238 research outputs found
Characterising Shape Variation in the Human Right Ventricle Using Statistical Shape Analysis: Preliminary Outcomes and Potential for Predicting Hypertension in a Clinical Setting
Variations in the shape of the human right ventricle (RV) have previously been shown to be predictive of heart function and long term prognosis in Pulmonary Hypertension (PH), a deadly disease characterised by high blood pressure in the pulmonary arteries. The extent to which ventricular shape is also affected by non-pathological features such as sex, body mass index (BMI) and age is explored in this thesis. If fundamental differences in the shape of a structurally normal RV exist, these might also impact the success of a predictive model. This thesis evaluates the extent to which non-pathological features affect the shape of the RV and determines the best ways, in terms of procedure and analysis, to adapt the model to consistently predict PH. It also identifies areas where the statistical shape analysis procedure is robust, and considers the extent to which specific, non-pathological, characteristics impact the diagnostic potential of the statistical shape model. Finally, recommendations are made on next steps in the development of a classification procedure for PH. The dataset was composed of clinically-obtained, cardiovascular magnetic resonance images (CMR) from two independent sources; The University of Pittsburgh Medical Center and Newcastle University. Shape change is assessed using a 3D statistical shape analysis technique, which topologically maps heart meshes through an harmonic mapping approach to create a unique shape function for each shape. Proper Orthogonal Decomposition (POD) was applied to the complete set of shape functions in order to determine and rank a set of shape features (i.e. modes and corresponding coefficients from the decomposition). MRI scanning protocol produced the most significant difference in shape; a shape mode associated with detail at the RV apex and ventricular length from apex to base strongly correlated with the MRI sequence used to record each subject. Qualitatively, a protocol which skipped slices produced a shorter RV with less detail at the apex. Decomposition of sex, age and BMI also derives unique RV shape descriptors which correspond to anatomically meaningful features. The shape features are shown to be able to predict presence of PH. The predictive model can be improved by including BMI as a factor, but these improvements are mainly concentrated in identification of healthy subjects
Advanced lung imaging and lung function testing in Ataxia-Telangiectasia
Although a CT scan provides high-resolution images for lung, it involves use of ionising radiation, which in some patient groups might increase risk of cancer, for example, it increases the chances of malignancy in patients with ataxia telangiectasia (AT). Therefore, it is necessary to identify an alternative imaging modality for patients with AT and other patient groups with similar risks. Magnetic resonance imaging (MRI) is a potential alternative, but there are various obstacles to its use. MRI cannot produce high-resolution images of the lungs due to the lack of strong proton signals. However, over the last few decades, various developments in MRI have given glimmers of hope for high-quality lung imaging. Currently, there are three potential ways to image the lung using MRI: hyperpolarised noble gas MRI (129Xe), oxygen enhanced MR ventilation imaging (OE) and ultra-short echo time (UTE) proton imaging. Each of these methods has disadvantages and advantages but their use, either singly or in combination, has considerable potential. In this thesis, the potential to use OE-MRI has been assessed in patients with AT, because it is more readily available and inexpensive compared to hyperpolarised noble gas MRI. Moreover, it can provide temporal and spatial information compared to UTE technique, which provides only an anatomical image. Lung function can also be assessed using physiological measurements including spirometry and lung clearance index (LCI). In this thesis, spirometry, LCI and OE-MRI were assessed for their potential to provide useful information on lung function abnormalities in children with and without AT. The main conclusions were that children with AT find it difficult to perform spirometry and LCI to adequate standards, especially in the children aged over 11. Moreover, with further optimisation, oxygen-enhanced MRI might provide an alternative way of assessing lung abnormalities in this group of patients
Advance in Composite Gels
In the last few decades, various composite gels have been developed. In recent years, further advances have been made in the development of novel composite gels with potential applications in various fields. This reprint offers the latest findings of composite gels by experts throughout the world
Development of Needle Trap Devices for Particle Entrapment
The importance of studying particle-bound components in aerosol samples has been highlighted during the COVID-19 pandemic, when people tried to stop the spread of droplet-bound viruses by wearing face masks. While the importance of these droplet/particle-bound analytes is well-known, their study has been hampered by the lack of a proper device for sampling and detection of these compounds. All these reasons explain the need for development of an extraction device that, not only traps droplet/particles from aerosol samples, but also preconcentrates free and gaseous analytes to enable comprehensive analysis of aerosol samples.
Among various microextraction methods, the needle-trap device (NTD) is the best candidate for entrapment and investigation of particle or droplet-bound compounds. The dynamic sampling and packed design can improve the role of NTD as a trapping device. Still, the filtration efficiency of NTD packed with commercial sorbent particles is limited due to the large diameter of packing material and can be improved by addition of an appropriate filter into the NTD. To this end, in this thesis, initially the filter with required criteria was developed and optimized. Then, the filter was packed inside the needle, in addition to the commercial sorbent particles to trap droplets/particles and extract gaseous compounds, respectively. The prepared NTD was then applied to study the aerosol sample including breath, air pollutants, sprays and sparkling beverages. To compare total and free (gas-phase) concentrations, the results from filter-incorporated NTD was compared to the results of solid-phase microextraction (SPME) methods.
After device development, free (from SPME results) versus total (from NTD results) concentration of fragrance compounds in different types of sprays was studied. In this study, the trend of concentration of fragrances over a time span after administration and the effect of air circulation with fan on air pollution was studied and reported. It was shown that the actual exposure concentration to fragrances during application of sprays can be much higher than gas-phase concentration. In another study, the concentration of aroma compounds in real consumer experience condition from sparkling beverages was studied and it was shown that the type and extent of carbonation and the physiochemical properties of aroma compounds plays influential roles on the distribution of these components between gas and droplet phase.
The next sections were dedicated to study of the most critical aerosol sample: breath samples and air pollutions. Based on the importance of these samples, various breath samples were studied from lung cancer patients or volunteers exposed to indoor air pollutants. The results showed that polar compounds have high tendencies to remain inside breath droplets, which mean during studying only gas-phase breath this type of information can be lost. For air pollution samples, it was revealed that less-volatile compounds such as large PAHs can be attached on the surface of smoke particles and carried to various locations by wind.
As the conclusion, it was shown that the developed NTD device is efficient and green for comprehensive study of aerosol samples. Among various potential applications, breath and air pollution provided the most critical and vital information, opening a new window to a novel type of information which was missing in previous studies in this area. The device is cheap and re-usable which highlights its environmental friendliness. While initial studies provided promising results, the application of NTD for aerosol samples is in its initial stages and there is a wide window of opportunities for future studies. The type and characteristics of filter can be varied and other types of samples can be studied. In the field of breath analysis, the application of studying droplet-bound compounds for diagnostic and treatments can be an opportunity for non-invasive and fast sampling
3D bioprinted heart patches for cardiac regeneration
BACKGROUND: epicardial patch transplantation is a promising approach to restore some of the cardiac
function lost after myocardial infarction (MI). Advances in 3D bioprinting, 3D cell culture and transplantation
methods at surgery have provided hope that this approach could soon benefit heart failure patients. The
optimal content of 3D bioprinted patches (the “bioink” extruded by a 3D bioprinter) is not known. Patches
containing a suspension of 3D vascularised cardiac spheroids (VCS; 3D aggregates of cells / microtissues) in
hydrogel may confer an advantage compared to freely suspended cells or hydrogel without cells. The
mechanisms underlying the benefit of epicardial patch transplantation approaches have not been fully
elucidated and this is needed for widespread clinical translation. To be fully compatible with cardiothoracic
surgical approaches in future, patches should be transplantable by minimally invasive robotic approaches.
METHOD: Alginate-gelatin (AlgGel) patches were optimised ex vivo for cardiac applications, followed by in
vivo transplantation of patches in mice modelling MI. For the ex vivo optimisation phase, three different
bioprinters were used to bioprint patches with different bioink contents which were incubated up to 28 days
and analysed. For the in vivo phase, new patches were 3D bioprinted using the optimal methods determined
in the previous (ex vivo) experiments and surgically transplanted to the epicardium in infarcted mice. For
these in vivo experiments, we cultured mixed cardiac cells: induced pluripotent stem cell derived
cardiomyocytes (iCMs), human coronary artery endothelial cells (HCAECs) and cardiac fibroblasts (CFs). Cells
were cultured using hanging drops to generate VCS which were suspended in AlgGel to create bioink for 3D
bioprinting of patches. Study control groups (in vivo) were: the same cells freely suspended in AlgGel, AlgGel
without cells, MI without treatment and sham surgery (no MI and no treatment). The primary outcome was
cardiac function (left ventricular ejection fraction, LVEF%) measured up to day 28 post surgery. Additional
analyses included: electrical mapping, histology, cell quantification by flow cytometry and mRNA (gene
expression) profiling. Alongside these experiments, we developed novel surgical robotic minimally invasive
instruments designed to transplant similar patches at human scale. We prototyped a heart patch transplanter
device and demonstrated its potential utility in a world-first operation on a pig cadaver. RESULTS: Ex vivo
patches incubated for 28 days allowed for self-organisation of endothelial cells into networks and contractile
activity within patches. In vivo transplantation of patches in mice modelling MI resulted in a “return to
baseline” improvement in median LVEF%. Our results measured median baseline (pre-surgery) LVEF% for all
mice at 66%. Post-surgery, LVEF% was 58% for Sham (non-infarcted) and 41% for MI (no treatment) mice.
Patch transplantation increased LVEF%: 55% (acellular; p=0.012), 59% (cells; p=0.106), 64% (spheroids;
p=0.010). The VCS group was associated with improved electrical mapping profiles, lower infarct sizes,
changes in host immune cell numbers and a gene expression (mRNA) profile which was closest to sham mice
(with no MI). As proof-of-concept, similar scaled-up AlgGel patches were successfully transplanted in a
porcine cadaver using a prototyped robotic minimally invasive surgical instrument. CONCLUSION: Epicardial
transplantation of patches improves cardiac function in mice modelling MI. The use of VCS in alginate-gelatin
bioink seems to offer advantages compared to freely suspended cells or hydrogel alone. The fact that
hydrogel alone without cells confers some restoration of myocardial function suggests that the mechanism
is not fully accounted for by the cellular portion of the bioink. Further studies are needed with a focus on
whether host immune cell modulation is a key mechanism underlying the benefit of this approach. Since our
most successful treatment group (VCS) had a similar transcriptome compared to non-infarcted (sham) mice,
further studies should also include transcriptomic analyses to confirm reproducibility of this finding. If it is
confirmed that immuno-genetic mechanisms underly patch-based approaches to myocardial protection after
MI, this may change the focus of treatment strategies and avoid wasted resources and potentially patient
harm (from treatments which are not aligned with the underlying mechanism). Our robotic minimally
invasive patch transplantation operation represents a first step on a potential pathway towards
transplantation at human surgery (without the need for traditional open surgery). For translatability, patch
development should work towards being compatible with robotic and/or minimally invasive transplantation
Proceedings of the YIC 2021 - VI ECCOMAS Young Investigators Conference
The 6th ECCOMAS Young Investigators Conference YIC2021 will take place from July 7th through 9th, 2021 at Universitat Politècnica de València, Spain. The main objective is to bring together in a relaxed environment young students, researchers and professors from all areas related with computational science and engineering, as in the previous YIC conferences series organized under the auspices of the European Community on Computational Methods in Applied Sciences (ECCOMAS). Participation of senior scientists sharing their knowledge and experience is thus critical for this event.YIC 2021 is organized at Universitat PolitĂ©cnica de València by the Sociedad Española de MĂ©todos NumĂ©ricos en IngenierĂa (SEMNI) and the Sociedad Española de Matemática Aplicada (SEMA). It is promoted by the ECCOMAS.The main goal of the YIC 2021 conference is to provide a forum for presenting and discussing the current state-of-the-art achievements on Computational Methods and Applied Sciences,including theoretical models, numerical methods, algorithmic strategies and challenging engineering applications.Nadal Soriano, E.; Rodrigo Cardiel, C.; MartĂnez Casas, J. (2022). Proceedings of the YIC 2021 - VI ECCOMAS Young Investigators Conference. Editorial Universitat Politècnica de València. https://doi.org/10.4995/YIC2021.2021.15320EDITORIA
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