Ultra-short echo time cardiovascular magnetic resonance of atherosclerotic carotid plaque.

BACKGROUND: Multi-contrast weighted cardiovascular magnetic resonance (CMR) allows detailed plaque characterisation and assessment of plaque vulnerability. The aim of this preliminary study was to show the potential of Ultra-short Echo Time (UTE) subtraction MR in detecting calcification. METHODS: 14 ex-vivo human carotid arteries were scanned using CMR and CT, prior to histological slide preparation. Two images were acquired using a double-echo 3D UTE pulse, one with a long TE and the second with an ultra-short TE, with the same TR. An UTE subtraction (DeltaUTE) image containing only ultra-short T2 (and T2*) signals was obtained by post-processing subtraction of the 2 UTE images. The DeltaUTE image was compared to the conventional 3D T1-weighted sequence and CT scan of the carotid arteries. RESULTS: In atheromatous carotid arteries, there was a 71% agreement between the high signal intensity areas on DeltaUTE images and CT scan. The same areas were represented as low signal intensity on T1W and areas of void on histology, indicating focal calcification. However, in 15% of all the scans there were some incongruent regions of high intensity on DeltaUTE that did not correspond with a high intensity signal on CT, and histology confirmed the absence of calcification. CONCLUSIONS: We have demonstrated that the UTE sequence has potential to identify calcified plaque. Further work is needed to fully understand the UTE findings

A multi-center inter-manufacturer study of the temporal stability of phase-contrast velocity mapping background offset errors.

BACKGROUND: Phase-contrast velocity images often contain a background or baseline offset error, which adds an unknown offset to the measured velocities. For accurate flow measurements, this offset must be shown negligible or corrected. Some correction techniques depend on replicating the clinical flow acquisition using a uniform stationary phantom, in order to measure the baseline offset at the region of interest and subtract it from the clinical study. Such techniques assume that the background offset is stable over the time of a patient scan, or even longer if the phantom scans are acquired later, or derived from pre-stored background correction images. There is no published evidence regarding temporal stability of the background offset. METHODS: This study assessed the temporal stability of the background offset on 3 different manufacturers' scanners over 8 weeks, using a retrospectively-gated phase-contrast cine acquisition with fixed parameters and at a fixed location, repeated 5 times in rapid succession each week. A significant offset was defined as 0.6 cm/s within 50 mm of isocenter, based upon an accuracy of 10% in a typical cardiac shunt measurement. RESULTS: Over the 5 repeated cine acquisitions, temporal drift in the baseline offset was insignificant on two machines (0.3 cm/s, 0.2 cm/s), and marginally insignificant on the third machine (0.5 cm/s) due to an apparent heating effect. Over a longer timescale of 8 weeks, insignificant drift (0.4 cm/s) occurred on one, with larger drifts (0.9 cm/s, 0.6 cm/s) on the other machines. CONCLUSIONS: During a typical patient study, background drift was insignificant. Extended high gradient power scanning with work requires care to avoid drift on some machines. Over the longer term of 8 weeks, significant drift is likely, preventing accurate correction by delayed phantom corrections or derivation from pre-stored background offset data.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

Assessment of myocardial microstructural dynamics by in vivo diffusion tensor cardiac magnetic resonance

Background: Cardiomyocytes are organized in microstructures termed sheetlets that reorientate during left ventricular thickening. Diffusion tensor cardiac magnetic resonance (DT-CMR) may enable noninvasive interrogation of in vivo cardiac microstructural dynamics. Dilated cardiomyopathy (DCM) is a condition of abnormal myocardium with unknown sheetlet function. Objectives: This study sought to validate in vivo DT-CMR measures of cardiac microstructure against histology, characterize microstructural dynamics during left ventricular wall thickening, and apply the technique in hypertrophic cardiomyopathy (HCM) and DCM. Methods: In vivo DT-CMR was acquired throughout the cardiac cycle in healthy swine, followed by in situ and ex vivo DT-CMR, then validated against histology. In vivo DT-CMR was performed in 19 control subjects, 19 DCM, and 13 HCM patients. Results: In swine, a DT-CMR index of sheetlet reorientation (E2A) changed substantially (E2A mobility ∼46°). E2A changes correlated with wall thickness changes (in vivo r2 = 0.75; in situ r2 = 0.89), were consistently observed under all experimental conditions, and accorded closely with histological analyses in both relaxed and contracted states. The potential contribution of cyclical strain effects to in vivo E2A was ∼17%. In healthy human control subjects, E2A increased from diastole (18°) to systole (65°; p < 0.001; E2A mobility = 45°). HCM patients showed significantly greater E2A in diastole than control subjects did (48°; p < 0.001) with impaired E2A mobility (23°; p < 0.001). In DCM, E2A was similar to control subjects in diastole, but systolic values were markedly lower (40°; p < 0.001) with impaired E2A mobility (20°; p < 0.001). Conclusions: Myocardial microstructure dynamics can be characterized by in vivo DT-CMR. Sheetlet function was abnormal in DCM with altered systolic conformation and reduced mobility, contrasting with HCM, which showed reduced mobility with altered diastolic conformation. These novel insights significantly improve understanding of contractile dysfunction at a level of noninvasive interrogation not previously available in humans

The influence of the atmospheric boundary layer on nocturnal layers of noctuids and other moths migrating over southern Britain

Insects migrating at high altitude over southern Britain have been continuously monitored by automatically-operating, vertical-looking radars over a period of several years. During some occasions in the summer months, the migrants were observed to form well-defined layer concentrations, typically at heights of 200-400 m, in the stable night-time atmosphere. Under these conditions, insects are likely to have control over their vertical movements and are selecting flight heights which are favourable for long-range migration. We therefore investigated the factors influencing the formation of these insect layers by comparing radar measurements of the vertical distribution of insect density with meteorological profiles generated by the UK Met. Office’s Unified Model (UM). Radar-derived measurements of mass and displacement speed, along with data from Rothamsted Insect Survey light traps provided information on the identity of the migrants. We present here three case studies where noctuid and pyralid moths contributed substantially to the observed layers. The major meteorological factors influencing the layer concentrations appeared to be: (a) the altitude of the warmest air, (b) heights corresponding to temperature preferences or thresholds for sustained migration and (c), on nights when air temperatures are relatively high, wind-speed maxima associated with the nocturnal jet. Back-trajectories indicated that layer duration may have been determined by the distance to the coast. Overall, the unique combination of meteorological data from the UM and insect data from entomological radar described here show considerable promise for systematic studies of high-altitude insect layering

Potential effects of oilseed rape expressing oryzacystatin-1 (OC-1) and of purified insecticidal proteins on larvae of the solitary bee Osmia bicornis

Despite their importance as pollinators in crops and wild plants, solitary bees have not previously been included in non-target testing of insect-resistant transgenic crop plants. Larvae of many solitary bees feed almost exclusively on pollen and thus could be highly exposed to transgene products expressed in the pollen. The potential effects of pollen from oilseed rape expressing the cysteine protease inhibitor oryzacystatin-1 (OC-1) were investigated on larvae of the solitary bee Osmia bicornis (= O. rufa). Furthermore, recombinant OC-1 (rOC-1), the Bt toxin Cry1Ab and the snowdrop lectin Galanthus nivalis agglutinin (GNA) were evaluated for effects on the life history parameters of this important pollinator. Pollen provisions from transgenic OC-1 oilseed rape did not affect overall development. Similarly, high doses of rOC-1 and Cry1Ab as well as a low dose of GNA failed to cause any significant effects. However, a high dose of GNA (0.1%) in the larval diet resulted in significantly increased development time and reduced efficiency in conversion of pollen food into larval body weight. Our results suggest that OC-1 and Cry1Ab expressing transgenic crops would pose a negligible risk for O. bicornis larvae, whereas GNA expressing plants could cause detrimental effects, but only if bees were exposed to high levels of the protein. The described bioassay with bee brood is not only suitable for early tier non-target tests of transgenic plants, but also has broader applicability to other crop protection products

Sequence optimization to reduce velocity offsets in cardiovascular magnetic resonance volume flow quantification--a multi-vendor study.

PURPOSE: Eddy current induced velocity offsets are of concern for accuracy in cardiovascular magnetic resonance (CMR) volume flow quantification. However, currently known theoretical aspects of eddy current behavior have not led to effective guidelines for the optimization of flow quantification sequences. This study is aimed at identifying correlations between protocol parameters and the resulting velocity error in clinical CMR flow measurements in a multi-vendor study. METHODS: Nine 1.5T scanners of three different types/vendors were studied. Measurements were performed on a large stationary phantom. Starting from a clinical breath-hold flow protocol, several protocol parameters were varied. Acquisitions were made in three clinically relevant orientations. Additionally, a time delay between the bipolar gradient and read-out, asymmetric versus symmetric velocity encoding, and gradient amplitude and slew rate were studied in adapted sequences as exploratory measurements beyond the protocol. Image analysis determined the worst-case offset for a typical great-vessel flow measurement. RESULTS: The results showed a great variation in offset behavior among scanners (standard deviation among samples of 0.3, 0.4, and 0.9 cm/s for the three different scanner types), even for small changes in the protocol. Considering the absolute values, none of the tested protocol settings consistently reduced the velocity offsets below the critical level of 0.6 cm/s neither for all three orientations nor for all three scanner types. Using multilevel linear model analysis, oblique aortic and pulmonary slices showed systematic higher offsets than the transverse aortic slices (oblique aortic 0.6 cm/s, and pulmonary 1.8 cm/s higher than transverse aortic). The exploratory measurements beyond the protocol yielded some new leads for further sequence development towards reduction of velocity offsets; however those protocols were not always compatible with the time-constraints of breath-hold imaging and flow-related artefacts. CONCLUSIONS: This study showed that with current systems there was no generic protocol which resulted into acceptable flow offset values. Protocol optimization would have to be performed on a per scanner and per protocol basis. Proper optimization might make accurate (transverse) aortic flow quantification possible for most scanners. Pulmonary flow quantification would still need further (offline) correction.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

Fusion to snowdrop lectin magnifies the oral activity of insecticidal omega-Hexatoxin-Hv1a peptide by enabling its delivery to the central nervous system

Background: The spider-venom peptide v-hexatoxin-Hv1a (Hv1a) targets insect voltage-gated calcium channels, acting directly at sites within the central nervous system. It is potently insecticidal when injected into a wide variety of insect pests, but it has limited oral toxicity. We examined the ability of snowdrop lectin (GNA), which is capable of traversing the insect gut epithelium, to act as a ‘‘carrier’’ in order to enhance the oral activity of Hv1a. Methodology/Principal Findings: A synthetic Hv1a/GNA fusion protein was produced by recombinant expression in the yeast Pichia pastoris. When injected into Mamestra brassicae larvae, the insecticidal activity of the Hv1a/GNA fusion protein was similar to that of recombinant Hv1a. However, when proteins were delivered orally via droplet feeding assays, Hv1a/ GNA, but not Hv1a alone, caused a significant reduction in growth and survival of fifth stadium Mamestra brassicae (cabbage moth) larvae. Feeding second stadium larvae on leaf discs coated with Hv1a/GNA (0.1–0.2% w/v) caused $80% larval mortality within 10 days, whereas leaf discs coated with GNA (0.2% w/v) showed no acute effects. Intact Hv1a/GNA fusion protein was delivered to insect haemolymph following ingestion, as shown by Western blotting. Immunoblotting of nerve chords dissected from larvae following injection of GNA or Hv1a/GNA showed high levels of bound proteins. When insects were injected with, or fed on, fluorescently labelled GNA or HV1a/GNA, fluorescence was detected specifically associated with the central nerve chord. Conclusions/Significance: In addition to mediating transport of Hv1a across the gut epithelium in lepidopteran larvae, GNA is also capable of delivering Hv1a to sites of action within the insect central nervous system. We propose that fusion to GNA provides a general mechanism for dramatically enhancing the oral activity of insecticidal peptides and proteins

Effect of insecticidal fusion proteins containing spider toxins targeting sodium and calcium ion channels on pyrethroid-resistant strains of peach-potato aphid (Myzus persicae)

BACKGROUND: The recombinant fusion proteins Pl1a/GNA and Hv1a/GNA contain the spider venom peptides δ-amaurobitoxin-PI1a or ω-hexatoxin-Hv1a respectively, linked to snowdrop lectin (GNA). Pl1a targets receptor site 4 of insect voltage-gated sodium channels (NaCh), while Hv1a targets voltage-gated calcium channels. Insecticide-resistant strains of peach-potato aphid (Myzus persicae) contain mutations in NaCh. The pyrethroid-resistant kdr (794J) and super-kdr (UKO) strains contain mutations at residues L1014 and M918 in the channel α-subunit respectively, while the kdr + super-kdr strain (4824J), insensitive to pyrethroids, contains mutations at both L1014 and M918. RESULTS: Pl1a/GNA and Hv1a/GNA fusion proteins have estimated LC50 values of 0.35 and 0.19 mg mL−1 when fed to wild-type M. persicae. For insecticide-resistant aphids, LC50 for the Pl1a/GNA fusion protein increased by 2–6-fold, correlating with pyrethroid resistance (wild type < kdr < super-kdr < kdr + super-kdr strains). In contrast, LC50 for the Hv1a/GNA fusion protein showed limited correlation with pyrethroid resistance. CONCLUSION: Mutations in the sodium channel in pyrethroid-resistant aphids also protect against a fusion protein containing a sodium-channel-specific toxin, in spite of differences in ligand–channel interactions, but do not confer resistance to a fusion protein targeting calcium channels. The use of fusion proteins with differing targets could play a role in managing pesticide resistance

Synthetic velocity mapping cardiac MRI coupled with automated left ventricle segmentation

Temporal patterns of cardiac motion provide important information for cardiac disease diagnosis. This pattern could be obtained by three-directional CINE multi-slice left ventricular myocardial velocity mapping (3Dir MVM), which is a cardiac MR technique providing magnitude and phase information of the myocardial motion simultaneously. However, long acquisition time limits the usage of this technique by causing breathing artifacts, while shortening the time causes low temporal resolution and may provide an inaccurate assessment of cardiac motion. In this study, we proposed a frame synthesis algorithm to increase the temporal resolution of 3Dir MVM data. Our algorithm is featured by 1) three attention-based encoders which accept magnitude images, phase images, and myocardium segmentation masks respectively as inputs; 2) three decoders that output the interpolated frames and corresponding myocardium segmentation results; and 3) loss functions highlighting myocardium pixels. Our algorithm can not only increase the temporal resolution 3Dir MVMs, but can also generates the myocardium segmentation results at the same time