Identifying vulnerable carotid plaques in vivo using high resolution magnetic resonance imaging-based finite element analysis

Object. Individuals with carotid atherosclerosis develop symptoms following rupture of vulnerable plaques. Biomechanical stresses within this plaque may increase vulnerability to rupture. In this report the authors describe the use of in vivo carotid plaque imaging and computational mechanics to document the magnitude and distribution of intrinsic plaque stresses. Methods. Ten (five symptomatic and five asymptomatic) individuals underwent plaque characterization magnetic resonance (MR) imaging. Plaque geometry and composition were determined by multisequence review. Intrinsic plaque stress profiles were generated from 3D meshes by using finite element computational analysis. Differences in principal (shear) stress between normal and diseased sections of the carotid artery and between symptomatic and asymptomatic plaques were noted. Results. There was a significant difference in peak principal stress between diseased and nondiseased segments of the artery (mean difference 537.65 kPa, p < 0.05). Symptomatic plaques had higher mean stresses than asymptomatic plaques (627.6 kPa compared with 370.2 kPa, p = 0.05), which were independent of luminal stenosis and plaque composition. Conclusions. Significant differences in plaque stress exist between plaques from symptomatic individuals and those from asymptomatic individuals. The MR imaging-based computational analysis may therefore be a useful aid to identification of vulnerable plaques in vivo.

Structural analysis and magnetic resonance imaging predict plaque vulnerability: A study comparing symptomatic and asymptomatic individuals

Background: More than half of all cerebral ischemic events are the result of rupture of extracranial plaques. The clinical determination of carotid plaque vulnerability is currently based solely on luminal stenosis; however, it has been increasingly suggested that plaque morphology and biomechanical stress should also be considered. We used finite element analysis based on in vivo magnetic resonance imaging (MRI) to simulate the stress distributions within plaques of asymptomatic and symptomatic individuals. Methods: Thirty nonconsecutive subjects (15 symptomatic and 15 asymptomatic) underwent high-resolution multisequence in vivo MRI of the carotid bifurcation. Stress analysis was performed based on the geometry derived from in vivo MRI of the carotid artery at the point of maximal stenosis. The finite element analysis model considered plaque components to be hyperelastic. The peak stresses within the plaques of symptomatic and asymptomatic individuals were compared. Results: High stress concentrations were found at the shoulder regions of symptomatic plaques, and the maximal stresses predicted in this group were significantly higher than those in the asymptomatic group (508.2 ± 193.1 vs 269.6 ± 107.9 kPa; P = .004). Conclusions: Maximal predicted plaque stresses in symptomatic patients were higher than those predicted in asymptomatic patients by finite element analysis, suggesting the possibility that plaques with higher stresses may be more prone to be symptomatic and rupture. If further validated by large-scale longitudinal studies, biomechanical stress analysis based on high resolution in vivo MRI could potentially act as a useful tool for risk assessment of carotid atheroma. It may help in the identification of patients with asymptomatic carotid atheroma at greatest risk of developing symptoms or mild-to-moderate symptomatic stenoses, which currently fall outside current clinical guidelines for intervention.

Understanding how axial loads on the spine influence segmental biomechanics for idiopathic scoliosis patients: A magnetic resonance imaging study

Background Segmental biomechanics of the scoliotic spine are important since the overall spinal deformity is comprised of the cumulative coronal and axial rotations of individual joints. This study investigates the coronal plane segmental biomechanics for adolescent idiopathic scoliosis patients in response to physiologically relevant axial compression. Methods Individual spinal joint compliance in the coronal plane was measured for a series of 15 idiopathic scoliosis patients using axially loaded magnetic resonance imaging. Each patient was first imaged in the supine position with no axial load, and then again following application of an axial compressive load. Coronal plane disc wedge angles in the unloaded and loaded configurations were measured. Joint moments exerted by the axial compressive load were used to derive estimates of individual joint compliance. Findings The mean standing major Cobb angle for this patient series was 46°. Mean intra-observer measurement error for endplate inclination was 1.6°. Following loading, initially highly wedged discs demonstrated a smaller change in wedge angle, than less wedged discs for certain spinal levels (+ 2,+1,− 2 relative to the apex, (p < 0.05)). Highly wedged discs were observed near the apex of the curve, which corresponded to lower joint compliance in the apical region. Interpretation While individual patients exhibit substantial variability in disc wedge angles and joint compliance, overall there is a pattern of increased disc wedging near the curve apex, and reduced joint compliance in this region. Approaches such as this can provide valuable biomechanical data on in vivo spinal biomechanics of the scoliotic spine, for analysis of deformity progression and surgical planning.

Traffic and nucleation events as main sources of ultrafine particles in high-insolation developed world cities

Road traffic emissions are often considered the main source of ultrafine particles (UFP, diameter smaller than 100 nm) in urban environments. However, recent studies worldwide have shown that - in high-insolation urban regions at least - new particle formation events can also contribute to UFP. In order to quantify such events we systematically studied three cities located in predominantly sunny environments: Barcelona (Spain), Madrid (Spain) and Brisbane (Australia). Three long term datasets (1-2 years) of fine and ultrafine particle number size distributions (measured by SMPS, Scanning Mobility Particle Sizer) were analysed. Compared to total particle number concentrations, aerosol size distributions offer far more information on the type, origin and atmospheric evolution of the particles. By applying k-Means clustering analysis, we categorized the collected aerosol size distributions in three main categories: “Traffic” (prevailing 44-63% of the time), “Nucleation” (14-19%) and “Background pollution and Specific cases” (7-22%). Measurements from Rome (Italy) and Los Angeles (California) were also included to complement the study. The daily variation of the average UFP concentrations for a typical nucleation day at each site revealed a similar pattern for all cities, with three distinct particle bursts. A morning and an evening spike reflected traffic rush hours, whereas a third one at midday showed nucleation events. The photochemically nucleated particles burst lasted 1-4 hours, reaching sizes of 30-40 nm. On average, the occurrence of particle size spectra dominated by nucleation events was 16% of the time, showing the importance of this process as a source of UFP in urban environments exposed to high solar radiation. On average, nucleation events lasting for 2 hours or more occurred on 55% of the days, this extending to >4hrs in 28% of the days, demonstrating that atmospheric conditions in urban environments are not favourable to the growth of photochemically nucleated particles. In summary, although traffic remains the main source of UFP in urban areas, in developed countries with high insolation urban nucleation events are also a main source of UFP. If traffic-related particle concentrations are reduced in the future, nucleation events will likely increase in urban areas, due to the reduced urban condensation sinks.

Lung cancer risk of airborne particles for Italian population

Airborne particles, including both ultrafine and supermicrometric particles, contain various carcinogens. Exposure and risk-assessment studies regularly use particle mass concentration as dosimetry parameter, therefore neglecting the potential impact of ultrafine particles due to their negligible mass compared to supermicrometric particles. The main purpose of this study was the characterization of lung cancer risk due to exposure to polycyclic aromatic hydrocarbons and some heavy metals associated with particle inhalation by Italian non-smoking people. A risk-assessment scheme, modified from an existing risk model, was applied to estimate the cancer risk contribution from both ultrafine and supermicrometric particles. Exposure assessment was carried out on the basis of particle number distributions measured in 25 smoke-free microenvironments in Italy. The predicted lung cancer risk was then compared to the cancer incidence rate in Italy to assess the number of lung cancer cases attributed to airborne particle inhalation, which represents one of the main causes of lung cancer, apart from smoking. Ultrafine particles are associated with a much higher risk than supermicrometric particles, and the modified risk-assessment scheme provided a more accurate estimate than the conventional scheme. Great attention has to be paid to indoor microenvironments and, in particular, to cooking and eating times, which represent the major contributors to lung cancer incidence in the Italian population. The modified risk assessment scheme can serve as a tool for assessing environmental quality, as well as setting up exposure standards for particulate matter.

Insights into the growth of newly formed particles in a subtropical urban environment

The role of different chemical compounds, particularly organics, involved in the new particle formation (NPF) and its consequent growth are not fully understood. Therefore, this study was conducted to investigate the chemical composition of aerosol particles during NPF events in an urban subtropical environment. Aerosol chemical composition was measured along with particle number size distribution (PNSD) and several other air quality parameters at five sites across an urban subtropical environment. An Aerodyne compact Time-of-Flight Aerosol Mass Spectrometer (c-TOF-AMS) and a TSI Scanning Mobility Particle Sizer (SMPS) measured aerosol chemical composition (particles above 50 nm in vacuum aerodynamic diameter) and PNSD (particles within 9-414 nm in mobility diameter), respectively. Five NPF events, with growth rates in the range 3.3-4.6 nm, were detected at two of the sites. The NPF events happened on relatively warmer days with lower condensation sink (CS). Temporal percent fractions of organics increased after the particles grew enough to have a significant contribution to particles volume, while the mass fraction of ammonium and sulphate decreased. This uncovered the important role of organics in the growth of newly formed particles. Three organic markers, factors f43, f44 and f57, were calculated and the f44 vs f43 trends were compared between nucleation and non-nucleation days. K-means cluster analysis was performed on f44 vs f43 data and it was found that they follow different patterns on nucleation days compared to non-nucleation days, whereby f43 decreased for vehicle emission generated particles, while both f44 and f43 decreased for NPF generated particles. It was found for the first time that vehicle generated and newly formed particles cluster in different locations on f44 vs f43 plot and this finding can be potentially used as a tool for source apportionment of measured particles.

Magnetic resonance microimaging of cancer cell spheroid constructs

BACKGROUND Hydrogel-based cell cultures are excellent tools for studying physiological events occurring in the growth and proliferation of cells, including cancer cells. Diffusion magnetic resonance is a physical technique that has been widely used for the characterisation of biological systems as well as hydrogels. In this work, we applied diffusion magnetic resonance imaging (MRI) to hydrogel-based cultures of human ovarian cancer cells. METHODS Diffusion-weighted spin-echo MRI measurements were used to obtain spatially-resolved maps of apparent diffusivities for hydrogel samples with different compositions, cell loads and drug (Taxol) treatment regimes. The samples were then characterised using their diffusivity histograms, mean diffusivities and the respective standard deviations, and pairwise Mann-Whitney tests. The elastic moduli of the samples were determined using mechanical compression testing. RESULTS The mean apparent diffusivity of the hydrogels was sensitive to the polymer content, cell load and Taxol treatment. For a given sample composition, the mean apparent diffusivity and the elastic modulus of the hydrogels exhibited a negative correlation. CONCLUSIONS Diffusivity of hydrogel-based cancer cell culture constructs is sensitive to both cell proliferation and Taxol treatment. This suggests that diffusion-weighted imaging is a promising technique for non-invasive monitoring of cancer cell proliferation in hydrogel-based, cellularly-sparse 3D cell cultures. The negative correlation between mean apparent diffusivity and elastic modulus suggests that the diffusion coefficient is indicative of the average density of the physical microenvironment within the hydrogel construct.

Variability in exposure to ambient ultrafine particles in urban schools: Comparative assessment between Australia and Spain

Ambient ultrafine particle number concentrations (PNC) have inhomogeneous spatio-temporal distributions and depend on a number of different urban factors, including background conditions and distant sources. This paper quantitatively compares exposure to ambient ultrafine particles at urban schools in two cities in developed countries, with high insolation climatic conditions, namely Brisbane (Australia) and Barcelona (Spain). The analysis used comprehensive indoor and outdoor air quality measurements at 25 schools in Brisbane and 39 schools in Barcelona. PNC modes were analysed with respect to ambient temperature, land use and urban characteristics, combined with the measured elemental carbon concentrations, NOx (Brisbane) and NO2 (Barcelona). The trends and modes of the quantified weekday average daily cycles of ambient PNC exhibited significant differences between the two cities. PNC increases were observed during traffic rush hours in both cases. However, the mid-day peak was dominant in Brisbane schools and had the highest contribution to total PNC for both indoors and outdoors. In Barcelona, the contribution from traffic was highest for ambient PNC, while the mid-day peak had a slightly higher contribution for indoor concentrations. Analysis of the relationships between PNC and land use characteristics in Barcelona schools showed a moderate correlation with the percentage of road network area and an anti-correlation with the percentage of green area. No statistically significant correlations were found for Brisbane. Overall, despite many similarities between the two cities, school-based exposure patterns were different. The main source of ambient PNC at schools was shown to be traffic in Barcelona and mid-day new particle formation in Brisbane. The mid-day PNC peak in Brisbane could have been driven by the combined effect of background and meteorological conditions, as well as other local/distant sources. The results have implications for urban development, especially in terms of air quality mitigation and management at schools.

Enrichment and identification of glycoproteins in human saliva using lectin magnetic bead arrays

Aberrant glycosylation of proteins is a hallmark of tumorigenesis, and could provide diagnostic value in cancer detection. Human saliva is an ideal source of glycoproteins due to the relatively high proportion of glycosylated proteins in the salivary proteome. Moreover, saliva collection is non-invasive, technically straightforward and the sample collection and storage is relatively easy. Although, differential glycosylation of proteins can be indicative of disease states, identification of differential glycosylation from clinical samples is not trivial. To facilitate salivary glycoprotein biomarker discovery, we optimised a method for differential glycoprotein enrichment from human saliva based on lectin magnetic bead arrays (saLeMBA). Selected lectins from distinct reactivity groups were used in the saLeMBA platform to enrich salivary glycoproteins from healthy volunteer saliva. The technical reproducibility of saLeMBA was analysed with LC-MS/MS to identify the glycosylated proteins enriched by each lectin. Our saLeMBA platform enabled robust glycoprotein enrichment in a glycoprotein- and lectin-specific manner consistent with known protein-specific glycan profiles. We demonstrated that saLeMBA is a reliable method to enrich and detect glycoproteins present in human saliva.

What are the driving factors influencing the size distribution of airborne synthetic clay particles emitted from a jet milling process?

In the field of workplace air quality, measuring and analyzing the size distribution of airborne particles to identify their sources and apportion their contribution has become widely accepted, however, the driving factors that influence this parameter, particularly for nanoparticles (< 100 nm), have not been thoroughly determined. Identification of driving factors, and in turn, general trends in size distribution of emitted particles would facilitate the prediction of nanoparticles’ emission behavior and significantly contribute to their exposure assessment. In this study, a comprehensive analysis of the particle number size distribution data, with a particular focus on the ultrafine size range of synthetic clay particles emitted from a jet milling machine was conducted using the multi-lognormal fitting method. The results showed relatively high contribution of nanoparticles to the emissions in many of the tested cases, and also, that both surface treatment and feed rate of the machine are significant factors influencing the size distribution of the emitted particles of this size. In particular, applying surface treatments and increasing the machine feed rate have the similar effect of reducing the size of the particles, however, no general trend was found in variations of size distribution across different surface treatments and feed rates. The findings of our study demonstrate that for this process and other activities, where no general trend is found in the size distribution of the emitted airborne particles due to dissimilar effects of the driving factors, each case must be treated separately in terms of workplace exposure assessment and regulations.

Land use regression model (LUR) for ultrafine particles in Brisbane

Traffic-related air pollution has been associated with a wide range of adverse health effects. One component of traffic emissions that has been receiving increasing attention is ultrafine particles(UFP, < 100 nm), which are of concern to human health due to their small diameters. Vehicles are the dominant source of UFP in urban environments. Small-scale variation in ultrafine particle number concentration (PNC) can be attributed to local changes in land use and road abundance. UFPs are also formed as a result of particle formation events. Modelling the spatial patterns in PNC is integral to understanding human UFP exposure and also provides insight into particle formation mechanisms that contribute to air pollution in urban environments. Land-use regression (LUR) is a technique that can use to improve the prediction of air pollution.

Performance modulation of α-MnO2 nanowires by crystal facet engineering

Modulation of material physical and chemical properties through selective surface engineering is currently one of the most active research fields, aimed at optimizing functional performance for applications. The activity of exposed crystal planes determines the catalytic, sensory, photocatalytic, and electrochemical behavior of a material. In the research on nanomagnets, it opens up new perspectives in the fields of nanoelectronics, spintronics, and quantum computation. Herein, we demonstrate controllable magnetic modulation of α-MnO 2 nanowires, which displayed surface ferromagnetism or antiferromagnetism, depending on the exposed plane. First-principles density functional theory calculations confirm that both Mn- and O-terminated α-MnO2(1 1 0) surfaces exhibit ferromagnetic ordering. The investigation of surface-controlled magnetic particles will lead to significant progress in our fundamental understanding of functional aspects of magnetism on the nanoscale, facilitating rational design of nanomagnets. Moreover, we approved that the facet engineering pave the way on designing semiconductors possessing unique properties for novel energy applications, owing to that the bandgap and the electronic transport of the semiconductor can be tailored via exposed surface modulations.