of the two imaging modalities may provide complementary information for improving diagnosis, allows image guided surgery as well as fluorescence microscopy of tissue biopsies.
Methods
Ultrasmall silicon nanoparticles (SiNPs) of size <5 nm are potential candidates in this perspective due to their hydrophilicity, biocompatibility, luminescence properties and the possibility to covalently functionalize their surface [2,3]. Amine-terminated ultrasmall silicon nanoparticles were prepared according to a reported method with slight modifications [4]. Here we report the functionalization of amine-terminated SiNPs with the sulfo-cyanine 5 dye (sCy5) to obtain an optical imaging probe and with biomolecules, such as single-domain antibodies (sdAb) for active targeting of a cancer biomarker. SiNPs are also modified with radiolabel such as 64Cu, coordinated to bispidines [5], to obtain a dual, nuclear and optical, probe.
Results
The renal clearance property of these biocompatible, hydrophilic ultrasmall SiNPs are the major highlights of this research. The modified particles tend to eliminate from the body within very small period of time, rendering them as excellent tools for biomedical purposes.
Conclusions
The functionalization of SiNPs with fluorescent dyes, radiotracers and targeting moieties will open the path for targeted dual imaging of cancer, possibly allowing diagnosis and therapy in in vivo systems.
References
[1] G. Singh, M. D. Gott, H.-J. Pietzsch, and H. Stephan, Nuklearmedizin 2016, 55, 41–50.
[2] M. Rosso-Vasic, E. Spruijt, Z. Popović, K. Overgaag, B. van Lagen, B. Grandidier, D. Vanmaekelbergh, D. Domínguez-Gutiérrez, L. De Cola, H. Zuilhof, J. Mater. Chem., 2009, 19, 5926-5933.
[3] C.-H. Lai, J. Hütter, C.-W. Hsu, H. Tanaka, S. Varela-Aramburu, L. De Cola, B. Lepenies, and P. H. Seeberger, Nano Lett. 2016, 16, 807−811.
[4] Y. Zhong, F. Peng, F. Bao, S. Wang, X. Ji, L. Yang, Y. Su, S.-T. Lee, Y. He, J. Am. Chem. Soc. 2013, 135, 8350- 8356.
[5] H. Stephan, M. Walther, S. Fähnemann, P. Ceroni, J. Molloy, G. Bergamini, F. Heisig, C. E. Müller, W. Kraus, and P. Comba, Chem. Eur. J., 2014, 20, 17011-17018.
Keywords: Silicon nanoparticles; Biomedical applications; Radiolabeling; Positron emission tomography; Optical imaging
Involved research facilities
- PET-Center
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Poster
22nd International Symposium on Radiopharmaceutical Sciences, 14.-19.05.2017, Dresden, Germany
Permalink: https://www.hzdr.de/publications/Publ-25804
Synthesis of two new 11C-labelled a7 nicotinic acetylcholine receptor ligands.
Patt, J.-T.; Deuther-Conrad, W.; Peters, D.; Brust, P.; Sabri, O.; Patt, M.
Abstract
Introduction
NS-9011 (4-[5-(4-Methoxy-phenyl)-[1,3,4]oxadiazol-2-yl]-1,4-diaza-bizyclo[3.2.2]nonane) and NS-9030 (4-[5-(3-Methoxy-phenyl)-[1,3,4]oxadiazol-2-yl]-1,4-diaza-the desmethyl precursor compounds with [11C]methyltriflate. The precursor compounds showed a high reactivity towards [11C]iodomethane, unfortunately not in the desired labelling position. In order to decrease the selectivity for the undesired compound(s) [11C]methyltriflate instead of [11C]iodomethane was used. The higher reactivity of the [11C]methyltriflate in combination with elevated temperature of 60 °C and using water as solvent should result in a considerable decrease in selectivity.
Methods
The radiosynthesis was carried out in a modified TracerLab C system (GEMS) equipped with a reaction loop instead of the glass reactor in the heating zone of the module. [11C]iodomethane was subsequently passed over silver triflate at 200 °C and through the reaction loop containing the precursor solution (prepared from 0.5 – 1.0 mg precursor and 30μl of 0.5 M NaOH solution) and 30 μl of water) heated to 60 °C. The reaction mixture was transferred with eluent into a HPLC valve and injected on a ReproSil-Pur 120 C18-Aq 5μ (125 mm x 10 mm) HPLC column. An eluent composed of 10 % Ethanol (NS-9011) or 13 % Ethanol (NS-9030) and buffer solution (40 ml sodium phosphate (Braun) per 1000 ml adjusted to pH 2 with phosphorc acid was used for purification.The product peak was collected, diluted and concentrated on a Phenomenex Strata X cartridge. The radiotracer was eluted with acetone (1.5 ml). Evaporation was performed manually in a heating block (70 °C) in a stream of nitrogen. The product was dissolved in 500 μl of physiological NaCl solution. Radiochemical purity was determined on a radio-HPLC system on a ReproSil-Pur 120 C18-Aq 5μ (250 mm x 4.6 mm) HPLC column.
Results and Discussion
By applying the reaction conditions described above, despite highly favoured competing labelling sites in the precursor molecule up to 0.5 GBq of tracer compound could be synthesized. The product was obtained in high radiochemical purity (>95 %). Comparison of the UV trace of authentic standard compound and the radioactivity signal of radiotracer spiked with standard compound showed a full match of radioactivity and UV signal. The yield was sufficient for first animal experiments and the reaction conditions were not further optimized.
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Poster
The 22nd International Symposium on Radiopharmaceutical Sciences (ISRS 2017), 14.05.2017, Dresden, Germany
Permalink: https://www.hzdr.de/publications/Publ-25803
A clinical trial with (+)-[18F]Flubatine: evaluation of metabolism, plasma protein binding and parameters.
Patt, M.; Mishchenko, O.; Tiepolt, S.; Sattler, B.; Höpping, A.; Smits, R.; Becker, G. A. F.; Deuther-Conrad, W.; Steinbach, J.; Brust, P.; Sabri, O.
Abstract
Introduction
(+)-[18F]Flubatine ((+)[18F]NCFHEB), the enantiomer of the recently introduced radioligand for quantificati(-)-[18F]Flubatine, was investigated in a clinical trial with patients suffering from Alzheimer’s disease compared to healthy controls. In order to be able to apply full kinetic modelling biological parameters such as plasma protein binding, amount of parent compound over time and distribution between cellular and noncellular blood components, were determined. In addition the kinetics of the tracer distribution between plasma and whole blood was assessed.
Methods
Plasma protein binding was evaluated in vitro by means of ultracentrifugation using a blood sample from each subject prior to injection. The amount of unchanged tracer over time was determined at 11 time points ranging from 3 to 270 min p.i. by radio-HPLC analysis of protein free plasma obtained by centrifugation as described previously. The distribution of radioactivity between cellular and non-cellular blood components was determined at 11 time points p.i. after separation of the blood components by centrifugation.
Results/Discussion
Plasma protein binding of (-)-[18F]Flubatine was found to be 0.140.02 (meansd) without significant difference between AD and HC groups. Metabolic degradation of (+)-[18F]Flubatine was very low: the amount of parent compound was found to be 100 and 972 % at 90 and 270 min p.i., respectively. The activity distribution between plasma and whole blood was found to be 0.820.05 and did not change with time. Kinetics for the distribution of the tracer between plasma and whole blood was determined over a time period of 1.5 h and equilibrium was found to be reached instantaneously.
Conclusions Biological parameters such as plasma protein binding, metabolism and tracer/activity distribution between plasma and whole blood were investigated within a clinical trial using (+)-[1842 subtype of nAChRs. From the biological data obtained within this study we, conclude that (+)-[18F]Flubatine is a very suitable radiotracer for the determination of the 42 nAChRs by kinetic modelling since plasma protein binding is moderate and the equilibrium between whole blood and plasma is reached instantaneously. Furthermore, metabolic degradation of the radiotracer is negligible.
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Poster
The 22nd International Symposium on Radiopharmaceutical Sciences (ISRS 2017), 14.-19.05.2017, Dresden, Germany
Permalink: https://www.hzdr.de/publications/Publ-25802
Influence of bivalent metal ions on the self-assembly of S-layer proteins from Lysinibacillus sphaericus JG-B53
Raff, J.; Liu, J.; Falke, S.; Drobot, B.; Oberthuer, D.; Kikhney, A.; Guenther, T.; Fahmy, K.; Svergun, D.; Betzel, C.
Abstract
Many systems in nature are perfectly optimized for their function. Good examples therefore are surface layer (S-layer) proteins. These proteins form two-dimensional lattices acting as interfaces between prokaryotic cells and their environment and as such as selective and protecting barrier. Outstanding properties are their autocatalytic self-assembly, high physicochemical stability, many different and regular arranged functional groups and their nanoscale fine structure. Understanding the dynamic and complex process of self-assembly is not only highly interesting from a scientific point of view but also for the technical application of this group of proteins. Their use is particularly promising for nanotechnology, and here especially for surface modification creating metal selective filter materials, bio-sensors or improved catalytic materials. Especially challenging within an industrial process is controlling the speed of the lattice formation and the formation of large areas of undisturbed lattices. For the examination of the structure-function relationship and the process dynamics of the protein self-assembly of the S-layer from Lysinibacillus sphaericus JG-B53 several complementary analytical techniques and methods have been applied: 1) The secondary structure of the S-layer protein was analyzed by CD spectroscopy. 2) Small-angle X-ray scattering (SAXS) was applied to gain insights into the three dimensional structure in solution. 3) The interaction with bivalent cations was followed by differential scanning calorimetry (DSC). 4) The dynamics and time-dependent assembly of S-layers was also investigated applying dynamic light scattering. 5) The two dimensional structure of the para-crystalline S-layer lattice was additionally examined by atomic force microscopy (AFM). The data obtained provide essential structural insights into the mechanism of the S-layer self-assembly, particularly with respect to the binding of the bivalent cations Mg2+ and Ca2+.
Keywords: S-layer; self-assembly; metal ions
Involved research facilities
- Rossendorf Beamline at ESRF DOI: 10.1107/S1600577520014265
Related publications
- DOI: 10.1107/S1600577520014265 is cited by this (Id 25801) publication
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Lecture (Conference)
XXVI International Materials Research Congress (IMRC 2017), 20.-25.08.2017, Cancún, México
Permalink: https://www.hzdr.de/publications/Publ-25801
Superconductivity with broken time-reversal symmetry in ion irradiated Ba0.27K0.73Fe2As2 single crystals
Grinenko, V.; Materne, P.; Sarkar, R.; Luetkens, H.; Kihou, K.; Lee, C. H.; Akhmadaliev, S.; Efremov, D. V.; Drechsler, S.-L.; Klauss, H.-H.
Abstract
Over the last years a lot of theoretical and experimental efforts have been made to find states with broken time reversal symmetry (BTRS) in multi-band superconductors. In particular, it was theoretically proposed that in the Ba1−xKxFe2As2 system either an s + is or an s + id BTRS state may exist at high doping levels in a narrow region of the phase diagram. Here we report the observation of an enhanced zero field muon spin relaxation rate below the superconducting transition temperature for a high quality crystalline sample with x ≈ 0.73. This indicates that indeed the time reversal symmetry is broken in superconducting Ba1−xKxFe2As2 at this doping level.
Involved research facilities
- Ion Beam Center DOI: 10.17815/jlsrf-3-159
Related publications
- DOI: 10.17815/jlsrf-3-159 is cited by this (Id 25800) publication
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Physical Review B 95(2017), 214511
DOI: 10.1103/PhysRevB.95.214511
Cited 47 times in Scopus
Permalink: https://www.hzdr.de/publications/Publ-25800
Ptychographic analysis of the photorefractive effect in LiNbO3:Fe
Bernert, C.; Hoppe, R.; Wittwer, F.; Woike, T.; Schroer, C. G.
Abstract
We present light induced refractive index changes in iron doped lithium niobate detected with a novel microscopy technique called ptychography. This method determines the change of the refractive index together with the intensity distribution of the writing beam from one single measurement with \SI{3}{\micro \m} spatial resolution and a sensitivity of the refractive index change of $10^{-5}$. We show that the light induced refractive index change follows exactly the intensity distribution of the writing beam.
Keywords: ptychographie; LiNbO3; LiNbO3:Fe; photorefractive effect
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Optics Express 25(2017), 31640-31650
DOI: 10.1364/OE.25.031640
Cited 9 times in Scopus
Permalink: https://www.hzdr.de/publications/Publ-25798
Radiolabelled Nanomaterials for Imaging and Treatment of Cancer: Quo Vadis?
Stephan, H.
Abstract
Novel nanomaterials (NMs) offer excellent prospects for the development of new non-invasive strategies of early diagnosis and efficient monitoring of therapeutic treatments. Thanks to their structural variability, which facilitates setting up the basic structure, modifying the periphery as well as creating complex structures, their properties allow being tailored to both diagnosis and treatment of diseases (theranostic approach) [1]. Provided with special functionalities, NMs allow the simultaneous application of different molecular imaging methods. In the field of cancer medicine, the combination of different imaging techniques such as nuclear (PET: positron emission tomography and SPECT: single-photon emission computed tomography) and near-infrared fluorescence (NIRF) imaging for tracking down tumors and metastases is particularly attractive [2].
This lecture will focus on the development and application of very small radiolabeled NMs, embracing polymeric structures [3] and inorganic particles [4]. Novel strategies will be discussed to develop stealth NMs capable of avoiding biomolecular corona formation and thus evading scavenging of NMs by the mononuclear phagocyte system, leading to eventual accumulation in the liver and spleen [5].
References
[1] J. A. Barreto, W. O’Malley, M. Kubeil, B. Graham, H. Stephan, L. Spiccia, Adv Mater 23 (2011) H18-H40.
[2] G. Singh, M. D. Gott, H.-J. Pietzsch, H. Stephan, Nuklearmedizin 55 (2016) 41-50.
[3] K. Pant, O. Sedláček, R. A. Nadar, M. Hrubý, H. Stephan, Adv Healthcare Mat 6 (2017) 1601115.
[4] K. Zarschler, L. Rocks, N. Licciardello, L. Boselli, E. Polo, K. Pombo Garcia, L. De Cola, H. Stephan, K. A. Dawson, Nanomed-Nanotechnol 12 (2016) 1663-1701.
[5] K. Pombo-García, K. Zarschler, L. Barbaro, J. A. Barreto, W. O’ Malley, L. Spiccia, H. Stephan, B. Graham
Small 10 (2014) 2516-2529.
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Invited lecture (Conferences)
II International Caparica Congress on Translational Chemistry, 04.-07.12.2017, Caparica (Lisbon), Portugal
Permalink: https://www.hzdr.de/publications/Publ-25797
EGFR-amplification plus gene expression profiling predicts response to combined radiotherapy with EGFR-inhibition: a preclinical trial in 10 HNSCC-tumour-xenograft models
Koi, L.; Löck, S.; Linge, A.; Thurow, C.; Hering, S.; Baumann, M.; Krause, M.; Gurtner, K.
Abstract
Background and Purpose: Improvement of the results of radiotherapy by EGFR inhibitors is modest, suggesting significant intertumoral heterogeneity of response. To identify potential biomarkers, a preclinical trial was performed on ten different human squamous cell carcinoma xenografts of the head and neck (HNSCC) studying in vivo and ex vivo the effect of fractionated irradiation and EGFR inhibition. Local tumour control and tumour growth delay were correlated with potential biomarkers, e.g. EGFR gene amplification and radioresponseassociated gene expression profiles.
Material and methods: Local tumour control 120 days after end of irradiation was determined for fractionated radiotherapy alone (30f, 6 weeks) or after simultaneous EGFR-inhibition with cetuximab. The EGFR gene amplification status was determined using FISH. Gene expression analyses were performed using an in-house gene panel.
Results: Six out of 10 investigated tumour models showed a significant increase in local tumour control for the combined treatment of cetuximab and fractionated radiotherapy compared to irradiation alone. For 3 of the 6 responding tumour models, an amplification of the EGFR gene could be demonstrated. Gene expression profiling of untreated tumours revealed significant differences between amplified and non-amplified tumours as well as between responder and non-responder tumours to combined radiotherapy and cetuximab.
Conclusion: The EGFR amplification status, in combination with gene expression profiling, may serve as a predictive biomarker for personalized interventional strategies regarding combined treatment of cetuximab and fractionated radiotherapy and should, as a next step, be clinically validated.
Keywords: Keywords: Radiotherapy; Head and neck cancer; Biomarker; Cetuximab; Gene expression
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Radiotherapy and Oncology 124(2017), 496-503
DOI: 10.1016/j.radonc.2017.07.009
Cited 19 times in Scopus
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- Final Draft PDF 1,5 MB Secondary publication
Permalink: https://www.hzdr.de/publications/Publ-25796
Positioning of cobalt atoms in amorphous carbon films by pre-selecting the hydrogen concentration
Gupta, P.; Williams, G. V. M.; Vajandar, S.; Osipowicz, T.; Becker, H.-W.; Heinig, K.-H.; Hübner, R.; Leveneur, J.; Kennedy, J.; Markwitz, A.
Abstract
Amorphous carbon and hydrogenated amorphous carbon layers were implanted at room temperature with Co ions to investigate the role of hydrogen on the Co distribution. Amorphous carbon (a:C) and hydrogenated amorphous carbon (a:C-H) films were prepared by mass selective ion beam deposition with a 5 kV acceleration voltage using C+ and C3H6
+ ions, respectively. The typically 100 nm thin films were implanted with Co using a 30 kV acceleration voltage to a fluence of 4×1016 cm-2. Raman measurements showed that Co implantation in hydrogenated amorphous carbon causes increased sp2 clustering while in amorphous carbon there is significant rehybridisation of carbon from sp3 to sp2 bonding. High resolution Rutherford backscattering measurements indicated that in the absence of hydrogen in the base matrix, the implantation profile assumes a unimodal distribution as predicted by simulations. However, in the presence of hydrogen the effects of collision cascade enhanced diffusion are significant in altering the implantation profile resulting in a bimodal distribution. The difference in the Co depth distribution between a:C and a:C-H films is explained by the change in thermal conductivity of the carbon matrix in the presence of hydrogen. The ability to position Co (magnetic atoms) in the surface region of diamond-like carbon films offers great advantages for applications in novel magnetic devices.
Keywords: Atomic positioning; Bimodal distribution; Cobalt implantation; Diamond-like carbon; Hydrogen
Involved research facilities
- Ion Beam Center DOI: 10.17815/jlsrf-3-159
Related publications
- DOI: 10.17815/jlsrf-3-159 is cited by this (Id 25794) publication
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Nuclear Instruments and Methods in Physics Research B 409(2017), 116-120
DOI: 10.1016/j.nimb.2017.04.005
Cited 5 times in Scopus
Permalink: https://www.hzdr.de/publications/Publ-25794
Bimodale Systeme für die nukleare und optische Bildgebung
Stephan, H.; Singh, G.; Pant, K.; Steinbach, J.
Abstract
Die molekulare Bildgebung hat sich als eine wertvolle Technik zum Verfolgen und zur Charakterisierung biochemischer Prozesse auf molekularer Ebene in isolierten Zellen, Geweben und höheren Organismen bis hin zur Humandiagnostik etabliert. Innerhalb des breiten Spektrums der verschiedenen Bildgebungsmodalitäten sind bimodale Systeme für die nukleare und optische Bildgebung von besonderem Interesse. Das ergibt sich vor allem aus der vergleichbaren Nachweisempfindlichkeit [1].
Es werden aussichtsreiche Systeme auf der Basis von modularen Liganden sowie nanoskaligen Materialien vorgestellt, die bifunktionelle Chelatoren zur stabilen Bindung des Positronenstrahlers 64Cu sowie Fluoreszenzfarbstoffe enthalten. Dabei handelt es sich einmal um makrocyclische Liganden auf der Basis des 1,4,7-Triazacyclonanonans (TACN) mit zusätzlichen Picolylgruppen I. Insgesamt wird mit diesen Verbindungen eine hohe thermodynamische Stabilität bei gleichzeitig schneller Komplexbildungskinetik für entsprechende Cu(II)-Komplexe erzielt [2, 3]. Weiterhin werden Liganden auf der Basis des 3,7-Diazabicyclo[3.3.1]nonans (Bispidine) II diskutiert, die ebenfalls Cu(II)-Komplexe hoher Stabilität unter milden Bedingungen (Raumtemperatur, physiologischer pH-Wert) bilden [4]. Beide Ligandsysteme gestatten die zusätzliche Funktionalisierung mit Fluoreszenzfarbstoffen sowie die Bindung an geeignete zielsuchende Moleküle zum pharmazeutischen Targeting. Damit können die konzipierten bimodalen Systeme für die nukleare (Positronen-Emissions-Tomographie) und Nah-Infrarot-Fluoreszenz (NIRF)-Bildgebung in der Diagnostik von u. a. Tumoren eingesetzt werden.
References:
[1] G. Singh et al., Nuklearmedizin 2016, 55, 41. [2] K. Viehweger et al., Bioconjugate Chem. 2014, 25, 1011. [3] K. Pant et al., Bioconjugate Chem. 2015, 26, 906. [4] H. Stephan et al., Chem. Eur. J. 2014, 20, 17011.
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Poster
GDCh-Wissenschaftsforum Chemie 2017, 10.-14.09.2017, Berlin, Deutschland
Permalink: https://www.hzdr.de/publications/Publ-25792
Bispidine ligands for the potential application in nuclear medicine
Comba, P.; Pietzsch, J.; Rück, K.; Starke, M.; Stephan, H.; Wadepohl, H.
Abstract
Objectives
An important part of radiopharmaceuticals containing radiometals is the so-called bifunctional chelator (BFC). Bispidine ligands (3,7-diazabicyclo[3.3.1]nonane) (see Figure 1) developed in the Comba group are perfectly suited BFCs for the application in nuclear medicine. Due to their preorganisation and rigidity of the backbone with the donor atoms N3 and N7 they generally form complexes fastly and with high stability.[1]
Methods
By choosing suitable moieties at position R1 and R2 and by fine tuning of the pyridyl groups at C2 and C4,[2] bispidines can be tailored for the complexation of many different metal ions. Coupling to vector entities is performed at the ester groups at C1/5 or the hydroxyl group at C9.[3-4] One of the applications for bispidine ligands is 64CuII PET imaging (positron emission tomography).[3,5] We design bispidine ligand systems for PET and evaluate their potential in radiolabeling experiments and stability studies.
Results
First in vitro and in vivo studies show the high potential of the bispidine chelators for PET application.[3] The hexadentate ligands N2Py4, N2Py3Pdz and the isomers Hbispa1a/b with pyridyl, pyridazyl or picolinic acid groups at R1 and/or R2 (see Figure 1) are promising BFCs for 64CuII PET imaging.[6-7]
Conclusions
The hexadentate ligands shown in Figure 1 and derivatives are further investigated regarding the application in nuclear medicine.
References
[1] P. Comba, M. Kerscher, W. Schiek, Prog Inorg Chem 2007, 55, 613-704.
[2] P. Comba, S. Hunoldt, M. Morgen, J. Pietzsch, H. Stephan, H. Wadepohl, Inorg Chem 2013, 52, 8131-8143.
[3] S. Juran, M. Walther, H. Stephan, R. Bergmann, J. Steinbach, W. Kraus, F. Emmerling, P. Comba, Bioconjugate Chem 2009, 20, 347-359.
[4] H. Stephan, M. Walther, S. Fahnemann, P. Ceroni, J. K. Molloy, G. Bergamini, F. Heisig, C. E. Muller, W. Kraus, P. Comba, Chem-Eur J 2014, 20, 17011-17018.
[5] A. Roux, A. M. Nonat, J. Brandel, V. Hubscher-Bruder, L. J. Charbonniere, Inorg Chem 2015, 54, 4431-4444.
[6] C. Bleiholder, H. Borzel, P. Comba, R. Ferrari, M. Heydt, M. Kerscher, S. Kuwata, G. Laurenczy, G. A. Lawrance, A. Lienke, B. Martin, M. Merz, B. Nuber, H. Pritzkow, Inorg Chem 2005, 44, 8145-8155.
[7] P. Comba, L. Grimm, C. Orvig, K. Rück, H. Wadepohl, Inorg Chem 2016, manuscript accepted.
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Poster
22nd International Symposium on Radiopharmaceutical Sciences, 14.-19.05.2017, Dresden, Germany -
Abstract in refereed journal
Journal of Labelled Compounds and Radiopharmaceuticals 60(2017)Suppl 1, S500
DOI: 10.1002/jlcr.3508
Cited 3 times in Scopus
Permalink: https://www.hzdr.de/publications/Publ-25791
Yedoma Ice Complex of the Buor Khaya Peninsula (southern Laptev Sea)
Schirrmeister, L.; Schwamborn, G.; Overduin, P. P.; Strauss, J.; Fuchs, M. C.; Grigoriev, M.; Yakshina, I.; Rethemeyer, J.; Dietze, E.; Wetterich, S.
Abstract
The composition of perennially frozen deposits holds information on the palaeo-environment during and following deposition. In this study, we investigate late Pleistocene permafrost at the western coast of the Buor Khaya Peninsula in the south-central Laptev Sea (Siberia), namely the prominent eastern Siberian Yedoma Ice Complex (IC). Two Yedoma IC exposures and one drill core were studied for cryolithological (i.e. ice and sediment features), geochemical, and geochronological parameters. Borehole temperatures were measured for 3 years to capture the current thermal state of permafrost. The studied sequences were composed of ice-oversaturated silts and fine-grained sands with considerable amounts of organic matter (0.2 to 24 wt %). Syngenetic ice wedges intersect the frozen deposits. The deposition of the Yedoma IC, as revealed by radiocarbon dates of sedimentary organic matter, took place between 54.1 and 30.1 kyr BP. Continued Yedoma IC deposition until about 14.7 kyr BP is shown by dates from organic matter preserved in ice-wedge ice. For the lowermost and oldest Yedoma IC part, infrared-stimulated luminescence dates on feldspar show deposition ages between 51.1 ± 4.9 and 44.2 ± 3.6 kyr BP. End-member modelling was applied to grain-size-distribution data to determined sedimentation processes during Yedoma IC formation. Three to five robust end-members were detected within Yedoma IC deposits, which we interpret as different modes of primary and reworked unconfined alluvial slope and fan deposition as well as of localized eolian and fluvial sediment, which is overprinted by in situ frost weathering. The cryolithological inventory of the Yedoma IC preserved on the Buor Khaya Peninsula is closely related to the results of other IC studies, for example, to the west on the Bykovsky Peninsula, where formation time (mainly during the late Pleistocene marine isotope stages (MIS) 3 interstadial) and formation conditions were similar. Local freezing conditions on Buor Khaya, however, differed and created solute-enriched (salty) and isotopically light pore water pointing to a small talik layer and thaw-bulb freezing after deposition. Due to intense coastal erosion, the biogeochemical signature of the studied Yedoma IC represents the terrestrial end-member, and is closely related to organic matter currently being deposited in the marine realm of the Laptev Sea shelf.
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Biogeosciences 14(2017), 1261-1283
DOI: 10.5194/bg-14-1261-2017
Cited 35 times in Scopus
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Permalink: https://www.hzdr.de/publications/Publ-25790
Development of a modular micro reactor for the partial hydrocarbon oxidation
Willms, T.; Kryk, H.; Wiezorek, M.; Hampel, U.
Abstract
The partial oxidation of hydrocarbons is currently the usual method for the industrial production of a variety of important products. Such processes are frequently characterized by low conversions and yields, which are mostly related to mass and heat transfer problems. Due to the reaction conditions, such processes include also important safety risks and are therefore still not sufficiently investigated. To study the influence of the residence time, oxygen concentration, initiator, additives, temperature and pressure on the product selectivity, a modular micro reactor has been developed and constructed, which permits to perform this class of reactions for the first time as a two phase process in a capillary reactor in an especially wide range of residence times, temperatures and pressures. The production of TBHP by partial oxidation of liquid isobutane is an example for the non-catalyzed oxidation of hydrocarbons with oxygen. Flow rates in the range of 15 µL/ min to 188 µL/ min for isobutane and in the range of 0.1 up to 1.5 mL/ min for oxygen were realized, using capillary lengths of up to 100 m. To characterize the two-phase flow inside the reactor, preliminary measurements of the system isobutane - nitrogen were performed in a glass capillary. Since both, initiators and reaction products are sensitive to most metals, the micro reactor and further parts of the lab facility have been coated. To analyze the reaction mixture, a GC/MS - method has been developed. The challenges of the reactor construction and their solutions are discussed.
Keywords: Micro reactor; process intensification; isobutane; hydrocarbon oxidation; Taylor flow; t-butyl hydroperoxide; multiphase flow
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Chemical Engineering Communications 205(2018)3, 269-280
Online First (2017) DOI: 10.1080/00986445.2017.1384728
Cited 5 times in Scopus
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- Final Draft PDF 707 kB Secondary publication
Permalink: https://www.hzdr.de/publications/Publ-25789
On the thermal decomposition of tert.-butyl hydroperoxide, its sensitivity to metals and its kinetics, studied by thermoanalytic methods.
Willms, T.; Kryk, H.; Oertel, J.; Hempel, C.; Hampel, U.; Knitt, F.
Abstract
The decomposition of hydroperoxides like tert.-butyl hydroperoxide (TBHP) due to reactions with reactor materials (wall reactions) is an important issue in the frame of industrial processes and the analysis of such compounds. Because of the high surface-volume ratio such heterogeneous reactions are also especially important in case of thermo-analytical measurements. Therefore, the decomposition of TBHP has been studied for the first time extensively by Differential Scanning Calorimetry (DSC) using differently coated high pressure stainless steel crucibles (uncoated, gilded, silicon coated) and a medium pressure crucible. Furthermore, the interaction of such materials with TBHP has been measured for the first time by Thermal Activity Monitoring (TAM). The material of the gilded copper blowout disc turned out to be the reason for the very different DSC curves published in literature and had the highest influence compared to the crucible body material and the pressure. To protect the sample against the blowout disc, an aluminium foil has been placed below the blowout disc. This changed the shape of the DSC curve completely. It became more similar to that obtained with the medium pressure crucible. Furthermore, the reaction mechanism, kinetics and chemical aspects of the decomposition of TBHP at different conditions have been discussed and kinetics has been investigated for the first time by an overall evaluation of the DSC curves and a model free kinetics approach. Using the linear relationship between the kinetic activation parameters the published values are compared to those of the present work.
Keywords: t-butyl hydroperoxide; DSC; steel crucible; silcosteel®; gold; TAM
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Thermochimica Acta 672(2019), 25-42
Online First (2018) DOI: 10.1016/j.tca.2018.12.007
Cited 12 times in Scopus
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- Final Draft PDF 80,7 MB Secondary publication
Permalink: https://www.hzdr.de/publications/Publ-25788
The decomposition of tert.-butyl hydroperoxide studied by differential scanning calorimetry.
Willms, T.; Kryk, H.; Hampel, U.
Abstract
Due to the investigation the oxidation of isobutane to t-butyl hydroperoxide (TBHP), studied for the first time as a two-phase process in a micro reactor at high temperatures and pressures, the prevention of the decomposition of TBHP was crucial. The observed by-products t butyl per-oxide, tert.butanol, acetone, and methanol decreasing the selectivity and thus the TBHP yield are due to the thermal decomposition of TBHP, which is influenced by the wall effect to a large extend. Therefore, the decomposition of TBHP has been studied by Differential Scanning Calorimetry (DSC) at higher temperatures using for the first time different crucible types, pressure conditions, heating rates etc.. Aluminium (low pressure) crucibles, medium pressure crucibles and differently coated high pressure stainless steel crucibles (uncoated, gilded, silicon coated) have been utilized to show the influence of the crucible material as well as of the pressure on the DSC curve. It has been found that the material of the blowout disk has an important influence on the thermal decomposition behaviour. Therefore, within further DSC studies, the sample has been protected against the gilded copper blowout disk by aluminium foil in the crucible. Kinetics of the decomposition reactions has been investigated experimentally by evaluation of the DSC curves using an nth order approach and by a model free kinetics (MFK) approach.
Keywords: differential scanning calorimetry; t-butyl hydroperoxide; crucible type; material
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Lecture (Conference)
22. Kalorimetrietage Braunschweig, 07.-09.06.2017, Braunschweig, Deutschland -
Contribution to proceedings
22. Kalorimetrietage Braunschweig, 07.-09.06.2017, Braunschweig, Deutschland
Permalink: https://www.hzdr.de/publications/Publ-25787
Oxidation of isobutane to TBHP – a chemical process with high energy saving potential.
Willms, T.; Kryk, D. H.; Hampel, U.
Abstract
Tertiary butyl hydroperoxide (TBHP), as an intermediate for the production of propylene oxide according to the Oxirane process, is currently produced at industrial scale by the partial oxidation of liquid isobutane using bubble columns or bubble tray reactors. In this process, liquid isobutane reacts with oxygen under two phase conditions at temperatures of 120 to 140 °C and pressures of 25 to 37 bars at high residence times of up to 12 hours. The conversion is limited to 35 to 50 % in order to obtain a TBHP selectivity of 50 to 60 % minimizing the formation of by-products, which are caused by the decomposition of the TBHP due to the complex reaction mechanism. Besides safety aspects, the high reaction enthalpy of the oxidation as well as heat and mass transport problems are further issues of this process. In the frame of the Helmholtz-Energy-Alliance project “Energy efficient chemical multiphase processes“, this reaction is investigated for the first time at supercritical conditions using DTBP as an initiator in a broad range of flow rates, temperatures and pressures in a micro reactor with the aim to enhance the space-time yield of the process. The advantage of micro reactors are the high surface – volume ratio for an efficient heat transfer, the related, improved – nearly inherent – safety and the resulting possibility to investigate unusual process windows, for instance within the explosive region of a reaction mixture using high oxygen concentrations. Besides two phase flow conditions, super¬critical conditions i.e. pressures above 40 bars and temperatures above 140°C are especially interesting because of the higher reaction rate and lacking mass transfer limitations. The reaction has been performed in both regimes at different conditions and the results compared. Furthermore, the influence of process parameters on the start-up time has been investigated. For all experiments, the selectivity and conversion of the reaction have been studied. Therefor, the reaction course is followed by sampling and analyzing the reaction by GC/MS and GC–TCD where analytical methods have been developed to detect a maximum of by-products and inter¬mediates.
Keywords: isobutane; oxidation; energy efficiency; t-butyl hydroperoxide; micro reactor
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Poster
Jahrestreffen Frankfurt I Jahrestreffen der ProcessNet-Fachgruppen Hochdruckverfahrenstechnik, Mikroverfahrenstechnik, Molekulare Modellierung, 08.-10.03.2017, Frankfurt, Deutschland -
Contribution to proceedings
Jahrestreffen Frankfurt I Jahrestreffen der ProcessNet-Fachgruppen Hochdruckverfahrenstechnik, Mikroverfahrenstechnik, Molekulare Modellierung, 08.-10.03.2017, Frankfurt, Deutschland
Permalink: https://www.hzdr.de/publications/Publ-25786
Micro reactor experiments on the partial isobutane oxidation as a multiphase process - Comparison of t-butyl hydroperoxide and di-t-butyl peroxide as initiators.
Willms, T.; Kryk, H.; Hampel, U.
Abstract
Tertiary butyl hydroperoxide (TBHP), as an intermediate for the production of propylene oxide according to the Oxirane process, is currently produced at industrial scale by the partial oxidation of liquid isobutane using bubble columns or bubble tray reactors. In this process, liquid isobutane reacts with oxygen at temperatures of 120 to 140 °C and pressures of 25 to 37 bars at high residence times of up to 12 hours. The conversion is limited to 35 to 50 % in order to obtain a TBHP selectivity of 50 to 60 % minimizing the formation of by-products, which are caused by the decom-position of the TBHP due to the complex reaction mechanism. Besides safety aspects, the high reaction enthalpy of the oxidation as well as heat and mass transport problems are further issues of this process. In the frame of the Helmholtz-Energy-Alliance project “Energy efficient chemical multiphase processes“, this reaction has been investigated for the first time as a Taylor-Flow process in a broad range of flow rates, temperatures and pressures in a micro reactor with the aim to enhance the space-time yield of the process. The advantages of micro reactors are the high surface – volume ratio for an efficient heat transfer and the improved, nearly inherent, safety. This permits to investigate yet unexplored process windows, for instance within the explosive region of a reaction mixture.
The reaction has been studied varying the molar ratio of the starting pro¬ducts, temperature, pressure, and initiator concentration using two different initiators, namely TBHP and di-t-butyl peroxide (DTBP). For all experiments the selectivity of the reaction products and the conversion of the reaction have been studied. The reaction course has been followed by sampling and analyzing the reaction by GC/MS where a new analytical method has been developed. The use of TBHP as initiator increases the selectivity of the reaction for the target product TBHP. The beneficial effect on the TBHP selectivity compared to DTBP might be explained on the basis of the suitable thermochemical properties of TBHP. TBHP seems to give a better selectivity since at high temperatures as they are necessary for the initiator effect of DTBP the formation of propanone already becomes important which favours the decomposition of TBHP.
Keywords: isobutane; oxidation; t-butyl hydroperoxide; t-butyl peroxide; micro reactor
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Poster
Jahrestreffen Reaktionstechnik 2017, 22.-24.05.2017, Würzburg, Deutschland -
Contribution to proceedings
Jahrestreffen Reaktionstechnik 2017, 22.-24.05.2017, Würzburg, Deutschland
Permalink: https://www.hzdr.de/publications/Publ-25785
TACN Ligands – A journey through radiopharmaceutical applications
Stephan, H.; Graham, B.; Spiccia, L.
Abstract
The design of tailor-made bifunctional copper radionuclide-complexing agents for nuclear medical application as well as acquisition of reliable information about the biodistribution of different materials represents an intensive and rapidly developing field of research. In this context, the tridentate macrocycle 1,4,7-triazacyclononane (TACN) is of special interest since it forms stable complexes with Cu(II) and the ligand structure can be easily modified. The introduction of further donor groups on the ligand scaffold, such as pyridine units, significantly enhances the thermodynamic stability as well as the kinetic inertness of the Cu(II) complexes formed. TACN ligands containing one or two pendant 2-picolyl arms prefer the formation of square-pyramidal coordination geometry with Cu(II). A hexadentate ligand with two picoline coordination groups as well as a carboxylic functionality, 2-[4,7-bis(2-pyridylmethyl)-1,4,7-triazacyclononan-1-yl]acetic acid (DMPTACN-COOH), enforces a six-coordinate, distorted octahedral structure. DMPTACN-based ligands rapidly chelate copper(II) radionuclides under ambient conditions and the resulting complexes show high in vivo stability. The carboxylic acid group in DMPTACN-COOH allows for the ready introduction of linker groups, such as maleimide or isothiocyanate, thereby facilitating coupling of targeting molecules and bio(nano)materials.
Examples of target-specific peptides and bio(nano)materials equipped with DMPTACN ligands for labeling with 64Cu as an ideal positron emitter are discussed. This enables tumor imaging and the biodistribution of the materials to be studied over a period of days via positron emission tomography (PET).
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Invited lecture (Conferences)
6th Asian Conference on Coordination Chemistry, 24.-28.07.2017, Melbourne, Australia
Permalink: https://www.hzdr.de/publications/Publ-25784
MicroTCA.4-based LLRF for the superconducting CW Linac ELBE – Status and Outlook
Kuntzsch, M.; Steinbrück, R.; Schurig, R.; Hierholzer, M.; Killenberg, M.; Schmidt, C.; Gümüs, C.; Butkowski, L.; Hoffmann, M.; Iatrou, C.; Rahm, J.; Rutkowski, I.; Grzegrzółka, M.
Abstract
The superconducting linear accelerator ELBE is operated in continuous wave operation (CW). The analogue LLRF system, used since 2001, is going to be replaced by a digital solution based on µTCA.4. The new system enables a higher flexibility, better performance and more advanced diagnostics. The contribution will show the performance of the system at ELBE, the hardware and the software structure.
Further it will summarize the last steps to bring it into full user operation and give an outlook to the envisioned beam-based feedback system that will take advantage of the capabilities of the digital LLRF system.
Keywords: ELBE LLRF Feedback MicroTCA µTCA MTCA
Involved research facilities
- Radiation Source ELBE DOI: 10.17815/jlsrf-2-58
Related publications
- DOI: 10.17815/jlsrf-2-58 is cited by this (Id 25783) publication
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Poster
Low Level Radio Frequency Workshop 2017, 16.-19.10.2017, Barcelona, Spain
Permalink: https://www.hzdr.de/publications/Publ-25783
MicroTCA.4-based LLRF for CW operation at ELBE – Status and Outlook
Kuntzsch, M.; Steinbrück, R.; Hierholzer, M.; Killenberg, M.; Schmidt, C.; Butkowski, L.; Hoffmann, M.; Iatrou, C.; Rahm, J.; Rutkowski, I.; Grzegrzółka, M.
Abstract
The superconducting linear accelerator ELBE is operated in continuous wave operation (CW). The analogue LLRF system, used since 2001, is going to be replaced by a digital solution based on µTCA.4. The new system enables a higher flexibility, better performance and more advanced diagnostics. The contribution will show the performance of the system at ELBE, the hardware and the software structure.
Further it will summarize the last steps to bring it into full user operation and give an outlook to the envisioned beam-based feedback system that will take advantage of the capabilities of the digital LLRF system.
Keywords: ELBE LLRF Feedbacks MicroTCA µTCA MTCA
Involved research facilities
- Radiation Source ELBE DOI: 10.17815/jlsrf-2-58
Related publications
- DOI: 10.17815/jlsrf-2-58 is cited by this (Id 25782) publication
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Poster
International Beam Instrumentation Conference, 20.-24.08.2017, Grand Rapids, USA -
Contribution to proceedings
International Beam Instrumentation Conference, 20.-24.08.2017, Grand Rapids, USA
MicroTCA.4-based LLRF for CW operation at ELBE – Status and Outlook
Permalink: https://www.hzdr.de/publications/Publ-25782
Optical Synchronization and Electron Bunch Diagnostic at ELBE
Kuntzsch, M.
Abstract
The talk summarizes the activities at ELBE in the fields of optical synchronization and electron bunch diagnostic.
Keywords: Optical Synchronization Diagnostic ELBE
Involved research facilities
- Radiation Source ELBE DOI: 10.17815/jlsrf-2-58
Related publications
- DOI: 10.17815/jlsrf-2-58 is cited by this (Id 25781) publication
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Invited lecture (Conferences)
Graduiertenkolleg "Accelence", 06.07.2017, Mainz, Deutschland
Permalink: https://www.hzdr.de/publications/Publ-25781
Active tumor pretargeting using peptide nucleic acid bioconjugates as complementary system
Zarschler, K.
Abstract
The ability of early-stage diagnosis of tumor malignancies and personalized treatment ultimately relies on the availability of highly tumor-affine compounds with purposeful pharmacological profile. In this regard, monoclonal antibodies (mAbs) are particularly valuable as these molecules bind to tumor-associated epitopes with high specificity and affinity. The conventional concept of directly radiolabeled tumor-specific mAbs for radioimmunodetection (RID) and -therapy (RIT) has certainly several drawbacks, most prominently the prolonged radiation exposure of healthy tissues and organs. Fortunately, however, several of these shortcomings can be eliminated by implementing the pretargeting strategy allowing for the rational use of long circulating, high-affinity mAbs for both non-invasive cancer RID and RIT [1].
This keynote lecture will give a general overview about the pre-targeting strategy and present the different approaches for specific radionuclide delivery to pretargeted tissues. Furthermore, the different in vivo recognition systems will be introduced, with particular emphasis on synthetic complementary oligonucleotides such as peptide nucleic acid (PNA) derivatives. Regarding the latter, their synthesis as well as characterization will be described and, finally, an active tumor pretargeting approach using PNA bioconjugates will be exemplified [2].
References
[1] M. Patra, K. Zarschler, H.-J. Pietzsch, H. Stephan and G. Gasser, Chem Soc Rev 45 (2016) 6415-6431.
[2] A. Leonidova, C. Foerster, K. Zarschler, M. Schubert, H.-J. Pietzsch, J. Steinbach, R. Bergmann, N. Metzler-Nolte, H. Stephan, and G. Gasser, Chem Sci 6 (2015) 5601-5616.
Involved research facilities
- PET-Center
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Invited lecture (Conferences)
2nd Internacional Caparica Christmas Congress on Translational Chemistry 2017 - IC3TC, 04.-07.12.2017, Caparica, Portugal
Permalink: https://www.hzdr.de/publications/Publ-25780
Diagnostic Tumor Imaging Using Renally Excretable Nanoparticles: Focus on Active and Passive Targeting
Zarschler, K.; Pant, K.; Neuber, C.; Pufe, J.; Steinbach, J.; Haag, R.; Pietzsch, J.; Stephan, H.
Abstract
Introduction
Depending on their size, shape and surface functionalities, nanoparticles can passively extravasate and accumulate in the tumor tissue through the enhanced permeability and retention (EPR) effect. Being an accumulative process, this effect favors nanoparticles with long blood retention time. Renally excretable, ultrasmall nanoparticles with short blood half-lives are therefore less prone to passive tumor targeting as they rapidly diffuse back to the vasculature and re-enter the systemic circulation, which results in only transient intratumoral presence without substantial retention. To prevent their rapid efflux from malignant tissues by increasing the interactions between nanoparticles and tumor cells as well as by improving cellular nanoparticle uptake, the strategy of active or ligand-mediated targeting is pursued. Here, we describe the development of renally excretable dendritic polyglycerols (dPGs) functionalized with different targeting units to differentiate between active and passive tumor targeting.
Methods
Fluorescent dye labels for optical imaging and small camelid single-domain antibodies (sdAbs) as targeting units - both equipped with maleimide functionalities - were simultaneously attached in a one-pot reaction to thiol groups of the dPGs. As the presented work focusses on the epidermal growth factor receptor (EGFR) acting as a model receptor, an EGFR-specific sdAb was attached to the dPGs to obtain an active targeting probe. In parallel, a probe with similar surface characteristics but a nonspecific sdAb (passive targeting) was synthesized. Both conjugates were purified using affinity chromatography, which selectively separates the sdAb-conjugated dPGs.
Results
In vitro binding studies on different human epithelial cancer cell lines using dye-labeled sdAb-conjugated dPGs showed a high specificity, co-localization and a receptor-mediated cellular uptake of the EGFR-specific probes. Optical imaging studies using murine xenografts revealed a substantial accumulation of the EGFR-specific probes in comparison to its nonspecific counterparts and a minimum off-target accumulation of both conjugates.
Discussion and Conclusion
The direct comparison of specific and nonspecific probes with similar surface characteristics allows the straight-forward preclinical discrimination between active and potential passive tumor targeting of renally excretable nanoparticles in small animal models. Furthermore, it provides important information on the extent to which ligand-mediated targeting contributes to total nanoparticle accumulation in malignant and normal tissues.
Involved research facilities
- PET-Center
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Lecture (Conference)
EANM'17 - Annual Congress of the European Association of Nuclear Medicine, 21.-25.10.2017, Wien, Österreich
Permalink: https://www.hzdr.de/publications/Publ-25779
DFO* - An Improved Chelating System for 89Zr-Immuno-PET Applications
Briand, M.; Zarschler, K.; Vugts, D.; Stephan, H.; Steinbach, J.; Gasser, G.; Mindt, T.
Abstract
Objectives
The potential of 89Zr-labelled antibodies as diagnostic probes for 89Zr-immuno-PET has been demonstrated by a number of clinical trials.[1] The only chelator used thus far in the clinic is the siderophore desferrioxamine (DFO). However, DFO does not satisfy the preferred ocatadentate coordination of zirconium-89, which results in vivo into unspecific uptake of the radiometal in, e.g., the bones. This can interfere with the detection of bone metastases and leads to additional radiation dose to non-targeted tissue.
We have previously reported the development of an extended, octadentate version of DFO, termed DFO*,[2] which provides complexes with [89Zr]Zr4+ of remarkably increased stability in vitro and in vivo. [2, 3] DFO* and derivatives thereof already fulfil a number of prerequisites to become a new standard chelator for zirconium-89; however, its solubility could be improved to facilitate further its application in conjugation chemistry. We here wish to report our efforts in developing novel DFO* derivatives which display an improved water solubility.
Methods
Based on the DFO* scaffold, new derivatives containing pharmacological modifiers to improve the water solubility were synthesized. In addition, different functional groups for bioconjugation chemistry were included. LogP values of the novel bifunctional chelating agents were determined by HPLC. First bioconjugations and radiolabelling experiments with 89Zr were performed according to published procedures. [1,3]
Results
All new derivatives exhibited an increased hydrophilicity and thus, enhanced water solubility in comparison to the original DFO* (as well as DFO) system. Preliminary results on their reactivity in bioconjugations, capability of 89Zr-complexation, and stability of radiometal complexes will be reported.
Conclusions
Structural modifications provided novel derivatives of DFO* with improved water solubility which could facilitate their application in bioconjugation chemistry for the 89Zr-labelling of delicate proteins under aqueous (e.g., organic solvent free) reaction conditions.
Acknowledgements
This work is supported by the Swiss National Sciences Foundation (grant N° 205321–157216).
References
[1] G.A.M.S. Van Dongen, M.C. Huisman, R. Boellaard et al. Q. J. Nucl. Med. Mol. Imaging 2015, 59, 18-38
[2] M. Patra, A. Bauman, C. Mari et al. Chem. Commun. 2014, 50, 11523-11525
[3] D. Vugts, C. Klaver, C. Sewing et al. Eur. J. Nucl. Med. Mol. Im. 2016, doi:10.1007/s00259-016-3499-x S394: Poster 22nd International Symposium on Radiopharmaceutical Sciences
Involved research facilities
- PET-Center
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Poster
22nd International Symposium on Radiopharmaceutical Sciences (ISRS 2017), 14.-19.05.2017, Dresden, Deutschland
Permalink: https://www.hzdr.de/publications/Publ-25778
Kombinierte externe und interne Bestrahlung von Tumoren: präklinischer Nachweis des kurativen Potenzials
Pietzsch, H.-J.; Dietrich, A.; Andreeff, M.; Koi, L.; Schreiner, L.; Bergmann, R.; Löck, S.; Sihver, W.; Faulhaber, D.; Kotzerke, J.; Baumann, M.; Krause, M.; Steinbach, J.
Abstract
Die Therapie von Tumorerkrankungen gründet sich stadienabhängig auf die drei Säulen Chirurgie, Strahlen- und Chemotherapie. Grundprinzip der Strahlentherapie ist die gezielte Einwirkung von ionisierender Strahlung auf erkranktes Gewebe, um die Zerstörung maligner Tumorzellen zu erreichen. Neben der klassischen externen Strahlentherapie unter Verwendung von Photonen hat sich die Endoradionuklidtherapie durch Entwicklung geeigneter Targetingvektoren in den letzten Jahren zu einer zunehmend angewandten Therapieform entwickelt. Insbesondere die Radioimmuntherapie hat das Potential, auch (Mikro-) Metastasen zu zerstören. Die Kombination von externer und interner Strahlentherapie ist eine vielversprechende Behandlungsstrategie, da sie unter Schonung gesunden Gewebes potenziell die Vorteile beider Modalitäten kombiniert.
Ziel dieses Projektes war es, im Tiermodell zu überprüfen, ob eine interne Bestrahlung mit Hilfe des anti-EGFR-gerichteten, 90Y-markierten Antikörpers Cetuximab (C225) eine lokale Tumorkontrolle nach vorhergehender externer Bestrahlung bei verringerter Dosis ermöglicht.
Cetuximab wurde mit dem bifunktionellen Chelator p-SCN-Bn-CHX-A‘‘-DTPA funktionalisiert und nach 90Y-Markierung in einem Kopf-Hals-Plattenepithelkarzinom-Xenograftmodell (FaDu) eingesetzt. Die externe Bestrahlung erfolgte nach klinisch relevanten Protokollen mit 30 Bestrahlungsfraktionen (fx) verteilt über 6 Wochen. Nach 10 Fraktionen wurden jeweils 2,3 MBq des 90Y-markierten Cetuximab-Konjugats injiziert.
Die kombinierte Anwendung von externer und interner Bestrahlung erhöhte massiv die Wahrscheinlichtkeit einer lokalen Tumorkontrolle im Vergleich zur externen Bestrahlung allein oder in Kombination mit unmarkiertem Cetuximab.
In der Gruppe mit der niedrigsten externen Strahlendosis (1 Gy/Fraktion, Gesamtdosis = 30 Gy,) plus 90Y-Cetuximab wurden alle Tumore noch permanent kontrolliert (Beobachtungszeitraum = 120 d). Im Gegensatz dazu betrug die gesamte externe Strahlendosis, die notwendig ist um 50% der Tumore ohne zusätzliche Gabe von 90Y-Cetuximab zu heilen, 63,9 Gy (58,7, 73,9).
Unsere Ergebnisse zeigen, dass die kombinierte Anwendung von radiomarkierten Therapeutika nach fraktionierter externer Strahlentherapie ein bemerkenswertes Potenzial hat, das Behandlungsergebnis zu verbessern. Eine effiziente Aufnahme des Y-90-markierten Cetuximab-Konjugates ist die Voraussetzung für den Erfolg der kombinierten Strahlentherapie.
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Lecture (Conference)
Wissenschaftsforum Chemie, 10.-14.09.2017, Berlin, Deutschland
Permalink: https://www.hzdr.de/publications/Publ-25777
Recovery of iron and lead from a secondary lead smelter matte by magnetic separation
Kukurugya, F.; Rahfeld, A.; Möckel, R.; Nielsen, P.; Horckmans, L.; Spooren, J.; Broos, K.
Abstract
A secondary Pb smelter matte containing ca. 50 wt.% Fe (as FeS, Fe3O4, FeO and metallic Fe), shows good potential for being used as a secondary Fe source. However, requirements for Fe ore are: Fe content >60% and absence of sulphide phases. Therefore, further pre-treatment steps are necessary to increase the Fe content in the matte. Dry low intensity, wet low intensity and wet high intensity magnetic separation experiments were performed on different particle size fractions of the matte. Mineral liberation analysis (MLA) was performed to explain different behaviour of Pb in the different size fractions during magnetic separation. Moreover, oxidizing roasting at 600°C was performed to transform FeS to Fe2O3. Results show that by combining low and high intensity magnetic separation and oxidizing roasting, material containing up to 61 wt% Fe (as oxide) can be recovered in the magnetic fraction representing circa 50% of the initial weigth of the sample.
Keywords: matte; MLA; LIMS; WLIMS; WHIMS; recycling
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Minerals Engineering 122(2018), 17-25
DOI: 10.1016/j.mineng.2018.03.030
Cited 12 times in Scopus
Permalink: https://www.hzdr.de/publications/Publ-25776
Upgrade of the Superconducting CW Linac ELBE From Klystrons zu Silid State Amplifiers
Büttig, H.
Abstract
Overview on the status of ELBE and the activities to upgrade ELBE within the HSQ project.
Keywords: Solid state RF power amplifiers; Resonant ring
Involved research facilities
- Radiation Source ELBE DOI: 10.17815/jlsrf-2-58
Related publications
- DOI: 10.17815/jlsrf-2-58 is cited by this (Id 25775) publication
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Invited lecture (Conferences)
Graduiertenkolleg Seminar Uni Mainz und Uni Darmstadt, 06.07.2017, Mainz, Deutschland
Permalink: https://www.hzdr.de/publications/Publ-25775
Polyethyleneimine Methylphosphonate : towards the design of a new class of macromolecular actinide chelating agent in case of human exposition
Lahrouch, F.; Sofronov, O.; Creff, G.; Rossberg, A.; Hennig, C.; Den Auwer, C.; Di Giorgio, C.
Abstract
The use of uranium and to a minor extent plutonium as fuel for nuclear energy production or as components in military applications is under increasing public pressure. Uranium is weakly radioactive in its natural isotopy but its chemical toxicity, combined with its large scale industrial utilization, makes it a source of concern in terms of health impact for workers and possibly the general population. Plutonium is an artificial element that exhibits both chemical and radiological toxicities.
So far, uranium (under its form uranyl, U(VI)) or plutonium (as Pu(IV)) decorporation or protecting strategies based on molecular design have been of limited efficiency to remove the actinide once incorporated after human exposure. In all cases, after human exposure, plutonium and uranium are retained in main target organs (liver, kidneys) as well as skeleton although they exhibit differences in their biodistribution. Polymers could represent an alternative strategy as their tropism for specific target organs has been reported. We recently reported a methylcarboxylated polyethyleneimine (PEIMC) as a potential uranium decorporation agent. In this report, we extend our work and report on the ability of methylphosphonated polyethyleneimine (PEI-MP) to act as a new class of uranyl and plutonium chelating agent. As a first step, thorium (Th(IV)) was used as a chemical surrogate of plutonium because of the difficulty of handling the latter in the laboratory. For both cations, U(VI) and Th(IV), the uptake curve of PEI-MP was recorded. The functionalized PEI-MP exhibits a maximum loading capacity comprised of between 0.56 and 0.80 mg of uranium (elemental) and 0.15 - .20 mg of thorium (elemental) per milligram of PEI-MP. Complexation sites of U(VI) and Th(IV) in model conditions close to physiological pH were then characterized with a combination of Fourier transformed Infra Red (FT-IR) and Extended X-Ray Absorption Fine Structure (EXAFS). Although both cations exhibit different coordination modes, similar structural parameters with phosphonate functions were obtained. For example, the coordination sites are composed of fully monodentate phosphonate functions of the polymer chains.
Keywords: Polyethyleneimine Methylphosphonate; macromolecular actinide chelating agent; FT-IR; EXAFS; uranium; thorium
Involved research facilities
- Rossendorf Beamline at ESRF DOI: 10.1107/S1600577520014265
Related publications
- DOI: 10.1107/S1600577520014265 is cited by this (Id 25774) publication
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Dalton Transactions 46(2017), 13869-13877
DOI: 10.1039/c7dt02643a
Cited 13 times in Scopus
Permalink: https://www.hzdr.de/publications/Publ-25774
Structural characterization of Am(III) and Pu(III)-DOTA complexes
Audras, M.; Berthon, L.; Berthon, C.; Guillaumont, D.; Dumas, T.; Illy, M. C.; Martin, N.; Zilbermann, I.; Ben-Eliyahu, Y.; Moissev, Y.; Bettelheim, A.; Camelli, S.; Hennig, C.; Moisy, P.
Abstract
The complexation of DOTA ligand (1,4,7,10-tetrazacyclodecane-1,4,7,10-tetraacetic acid) with two trivalent actinides (Am3+ and Pu3+) was investigated by UV-visible spectrophotometry, Nuclear Magnetic Resonance (NMR) spectroscopy and extended X-ray absorption fine structure (EXAFS) in conjunction with computational methods. The complexation process of these two cations is similar to what has been previously observed with lanthanides(III) of similar ionic radius. The complexation takes places in different steps and ends up with the formation of a (1:1) complex [(An(III)DOTA)(H2O)]- where the cation is bonded to the nitrogen atoms of the ring, the four carboxylate arms and a water molecule is completing the coordination sphere. Nevertheless, the formation of An(III)-DOTA complexes is faster than the Ln(III)-DOTA systems of equivalent ionic radius. Furthermore, it is found that An-N distances are slightly shorter than Ln-N distances. Theoretical calculations have shown that the slightly higher affinity of DOTA toward Am over Nd is correlated with slightly enhanced Ligand-to-metal charge donation arising from oxygen and nitrogen atoms.
Keywords: DOTA; UV-visible spectrophotometry; NMR; EXAFS; DFT calculations; Americium; Plutonium; lanthanides
Involved research facilities
- Rossendorf Beamline at ESRF DOI: 10.1107/S1600577520014265
Related publications
- DOI: 10.1107/S1600577520014265 is cited by this (Id 25773) publication
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Inorganic Chemistry 56(2017), 12248-12259
DOI: 10.1021/acs.inorgchem.7b01666
Cited 23 times in Scopus
Permalink: https://www.hzdr.de/publications/Publ-25773
Purely Antiferromagnetic Magnetoelectric Random Access Memory
Kosub, T.
Abstract
Magnetic random access memory schemes employing magnetoelectric coupling to write binary information promise outstanding energy efficiency1. We propose and demonstrate a purely antiferromagnetic magnetoelectric random access memory (AF-MERAM)2 that offers a remarkable 50 fold reduction of the writing threshold compared to state-of-the-art ferromagnet-based counterparts2,3, is robust against magnetic disturbances and exhibits no ferromagnetic hysteresis losses. Using the magnetoelectric antiferromagnet Cr2O3, we demonstrate reliable isothermal switching via gate voltage pulses and all-electric readout at room temperature [Figure 1], The basics of RAM operation - writing, storage and reading information - are demonstrated repeatedly. Furthermore, the all-electric writing and read out interfaces can be harnessed for in-depth studies of the magnetoelectric selection processes in these thin film elements, which turn out to be markedly deviant from the theory of the linear magnetoelectric effect.
While omitting the ferromagnet enables the large improvement in the writing threshold over conventional exchange biased MERAM2,3, it also eliminates all possibilities for conventional magnetoresistive read out, such as the AMR/GMR/TMR effects. Thus, a key aspect of the AF-MERAM functionality is its new all-electric read out of the pure Hall resistance4. This method is both ultra-sensitive to tiny net magnetization in metallic antiferromagnets and to boundary magnetism between nonmagnetic metals and magnetic insulators, suggesting its considerable applicability to the growing fields of antiferromagnetic spintronics and insulator spintronics.
Access to the pure Hall resistance is enabled by a new electric measurement scheme called Resistance Tensormetry, which determines electrical resistance not as a scalar quantity peculiar to the used measurement layout but instead as a tensor quantity including diagonal and off-diagonal (Hall) components. Since electrical resistance is one of the most crucial material properties for both science and technology, the more comprehensive view provided by resistance tensormetry is highly relevant for emergent topics and materials. Via µΩ level sensitivity and tensor resolution, previously unattainable figures are now open to experimental scrutiny.
1. Matsukura, F., Tokura, Y. & Ohno, H., Nat. Nano. 10, 209–220 (2015).
2. Kosub, T. et al., Nat. Commun. 7, 13985 (2017).
3. He, X. et al., Nat. Mater. 9, 579–585 (2010).
4. Kosub, T., Kopte, M., Radu, F., Schmidt, O. G. & Makarov, D., Phys. Rev. Lett. 115, 097201 (2015).
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Invited lecture (Conferences)
Spin X Seminar Mainz/Kaiserslautern, 08.06.2017, Mainz, Deutschland
Permalink: https://www.hzdr.de/publications/Publ-25772
Biasing in MC transport calculations
Abstract
The method of biasing in radiation transport simulations is described.
Keywords: Radiation transport; variance reduction; biasing; simulation
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Lecture (others)
Mu2e software and simulations workshop, 21.06.2017, Batavia, USA
Permalink: https://www.hzdr.de/publications/Publ-25771
The use of FLUKA in the Mu2e experiment
Abstract
The use of FLUKA in the mu2e experiment
Keywords: FLUKA; mu2e
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Lecture (others)
Mu2e Sotware and Simulation Meeting, 07.06.2017, Batavia, USA
Permalink: https://www.hzdr.de/publications/Publ-25770
LaFeOxNy perovskite thin films: Nitrogen location and its effect on morphological, optical and structural properties
Haye, E.; Bruyère, S.; André, E.; Boulet, P.; Barrat, S.; Capon, F.; Miska, P.; Migot, S.; Carteret, C.; Coustel, R.; Gendarme, C.; Munnik, F.
Abstract
This paper reports on the first study of chemical, optical, and structural properties of lanthanum ferrite oxynitride thin films deposited by reactive magnetron sputtering. Thin films were deposited in a Ar/O2/N2 mixture as reactive plasma, from two elemental La and Fe targets, at room and high temperature (25 and 800°C). Films deposited at room temperature are amorphous and have been flash annealed to crystallize the perovskite. Oxynitride properties were investigated and compared to oxide films deposited in Ar/O2 gas mixture. All oxide and oxynitride films present an orthorhombic structure. However, nitrogen doping limited to 1-1.5% leads to lattice expansion (4%), bandgap narrowing, a lower electrical resistivity in range [25-350°C] , and modification of Infrared and Raman spectra. Electron Energy Loss Spectroscopy measurements clearly show the presence of two nitrogen sites with an “active” intra-granular nitrogen associated to an enhancement of the physical properties.
Keywords: Oxynitride perovskite; Thin film; LaFeO3; Nitrogen doping
Involved research facilities
- Ion Beam Center DOI: 10.17815/jlsrf-3-159
Related publications
- DOI: 10.17815/jlsrf-3-159 is cited by this (Id 25769) publication
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Journal of Alloys and Compounds 724(2017), 74-83
DOI: 10.1016/j.jallcom.2017.07.025
Cited 9 times in Scopus
Permalink: https://www.hzdr.de/publications/Publ-25769
Preliminary combination of the KLOE08, KLOE10 KLOE12 ISR measurements
Keshavarzi, A.; Müller, S. E.; Teubner, T.; Venanzoni, G.
Abstract
Preliminary combination of the KLOE08, KLOE10 KLOE12 ISR measurements
Keywords: KLOE; g-2; hadronic contribution
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Invited lecture (Conferences)
First Workshop of the muon g-2 Theory Initiative, 04.06.2017, St. Charles, USA
Permalink: https://www.hzdr.de/publications/Publ-25768
Irradiation study of UV Silicon Photomultipliers for the Mu2e calorimeter
Baccaro, S.; Cemmi, A.; Cordelli, M.; Diociaiuti, E.; Donghia, R.; Ferrari, A.; Giovannella, S.; Loreti, S.; Miscetti, S.; Müller, S.; Pillon, M.; Sarra, I.
Abstract
The Mu2e calorimeter is composed of 1400 un-doped CsI crystals, coupled to large area UV extended Silicon Photomultipliers (SiPMs), arranged in two annular disks. This calorimeter has to provide precise information on energy, timing and position resolutions. It should also be fast enough to handle the high rate background and it must operate and survive in the high radiation environment. Simulation studies estimated that, in the highest irradiated regions, each photo-sensor will absorb a dose of 20 krad and will be exposed to a neutron fluency of 5.5E11 n(1MeV)/cm2 in three years of running, with a safety factor of 3 included. At the end of 2015, we have concluded an irradiation campaign at the Frascati Neutron Generator (FNG, Frascati, Italy) measuring the response of two different 16 array models from Hamamatsu, which differ for the protection windows and a SiPM from FBK. In 2016, we have carried out two additional irradiation campaigns with neutrons and photons at the Helmholtz-Zentrum Dresden-Rossendorf (HZDR, Dresden, Germany) and at the Calliope gamma irradiation facility at ENEA-Casaccia, respectively. A negligible increment of the leakage current and no gain change have been observed with the dose irradiation. On the other hand, at the end of the neutron irradiation, the gain does not show large changes whilst the leakage current increases by around a factor of 2000. In these conditions, the too high leakage current makes problematic to bias the SiPMs, thus requiring to cool them down to a running temperature of ~0 C.
Keywords: Calorimeters; Photon detectors for UV; EMCCDs; EBCCDs; CCDs; G-APDs; Si-PMTs; APDs; PIN diodes; visible and IR photons (solid-state)
Involved research facilities
- Radiation Source ELBE DOI: 10.17815/jlsrf-2-58
Related publications
- DOI: 10.17815/jlsrf-2-58 is cited by this (Id 25767) publication
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Lecture (Conference)
14th Topical Seminar on Innovative Particle and Radiation Detectors, 03.-06.10.2016, Siena, Italy -
Contribution to proceedings
14th Topical Seminar on Innovative Particle and Radiation Detectors (IPRD16), 03.-06.10.2016, Siena, Italy
Irradiation study of UV Silicon Photomultipliers for the Mu2e calorimeter: Journal of Instrumentation 12 (2017), IOP Pub.
DOI: 10.1088/1748-0221/12/02/C02022
Cited 5 times in Scopus
Permalink: https://www.hzdr.de/publications/Publ-25767
Measurement techniques for liquid metals
Ratajczak, M.; Hernández, D.; Richter, T.; Otte, D.; Buchenau, D.; Krauter, N.; Wondrak, T.
Abstract
The measurement of flow properties of liquid metals, such as flow rate, flow structure and gas distribution, is a challenging task due to the opaqueness, the high temperatures (e. g. 1500 ◦ C for liquid steel or liquid silicon) and the corrosiveness of those fluids. In this paper a short review about the recent developments of measurement techniques in the framework of the Helmholtz Alliance Liquid Metal Technologies (LIMTECH) is presented which focuses on the development of contactless inductive measurement techniques exploiting the high electrical conductivity of those melts. These measurement techniques include the contactless inductive flow tomography (CIFT), which is able to reconstruct the mean three-dimensional velocity structure in liquid melts, local Lorentz force velocimetry (local LFV), which enables the local assessment of flows close to the wall, and inductive methods for bubble detection, which are based on mutual inductance tomography (MIT). Additionally, a short overview of contactless inductive flow rate measurement techniques is given. Furthermore, an ultrasound technique called ultrasound transit-time technique (UTTT) will be presented which enables the measurement of position and size of bubbles in large vessels.
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IOP Conference Series: Materials Science and Engineering 228(2017), 012023
DOI: 10.1088/1757-899X/228/1/012023
Cited 26 times in Scopus
Permalink: https://www.hzdr.de/publications/Publ-25766
Energy Transfer Kinetics in Photosynthesis as an Inspiration for Improving Organic Solar Cells
Nganou, C.; Lackner, G.; Teschome, B.; Deen, M. J.; Adir, N.; Pouhe, D.; Lupascu, D. C.; Mkandawire, M.
Abstract
Clues to designing highly efficient organic solar cells may lie in understanding the architecture of light-harvesting systems and exciton energy transfer (EET) processes in very efficient photosynthetic organisms. Here, we compare the kinetics of excitation energy tunnelling from the intact phycobilisome (PBS) light-harvesting antenna system to the reaction center in photosystem II in intact cells of the cyanobacterium Acaryochloris marina with the charge transfer after conversion of photons into photocurrent in vertically aligned carbon nanotube (va-CNT) organic solar cells with poly(3-hexyl)thiophene (P3HT) as the pigment. We find that the kinetics in electron hole creation following excitation at 600 nm in both PBS and va-CNT solar cells to be 450 and 500 fs, respectively. The EET process has a 3 and 14 ps pathway in the PBS, while in va-CNT solar cell devices, the charge trapping in the CNT takes 11 and 258 ps. We show that the main hindrance to efficiency of va-CNT organic solar cells is the slow migration of the charges after exciton formation.
Keywords: Acaryochloris marina; carbon nanotubes; chromophore; exciton; photosynthesis; photovoltaic; polarons; solar energy conversion
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ACS Applied Materials and Interfaces 9(2017)22, 19030-19039
DOI: 10.1021/acsami.7b04028
Cited 5 times in Scopus
Permalink: https://www.hzdr.de/publications/Publ-25765
First application of the Oslo method in inverse kinematics - Nuclear level densities and gamma-ray strength functions of 87Kr
Ingeberg, V. W.; Siem, S.; Wiedeking, M.; Sieja, K.; Zeiser, F.; Bleuel, D. L.; Brits, C. P.; Bucher, D. T.; Dinoko, T. S.; Easton, J. L.; Görgen, A.; Jones, P.; Kheswa, B. V.; Khumalo, N. A.; Larsen, A. C.; Lawrie, E. A.; Lawrie, J. J.; Majola, S. N. T.; Malatji, K. L.; Makhathini, L.; Maqabuka, B.; Negi, D.; Noncolela, S. P.; Papka, P.; Sahin, E.; Schwengner, R.; Tveten, G. M.; Zikhali, B. R.
Abstract
A novel technique for extracting the gamma-ray strength function (SF) and nuclear level density (NLD) from inverse kinematics experiments is presented, which allows for measurements of these properties, across a vast range of previously inaccessible nuclei. Proton-gamma coincidence events from the d(86Kr, p)87Kr reaction were measured at iThemba LABS and the SF and NLD in 87 Kr obtained with the Oslo Method.The SF and NLD are important parameters in Hauser-Feshbach calculations to constrain (n,gamma) cross sections of nuclei for which these cannot be measured directly. The extracted SF and NLD are used as input in Hauser-Feshbach calculations to constrain the 86Kr(n,gamma)87Kr cross section which is important for the 87Rb production in the s-process. The nature of the low-energy region of the SF is explored through comparison to shell model calculations with the LNPS-SDG interaction.
Keywords: Nuclear structure; nuclear reactions; (d; p) recation; inverse kinematics; gamma-ray strength function; level density; shell model; Hauser-Feshbach model; s-process
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European Physical Journal A 56(2020), 68
DOI: 10.1140/epja/s10050-020-00070-7
Cited 16 times in Scopus
Permalink: https://www.hzdr.de/publications/Publ-25764
Single bubble rise in GaInSn in a horizontal magnetic field
Richter, T.; Keplinger, O.; Shevchenko, N.; Wondrak, T.; Eckert, K.; Eckert, S.; Odenbach, S.
Abstract
The rise of single gas bubbles of moderate size in a liquid metal was studied in a flat container filled with the eutectic alloy GaInSn. The bubble motion is affected by a homogeneous horizontal magnetic field which is perpendicular to the width side of the fluid container. Measurements of the bubble trajectory, bubble velocity and deformation were performed by means of a combination of ultrasound transit time technique and X-ray radiography. In the hydrodynamic case without a magnetic field, the bubbles show the typical zig-zag movement whose attenuation can be observed for sufficiently high magnetic fields of B > 270 mT. The bubble trajectory becomes straight at a field strength of about 500 mT. A damping of the zig-zag path does not result in case of small magnetic fields applied. In this parameter range, even an increase of the amplitude of the lateral path oscillation is observed. Furthermore, this study revealed a discontinuity in the bubble path, which is called as ”initial path instability” on the basis of its occurrence in the early stage of the bubble rise shortly after the bubble injection. This instability is characterized by an extreme inclination of the ellipsoidal bubble which often leads to a bubble “somersault”. This instability is suppressed by a suffciently high enough magnetic field. The reason for this instability and the magnetic field effect thereon are qualitatively discussed.
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International Journal of Multiphase Flow 104(2018), 32-41
DOI: 10.1016/j.ijmultiphaseflow.2018.03.012
Cited 27 times in Scopus
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- Final Draft PDF 759 kB Secondary publication
Permalink: https://www.hzdr.de/publications/Publ-25763
A Review of Surfactant Role in Soil Clogging Processes at Wastewater Exfiltration Locations in Sewers
Nikpay, M.; Krebs, P.; Ellis, B.
Abstract
Wastewater contains significant sources of pollutants and contaminants. often the failure of a pipe, inadequate sealing or corrupt pipe-connections cause the loss of raw sewage, which percolates into the nearby soil. As a consequence, a colmation layer in conjunction with soil clogging is developing, which regulates the exfiltration rate. Recently, literature has emerged that offers findings about the effects of wastewater surfactants on the change of physical properties of the soil. A survey of published literature in this field provides information highlighting the influential mechanisms of surfactants in soil clogging through physical, chemical and biological processes. Therefore, to provide a comprehensive approach, this review describes the adsorption mechanisms of surfactants on organic and inorganic particles, at gas-bubbles and at biomass.
We also provided our own input to the description of the adsorption of surfactants at fluid/fluid and fluid/solid interfaces in porous media associated with the clogging process.
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Water Environment Research 89(2017)8, 714-723
DOI: 10.2175/106143017X14902968254647
Cited 7 times in Scopus
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- Final Draft PDF 370 kB Secondary publication
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Liquid metal based magnetic cooling: velocity measurements
Lei, Z.; Raebiger, D.; Eckert, S.; Eckert, K.
Abstract
Heat transfer enhancement in a segment of the active magnetic regenerator (AMR), consisting of a magnetocaloric material (Gadolinium) and a heat transfer fluid in between, which is periodically magnetized and demagnetized, is investigated in this work. After giving a brief account on how magnetohydrodynamic (MHD) convection can be used to enhance the heat transfer from flat plate gadolinium toward the heat transfer fluid we apply two different techniques for MHD flow generation. In the first approach, an electric current I was injected into an electrically conducting, aqueous heat transfer fluid (NaOH). A heat transfer enhancement of about 40% (I=3mA) was found by means of a Mach-Zehnder interferometer. In the second approach, a liquid metal (GaInSn) was used which is potentially an interesting candidate for a heat transfer fluid in an AMR operating with high cycling frequency. Velocity measurements by means of ultrasound doppler velocimetry with a quasi uniform static magnetic field (220mT) in the gadolinium channel are presented.
- Magnetohydrodynamics 53(2017)2, 403-410
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Ultrasonic measurements of the bulk flow field in foams
Nauber, R.; Büttner, L.; Eckert, K.; Fröhlich, J.; Czarske, J.; Heitkam, S.
Abstract
The flow field of moving foams is relevant for basic research and for the optimization of industrial processes such as froth flotation. However, no adequate measurement technique exists for the local velocity distribution inside the foam bulk. We have investigated the ultrasound Doppler velocimetry (UDV), providing the first two-dimensional, non-invasive velocity measurement technique with an adequate spatial (10 mm) and temporal resolution (2.5 Hz) that is applicable to medium scale foam flows. The measurement object is dry aqueous foam flowing upward in a rectangular channel. An array of ultrasound transducers is mounted within the channel, sending pulses along the main flow axis and receiving echoes from the foam bulk. This results in a temporally and spatially resolved, planar velocity field up to a measurement depth of 200 mm, which is approximately one order of magnitude larger than those of optical techniques. A comparison with optical reference measurements of the surface velocity of the foam allows to validate the UDV results. At 2.5 Hz frame rate an uncertainty below 15 percent and an axial spatial resolution better than 10 mm is found. Therefore, UDV is a suitable tool for monitoring of industrial processes as well as the scientific investigation of three-dimensional foam flows on medium scales.
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Physical Review E 97(2018), 013113
DOI: 10.1103/PhysRevE.97.013113
Cited 14 times in Scopus
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- Final Draft PDF 2,4 MB Secondary publication
Permalink: https://www.hzdr.de/publications/Publ-25760
Demonstration of a beam loaded nanocoulomb-class laser wakefield accelerator
Couperus, J. P.; Pausch, R.; Köhler, A.; Zarini, O.; Krämer, J. M.; Garten, M.; Huebl, A.; Gebhardt, R.; Helbig, U.; Bock, S.; Zeil, K.; Debus, A.; Bussmann, M.; Schramm, U.; Irman, A.
Abstract
Laser-plasma wakefield accelerators have seen tremendous progress, now capable of producing quasi-monoenergetic electron beams in the GeV energy range with few-femtoseconds bunch duration. Scaling these accelerators to the nanocoulomb range would yield hundreds of kiloamperes peak-current and stimulate the next generation of radiation sources covering high-field THz, high-brightness X-ray and γ-ray sources, compact FELs and laboratory-size beam-driven plasma accelerators. However, accelerators generating such currents operate in the beam loading regime where the accelerating field is strongly modified by the self-fields of the injected bunch, potentially deteriorating key beam parameters.
Here we demonstrate that, if appropriately controlled, the beam loading effect can be employed to improve the accelerator's performance. Self-truncated ionization injection enabled loading of unprecedented charges of about 0.5 nC within a mono-energetic peak. As the energy balance is reached, we show that the accelerator operates at the theoretically predicted optimal loading condition and the final energy spread is minimized.
Keywords: LWFA; beam loading
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Nature Communications 8(2017), 487
DOI: 10.1038/s41467-017-00592-7
Cited 132 times in Scopus
Permalink: https://www.hzdr.de/publications/Publ-25759
Multidisciplinary characterization of U(VI) sequestration by Acidovorax facilis for bioremediation purposes
Krawczyk-Bärsch, E.; Gerber, U.; Müller, K.; Moll, H.; Rossberg, A.; Steudtner, R.; Merroun, M.
Abstract
The contamination of the environment by U may affect plant life and consequently may have an impact on animal and human health. The present work describesU(VI) sequestration by Acidovorax facilis using a multidisciplinary approach combining wet chemistry, transmission electron microscopy, and spectroscopy methods (e.g.cryo-time resolved laser-induced fluorescence spectroscopy, extended X-ray absorption fine structure spectroscopy, and in-situ attenuated total reflection Fourier transform infrared spectroscopy). This bacterial strain is widely distributed in nature including U-contaminated sites. In kinetic batch experiments cells of A. facilis were contacted for 5 minutes to 48 hours with 0.1 mM U(VI). The results show that the local coordination of U species associated with the cells depends upon time contact. U is bound mainly to phosphate groups of lipopolysaccharide (LPS) at the outer membrane within the first hour. And, that both, phosphoryl and carboxyl functionality groups of LPS and peptidoglycan of A. facilis cells may effectuate the removal of high U amounts from solution at 24-48 hours of incubation. It is clearly demonstrated that A. facilis may play an important role in predicting the transport behaviour of U in the environment and that the results will contribute to the improvement of bioremediation methods of U-contaminated sites.
Keywords: Uranium; Acidovorax facilis; spectroscopy; bioremediation
Involved research facilities
- Rossendorf Beamline at ESRF DOI: 10.1107/S1600577520014265
Related publications
- DOI: 10.1107/S1600577520014265 is cited by this (Id 25758) publication
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Journal of Hazardous Materials 147(2018), 233-241
DOI: 10.1016/j.jhazmat.2017.12.030
Cited 18 times in Scopus
Permalink: https://www.hzdr.de/publications/Publ-25758
Development and validation of a gene signature for patients with head and neck carcinomas treated by postoperative radio(chemo)therapy
Schmidt, S.; Linge, A.; Zwanenburg, A.; Leger, S.; Lohaus, F.; Krenn, C.; Appold, S.; Gudziol, V.; Nowak, A.; von Neubeck, C.; Tinhofer, I.; Budach, V.; Sak, A.; Stuschke, M.; Balermpas, P.; Rödel, C.; Bunea, H.; Grosu, A.-L.; Abdollahi, A.; Debus, J.; Ganswindt, U.; Belka, C.; Pigorsch, S.; Combs, S. E.; Mönnich, D.; Zips, D.; Baretton, G. B.; Buchholz, F.; Baumann, M.; Krause, M.; Löck, S.
Abstract
The aim of this study was to identify and independently validate a novel gene signature predicting loco-regional tumor control (LRC) for treatment individualization of patients with locally advanced head and neck squamous cell carcinomas (HNSCC) who are treated with postoperative radio(chemo)therapy (PORT-C). Gene expression analyses were performed using nanoString technology on a multicenter training cohort of 195 patients and an independent validation cohort of 142 patients. The analyzed gene set was composed hypothesis-driven and included genes with previously reported association to radio(chemo)sensitivity or resistance to radio(chemo)therapy. Gene selection and model building were performed within a specifically developed statistical framework comparing several machine-learning algorithms. This procedure identified a 7-gene signature for HPV16 DNA negative tumors consisting of the genes: SERPINE1, INHBA, P4HA2, ACTN1, HILPDA, CD24 and TCF3. The 7-gene signature was used to fit a multivariable Cox model to the training data (concordance index, ci=0.84), which was successfully validated (ci=0.71). Thus, the signature showed improved performance compared to a clinical model (ci=0.66) and to a previously published model including hypoxia-associated genes and cancer stem cell markers (ci=0.65). Furthermore, the signature was used to stratify patients into groups with low and high risk of recurrence. Significant differences in LRC between these groups were found in training and validation (p<0.001). A prospective validation is planned in an ongoing prospective clinical trial of the DKTK-ROG before potential application in clinical trials for patient stratification.
Keywords: Radiochemotherapy; HNSCC; Biomarker; Loco-regional control; Gene signature; HPV status
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Clinical Cancer Research 24(2018)6, 1364-1374
Online First (2017) DOI: 10.1158/1078-0432.CCR-17-2345
Cited 43 times in Scopus
Permalink: https://www.hzdr.de/publications/Publ-25757
Laser spectroscopy measurement of the 2s-hyperfinesplitting in lithium-like bismuth
Sánchez, R.; Lochmann, M.; Jöhren, R.; Andelkovic, Z.; Anielski, D.; Botermann, B.; Bussmann, M.; Dax, A.; Frömmgen, N.; Geppert, C.; Hammen, M.; Hannen, V.; Kuehl, T.; Litvinov, Y.; Coto, R. L.; Stoehlker, T.; Thompson, R.; Vollbrecht, J.; Wen, W.; Weinheimer, C.; Will, E.; Winters, D.; Noertershaeuser, W.
Abstract
We have recently reported on the first direct measurement of the 2s hyperfine transition in lithium-like bismuth (209Bi80+) at the GSI Helmholtz Centrefor Heavy Ion Research (GmbH) in Darmstadt, Germany. Combined with a newmeasurement of the 1s hyperfine splitting in hydrogen-like (209Bi82+) the so-called specific difference Δ’E = -61.37(36) meV could be determined and was found to bein good agreement with its prediction from strong-field bound-state QED. Here wereport on additional investigations performed to estimate systematic uncertainties of these results and on details of the experimental setup. We show that the dominating uncertainty arises from insufficient knowledge of the ion beam velocity which is determined by the electron-cooler (voltage). Two routes to obtain a cooler-voltage calibration are discussed and it is shown that agreement can be reached either of the experimental Δ’E with the theoretical result, or between the two measurements of the hyperfine splitting in hydrogen-like bismuth, but not both at the same time.
Keywords: qed; spectroscopy; bismuth; hyperfine; lithium-like; storage ring; laser
Involved research facilities
- Radiation Source ELBE DOI: 10.17815/jlsrf-2-58
Related publications
- DOI: 10.17815/jlsrf-2-58 is cited by this (Id 25756) publication
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Journal of Physics B 50(2017)8, 085004
DOI: 10.1088/1361-6455/aa63a0
Cited 17 times in Scopus
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- Final Draft PDF 714 kB Secondary publication
Permalink: https://www.hzdr.de/publications/Publ-25756
Structure and energetics of Y-Ti-O nanoclusters in bcc Fe
Vallinayagam, M.; Posselt, M.; Faßbender, J.
Abstract
Nanostructured Ferritic Alloys (NFA) are considered as promising candidates for the structural materials of future fusion and fission reactors [1]. They consist of a ferritic or ferritic/martensitic Fe-Cr matrix with a high dispersion of nanometer size yttria-based oxide particles. In this research project (started in November 2016) the nature of nanometer-size yttria-based oxide clusters in a bcc Fe matrix are investigated by DFT calculations. The main goal of these studies is the better understanding of the nucleation as well as the structure and composition of the nanoclusters.
The investigations shall clarify the conditions for the formation of nonstoichiometric clusters that are coherent with the bcc lattice and for the formation of oxide phases (in particular Y2O3 and Y2Ti2O7). Three models are considered: (i) clusters consisting of Y, Ti atoms on bcc lattice sites and O on octahedral site [2-4], termed as On-Lattice (OL) model, (ii) cluster consisting of parts of the bixbyite (Y2O3) or pyrochlore (Y2Ti2O7) structure embedded in bcc Fe [5] termed as Structure Matching (SM) model, and (iii) substituting O also on Fe site, termed as OFe model. In all cases vacancies are introduced into the simulation cell in order to provide additional volume for O atoms. We studied clusters of different sizes in the framework of the three models. Our results show that all three models lead to almost the same energy for considered cluster configurations. This revises the statement of Barnard et al. [5] who claimed that clusters with SM configuration are generally favored energetically.
[1] G. R. Odette, JOM-J. Min. Met. Mat. S. 66, 2427 (2014)
[2] D. Murali, B.K. Panigrahi, M.C. Valsakumar, S. Chandra, C.S. Sundar, B. Raj, J. Nucl. Mater. 403,
113 (2010)
[3] A. Claisse, P. Olsson, Nucl. Instr. Meth. B 303, 18 (2013)
[4] M. Posselt, D. Murali, B. K. Panigrahi, Model. Simul. Mater. Sc. 22, 085003 (2014)
[5] L. Barnard, G. R. Odette, I. Szlufarska, D. Morgan. Acta Mater. 60 (2012) 935 (2012)
Keywords: DFT; Y-Ti-O nanoclusters in bcc-Fe; structure and energetics
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Lecture (Conference)
4th International Workshop on ODS materials, 26.-28.06.2017, Dresden, Germany
Permalink: https://www.hzdr.de/publications/Publ-25755
Years: 2024 2023 2022 2021 2020 2019 2018 2017 2016
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