Macromolecular background signal and non-Gaussian metabolite diffusion determined in human brain using ultra-high diffusion weighting.

PURPOSE Definition of a macromolecular MR spectrum based on diffusion properties rather than relaxation time differences and characterization of non-Gaussian diffusion of brain metabolites with strongly diffusion-weighted MR spectroscopy. METHODS Short echo time MRS with strong diffusion-weighting with b-values up to 25 ms/μm2 at two diffusion times was implemented on a Connectom system and applied in combination with simultaneous spectral and diffusion decay modeling. Motion-compensation was performed with a combined method based on the simultaneously acquired water and a macromolecular signal. RESULTS The motion compensation scheme prevented spurious signal decay reflected in very small apparent diffusion constants for macromolecular signal. Macromolecular background signal patterns were determined using multiple fit strategies. Signal decay corresponding to non-Gaussian metabolite diffusion was represented by biexponential fit models yielding parameter estimates for human gray matter that are in line with published rodent data. The optimal fit strategies used constraints for the signal decay of metabolites with limited signal contributions to the overall spectrum. CONCLUSION The determined macromolecular spectrum based on diffusion properties deviates from the conventional one derived from longitudinal relaxation time differences calling for further investigation before use as experimental basis spectrum when fitting clinical MR spectra. The biexponential characterization of metabolite signal decay is the basis for investigations into pathologic alterations of microstructure

Quantification of NAD+ in human brain with 1 H MR spectroscopy at 3 T: Comparison of three localization techniques with different handling of water magnetization.

PURPOSE The detection of nicotinamide-adenine-dinucleotide (NAD+ ) is challenging using standard 1 H MR spectroscopy, because it is of low concentration and affected by polarization-exchange with water. Therefore, this study compares three techniques to access NAD+ quantification at 3 T-one with and two without water presaturation. METHODS A large brain volume in 10 healthy subjects was investigated with three techniques: semi-LASER with water-saturation (WS) (TE = 35 ms), semi-LASER with metabolite-cycling (MC) (TE = 35 ms), and the non-water-excitation (nWE) technique 2D ISIS-localization with chemical-shift-selective excitation (2D I-CSE) (TE = 10.2 ms). Spectra were quantified with optimized modeling in FiTAID. RESULTS NAD+ could be well quantified in cohort-average spectra with all techniques. Obtained apparent NAD+ tissue contents are all lower than expected from literature confirming restricted visibility by 1 H MRS. The estimated value from WS-MRS (58 μM) was considerably lower than those obtained with non-WS techniques (146 μM for MC-semi-LASER and 125 μM for 2D I-CSE). The nWE technique with shortest TE gave largest NAD+ signals but suffered from overlap with large amide signals. MC-semi-LASER yielded best estimation precision as reflected in relative Cramer-Rao bounds (14%, 21 μM/146 μM) and also best robustness as judged by the coefficient-of-variance over the cohort (11%, 10 μM/146 μM). The MR-visibility turned out as 16% with WS and 41% with MC. CONCLUSION Three methods to assess NAD+ in human brain at 3 T have been compared. NAD+ could be detected with a visibility of ∼41% for the MC method. This may open a new window for the observation of pathological changes in the clinical research setting

In vivo vasospasm induction by ultrasound application in the chicken chorioallantoic membrane model

Cerebral vasospasm is a highly investigated phenomenon in neurovascular research. Experimental vasospasm models are irreplaceable for the evaluation of new antivasospastic drugs. In this study, we assessed the reliability of in vivo vasospasm induction by ultrasound application in the chicken chorioallantoic membrane (CAM) model. After incubation of fertilized chicken eggs for four days, a fenestration was performed to enable examination of the CAM vessels. On the thirteenth day, continuous-wave ultrasound (3 MHz, 1 W/cm(2)) was applied on the CAM vessels for 60 s. The ultrasound effect on the vessels was recorded by life imaging (5-MP HD-microscope camera, Leica®). The induced vessel diameter changes were evaluated in a defined time interval of 20 min using a Fiji macro. The vessel diameter before and after sonication was measured and the relative diameter reduction was determined. A first reduction of vessel diameter was observed after three minutes with an average vessel-diameter decrease to 77%. The maximum reduction in vessel diameter was reached eight minutes after sonication with an average vessel diameter decrease to 57% (mean relative diameter reduction of 43%, range 44–61%), ANOVA, p = 0.0002. The vasospasm persisted for all 20 recorded minutes post induction. Vasospasm can be reliably induced by short application of 3 MHz-ultrasound to the CAM vessels. This might be a suitable in vivo model for the evaluation of drug effects on vasospasm in an experimental setting as intermediary in the transition process from in vitro to in vivo assessment using animal models

Diffusion-weighted magnetic resonance spectroscopy boosted by simultaneously acquired water reference signals.

PURPOSE To combine the metabolite-cycling technique with diffusion-weighted H-MR spectroscopy and to use the inherent water reference for compensation of motion-related signal loss for improved estimation of metabolite apparent diffusion coefficients (ADCs). METHODS Diffusion-weighted spectra of water and metabolites were acquired simultaneously using metabolite-cycling at 3 T. The water information was used for signal correction of phase, frequency, and eddy currents, as well as for compensation of motion-induced signal loss. ADCs were estimated by 2D simultaneous fitting. The quality of ADC restoration was investigated in vitro. Subsequently, the new approach was applied in 13 subjects for enhanced metabolite ADC estimation in gray matter. RESULTS Metabolite-cycled diffusion H-MRS is suitable to measure metabolite and water ADCs simultaneously. The water reference facilitates signal amplitude restoration, compensating for motion-related artefacts. 2D fitting stabilizes the fitting procedure and allows the estimation of ADCs even for low signal-to-noise metabolites. Use of the motion-compensation scheme leads to estimation of smaller ADCs for virtually all metabolites (44% smaller ADC on average), to a reduction of fitting uncertainties for metabolite ADCs in individual subjects and reduced variance over the cohort (45% smaller SD on average). CONCLUSION Using the simultaneously acquired water signal as internal reference allows not only for compensation of phase and frequency fluctuations but also for signal amplitude restoration, and thus improved metabolite ADC estimation. Combination with 2D simultaneous fitting promises access to the diffusion properties even for low signal-to-noise metabolites. The combination of both techniques increases the specificity and sensitivity of estimated metabolite ADC values in the cohort

Ultrasound-induced release of nimodipine from drug-loaded block copolymer micelles: in vivo analysis

Nimodipine prevents cerebral vasospasm and improves functional outcome after aneurysmal subarachnoid hemorrhage (aSAH). The beneficial effect is limited by low oral bioavailability of nimodipine, which resulted in an increasing use of nanocarriers with sustained intrathecal drug release in order to overcome this limitation. However, this approach facilitates only a continuous and not an on-demand nimodipine release during the peak time of vasospasm development. In this study, we aimed to assess the concept of controlled drug release from nimodipine-loaded copolymers by ultrasound application in the chicken chorioallantoic membrane (CAM) model. Nimodipine-loaded copolymers were produced with the direct dissolution method. Vasospasm of the CAM vessels was induced by means of ultrasound (Physiomed, continuous wave, 3 MHz, 1.0 W/cm(2)). The ultrasound-mediated nimodipine release (Physiomed, continuous wave, 1 MHz, 1.7 W/cm(2)) and its effect on the CAM vessels were evaluated. Measurements of vessel diameter before and after ultrasound-induced nimodipine release were performed using ImageJ. The CAM model could be successfully carried out in all 25 eggs. After vasospasm induction and before drug release, the mean vessel diameter was at 57% (range 44–61%) compared to the baseline diameter (set at 100%). After ultrasound-induced drug release, the mean vessel diameter of spastic vessels increased again to 89% (range 83–91%) of their baseline diameter, which was significant (p = 0.0002). We were able to provide a proof of concept for in vivo vasospasm induction by ultrasound application in the CAM model and subsequent resolution by ultrasound-mediated nimodipine release from nanocarriers. This concept merits further evaluation in a rat SAH model. GRAPHICAL ABSTRACT: [Image: see text

Podiumsdiskussion: "Auf dem Weg zu einem Bibliotheksgesetz"

Teilnehmer: - André Blechschmidt MdL, Sprecher für Justiz, Medien und Sport der Landtagsfraktion Die Linke. PDS - Hans-Jürgen Döring MdL, Sprecher für Bildung und Kultur der SPD-Landtagsfraktion - Christian Hasiewicz, Bertelsmann Stiftung - Barbara Schleihagen, Leiterin der Geschäftsstelle des DBV e.V. - Jörg Schwäblein MdL, Sprecher des Arbeitskreises Wissenschaft, Kunst und Medien der CDU-Landtagsfraktion - Eric W. Steinhauer, Universitätsbibliothek Ilmenau/VDB-Regionalvorsitzender Moderation: Dr. Frank Simon-Ritz, Direktor der Universitätsbibliothek der Bauhaus Universität Weima

Parkes Weber Syndrome: Contribution of the Genotype to the Diagnosis

Objectives: Parkes Weber syndrome (PWS) is a rare disorder that combines overgrowth, capillary malformations, and arteriovenous malformations (AVM)/arteriovenous fistulas, for which underlying activating mutations in the ras/mitogen-activated protein kinase/extracellular-signal-regulated kinase signaling pathway have been described. The clinical overlap with Klippel-Trenauny syndrome, associated with mutations in PIK3CA, is significant. This case series aimed to elaborate on the phenotypic description of PWS, to underline its clinical overlap with Klippel-Trenauny syndrome and nonsyndromic AVM, and to evaluate the contribution of genotypic characterization to the diagnosis. Methods: All patients diagnosed with PWS upon enrollment in the Bernese VAScular COngenital Malformations (VASCOM) cohort were included. The diagnostic criteria of PWS were retrospectively reviewed. A next-generation sequencing (NGS) gene panel (TSO500, Illumina) was used on tissue biopsy samples. Results: Overall, 10/559 patients of the VAScular COngenital Malformations cohort were initially diagnosed with PWS. Three patients were reclassified as nonsyndromic AVM (Kristen Rat Sarcoma Viral oncogene homolog [KRAS], KRAS+tumor protein p53, and protein tyrosine phosphatase non-receptor type 11). Finally, 7 patients fulfilled all clinical diagnostic criteria of PWS. Genetic testing was available in 5 PWS patients. Only 1 patient had the classic RASA1 mutation; another patient had mutations in G protein subunit alpha q (GNAQ) and phosphatase and tensin homolog. In a third case, a PIK3CA mutation was detected. In 2 patients, no mutations were identified. Conclusion: Overgrowth syndromes with vascular malformations are rare and their clinical overlap hampers the classification of individual phenotypes under specific syndrome labels, sometimes even despite genetic testing. To provide optimal patient care, an accurate phenotypic description combined with the identification of molecular targets for precision medicine may be more meaningful than the syndrome classification itself

Impact of the Scheduling Strategy in Heterogeneous Systems That Provide Co-Scheduling

ABSTRACT In recent years, the number of processing units per compute node has been increasing. In order to utilize all or most of the available resources of a high-performance computing cluster, at least some of its nodes will have to be shared by several applications at the same time. Yet, even if jobs are co-scheduled on a node, it can happen that high performance resources remain idle, although there are jobs that could make use of them (e. g. if the resource was temporarily blocked when the job was started). Heterogeneous schedulers, which schedule tasks for different devices, can bind jobs to resources in a way that can significantly reduce the idle time. Typically, those schedulers make their decisions based on a static strategy. In this paper, we investigate the impact if a heterogeneous scheduler allows modifications of the strategies at runtime. For a set of applications, we determine the makespan and show how it is influenced by four different scheduling strategies. A well-chosen strategy can result in a speedup of more the 2.5 in comparison to other strategies

Practical considerations of diffusion-weighted MRS with ultra-strong diffusion gradients

Introduction: Diffusion-weighted magnetic resonance spectroscopy (DW-MRS) offers improved cellular specificity to microstructure—compared to water-based methods alone—but spatial resolution and SNR is severely reduced and slow-diffusing metabolites necessitate higher b-values to accurately characterize their diffusion properties. Ultra-strong gradients allow access to higher b-values per-unit time, higher SNR for a given b-value, and shorter diffusion times, but introduce additional challenges such as eddy-current artefacts, gradient non-uniformity, and mechanical vibrations. Methods: In this work, we present initial DW-MRS data acquired on a 3T Siemens Connectom scanner equipped with ultra-strong (300 mT/m) gradients. We explore the practical issues associated with this manner of acquisition, the steps that may be taken to mitigate their impact on the data, and the potential benefits of ultra-strong gradients for DW-MRS. An in-house DW-PRESS sequence and data processing pipeline were developed to mitigate the impact of these confounds. The interaction of TE, b-value, and maximum gradient amplitude was investigated using simulations and pilot data, whereby maximum gradient amplitude was restricted. Furthermore, two DW-MRS voxels in grey and white matter were acquired using ultra-strong gradients and high b-values. Results: Simulations suggest T2-based SNR gains that are experimentally confirmed. Ultra-strong gradient acquisitions exhibit similar artefact profiles to those of lower gradient amplitude, suggesting adequate performance of artefact mitigation strategies. Gradient field non-uniformity influenced ADC estimates by up to 4% when left uncorrected. ADC and Kurtosis estimates for tNAA, tCho, and tCr align with previously published literature. Discussion: In conclusion, we successfully implemented acquisition and data processing strategies for ultra-strong gradient DW-MRS and results indicate that confounding effects of the strong gradient system can be ameliorated, while achieving shorter diffusion times and improved metabolite SNR