Maximum Spherical Mean Value (mSMV) Filtering for Whole Brain Quantitative Susceptibility Mapping

To develop a tissue field filtering algorithm, called maximum Spherical Mean Value (mSMV), for reducing shadow artifacts in quantitative susceptibility mapping (QSM) of the brain without requiring brain tissue erosion.Residual background field is a major source of shadow artifacts in QSM. The mSMV algorithm filters large field values near the border, where the maximum value of the harmonic background field is located. The effectiveness of mSMV for artifact removal was evaluated by comparing with existing QSM algorithms in numerical brain simulation as well as using in vivo human data acquired from 11 healthy volunteers and 93 patients. Numerical simulation showed that mSMV reduces shadow artifacts and improves QSM accuracy. Better shadow reduction, as demonstrated by lower QSM variation in the gray matter and higher QSM image quality score, was also observed in healthy subjects and in patients with hemorrhages, stroke and multiple sclerosis. The mSMV algorithm allows QSM maps that are substantially equivalent to those obtained using SMV-filtered dipole inversion without eroding the volume of interest.Comment: 12 pages, 5 figure

Bone quantitative susceptibility mapping using a chemical species-specific R2* signal model with ultrashort and conventional echo data.

PurposeTo develop quantitative susceptibility mapping (QSM) of bone using an ultrashort echo time (UTE) gradient echo (GRE) sequence for signal acquisition and a bone-specific effective transverse relaxation rate ( R2*) to model water-fat MR signals for field mapping.MethodsThree-dimensional radial UTE data (echo times ≥ 40 μs) was acquired on a 3 Tesla scanner and fitted with a bone-specific signal model to map the chemical species and susceptibility field. Experiments were performed ex vivo on a porcine hoof and in vivo on healthy human subjects (n = 7). For water-fat separation, a bone-specific model assigning R2* decay mostly to water was compared with the standard models that assigned the same decay for both fat and water. In the ex vivo experiment, bone QSM was correlated with CT.ResultsCompared with standard models, the bone-specific R2* method significantly reduced errors in the fat fraction within the cortical bone in all tested data sets, leading to reduced artifacts in QSM. Good correlation was found between bone CT and QSM values in the porcine hoof (R2  = 0.77). Bone QSM was successfully generated in all subjects.ConclusionsThe QSM of bone is feasible using UTE with a conventional echo time GRE acquisition and a bone-specific R2* signal model. Magn Reson Med 79:121-128, 2018. © 2017 International Society for Magnetic Resonance in Medicine

In Situ and Real-Time Studies, via Synchrotron X‑ray Scattering, of the Orientational Order of Cellulose Nanocrystals during Solution Shearing

In this manuscript, we report on the ordering of the cellulose nanocrystals (CNCs) as they experience shear forces during the casting process. To achieve these measurements, in situ and in real time, we used synchrotron-based grazing incidence wide-angle X-ray scattering (GIWAX). We believe that the GIWAX technique, although not commonly used to probe these types of phenomena, can open new avenues to gain deeper insights into film formation processes and surface-driven phenomena. In particular, we investigated the influence of solution concentration, shear-cast velocity, and drying temperature on the ordering of cellulose nanocrystals (CNCs) using GIWAXS. The films were prepared from aqueous suspensions of cellulose nanocrystals at two concentration values (7 and 9 wt %). As the films were cast, the X-ray beam was focused on a fixed position and GIWAXS patterns were recorded at regular time intervals. Structural characterization of the dry films was carried out via polarized optical microscopy and scanning electron microscopy. In addition, a rheological study of the CNC suspensions was performed. Our results show that the morphology of the CNC films was significantly influenced by shear velocity, concentration of the precursor suspension, and evaporation temperature. In contrast, we observed that the orientation parameter of the films was not significantly affected. The scattering intensity of the peak (200) was analyzed as a function of time, following a sigmoidal profile, hence indicating short- and long-range interactions within the anisotropic domains as they reached their final orientation state. A model capable of describing the resulting film morphologies is also proposed. The results and analysis presented in this manuscript provide new insights into the controlled alignment of cellulose nanocrystals under shear. This controlled alignment has significant implications in the development of advanced coatings and films currently used in a myriad of applications, such as catalysis, optics, electronics, and biomedicine

Ticagrelor in patients with diabetes and stable coronary artery disease with a history of previous percutaneous coronary intervention (THEMIS-PCI) : a phase 3, placebo-controlled, randomised trial

Background: Patients with stable coronary artery disease and diabetes with previous percutaneous coronary intervention (PCI), particularly those with previous stenting, are at high risk of ischaemic events. These patients are generally treated with aspirin. In this trial, we aimed to investigate if these patients would benefit from treatment with aspirin plus ticagrelor. Methods: The Effect of Ticagrelor on Health Outcomes in diabEtes Mellitus patients Intervention Study (THEMIS) was a phase 3 randomised, double-blinded, placebo-controlled trial, done in 1315 sites in 42 countries. Patients were eligible if 50 years or older, with type 2 diabetes, receiving anti-hyperglycaemic drugs for at least 6 months, with stable coronary artery disease, and one of three other mutually non-exclusive criteria: a history of previous PCI or of coronary artery bypass grafting, or documentation of angiographic stenosis of 50% or more in at least one coronary artery. Eligible patients were randomly assigned (1:1) to either ticagrelor or placebo, by use of an interactive voice-response or web-response system. The THEMIS-PCI trial comprised a prespecified subgroup of patients with previous PCI. The primary efficacy outcome was a composite of cardiovascular death, myocardial infarction, or stroke (measured in the intention-to-treat population). Findings: Between Feb 17, 2014, and May 24, 2016, 11 154 patients (58% of the overall THEMIS trial) with a history of previous PCI were enrolled in the THEMIS-PCI trial. Median follow-up was 3·3 years (IQR 2·8–3·8). In the previous PCI group, fewer patients receiving ticagrelor had a primary efficacy outcome event than in the placebo group (404 [7·3%] of 5558 vs 480 [8·6%] of 5596; HR 0·85 [95% CI 0·74–0·97], p=0·013). The same effect was not observed in patients without PCI (p=0·76, p interaction=0·16). The proportion of patients with cardiovascular death was similar in both treatment groups (174 [3·1%] with ticagrelor vs 183 (3·3%) with placebo; HR 0·96 [95% CI 0·78–1·18], p=0·68), as well as all-cause death (282 [5·1%] vs 323 [5·8%]; 0·88 [0·75–1·03], p=0·11). TIMI major bleeding occurred in 111 (2·0%) of 5536 patients receiving ticagrelor and 62 (1·1%) of 5564 patients receiving placebo (HR 2·03 [95% CI 1·48–2·76], p<0·0001), and fatal bleeding in 6 (0·1%) of 5536 patients with ticagrelor and 6 (0·1%) of 5564 with placebo (1·13 [0·36–3·50], p=0·83). Intracranial haemorrhage occurred in 33 (0·6%) and 31 (0·6%) patients (1·21 [0·74–1·97], p=0·45). Ticagrelor improved net clinical benefit: 519/5558 (9·3%) versus 617/5596 (11·0%), HR=0·85, 95% CI 0·75–0·95, p=0·005, in contrast to patients without PCI where it did not, p interaction=0·012. Benefit was present irrespective of time from most recent PCI. Interpretation: In patients with diabetes, stable coronary artery disease, and previous PCI, ticagrelor added to aspirin reduced cardiovascular death, myocardial infarction, and stroke, although with increased major bleeding. In that large, easily identified population, ticagrelor provided a favourable net clinical benefit (more than in patients without history of PCI). This effect shows that long-term therapy with ticagrelor in addition to aspirin should be considered in patients with diabetes and a history of PCI who have tolerated antiplatelet therapy, have high ischaemic risk, and low bleeding risk

Cardiac myosin activation with omecamtiv mecarbil in systolic heart failure

BACKGROUND The selective cardiac myosin activator omecamtiv mecarbil has been shown to improve cardiac function in patients with heart failure with a reduced ejection fraction. Its effect on cardiovascular outcomes is unknown. METHODS We randomly assigned 8256 patients (inpatients and outpatients) with symptomatic chronic heart failure and an ejection fraction of 35% or less to receive omecamtiv mecarbil (using pharmacokinetic-guided doses of 25 mg, 37.5 mg, or 50 mg twice daily) or placebo, in addition to standard heart-failure therapy. The primary outcome was a composite of a first heart-failure event (hospitalization or urgent visit for heart failure) or death from cardiovascular causes. RESULTS During a median of 21.8 months, a primary-outcome event occurred in 1523 of 4120 patients (37.0%) in the omecamtiv mecarbil group and in 1607 of 4112 patients (39.1%) in the placebo group (hazard ratio, 0.92; 95% confidence interval [CI], 0.86 to 0.99; P = 0.03). A total of 808 patients (19.6%) and 798 patients (19.4%), respectively, died from cardiovascular causes (hazard ratio, 1.01; 95% CI, 0.92 to 1.11). There was no significant difference between groups in the change from baseline on the Kansas City Cardiomyopathy Questionnaire total symptom score. At week 24, the change from baseline for the median N-terminal pro-B-type natriuretic peptide level was 10% lower in the omecamtiv mecarbil group than in the placebo group; the median cardiac troponin I level was 4 ng per liter higher. The frequency of cardiac ischemic and ventricular arrhythmia events was similar in the two groups. CONCLUSIONS Among patients with heart failure and a reduced ejection, those who received omecamtiv mecarbil had a lower incidence of a composite of a heart-failure event or death from cardiovascular causes than those who received placebo. (Funded by Amgen and others; GALACTIC-HF ClinicalTrials.gov number, NCT02929329; EudraCT number, 2016 -002299-28.)