Enhanced and robust contrast in CEST MRI: Saturation pulse shape design via optimal control.

PURPOSE: To employ optimal control for the numerical design of Chemical Exchange Saturation Transfer (CEST) saturation pulses to maximize contrast and stability against B 0 $$ {\mathrm{B}}_0 $$ inhomogeneities. THEORY AND METHODS: We applied an optimal control framework for the design pulse shapes for CEST saturation pulse trains. The cost functional minimized both the pulse energy and the discrepancy between the corresponding CEST spectrum and the target spectrum based on a continuous radiofrequency (RF) pulse. The optimization is subject to hardware limitations. In measurements on a 7 T preclinical scanner, the optimal control pulses were compared to continuous-wave and Gaussian saturation methods. We conducted a comparison of the optimal control pulses with Gaussian, block pulse trains, and adiabatic spin-lock pulses. RESULTS: The optimal control pulse train demonstrated saturation levels comparable to continuous-wave saturation and surpassed Gaussian saturation by up to 50 % in phantom measurements. In phantom measurements at 3 T the optimized pulses not only showcased the highest CEST contrast, but also the highest stability against field inhomogeneities. In contrast, block pulse saturation resulted in severe artifacts. Dynamic Bloch-McConnell simulations were employed to identify the source of these artifacts, and underscore the B 0 $$ {\mathrm{B}}_0 $$ robustness of the optimized pulses. CONCLUSION: In this work, it was shown that a substantial improvement in pulsed saturation CEST imaging can be achieved by using Optimal Control design principles. It is possible to overcome the sensitivity of saturation to B0 inhomogeneities while achieving CEST contrast close to continuous wave saturation.

Robust dual-angle T 1 $$ {T}_1 $$ measurement in magnetization transfer spectroscopy by time-optimal control.

Magnetization transfer spectroscopy relies heavily on the robust determination of T 1 $$ {T}_1 $$ relaxation times of nuclei participating in metabolic exchange. Challenges arise due to the use of surface RF coils for transmission (high B 1 + $$ {B}_1^{+} $$ variation) and the broad resonance band of most X nuclei. These challenges are particularly pronounced when fast T 1 $$ {T}_1 $$ mapping methods, such as the dual-angle method, are employed. Consequently, in this work, we develop resonance offset and B 1 + $$ {B}_1^{+} $$ robust excitation RF pulses for 31P magnetization transfer spectroscopy at 7T through ensemble-based time-optimal control. In our approach, we introduce a cost functional for designing robust pulses, incorporating the full Bloch equations as constraints, which are solved using symmetric operator splitting techniques. The optimal control design of the RF pulses developed demonstrates improved accuracy, desired phase properties, and reduced RF power when applied to dual-angle T 1 $$ {T}_1 $$ mapping, thereby improving the precision of exchange-rate measurements, as demonstrated in a preclinical in vivo study quantifying brain creatine kinase activity.

Reactivity of Superbasic Carbanions Generated via Reductive Radical-Polar Crossover in the Context of Photoredox Catalysis.

Photocatalytic reactions involving a reductive radical-polar crossover (RRPCO) generate intermediates with carbanionic reactivity. Many of these proposed intermediates resemble highly reactive organometallic compounds. However, conditions of their formation are generally not tolerated by their isolated organometallic versions and often a different reactivity is observed. Our investigations on their nature and reactivity under commonly used photocatalytic conditions demonstrate that these intermediates are indeed best described as free, superbasic carbanions capable of deprotonating common polar solvents usually assumed to be inert such as acetonitrile, dimethylformamide, and dimethylsulfoxide. Their basicity not only towards solvents but also towards electrophiles, such as aldehydes, ketones, and esters, is comparable to the reactivity of isolated carbanions in the gas-phase. Previously unsuccessful transformations thought to result from a lack of reactivity are explained by their high reactivity towards the solvent and weakly acidic protons of reaction partners. An intuitive explanation for the mode of action of photocatalytically generated carbanions is provided, which enables methods to verify reaction mechanisms proposed to involve an RRPCO step and to identify the reasons for the limitations of current methods.

Whole-Cerebrum distortion-free three-dimensional pseudo-continuous arterial spin labeling at 7T.

Fulfilling potentials of ultrahigh field for pseudo-Continuous Arterial Spin Labeling (pCASL) has been hampered by B1/B0 inhomogeneities that affect pCASL labeling, background suppression (BS), and the readout sequence. This study aimed to present a whole-cerebrum distortion-free three-dimensional (3D) pCASL sequence at 7T by optimizing pCASL labeling parameters, BS pulses, and an accelerated Turbo-FLASH (TFL) readout. A new set of pCASL labeling parameters (Gave = 0.4 mT/m, Gratio = 14.67) was proposed to avoid interferences in bottom slices while achieving robust labeling efficiency (LE). An OPTIM BS pulse was designed based on the range of B1/B0 inhomogeneities at 7T. A 3D TFL readout with 2D-CAIPIRINHA undersampling (R = 2 × 2) and centric ordering was developed, and the number of segments (Nseg) and flip angle (FA) were varied in simulation to achieve the optimal trade-off between SNR and spatial blurring. In-vivo experiments were performed on 19 subjects. The results showed that the new set of labeling parameters effectively achieved whole-cerebrum coverage by eliminating interferences in bottom slices while maintaining a high LE. The OPTIM BS pulse achieved 33.3% higher perfusion signal in gray matter (GM) than the original BS pulse with a cost of 4.8-fold SAR. Incorporating a moderate FA (8°) and Nseg (2), whole-cerebrum 3D TFL-pCASL imaging was achieved with a 2 × 2 × 4 mm3 resolution without distortion and susceptibility artifacts compared to 3D GRASE-pCASL. In addition, 3D TFL-pCASL showed a good to excellent test-retest repeatability and potential of higher resolution (2 mm isotropic). The proposed technique also significantly improved SNR when compared to the same sequence at 3T and simultaneous multislice TFL-pCASL at 7T. By combining a new set of labeling parameters, OPTIM BS pulse, and accelerated 3D TFL readout, we achieved high resolution pCASL at 7T with whole-cerebrum coverage, detailed perfusion and anatomical information without distortion, and sufficient SNR.

Advanced design of MRI inversion pulses for inhomogeneous field conditions by optimal control.

Non-selective inversion pulses find widespread use in MRI applications, where requirements on them are increasingly demanding. With the use of high and ultra-high field strength systems, robustness to Δ B 0 and B 1 + inhomogeneities, while tackling SAR and hardware limitations, has rapidly become important. In this work, we propose a time-optimal control framework for the optimization of Δ B 0 - and B 1 + -robust inversion pulses. Robustness is addressed by means of ensemble formulations, while allowing inclusion of hardware and energy limitations. The framework is flexible and performs excellently for various optimization goals. The optimization results are analyzed extensively in numerical experiments. Furthermore, they are validated, and compared with adiabatic RF pulses, in various phantom and in vivo measurements on a 3 T MRI system.

The presence of liver cirrhosis is a strong negative predictor of survival for patients admitted to the intensive care unit - Cirrhosis in intensive care patients.

BACKGROUND AND AIMS: Liver cirrhosis is a systemic disease that substantially impacts the body's physiology, especially in advanced stages. Accordingly, the outcome of patients with cirrhosis requiring intensive care treatment is poor. We aimed to analyze the impact of cirrhosis on mortality of intensive care unit (ICU) patients compared to other frequent chronic diseases and conditions. METHODS: In this retrospective study, patients admitted over three years to the ICU of the Department of Medicine of the University Hospital Frankfurt were included. Patients were matched for age, gender, pre-existing conditions, simplified acute physiology score (SAPS II), and therapeutic intervention scoring system (TISS). RESULTS: A total of 567 patients admitted to the ICU were included in the study; 99 (17.5 %) patients had liver cirrhosis. A total of 129 patients were included in the matched cohort for the sensitivity analysis. In-hospital mortality was higher in cirrhotic patients than non-cirrhotic patients (p < 0.0001) in the entire and matched cohort. Liver cirrhosis remained one of the strongest independent predictors of in-hospital mortality (entire cohort p = 0.001; matched cohort p = 0.03) along with dialysis and need for transfusion in the multivariate logistic regression analysis. Furthermore, in the cirrhotic group, the need for kidney replacement therapy (p < 0.001) and blood transfusion (p < 0.001) was significantly higher than in the non-cirrhotic group.  CONCLUSIONS: In the presented study, liver cirrhosis was one of the strongest predictors of in-hospital mortality in patients needing intensive care treatment along with dialysis and the need for ventilation. Therefore, concerted efforts are needed to improve cirrhotic patients' outcomes, prevent disease progression, and avoid complications with the need for ICU treatment in the early stages of the disease.

The pathologist and "short-term rector" Albert Dietrich (1873-1961) and his ambivalent relationship with the Nazi regime : Not Nazi enough?

Throughout his professional life, the pathologist Albert Dietrich devoted himself to researching and combating cancer. Due to his considerable reputation and success, he was one of the first doctors to be awarded the Paracelsus Medal for his scientific services in 1952.However, Dietrich's role in the Third Reich was - and still is - far less defined. In May 1933, he became rector of the Eberhard Karls University in Tübingen, which at that time was one of the most Nazi-oriented universities. However, his term of office was short - by the end of 1933 he had already been replaced by the protestant theologian Karl Fezer.This article sheds light on Dietrich's ambivalent relationship to National Socialism and analyzes and discusses the background to his dismissal, his later (also politically influenced) emeritus status (1938/39), and his entry into the NSDAP, which took place at retirement age (1941). The study is based on archival sources partly evaluated for the first time and on a reanalysis of the relevant research literature.The study shows that Dietrich was targeted by individual Nazi decision-makers primarily because he advocated a supposedly "liberalist" university policy. Dietrich thus ultimately stands for a type of university lecturer who renounced a decidedly Nazi stance in public without, however, placing himself in a critical relationship to Nazi ideology. Against this background, statements from the postwar period that saw him retrospectively near Nazi opposition are to be classified as the formation of legends.

Virchow medallists and honorary members of the German Society of Pathology and their relationship with National Socialism : A cross-sectional study.

The present study focuses on the group of pathologists who (1) were appointed honorary members or bearers of the Rudolf Virchow Medal by the German Society for Pathology (DGP) and (2) experienced the Third Reich as a citizen of the Third Reich. In particular, it examines the relationship between those distinguished persons and National Socialism, and, at the same time, the criteria of the professional society when awarding such honors. Specifically, it is important to clarify what role the DGP officials ascribed to the political stance or experience of the candidates in the Nazi dictatorship during the selection process: were there victims of the Nazis among the honorees whose repressive experiences and personal fates were intended to be acknowledged in this way? Of equal interest is the counter-question: were pathologists honored who had made (party) political commitments to National Socialism during the Third Reich?A total of nine Virchow medallists and three honorary members met the inclusion criteria. None of those affected belonged to the group of pathologists who suffered injustice during the Third Reich or who could be described as victims of the Nazis. On the other hand, four of the nine German Virchow medal winners and one of the three honorary members had joined the National Socialist Party and to some extent other Nazi organisations. Obviously, previous closeness to National Socialism was not a decisive factor in the selection of honorary members and Virchow medallists and, in particular, was not an exclusion criterion.The aforementioned results correspond to the findings of a parallel study, in which the political past of the German DGP chairmen appointed up to 1986 was examined. This showed that two thirds of them had joined the National Socialist Party during the Third Reich.

Versatile Visible-Light-Driven Synthesis of Asymmetrical Phosphines and Phosphonium Salts.

Asymmetrically substituted tertiary phosphines and quaternary phosphonium salts are used extensively in applications throughout industry and academia. Despite their significance, classical methods to synthesize such compounds often demand either harsh reaction conditions, prefunctionalization of starting materials, highly sensitive organometallic reagents, or expensive transition-metal catalysts. Mild, practical methods thus remain elusive, despite being of great current interest. Herein, we describe a visible-light-driven method to form these products from secondary and primary phosphines. Using an inexpensive organic photocatalyst and blue-light irradiation, arylphosphines can be both alkylated and arylated using commercially available organohalides. In addition, the same organocatalyst can be used to transform white phosphorus (P4 ) directly into symmetrical aryl phosphines and phosphonium salts in a single reaction step, which has previously only been possible using precious metal catalysis.

Controlling the Interparticular Distances of Extended Non-Close-Packed Colloidal Monolayers.

A versatile method for the preparation extended, well-ordered, non-close-packed monolayers of silica nanoparticles (137 ± 4 nm diameter) with adjustable interparticle distances is presented, which is based on a simple self-assembly procedure using aqueous dispersion with different ionic strengths. It is shown that these structures can be successfully transferred to air without suffering from aggregation. Scanning electron microscopy (SEM) is used to characterize the structures after transfer into the atmosphere. These investigations were combined with a quartz crystal microbalance with dissipation (QCM-D) experiments to follow the self-assembly process in solution. The nearest-neighbor distance distribution reveals a monotonous decrease of the average nearest-neighbor distance from 290 to 200 nm with increasing ionic strength from 0.05 to 1 mM, which indicates an increased shielding of the electrostatic interaction with increasing ionic strength. The observed saturation coverages for all studied ionic strengths are well explained with an effective hard-sphere model in which the saturation coverage is limited by Coulomb repulsion. However, at ionic strengths above 1 mM, significant amounts of aggregates are found in the dried samples, suggesting that the observed aggregates at high ionic strengths are formed during the drying process caused by capillary forces between the particles. Tuning the barrier for lateral diffusion, e.g., by changing the surface morphology or functionalization of the particles will offer a route to further extend the range of particle distances. The present approach can be easily expanded to a broad range of colloidal materials on surfaces, while it only requires low-cost laboratory equipment.

[Walter Büngeler (1900-1987) : Nazi victim or political influencer in Brazil?] / Walter Büngeler (1900­1987) : Opfer der NS-Zeit oder nationalsozialistischer Kontaktmann in Brasilien?

Walter Büngeler is one of the best known German pathologists of the 20th century. He became internationally known for his basic research on leukaemia and the pathology of tumours. In 1936 he left Europe for Brazil but returned in 1942. After 1945, he staged himself as a political victim who had been expelled first by the National Socialists and later from Brazil. In fact, with this portrayal he succeeded in passing the denazification procedure without any damage and in continuing and considerably expanding his university career. Until the recent past, Büngeler was described in the relevant literature as a Nazi critic or victim. But does the presentation handed down by Büngeler stand up to a critical examination of the facts?On the basis of contemporary sources, the article reveals serious differences between Büngeler's statements and historical facts. It can be shown that Büngeler's allegations in denazification were incorrect in all relevant aspects.

[Virchow medallists and honorary members of the German Society for Pathology and their relationship with National Socialism : A cross-sectional study. German version]. / Virchow-Medaillenträger und Ehrenmitglieder der DGP und ihr Verhältnis zum Nationalsozialismus : Eine Querschnittsstudie.

The present study focuses on the group of pathologists who (1) were appointed honorary members or bearers of the Rudolf Virchow Medal by the German Society for Pathology (DGP) and (2) experienced the "Third Reich" as a citizen of the "Third Reich". In particular, it examines the relationship between those distinguished persons and National Socialism, and, at the same time, the criteria of the professional society when awarding such honours. Specifically, it is important to clarify what role the DGP officials ascribed to the political stance or experience of the candidates in the Nazi dictatorship during the selection process: were there victims of the Nazis among the honourees whose repressive experiences and personal fates were intended to be acknowledged in this way? Of equal interest is the counter-question: were pathologists honoured who had made (party)political commitments to National Socialism during the "Third Reich"?A total of 9 Virchow medallists and 3 honorary members met the inclusion criteria. None of those affected belonged to the group of pathologists who suffered injustice during the "Third Reich" or who could be described as victims of the Nazis. On the other hand, 4 of the 9 German Virchow medal winners and 1 of the 3 honorary members had joined the National Socialist Party and to some extent other Nazi organisations. Obviously, previous closeness to National Socialism was not a decisive factor in the selection of honorary members and Virchow medallists and, in particular, was not an exclusion criterion.The aforementioned results correspond to the findings of a parallel study, in which the political past of the German DGP chairmen appointed up to 1986 was examined. This showed that two thirds of them had joined the National Socialist Party during the "Third Reich".

Adsorption of Mono- and Divalent 4-(Dimethylamino)pyridines on Gold Surfaces: Studies by Surface-Enhanced Raman Scattering and Density Functional Theory.

The adsorption thermodynamics of 4-(dimethylamino)pyridine (DMAP) and its five divalent derivatives di-DMAP- n (2 ≤ n ≤ 6) with gradually increasing methylene-spacer lengths n binding to planar gold surfaces has been studied by surface-enhanced Raman spectroscopy (SERS) and density functional theory (DFT). SERS intensities of the totally symmetrical breathing mode of the pyridine ring at approximately 1007 cm-1 are used to monitor the surface coverage of the DMAP and di-DMAP- n ligands on gold surfaces at different concentrations. The equilibrium constant as a measure of the binding affinity is obtained from these measurements by using a modified Langmuir isotherm. Due to multivalent binding to the gold substrate, a characteristic enhancement of the binding affinity of di-DMAP- n compared to the monovalent DMAP is observed for all divalent species. First principles calculations of the di-DMAP- n ligands on an ideal Au(111) surface model as well as step terrace models have been performed to understand the adsorption structures and the multivalent binding enhancements. Furthermore, Raman spectra of the adsorbed molecules have been studied by first principles calculations to correlate the binding affinities to experimentally determined adsorption constants. The joint experimental and theoretical investigation of an oscillatory behavior of the binding affinity as a function of the methylene-spacer length in mono- and divalent 4-(dimethylamino)pyridines reveals that the molecular architecture plays an important role for the structure-function interplay of multivalently bound adsorbates.

Shape-Dependent Dissolution and Cellular Uptake of Silver Nanoparticles.

The cellular uptake and dissolution of trigonal silver nanoprisms (edge length 42 ± 15 nm, thickness 8 ± 1 nm) and mostly spherical silver nanoparticles (diameter 70 ± 25 nm) in human mesenchymal stem cells (hMSC's) and human keratinocytes (HaCaT cells) were investigated. Both particles are stabilized by polyvinylpyrrolidone (PVP), with the prisms additionally stabilized by citrate. The nanoprisms dissolved slightly in pure water but strongly in isotonic saline or at pH 4, corresponding to the lowest limit for the pH during cellular uptake. The tips of the prisms became rounded within minutes due to their high surface energy. Afterward, the dissolution process slowed down due to the presence of both PVP stabilizing Ag{100} sites and citrate blocking Ag{111} sites. On the contrary, nanospheres, solely stabilized by PVP, dissolved within 24 h. These results correlate with the finding that particles in both cell types have lost >90% of their volume within 24 h. hMSC's took up significantly more Ag from nanoprisms than from nanospheres, whereas HaCaT cells showed no preference for one particle shape. This can be rationalized by the large cellular interaction area of the plateletlike nanoprisms and the bending stiffness of the cell membranes. hMSC's have a highly flexible cell membrane, resulting in an increased uptake of plateletlike particles. HaCaT cells have a membrane with a 3 orders of magnitude higher Young's modulus than for hMSC. Hence, the energy gain due to the larger interaction area of the nanoprisms is compensated for by the higher energy needed for cell membrane deformation compared to that for spheres, leading to no shape preference.

Lysosomal Dysfunction Caused by Cellular Accumulation of Silica Nanoparticles.

Nanoparticles (NPs) are widely used as components of drugs or cosmetics and hold great promise for biomedicine, yet their effects on cell physiology remain poorly understood. Here we demonstrate that clathrin-independent dynamin 2-mediated caveolar uptake of surface-functionalized silica nanoparticles (SiNPs) impairs cell viability due to lysosomal dysfunction. We show that internalized SiNPs accumulate in lysosomes resulting in inhibition of autophagy-mediated protein turnover and impaired degradation of internalized epidermal growth factor, whereas endosomal recycling proceeds unperturbed. This phenotype is caused by perturbed delivery of cargo via autophagosomes and late endosomes to SiNP-filled cathepsin B/L-containing lysosomes rather than elevated lysosomal pH or altered mTOR activity. Given the importance of autophagy and lysosomal protein degradation for cellular proteostasis and clearance of aggregated proteins, these results raise the question of beneficial use of NPs in biomedicine and beyond.

Structural Characterization of Ordered, Non-Close-Packed Functionalized Silica Nanoparticles on Gold Surfaces.

Nanostructured surfaces play an important role in modern science and technology. In particular, ordered arrangements of nonclose-packed nanoparticles created by self-assembly offer a versatile route to prepare systems, which can be used in various applications such as sensing, plasmonic devices or antireflection coatings. Self-assembly based systems are particularly appealing as preparation is rather simple. The ability of nanoparticle systems to form nonclosed packed monolayers by self-assembly depends on the balance of various energetic contributions in particular the adsorption energy, the lateral barrier for diffusion and the repulsion between particles. Even for simple model systems such as the monodispersed silica particles adsorbed on a bare gold surface investigated here, none of these quantities is easy to determine experimentally. To this end, we will report on a detailed characterization of the adsorption in particular with respect to the structural properties of the above-mentioned model system. Based on experimental results obtained by using quartz crystal microbalance with dissipation monitoring (QCM-D) as well as scanning electron microscopy (SEM) it is possible to determine the electrostatic pair potential from the lateral arrangement of the nano particles in the limit of low coverage.

Ordered Structures of Functionalized Silica Nanoparticles on Gold Surfaces: Correlation of Quartz Crystal Microbalance with Structural Characterization.

Quartz crystal microbalance (QCM) is frequently used to investigate adsorption of nanometer-sized objects such as proteins, viruses, or organic as well as inorganic nanoparticles from solution. The interpretation of the data obtained for heterogeneous adsorbate layers is not straightforward in particular if the systems exhibit sizable amounts of dissipation. In this study we investigate the deposition of monodisperse, amine functionalized silica nanoparticles on gold surfaces using QCM with dissipation (QCM-D) to obtain frequency and dissipation changes during adsorption from the liquid phase. These investigations are combined with ex situ scanning electron microscopy (SEM) measurements to study both coverage as well as lateral arrangement of the particles. An ordered layer of particles is found at saturation coverage due to the charged particle surface resulting in a repulsive interaction between the particles. The repulsion ensures a minimal distance between the particles, which leads to a saturation coverage of 15% for particles of 137 nm diameter. The frequency shift is shown to be a linear function of coverage which is a behavior expected for an elastic medium according to the Sauerbrey equation. However, the system shows a strong dependence of the normalized frequency shift on the overtones as well as a large dissipation, which is a clear indication for a system with viscoelastic properties. The analysis of the data show that a reliable determination of the adsorbed mass solely on the basis of QCM-D results is not possible, but additional information as determined by SEM in the present case is required to determine the coverage. From a correlation of the QCM-D results with the structural characterization it is possible to infer that the dissipation is a long ranged phenomenon. A lower boundary of the interaction length could be derived being twice the particle diameter for the particles studied here. In contrast to that the frequency response behaves like local phenomenon.

Skin barrier disruptions in tape stripped and allergic dermatitis models have no effect on dermal penetration and systemic distribution of AHAPS-functionalized silica nanoparticles.

The skin is a potential site of entry for nanoparticles (NP) but the role of disease-associated barrier disturbances on the path and extent of skin penetration of NP remains to be characterized. Silica nanoparticles (SiO2-NP) possess promising potential for various medical applications. Here, effects of different skin barrier disruptions on the penetration of N-(6-aminohexyl)-aminopropyltrimethoxysilane (AHAPS) functionalized SiO2-NP were studied. AHAPS-SiO2-NP (55±6 nm diameter) were topically applied on intact, tape stripped or on inflamed skin of SKH1 mice with induced allergic contact dermatitis for one or five consecutive days, respectively. Penetration of AHAPS-SiO2-NP through the skin was not observed regardless of the kind of barrier disruption. However, only after subcutaneous injection, AHAPS-SiO2-NP were incorporated by macrophages and transported to the regional lymph node only. Adverse effects on cells or tissues were not observed. In conclusion, AHAPS-SiO2-NP seem to not cross the normal or perturbed mouse skin. From the clinical editor: Skin is a potential site of entry for nanoparticles; however, it is poorly understood how skin diseases may alter this process. In tape-stripped skin and allergic contact dermatitis models the delivery properties of AHAPS-SiO2 nanoparticles remained unchanged, and in neither case were these NP-s able to penetrate the skin. No adverse effects were noted on the skin in these models and control mice.

Rational Approximation of Golden Angles: Accelerated Reconstructions with Simple and Numerically Reproducible Radial Sampling.

PURPOSE: To develop a generic radial sampling scheme that combines the advantages of golden ratio sampling with simplicity of equidistant angular patterns. The irrational angle between consecutive spokes in golden ratio based sampling schemes enables a flexible retrospective choice of temporal resolution, while preserving good coverage of k-space for each individual bin. Nevertheless, irrational increments prohibit precomputation of the point-spread function (PSF), can lead to numerical problems, and require more complex processing steps. To avoid these problems, a new sampling scheme based on a rational approximation of golden angles (RAGA) is developed. METHODS: The theoretical properties of RAGA sampling are mathematically derived. Sidelobe-to-peak ratios (SPR) are numerically computed and compared to the corresponding golden ratio sampling schemes. The sampling scheme is implemented in the BART toolbox and in a radial gradient-echo sequence. Feasibility is shown for quantitative imaging in a phantom and a cardiac scan of a healthy volunteer. RESULTS: RAGA sampling can accurately approximate golden ratio sampling and has almost identical PSF and SPR. In contrast to golden ratio sampling, each frame can be reconstructed with the same equidistant trajectory using different sampling masks, and the angle of each acquired spoke can be encoded as a small index, which simplifies processing of the acquired data. CONCLUSION: RAGA sampling provides the advantages of golden ratio sampling while simplifying data processing, rendering it a valuable tool for dynamic and quantitative MRI.

Improved stability of "naked" gold nanoparticles enabled by in situ coating with mono and multivalent thiol PEG ligands.

Unprotected ("naked") gold nanoparticles with high monodispersity ([d], 5.5± 0.5 nm) were obtained in a facile and single-step microwave-assisted hydrolytic decomposition of the molecular precursor [NMe4][Au(CF3)2]. Given their chloride-free surface chemistry, the as-obtained gold nanoparticles were in situ functionalized with mono-, di-, and trivalent thiolated PEG ligands in order to study the influence of multivalent character of the ligands on the stability of the colloidal solutions. For this purpose, a novel tridentate ligand was synthesized and the previously reported syntheses of mono- and divalent thiol ligands were improved. Owing to the pristine character of the Au nanoparticles no ligand exchange was required, and the colloidal and chemical stability of the mono- and multivalent functionalized particles purely depended on the ligating ability of the thiolated groups. In situ-functionalized Au nanoparticles showed a strikingly (2 orders of magnitude higher) improved stability against small nucleophiles such as sodium cyanide compared to gold nanoparticles coated with citrate ligands and functionalized via a ligand-exchange reaction. The monovalent thiol PEG ligand produced most stable colloids against cyanide, which is explained by a strongly increased numerical ligand-density on the surface. Gold colloids stabilized by di- and trivalent ligands exhibited high stability in aqueous solutions with high NaCl concentrations (2 M) in contrast to those functionalized with the monovalent PEG ligand, which were only temporally stable in dilute NaCl solutions. The beneficial effect of the multivalence of the ligands was further demonstrated by the incorporation of an additional chelating ligand (dithiothreitol) to the colloidal dispersions.