Diffusion tensor imaging and fiber tractography of the median nerve at 1.5T: optimization of b value

Objective: The objective of this study was to systematically assess the optimal b value for diffusion tensor imaging and fiber tractography of the median nerve at 1.5T. Materials and methods: This is a prospective study which was carried out with institutional review board approval and written informed consent from the study subjects. Fifteen healthy volunteers (seven men, eight women; mean age, 31.2years) underwent diffusion tensor imaging of the wrist. A single-shot spin-echo-based echo-planar imaging sequence (TR/TE, 7000/103ms) was performed in each subject at eight different b values ranging from 325 to 1,550s/mm2. Number and length of reconstructed fiber tracts, fiber density index (FDi), fractional anisotropy (FA), and apparent diffusion coefficient (ADC) were calculated for the median nerve. Signal-to-noise ratio (SNR) was also calculated for each acquisition. The overall image quality was assessed by two readers in consensus by ranking representative fiber tract images for each subject using a scale range from 1 to 8 (1 = best to 8 = worst image quality). Results: Longest fibers were observed for b values between 675 and 1,025s/mm2. Maximum FDi was found at b values of 1,025s/mm2. FA was between 0.5 and 0.6 for all b values. ADC gradually decreased from 1.44 × 10−3 to 0.92 × 10−3mm2/s with increasing b values. Maximum SNR ± standard deviation (175.4 ± 72.6) was observed at the lowest b value and decreased with increasing b values. SNR at b values of 1,025s/mm2 was 48.5% of the maximum SNR. Optimal fiber tract image quality was found for b values of 1,025s/mm2. Conclusions: The optimal b value for diffusion tensor imaging and fiber tractography of the median nerve at 1.5T was 1,025s/mm

Accuracy of magnetic resonance imaging for measuring maturing cartilage: A phantom study

OBJECTIVES: To evaluate the accuracy of magnetic resonance imaging measurements of cartilage tissue-mimicking phantoms and to determine a combination of magnetic resonance imaging parameters to optimize accuracy while minimizing scan time. METHOD: Edge dimensions from 4 rectangular agar phantoms ranging from 10.5 to 14.5 mm in length and 1.25 to 5.5 mm in width were independently measured by two readers using a steel ruler. Coronal T1 spin echo (T1 SE), fast spoiled gradient-recalled echo (FSPGR) and multiplanar gradient-recalled echo (GRE MPGR) sequences were used to obtain phantom images on a 1.5-T scanner. RESULTS: Inter- and intra-reader reliability were high for both direct measurements and for magnetic resonance imaging measurements of phantoms. Statistically significant differences were noted between the mean direct measurements and the mean magnetic resonance imaging measurements for phantom 1 when using a GRE MPGR sequence (512x512 pixels, 1.5-mm slice thickness, 5:49 min scan time), while borderline differences were noted for T1 SE sequences with the following parameters: 320x320 pixels, 1.5-mm slice thickness, 6:11 min scan time; 320x320 pixels, 4-mm slice thickness, 6:11 min scan time; and 512x512 pixels, 1.5-mm slice thickness, 9:48 min scan time. Borderline differences were also noted when using a FSPGR sequence with 512x512 pixels, a 1.5-mm slice thickness and a 3:36 min scan time. CONCLUSIONS: FSPGR sequences, regardless of the magnetic resonance imaging parameter combination used, provided accurate measurements. The GRE MPGR sequence using 512x512 pixels, a 1.5-mm slice thickness and a 5:49 min scan time and, to a lesser degree, all tested T1 SE sequences produced suboptimal accuracy when measuring the widest phantom

Ligelizumab for Chronic Spontaneous Urticaria

Background: In the majority of patients with chronic spontaneous urticaria, most currently available therapies do not result in complete symptom control. Ligelizumab is a next-generation high-affinity humanized monoclonal anti-IgE antibody. Data are limited regarding the dose–response relationship of ligelizumab and the efficacy and safety of ligelizumab as compared with omalizumab and placebo in patients who have moderate-to-severe chronic spontaneous urticaria that is inadequately controlled with H1-antihistamines at approved or increased doses, alone or in combination with H2-antihistamines or leukotriene-receptor antagonists. Methods: In a phase 2b dose-finding trial, we randomly assigned patients to receive ligelizumab at a dose of 24 mg, 72 mg, or 240 mg, omalizumab at a dose of 300 mg, or placebo, administered subcutaneously every 4 weeks for a period of 20 weeks, or a single 120-mg dose of ligelizumab. Disease symptoms of hives, itch, and angioedema were monitored by means of weekly activity scores. The main objective was to determine a dose–response relationship for the complete control of hives (indicated by a weekly hives-severity score of 0, on a scale from 0 to 21, with higher scores indicating greater severity); the primary end point of this response was assessed at week 12. Complete symptom control was indicated by a weekly urticaria activity score of 0 (on a scale from 0 to 42, with higher scores indicating greater severity). Safety was analyzed throughout the trial. Results: A total of 382 patients underwent randomization. At week 12, a total of 30%, 51%, and 42% of the patients treated with 24 mg, 72 mg, and 240 mg, respectively, of ligelizumab had complete control of hives, as compared with 26% of the patients in the omalizumab group and no patients in the placebo group. A dose–response relationship was established. At week 12, a total of 30%, 44%, and 40% of the patients treated with 24 mg, 72 mg, and 240 mg, respectively, of ligelizumab had complete control of symptoms, as compared with 26% of the patients in the omalizumab group and no patients in the placebo group. In this small and short trial, no safety concerns regarding ligelizumab or omalizumab emerged. Conclusions: A higher percentage of patients had complete control of symptoms of chronic spontaneous urticaria with ligelizumab therapy of 72 mg or 240 mg than with omalizumab or placebo. (Funded by Novartis Pharma; ClinicalTrials.gov number, NCT02477332. opens in new tab.

Coherent ultrafast torsional motion and isomerization of a biomimetic dipolar photoswitch

Femtosecond fluorescence up-conversion, UV-Vis and IR transient absorption spectroscopy are used to study the photo-isomerization dynamics of a new type of zwitterionic photoswitch based on a N-alkylated indanylidene pyrroline Schiff base framework (ZW-NAIP). The system is biomimetic, as it mimics the photophysics of retinal, in coupling excited state charge translocation and isomerization. While the fluorescence lifetime is 140 fs, excited state absorption persists over 230 fs in the form of a vibrational wavepacket according to twisting of the isomerizing double bond. After a short "dark'' time window in the UV-visible spectra, which we associate with the passage through a conical intersection (CI), the wavepacket appears on the ground state potential energy surface, as evidenced by the transient mid-IR data. This allows for a precise timing of the photoreaction all the way from the initial Franck-Condon region, through the CI and into both ground state isomers, until incoherent vibrational relaxation dominates the dynamics. The photo-reaction dynamics remarkably follow those observed for retinal in rhodopsin, with the additional benefit that in ZW-NAIP the conformational change reverses the zwitterion dipole moment direction. Last, the pronounced low-frequency coherences make these molecules ideal systems for investigating wavepacket dynamics in the vicinity of a CI and for coherent control experiments

The small RNA repertoire of Dictyostelium discoideum and its regulation by components of the RNAi pathway

Small RNAs play crucial roles in regulation of gene expression in many eukaryotes. Here, we report the cloning and characterization of 18–26 nt RNAs in the social amoeba Dictyostelium discoideum. This survey uncovered developmentally regulated microRNA candidates whose biogenesis, at least in one case, is dependent on a Dicer homolog, DrnB. Furthermore, we identified a large number of 21 nt RNAs originating from the DIRS-1 retrotransposon, clusters of which have been suggested to constitute centromeres. Small RNAs from another retrotransposon, Skipper, were significantly up-regulated in strains depleted of the second Dicer-like protein, DrnA, and a putative RNA-dependent RNA polymerase, RrpC. In contrast, the expression of DIRS-1 small RNAs was not altered in any of the analyzed strains. This suggests the presence of multiple RNAi pathways in D. discoideum. In addition, we isolated several small RNAs with antisense complementarity to mRNAs. Three of these mRNAs are developmentally regulated. Interestingly, all three corresponding genes express longer antisense RNAs from which the small RNAs may originate. In at least one case, the longer antisense RNA is complementary to the spliced but not the unspliced pre-mRNA, indicating synthesis by an RNA-dependent RNA polymerase