Analysis of partial volume correction on quantification and regional heterogeneity in cardiac PET.

BACKGROUND: The partial volume correction (PVC) of cardiac PET datasets using anatomical side information during reconstruction is appealing but not straightforward. Other techniques, which do not make use of additional anatomical information, could be equally effective in improving the reconstructed myocardial activity. METHODS: Resolution modeling in combination with different noise suppressing priors was evaluated as a means to perform PVC. Anatomical priors based on a high-resolution CT are compared to non-anatomical, edge-preserving priors (relative difference and total variation prior). The study is conducted on ex vivo datasets from ovine hearts. A simulation study additionally clarifies the relationship between prior effectiveness and myocardial wall thickness. RESULTS: Simple resolution modeling during data reconstruction resulted in over- and underestimation of activity, which hampers the absolute left ventricular quantification when compared to the ground truth. Both the edge-preserving and the anatomy-based PVC techniques improve the absolute quantification, with comparable results (Student t-test, P = .17). The relative tracer distribution was preserved with any reconstruction technique (repeated ANOVA, P = .98). CONCLUSIONS: The use of edge-preserving priors emerged as optimal choice for quantification of tracer uptake in the left ventricular wall of the available datasets. Anatomical priors visually outperformed edge-preserving priors when the thinnest structures were of interest.

New Limit on the Permanent Electric Dipole Moment of

We report results of a new technique to measure the electric dipole moment of ^{129}Xe with ^{3}He comagnetometry. Both species are polarized using spin-exchange optical pumping, transferred to a measurement cell, and transported into a magnetically shielded room, where SQUID magnetometers detect free precession in applied electric and magnetic fields. The result from a one week measurement campaign in 2017 and a 2.5 week campaign in 2018, combined with detailed study of systematic effects, is d_{A}(^{129}Xe)=(1.4±6.6_{stat}±2.0_{syst})×10^{-28} e cm. This corresponds to an upper limit of |d_{A}(^{129}Xe)|<1.4×10^{-27} e cm (95% C.L.), a factor of 5 more sensitive than the limit set in 2001.

Partial volume and motion correction in cardiac PET: First results from an in vs ex vivo comparison using animal datasets.

BACKGROUND: In a previous study on ex vivo, static cardiac datasets, we investigated the benefits of performing partial volume correction (PVC) in cardiac 18F-Fluorodeoxyglucose(FDG) PET datasets. In the present study, we extend the analysis to in vivo cardiac datasets, with the aim of defining which reconstruction technique maximizes quantitative accuracy and, ultimately, makes PET a better diagnostic tool for cardiac pathologies. METHODS: In vivo sheep datasets were acquired and reconstructed with/without motion correction and using several reconstruction algorithms (with/without resolution modeling, with/without non-anatomical priors). Corresponding ex vivo scans of the excised sheep hearts were performed on a small-animal PET scanner (Siemens Focus 220, microPET) to provide high-resolution reference data unaffected by respiratory and cardiac motion. A comparison between the in vivo cardiac reconstructions and the corresponding ex vivo ground truth was performed. RESULTS: The use of an edge-preserving prior (Total Variation (TV) prior in this work) in combination with motion correction reduces the bias in absolute quantification when compared to the standard clinical reconstructions (- 0.83 vs - 3.74 SUV units), when the end-systolic gate is considered. At end-diastole, motion correction improves absolute quantification but the PVC with priors does not improve the similarity to the ground truth more than a regular iterative reconstruction with motion correction and without priors. Relative quantification was not influenced much by the chosen reconstruction algorithm. CONCLUSIONS: The relative ranking of the algorithms suggests superiority of the PVC reconstructions with dual gating in terms of overall absolute quantification and noise properties. A well-tuned edge-preserving prior, such as TV, enhances the noise properties of the resulting images of the heart. The end-systolic gate yields the most accurate quantification of cardiac datasets.

Sensitive and stable vector magnetometer for operation in zero and finite fields.

We report on an optically pumped magnetometer that uses multiple laser beams to pump and probe spin-polarized Cs atoms. The selected sensor geometry allows for operation in finite magnetic fields as well as close to zero field. In finite fields the magnetometer employs free spin precession signals to determine the field modulus and direction as described in a separate publication. This publication focuses on the magnetometer operation close to zero field, which is based on a ground state Hanle resonance. The four laser beams permit the simultaneous measurement of two orthogonal magnetic field components in a differential detection scheme that greatly suppresses technical laser power noise. Sensitivities better than 54 fT/Hz1/2 could be demonstrated simultaneously for both measurement channels in a well shielded environment. A minimum Allan deviation, limited by residual field fluctuations, of better than 40 fT was observed for integration times of 2s. The magnetometer achieves high sensitivity and stability in offset fields as well as close to zero field and is, thus, a universal tool for low frequency magnetic field measurements.

EUROPattern Suite technology for computer-aided immunofluorescence microscopy in autoantibody diagnostics.

Antinuclear autoantibodies (ANA) are highly informative biomarkers in autoimmune diagnostics. The increasing demand for effective test systems, however, has led to the development of a confusingly large variety of different platforms. One of them, the indirect immunofluorescence (IIF), is regarded as the common gold standard for ANA screening, as described in a position statement by the American College of Rheumatology in 2009. Technological solutions have been developed aimed at standardization and automation of IIF to overcome methodological limitations and subjective bias in IIF interpretation. In this review, we present the EUROPattern Suite, a system for computer-aided immunofluorescence microscopy (CAIFM) including automated acquisition of digital images and evaluation of IIF results. The system was originally designed for ANA diagnostics on human epithelial cells, but its applications have been extended with the latest system update version 1.5 to the analysis of antineutrophil cytoplasmic antibodies (ANCA) and anti-dsDNA antibodies.

Conceptual design of a macromolecular diffractometer for the Jülich high brilliance source.

In this work, a concept for a neutron diffractometer for high-resolution macromolecular structures has been developed within the Jülich High Brilliance Neutron Source (HBS) project. The SELENE optics are adapted to the requirements of the instrument to achieve a tunable low background neutron beam at mm2 scale sample area. With the optimized guide geometry, a low background neutron beam can be achieved at the small sample area with tunable divergence and size. For the 1 × 1 mm2 sample, a flux of 1.10 × 107 n/s/cm2 for 0.38° divergence is calculated in the 2-4 Å wavelength range, which is about 84.6% of the flux at MaNDi of the high-power spallation source SNS at ORNL. Virtual neutron scattering experiments have been performed to demonstrate the instrument's capabilities for studies of mm scale samples with large unit cells. Results of Vitesse simulations indicate that unit cell sizes of up to 200 Å are possible to be resolved with the proposed instrument.

Preliminary searches for spin-dependent interactions using sidebands of nuclear spin-precession signals.

Various theories beyond the Standard Model predict new particles with masses in the sub-eV range with very weak couplings to ordinary matter. A new P-odd and T-odd interaction between polarized and unpolarized nucleons proportional to s⃗⋅r̂ is one such possibility, where r⃗=rr̂ is the spatial vector connecting the nucleons, and s⃗ is the spin of the polarized nucleon. Such an interaction involving a scalar coupling gsN at one vertex and a pseudoscalar coupling gpn at the polarized nucleon vertex can be induced by the exchange of spin-0 pseudoscalar bosons. We describe a new technique to search for interactions of this form and present the first measurements of this type. We show that future improvements to this technique can improve the laboratory upper bound on the product gsNgpn by two orders of magnitude for interaction ranges at the 100 micron scale.

Achieving ultra-low and -uniform residual magnetic fields in a very large magnetically shielded room for fundamental physics experiments.

High-precision searches for an electric dipole moment of the neutron (nEDM) require stable and uniform magnetic field environments. We present the recent achievements of degaussing and equilibrating the magnetically shielded room (MSR) for the n2EDM experiment at the Paul Scherrer Institute. We present the final degaussing configuration that will be used for n2EDM after numerous studies. The optimized procedure results in a residual magnetic field that has been reduced by a factor of two. The ultra-low field is achieved with the full magnetic-field-coil system, and a large vacuum vessel installed, both in the MSR. In the inner volume of ∼1.4m3, the field is now more uniform and below 300 pT. In addition, the procedure is faster and dissipates less heat into the magnetic environment, which in turn, reduces its thermal relaxation time from 12h down to 1.5h.

Potential of dosage reduction in cone-beam-computed tomography (CBCT) for radiological diagnostics of the paranasal sinuses.

More than 10 years ago, cone-beam-computed tomography (CBCT) was introduced in ENT radiology. Until now, the focus of research was to evaluate clinical limits of this technique. The aim of this work is the evaluation of specific dosages and the identification of potential optimization in the performance of CBCT of the paranasal sinuses. Based on different tube parameters (tube current, tube voltage, and rotation angles), images of the nose and the paranasal sinuses were taken on a phantom head with the Accu-I-tomo F17 (Morita, Kyoto, Japan). The dosages applied to the lens and parotid gland were measured with OSL dosimetry. The imaging quality was evaluated by independent observers. All datasets were reviewed according to a checklist of surgically important anatomic structures. Even for lowest radiation exposure (4 mA, 76 kV, 180°, computed tomography dosage index (CTDI) = 1.8 mGy), the imaging quality was sufficient. Of course a significant reduction of the imaging quality could be seen, so a reliable mean was set for 4 mA, 84 kV, and 180° rotation angle (CTDI = 2.4 mGy). In this combination, a reduction of 92 % in lens-dose and of 77 % of dosage at the parotid gland was observed in comparison to the maximal possible adjustments (8 mA, 90 kV, 360°, CTDI = 10.9 mGy). There is potential for optimization in CBCT. Changing the rotation angle (180° instead of 360°) leads to a dose reduction of 50 %. Furthermore from clinical point of view in case of chronic rhinosinusitis a relevant reduction of dosage is possible. Therefore, it is necessary to intensify the interdisciplinary discussion about the disease specifics required quality of imaging.

Structural insight into the cooperativity of spin crossover compounds.

Spin-crossover (SCO) compounds are promising materials for a wide variety of industrial applications. However, the fundamental understanding of their nature of transition and its effect on the physical properties are still being fervently explored; the microscopic knowledge of their transition is essential for tailoring their properties. Here an attempt is made to correlate the changes in macroscopic physical properties with microscopic structural changes in the orthorhombic and monoclinic polymorphs of the SCO compound Fe(PM-Bia)2(NCS)2 (PM = N-2'-pyridylmethylene and Bia = 4-aminobiphenyl) by employing single-crystal X-ray diffraction, magnetization and DSC measurements. The dependence of macroscopic properties on cooperativity, highlighting the role of hydrogen bonding, π-π and van der Waals interactions is discussed. Values of entropy, enthalpy and cooperativity are calculated numerically based on the Slichter-Drickamer model. The particle size dependence of the magnetic properties is probed along with the thermal exchange and the kinetic behavior of the two polymorphs based on the dependence of magnetization on temperature scan rate and a theoretical model is proposed for the calculation of the non-equilibrium spin-phase fraction. Also a scan-rate-dependent two-step behavior observed for the orthorhombic polymorph, which is absent for the monoclinic polymorph, is reported. Moreover, it is found that the radiation dose from synchrotron radiation affects the spin-crossover process and shifts the transition region to lower temperatures, implying that the spin crossover can be tuned with radiation damage.

Prognostic utility of the assessment of diastolic function in patients undergoing cardiac resynchronization therapy.

Conflicting data exist about the relationship between cardiac resynchronization therapy (CRT) and diastolic function. Aims of the study are to assess diastolic patterns in patients undergoing CRT according to the 2016 recommendations of the American Society of Echocardiography/European Association of Cardiovascular Imaging and to evaluate the prognostic value of diastolic dysfunction (DD) in CRT candidates. METHODS AND RESULTS: One-hundred ninety-three patients (age: 67 ± 11 years, QRS width: 167 ± 21 ms) were included in this multicentre prospective study. Mitral filling pattern, mitral tissue Doppler velocity, tricuspid regurgitation velocity, and indexed left atrial volume were used to classify DD from grade I to III. CRT-response, defined as a reduction of left ventricular (LV) end-systolic volume > 15% at 6-month follow-up (FU), occurred in 132 (68%) patients. The primary endpoint was a composite of heart transplantation, LV assisted device implantation, or all-cause death during FU and occurred in 29 (15%) patients. CRT was associated with a degradation of DD in non-responders. At multivariable analysis corrected for clinical variables, QRS duration, mitral regurgitation, CRT-response and LV dyssynchrony, grade I DD was associated with a better outcome (HR 0.37, 95% CI: 0.14-0.96). Non-responders with grade II-III DD had the worse prognosis (HR 4.36, 95%CI: 2.10-9.06). CONCLUSIONS: The evaluation of DD in CRT candidates allows the prognostic stratification of patients, independently from CRT-response.

Sequential changes in myocardial function after valve replacement for aortic stenosis by speckle tracking echocardiography.

AIMS: Regional myocardial function may change differently in different pathology. Speckle tracking echocardiography (STE) was applied to evaluate longitudinal, radial, and circumferential function in patients with aortic stenosis (AS) before, within 1 week, and 6 months after aortic valve replacement (AVR). METHODS AND RESULTS: In 40 consecutive patients with severe AS, we acquired apical four-, three-, and two-chamber views and standard short-axis view pre- and post-AVR and after 6 months. Longitudinal, radial, and circumferential (LS, RS, and CS) were calculated by commercial STE software. Further, we analysed diastolic myocardial function by measuring E/e' ratio. With AVR, valve area increased and remained stable at 6 months follow-up. Left ventricular mass was unchanged 1 week after AVR (270 +/- 58 g vs. 267 +/- 58 g, n.s.) but decreased significantly during the next 6 months (219 +/- 50 g, P < 0.05). Left ventricular ejection fraction remained unchanged. Strain values did not change significantly within 1 week after AVR but increased significantly after 6 months (LS by 16%, RS by 21%, and CS by 28% of baseline values). E/e' ratio was highly augmented before AVR (26.1 +/- 12.5) and decreased significantly 6 months after AVR (15.9 +/- 5.9). CONCLUSION: Myocardial function significantly recovers after replacing the stenosed aortic valve. However, there is a considerable difference between the response of longitudinal, radial, and circumferential function. Our data suggest that echocardiographic assessment of regional function is feasible and of potential clinical importance.

Energy expenditure, urea kinetics, and body weight gain within a segregating resource family population.

Beef and dairy cattle represent divergent metabolic types that disseminate nutrients into either meat or milk and differ in nutrient accretion. To investigate nutrient flow and turnover in an animal model combining beef and dairy cattle, a crossbred experiment has been started. An F(2) resource population was generated from Charolais (beef breed) sires and German Holstein (dairy breed) cows as P(0) founders by consistent use of embryo transfer to establish the F(1) and F(2) generations, which accordingly comprised half- and full-sib offspring. In 64 bulls of 5F(2) families, dry matter intake and growth performance were measured monthly, and carcass composition was determined after slaughtering at 18 mo of age. Energy expenditure and urea kinetics were investigated via stable isotope tracer techniques using an intravenous single bolus dose of sodium [(13)C]bicarbonate [2.5 µmol/kg of body weight (BW), 99 atom% (13)C] at 8 and 18 mo of age and of [(15)N]urea (0.28 mg/kg of BW, 99 atom% (15)N) at 8 mo of age, respectively. Insulin responses were measured via glucose tolerances tests at the age of 8 mo. The results revealed significant differences between families for growth performance, energy expenditure, and urea kinetics. In summary, low energy expenditure was associated with high average body mass gain and high insulin response. A greater urea loss was associated with reduced muscle protein in carcass. In addition, corresponding half-sib and full-sib sisters from bulls with highest growth rate indicated highest milk production. In conclusion, we have demonstrated that differences in energy expenditure and urea kinetics result in differences in average daily gain and carcass traits and vice versa in F(2) crossbred bulls with common beef and dairy genetic backgrounds.

Alterations in the jejunum of young goats caused by feeding soy protein-based diets.

This study was designed to investigate whether soy protein or soy protein supplemented with indispensable amino acids (AA) change the protein expression pattern and utilization of pre-cursors for RNA biosynthesis in jejunal mucosa in relation to casein and whether these changes affect mucosal cell growth. Kids were fed comparable diets based on cow;s milk, of which 50% of crude protein were replaced by either casein (CAS), soy protein (SP) or soy protein supplemented with indispensible AA (SPA) for 34 days (n = 4/group). Jejunal tissue was collected 5 h after adding a single dose of (15)N-RNA to the diet, in order to determine morphology, protein repertoire by two-dimensional gel electrophoresis and matrix-assisted laser desorption/ionisation time-of-flight mass spectrometry, and RNA biosynthesis by isotope ratio-mass spectrometry. In mid-jejunum, morphological alterations induced by partial replacement of casein with soy protein were accompanied by changes in mucosal proteins related to generation of the cytoskeleton and in pathways for mucosal RNA biosynthesis, resulting in a smaller re-utilization of dietary RNA pre-cursors and in an increased activity of enzymes involved in nucleic acid breakdown. Soy protein supplemented with indispensible aminoacids tended to revise mucosal growth retardation with no impact on salvage of dietary RNA pre-cursors for mucosal RNA biosynthesis, but changes in cytoskeleton generation. Feeding soy protein with supplementation of indispensible AA does not ameliorate soy protein effects on mucosal morphology and RNA metabolism in the jejunum in a significant manner.

[Echocardiographic assessment of myocardial function during His bundle and right ventricular pacing]. / Echokardiographische Beurteilung der myokardialen Funktion unter His-Bündel- und rechtsventrikulärer Schrittmacherstimulation.

INTRODUCTION: In patients with pacemaker (PM) therapy, His bundle stimulation (HBS) may lead to a more synchronous activation of the left ventricle (LV) than conventional right ventricular stimulation (RVS). In this study, we investigated to which extent this effect can be objectified by means of contemporary echocardiographic functional imaging. METHODS: In all, 15 RVS patients (6 women, mean age 76.6 ± 4.1 years) and 15 HBS patients (6 women, mean age 74.6 ± 3.7 years) underwent echocardiography with and without cardiac pacing. Besides LV end-diastolic volume (EDV), ejection fraction (EF), and global strain (GLS), we measured global and regional myocardial work and LV efficiency based on noninvasive pressure-strain loops. RESULTS: In all HBS patients, optimization of PM settings resulted in immediate changes in myocardial function parameters. With pacing, RVS patients showed a higher decrease in EF and GLS than HBS patients. Global LV work and LV work efficiency decreased significantly only in RVS patients. CONCLUSION: Changes in regional and global myocardial function can by proven and quantified by functional echocardiography. In patients under PM therapy, HBS shows functional advantages in comparison to conventional RVS.

Impact of growth kinetics on the interface morphology and magnetization in La1/3Sr2/3FeO3/La2/3Sr1/3MnO3 heterostructures.

The ability to create atomically perfect, epitaxial heterostructures of correlated complex perovskite oxides using state-of-art thin film deposition techniques has generated new physical phenomena at engineered interfaces. Here we report on the impact of growth kinetics on the magnetic structure and exchange coupling at the interface in heterostructures combining layers of antiferromagnetic La1/3Sr2/3FeO3 (LSFO) and ferromagnetic La2/3Sr1/3MnO3 (LSMO) on (0 0 1)-oriented SrTiO3 (STO) substrates. Two growth orders are investigated, (a) LSMO/LSFO/STO(0 0 1) and (b) LSFO/LSMO/STO(0 0 1), where the LSFO layer is grown by molecular beam epitaxy and the LSMO layer by high oxygen pressure sputtering. The interface has been investigated using electron microscopy and polarized neutron reflectometry. Interdiffusion over seven monolayers is observed in LSMO/LSFO (a) with an almost 50% reduction in magnetization at the interface and showing no exchange coupling. However, the exchange bias effect ([Formula: see text] mT at 10 K) could be realized when the interface is atomically sharp, as in LSFO/LSMO (b). Our study therefore reveals that, even for well ordered and lattice-matched structures, the kinetics involved in the growth processes drastically influences the interface quality with a strong correlation to the magnetic properties.

Indication of intracellular magnesium deficiency in lactating dairy cows revealed by magnesium loading and renal fractional excretion.

Nine non-pregnant, lactating dairy cows were used to study plasma and urinary magnesium concentrations ([Mg]pl; [Mg]u), and the urinary fractional excretion of magnesium (FE(Mg)) before, during and after an 120 min intravenous magnesium (Mg) administration (2.5 mg/kg body weight). Animals received a total mixed ration, and Mg content of the diet was within recommended range. Basal mean [Mg]pl, [Mg]u and FE(Mg) were 0.89 +/- 0.09 mm, 5.92 +/- 2.99 mm and 8.3 +/- 9.7% respectively. For all parameters, a substantial inter-individual variation was observed. Three cows showed suboptimal [Mg]pl and/or [Mg]u as well as low FE(Mg) values of approximately 2% indicating an insufficient Mg supply to these animals (depressed feed intake, reduced absorption of Mg). The applied Mg challenge induced no significant change of mean [Mg]pl in the cows because part of the excess Mg was excreted in the urine. But in five out of nine cows, a decrease of the FE(Mg), during and after an intravenous Mg load was observed showing that part of the infused Mg is used to replenish intracellular Mg pools. Thus, the existence of an intracellular Mg deficiency in these cows was unmasked by performing the Mg loading test only. Because a reduced free intracellular [Mg] impairs cell and tissue functions, the results highlight the importance of an accurate definition of the intracellular Mg status. The Mg loading test is a suitable procedure, however, for practical purposes less expensive and time consuming methods must be developed.

Impact of early exposure to a cafeteria diet on prefrontal cortex monoamines and novel object recognition in adolescent rats.

The prefrontal cortex (PFC) undergoes protracted postnatal development such that its structure and behavioural function may be profoundly altered by environmental factors. Here we investigate the effect of lactational dietary manipulations on novel object recognition (NOR) learning and PFC monoamine neurotransmitter metabolism in early adolescent rats. To this end, Wistar rat dams were fed a high caloric cafeteria diet (CD) during lactation and resultant 24-26 day old offspring exposed to NOR testing and simultaneous PFC dopamine and serotonin metabolism measurement. In the second NOR choice trial where one familiar and one novel object were presented controls explored the novel preferentially to the familiar object both after a 5 min (P < 0.001) or 30 min (P < 0.05) inter-trial intervals (ITI). By contrast, offspring from dams fed on lactational CD failed to show any significant preference for the novel object at either time point. Compared with chow fed controls, their average exploration ratio of the novel object was lower after the 5 min ITI (P < 0.05). Following a 60 min ITI, neither CD nor control offspring showed a preference for the novel object. PFC dopamine metabolism was significantly reduced in the CD group (P < 0.001), whereas serotonin metabolism was increased (P < 0.001). These results suggest that an obesogenic lactational diet can have a detrimental impact on cognition in adolescent offspring associated with aberrant PFC serotonin and dopamine metabolism.

Discovery of an orally efficaceous 4-phenoxypyrrolidine-based BACE-1 inhibitor.

Based on a lead compound identified from the patent literature, we developed patentably novel BACE-1 inhibitors by introducing a cyclic amine scaffold as embodied by 1a and 1b. Extensive SAR studies assessed a variety of isophthalamide replacements including substituted pyrrolidinones and ultimately led to the identification of 11. Due to its favorable overall profile, 11 has been extensively profiled in various in vivo settings.

Potent pyrrolidine- and piperidine-based BACE-1 inhibitors.

Based on lead compound 1 identified from the patent literature, we developed novel patentable BACE-1 inhibitors by introducing a cyclic amine scaffold. Extensive SAR studies on both pyrrolidines and piperidines ultimately led to inhibitor 2f, one of the most potent inhibitors synthesized to date.