Simultaneous mapping of temporally-resolved blood flow velocity and oxygenation in femoral artery and vein during reactive hyperemia

<p>Abstract</p> <p>Background</p> <p>Post-occlusive hyperemia is often used as a paradigm to evaluate vascular reactivity, for example by measuring post-ischemic flow-mediated dilation, arterial blood flow or temporally resolved venous blood oxygenation (HbO₂). Here we demonstrate the feasibility of a simultaneous measurement of blood flow and HbO₂in the femoral circulation as part of a single procedure.</p> <p>Methods</p> <p>A multi-echo GRE pulse sequence was designed and implemented to collect velocity-encoded projections in addition to full-image echoes for field mapping as a means to quantify intravascular magnetic susceptibility. The method's feasibility was evaluated at 3T in a small pilot study involving two groups of healthy subjects (mean ages 26 ± 1.6 and 59 ± 7.3 years, N = 7 and 5, respectively) in terms of six parameters characterizing the time-course of reactive hyperemia and their sensitivity to differentiate age effects. The reproducibility was assessed on two of the seven young healthy subjects with three repeated measurements.</p> <p>Results</p> <p>The physiological parameters agree with those obtained with current methods that quantify either velocity or HbO₂alone. Of the six measures of vascular reactivity, one from each group was significantly different in the two subject groups (p < 0.05) even though the study was not powered to detect differences. The mean coefficient of variation (CV) from two subjects undergoing repeat scans were approximately 8% for the oximetric and the arterial velocimetric parameters in the femoral vein and artery, respectively, considerably below intersubject CVs (20 and 35%, for the young and older subject groups, respectively).</p> <p>Conclusion</p> <p>The proposed method is able quantify multiple parameters that may lead to more detailed assessment of peripheral vascular reactivity in a single cuff paradigm rather than in separate procedures as required previously, thereby improving measurement efficiency and patient comfort.</p

Late Glacial and Holocene temperature changes at Egelsee, Switzerland, reconstructed using subfossil chironomids

A temperature reconstruction using chironomids was attempted at Egelsee, Switzerland, a site where pollen and macrofossil records showed a correspondence between vegetation and climatic changes inferred by other proxies in Europe. The general pattern of temperature changes inferred from chironomids during the Late Glacial [i.e. cold temperatures between ca. 16,500 and 14,800cal BP, close to present-day temperature between 15,000 and 13,000cal BP and colder temperatures during the Younger Dryas (YD)], and the major temperature changes of the Holocene (i.e. the Younger Dryas-Holocene transition and the Late Holocene cooling trend) at Egelsee, were mirrored in other European climate reconstructions using various proxies. However, the amplitude of temperature changes during the YD was smaller than reconstructed by other proxies at various sites, and the 8,200years BP event was not apparent. These differences between records were probably due to the dominance of Corynocera ambigua, with percentages reaching 60% in parts of the Egelsee sequence. This taxon was not present in any of the 103 lakes used for the transfer function and its absence may have yielded less accurate inferences. Its presence in samples only associated with cold inferences at Egelsee suggests that this taxon is a cold indicator. However, it was also found in warm Danish lakes and the factors that determine the presence of C. ambigua remain unexplained. Most samples had a poor fit to temperature and instead, dissolved organic carbon seemed to be a factor influencing the chironomid assemblages during the Holocene. These results illustrate the need to better understand the ecology of chironomids and to disentangle the various factors that affect chironomid communities through time. Ultimately, such information will lead to more accurate temperature reconstruction

Non-triggered quantification of central and peripheral pulse-wave velocity

<p>Abstract</p> <p>Purpose</p> <p>Stiffening of the arteries results in increased pulse-wave velocity (PWV), the propagation velocity of the blood. Elevated aortic PWV has been shown to correlate with aging and atherosclerotic alterations. We extended a previous non-triggered projection-based cardiovascular MR method and demonstrate its feasibility by mapping the PWV of the aortic arch, thoraco-abdominal aorta and iliofemoral arteries in a cohort of healthy adults.</p> <p>Materials and Methods</p> <p>The proposed method "simultaneously" excites and collects a series of velocity-encoded projections at two arterial segments to estimate the wave-front velocity, which inherently probes the high-frequency component of the dynamic vessel wall modulus in response to oscillatory pressure waves. The regional PWVs were quantified in a small pilot study in healthy subjects (N = 10, age range 23 to 68 yrs) at 3T.</p> <p>Results</p> <p>The projection-based method successfully time-resolved regional PWVs for 8-10 cardiac cycles without gating and demonstrated the feasibility of monitoring beat-to-beat changes in PWV resulting from heart rate irregularities. For dul-slice excitation the aliasing was negligible and did not interfere with PWV quantification. The aortic arch and thoracoabdominal aorta PWV were positively correlated with age (p < 0.05), consistent with previous reports. On the other hand, the PWV of the iliofemoral arteries showed decreasing trend with age, which has been associated with the weakening of muscular arteries, a natural aging process.</p> <p>Conclusion</p> <p>The PWV map of the arterial tree from ascending aorta to femoral arteries may provide additional insight into pathophysiology of vascular aging and atherosclerosis.</p

Abrupt onset of carbonate deposition in Lake Kivu during the 1960s: response to recent environmental changes

This study interprets the recent history of Lake Kivu, a tropical lake in the East African Rift Valley. The current gross sedimentation was characterized from a moored sediment trap array deployed over 2years. The past net sedimentation was investigated with three short cores from two different basins. Diatom assemblages from cores were interpreted as reflecting changes in mixing depth, surface salinity and nutrient availability. The contemporary sediment trap data indicate seasonal variability, governed by diatom blooms during the annual mixing in the dry season, similar to Lakes Malawi and Tanganyika. The ratio of settling fluxes to net sediment accumulation rates implies mineralization rates of 80-90% at the sediment-water interface. The sediment cores revealed an abrupt change ~40years ago, when carbonate precipitation started. Since the 1960s, deep-water methane concentrations, nutrient fluxes and soil mineral inputs have increased considerably and diatom assemblages have altered. These modifications probably resulted from a combination of three factors, commonly altering lake systems: the introduction of a non-native fish species, eutrophication, and hydrological changes inducing greater upwelling. Both the fish introduction and increased rainfall occurred at the time when the onset of carbonate precipitation was observed, whereas catchment population growth accompanied by intensified land use increased the flux of soil minerals already since the early twentieth century due to more intense erosio

Abrupt onset of carbonate deposition in Lake Kivu during the 1960s: response to recent environmental changes

This study interprets the recent history of Lake Kivu, a tropical lake in the East African Rift Valley. The current gross sedimentation was characterized from a moored sediment trap array deployed over 2 years. The past net sedimentation was investigated with three short cores from two different basins. Diatom assemblages from cores were interpreted as reflecting changes in mixing depth, surface salinity and nutrient availability. The contemporary sediment trap data indicate seasonal variability, governed by diatom blooms during the annual mixing in the dry season, similar to Lakes Malawi and Tanganyika. The ratio of settling fluxes to net sediment accumulation rates implies mineralization rates of 80–90% at the sediment-water interface. The sediment cores revealed an abrupt change ~40 years ago, when carbonate precipitation started. Since the 1960s, deep-water methane concentrations, nutrient fluxes and soil mineral inputs have increased considerably and diatom assemblages have altered. These modifications probably resulted from a combination of three factors, commonly altering lake systems: the introduction of a non-native fish species, eutrophication, and hydrological changes inducing greater upwelling. Both the fish introduction and increased rainfall occurred at the time when the onset of carbonate precipitation was observed, whereas catchment population growth accompanied by intensified land use increased the flux of soil minerals already since the early twentieth century due to more intense erosion

Influence of human impact and bedrock differences on the vegetational history of the Insubrian Southern Alps

Vegetation history for the study region is reconstructed on the basis of pollen, charcoal and AMS14C investigations of lake sediments from Lago del Segrino (calcareous bedrock) and Lago di Muzzano (siliceous bedrock). Late-glacial forests were characterised byBetula andPinus sylvestris. At the beginning of the Holocene they were replaced by temperate continental forest and shrub communities. A special type of temperate lowland forest, withAbies alba as the most important tree, was present in the period 8300 to 4500 B.P. Subsequently,Fagus, Quercus andAlnus glutinosa were the main forest components andA. alba ceased to be of importance.Castanea sativa andJuglans regia were probably introduced after forest clearance by fire during the first century A.D. On soils derived from siliceous bedrock,C. sativa was already dominant at ca. A.D. 200 (A.D. dates are in calendar years). In limestone areas, however,C. sativa failed to achieve a dominant role. After the introduction ofC. sativa, the main trees were initially oak (Quercus spp.) and later the walnut (Juglans regia). Ostrya carpinifolia became the dominant tree around Lago del Segrino only in the last 100–200 years though it had spread into the area at ca. 5000 cal. B.C. This recent expansion ofOstrya is confirmed at other sites and appears to be controlled by human disturbances involving especially clearance. It is argued that these forests should not be regarded as climax communities. It is suggested that under undisturbed succession they would develop into mixed deciduous forests consisting ofFraxinus excelsior, Tilia, Ulmus, Quercus and Acer

A Noninvasive Method for Quantifying Cerebral Metabolic Rate of Oxygen by Hybrid PET/MRI: Validation in a Porcine Model

The gold standard for imaging the cerebral metabolic rate of oxygen (CMRO2) is positron emission tomography (PET); however, it is an invasive and complex procedure that also requires correction for recirculating 15O-H2O and the blood-borne activity. We propose a noninvasive reference-based hybrid PET/magnetic resonance imaging (MRI) method that uses functional MRI techniques to calibrate 15O-O2-PET data. Here, PET/MR imaging of oxidative metabolism (PMROx) was validated in an animal model by comparison to PET-alone measurements. Additionally, we investigated if the MRI-perfusion technique arterial spin labelling (ASL) could be used to further simplify PMROx by replacing 15O-H2O-PET, and if the PMROx was sensitive to anesthetics-induced changes in metabolism. Methods: 15O-H2O and 15O-O2 PET data were acquired in a hybrid PET/MR scanner (3 T Siemens Biograph mMR), together with simultaneous functional MRI (OxFlow and ASL), from juvenile pigs (n = 9). Animals were anesthetized with 3% isoflurane and 6 mL/kg/h propofol for the validation experiments and arterial sampling was performed for PET-alone measurements. PMROx estimates were obtained using whole-brain (WB) CMRO2 from OxFlow and local cerebral blood flow (CBF) from either noninvasive 15O-H2O-PET or ASL (PMROxASL). Changes in metabolism were investigated by increasing the propofol infusion to 20 mL/kg/h. Results: Good agreement and correlation were observed between regional CMRO2 measurements from PMROx and PET-alone. No significant differences were found between OxFlow and PET-only measurements of WB oxygen extraction fraction (0.30 ± 0.09 and 0.31 ± 0.09) and CBF (54.1 ± 16.7 and 56.6 ± 21.0 mL/100 g/min), or between PMROx and PET-only CMRO2 estimates (1.89 ± 0.16 and 1.81 ± 0.10 mLO2/100 g/min). Moreover, PMROx and PMROxASL were sensitive to propofol-induced reduction in CMRO2 Conclusion: This study provides initial validation of a noninvasive PET/MRI technique that circumvents many of the complexities of PET CMRO2 imaging. PMROx does not require arterial sampling and has the potential to reduce PET imaging to 15O-O2 only; however, future validation involving human participants are required

Niclosamide Suppresses Cancer Cell Growth By Inducing Wnt Co-Receptor LRP6 Degradation and Inhibiting the Wnt/β-Catenin Pathway

The Wnt/β-catenin signaling pathway is important for tumor initiation and progression. The low density lipoprotein receptor-related protein-6 (LRP6) is an essential Wnt co-receptor for Wnt/β-catenin signaling and represents a promising anticancer target. Recently, the antihelminthic drug, niclosamide was found to inhibit Wnt/β-catenin signaling, although the mechanism was not well defined. We found that niclosamide was able to suppress LRP6 expression and phosphorylation, block Wnt3A-induced β-catenin accumulation, and inhibit Wnt/β-catenin signaling in HEK293 cells. Furthermore, the inhibitory effects of niclosamide on LRP6 expression/phosphorylation and Wnt/β-catenin signaling were conformed in human prostate PC-3 and DU145 and breast MDA-MB-231 and T-47D cancer cells. Moreover, we showed that the mechanism by which niclosamide suppressed LRP6 resulted from increased degradation as evident by a shorter half-life. Finally, we demonstrated that niclosamide was able to induce cancer cell apoptosis, and displayed excellent anticancer activity with IC50 values less than 1 µM for prostate PC-3 and DU145 and breast MDA-MB-231 and T-47D cancer cells. The IC50 values are comparable to those shown to suppress the activities of Wnt/β-catenin signaling in prostate and breast cancer cells. Our data indicate that niclosamide is a unique small molecule Wnt/β-catenin signaling inhibitor targeting the Wnt co-receptor LRP6 on the cell surface, and that niclosamide has a potential to be developed a novel chemopreventive or therapeutic agent for human prostate and breast cancer