Finite element and mechanobiological modelling of vascular devices

There are two main surgical treatments for vascular diseases, (i) percutaneous stent deployment and (ii) replacement of an atherosclerotic artery with a vascular graft or tissue engineered blood vessel. The aim of this thesis was to develop computational models that could assist in the design of vascular stents and tissue engineered vascular grafts and scaffolds. In this context, finite element (FE) models of stent expansion in idealised and patient specific models of atherosclerotic arteries were developed. Different modelling strategies were investigated and an optimal modelling approach was identified which minimised computational cost without compromising accuracy. Numerical models of thin and thick strut stents were developed using this modelling approach to replicate the ISAR-STEREO clinical trial and the models identified arterial stresses as a suitable measure of stent induced vascular injury. In terms of evaluating vascular graft performance, mechanical characterisation experiments can be conducted in order to develop constitutive models that can be used in FE models of vascular grafts to predict their mechanical behaviour in-situ. In this context, bacterial cellulose (BC), a novel biomaterial, was mechanically characterised and a constitutive model was developed to describe its mechanical response. In addition, the interaction of smooth muscle cells with BC was studied using cell culture experiments. The constitutive model developed for BC was used as an input for a novel multi-scale mechanobiological modelling framework. The mechanobiological model was developed by coupling an FE model of a vascular scaffold and a lattice free agent based model of cell growth dynamics and remodelling in vascular scaffolds. By comparison with published in-vivo and in-vitro works, the model was found to successfully capture the key characteristics of vascular remodelling. It can therefore be used as a predictive tool for the growth and remodelling of vascular scaffolds and graft

A novel small-caliber bacterial cellulose vascular prosthesis: production, characterization, and preliminary in vivo testing

Vascular grafts are used to bypass damaged or diseased blood vessels. Bacterial cellulose (BC) has been studied for use as an off-the-shelf graft. Herein, we present a novel, cost-effective, method for the production of small caliber BC grafts with minimal processing or requirements. The morphology of the graft wall produced a tensile strength above that of native vessels, performing similarly to the current commercial alternatives. As a result of the production method, the luminal surface of the graft presents similar topography to that of native vessels. We have also studied the in vivo behavior of these BC graft in order to further demonstrate their viability. In these preliminary studies, 1 month patency was achieved, with the presence of neo-vessels and endothelial cells on the luminal surface of the graft.This study was supported by the Portuguese Foundation for Science and Technology (FCT) and the European Community fund FEDER, through Program COMPETE, under the scope of the Projects FCOMP-01-0124-FEDER-007025 (PTDC/AMB/68393/2006), PEST-OE/EQB/LA0023/2013, PEST-C/FIS/UI607/2013, RECI/BBB-EBI/0179/2012 (FCOMP-01-0124-FEDER-027462) and the Projects "BioEnv-Biotechnology and Bioengineering for a sustainable world" and "Matepro-Optimizing Materials and Processes". NORTE-07-0124-FEDER-000048, co-funded by the Programa Operacional Regional do Norte (ON.2 - O Novo Norte), QREN, FEDER. The authors also acknowledge the fellowship awarded to Alexandre Felipe Leitao (SFRH/BD/66094/2009) funded by the Fundacao para a Ciencia e Tecnologia (FCT). The authors also thank support by FCT through the project BCGrafts, FCOMP-01-0124-FEDER-014773 (PTDC/EBB/EBI/112170/2009) and by the People Program (Marie Curie Actions) of the European Union's Seventh Framework Program FP7/2007-2013/under REA grant agreement n317512

Evaluation of economy and compared energy efficiency on grape in west Azerbaijan province

A way of estimation agriculture development and product stability agricultural location is using of energy flow method. In this consideration, energy flow at agricultural ecosystems of Grape in two cities from west Azerbaijan province was compared. The related data of inputs and outputs for evaluation of energy efficiency in these gardens are become equivalent value of input and output energy efficiency. Energy value of used factors and input in grape gardens of uremia and sardasht were respectively 6417773 and 862570 k cal/ha and output (production) energy value of the gardens were 25632600 and 10123800 k cal/ha respectively. Energy efficiency values (output: input ration) were 3.99 and 11.7 respectively. Data showed in grape gardens of uremia the most use of energy were nitrogen fertilized usage and irrigation. In grape gardens of sardasht the most use of energy was nitrogen fertilized. In general, because of the climate conditions, topography, society culture in these regions, difference in energy efficiency of these gardens almost was reasonable. The number of inputs increases; effect increases any one of input decrease. Grape garden system of sardasht hasn’t any contamination and agricultural systems because of much Annual rainfall in this region are dry farming. There for, costs of irrigation and poisoning are deleted but inordinately poisoning of uremia gardens result in contamination and transformed these ecosystems

Sequential Structural and Fluid Dynamics Analysis of Balloon-Expandable Coronary Stents: A Multivariable Statistical Analysis

Several clinical studies have identified a strong correlation between neointimal hyperplasia following coronary stent deployment and both stent-induced arterial injury and altered vessel hemodynamics. As such, the sequential structural and fluid dynamics analysis of balloon-expandable stent deployment should provide a comprehensive indication of stent performance. Despite this observation, very few numerical studies of balloon-expandable coronary stents have considered both the mechanical and hemodynamic impact of stent deployment. Furthermore, in the few studies that have considered both phenomena, only a small number of stents have been considered. In this study, a sequential structural and fluid dynamics analysis methodology was employed to compare both the mechanical and hemodynamic impact of six balloon-expandable coronary stents. To investigate the relationship between stent design and performance, several common stent design properties were then identified and the dependence between these properties and both the mechanical and hemodynamic variables of interest was evaluated using statistical measures of correlation. Following the completion of the numerical analyses, stent strut thickness was identified as the only common design property that demonstrated a strong dependence with either the mean equivalent stress predicted in the artery wall or the mean relative residence time predicted on the luminal surface of the artery. These results corroborate the findings of the large-scale ISAR-STEREO clinical studies and highlight the crucial role of strut thickness in coronary stent design. The sequential structural and fluid dynamics analysis methodology and the multivariable statistical treatment of the results described in this study should prove useful in the design of future balloon-expandable coronary stents

Tracking neurodegeneration spreading across the brain connectome in Parkinson's disease

LAUREA MAGISTRALEIntroduzione e Obiettivi. Le tecniche di analisi dei grafi e di connettomica possono essere un potente approccio per valutare le alterazioni cerebrali che sottendono la malattia di Parkinson (PD). In particolare, in questo studio è stata analizzata l'organizzazione cerebrale funzionale a riposo in un'ampia coorte di pazienti con PD, utilizzando tecniche di risonanza magnetica avanzate basate sull’analisi di networks. Materiali e Metodi. Sono stati arruolati 146 soggetti affetti da PD. Tutti i pazienti sono stati sottoposti a valutazione clinica neurologica e neuropsicologica e a risonanza magnetica funzionale a riposo (RS fMRI). È stata eseguita una cluster analysis, utilizzando dati demografici, sintomi/segni motori, test cognitivi e altre manifestazioni non cognitive e non motorie, che ha portato all’identificazione di due fenotipi di malattia: 86 pazienti con PD lieve (Early PD) e 60 pazienti con PD moderato/grave (Mild-to-severe PD). All'interno del fenotipo Early PD, sono stati identificati due ulteriori sottogruppi clinici: "early motor-predominant" e "early-diffuse". Questi ultimi presentavano maggiori deficit cognitivi e manifestazioni non motorie più gravi (es. disfunzione urinaria e disturbo comportamentale della fase REM del sonno). 60 soggetti sani, comparabili per età e sesso con il gruppo PD, sono stati sottoposti allo stesso protocollo clinico, neuropsicologico e di RM. L'analisi dei grafi e il calcolo delle misure di connettomica hanno valutato le proprietà topologiche locali e globali dell’organizzazione cerebrale e la connettività funzionale regionale (FC). Le immagini RS fMRI sono state pre-processate utilizzando FSL. Le matrici di FC sono state ottenute attraverso l’analisi di correlazione: considerando una regione i-esima del cervello, il valore medio della serie temporale RS fMRI è stato calcolato come la media delle serie temporali di tutti i voxels contenuti nell’i-esima regione. Allo stesso modo, è stata ottenuta una serie temporale RS fMRI media per la regione j-esima. Per quantificare il livello di connessione funzionale tra la regione i-esima e j-esima è stato calcolato il coefficiente di correlazione di Pearson tra le due serie temporali medie e inserito nella cella in posizione c (i, j) della matrice. La matrice di connettività funzionale risultante è stata mascherata con una matrice di connettività strutturale ottenuta da un campione di controlli sani indipendenti, con lo scopo di valutare solo il cambiamento funzionale tra due regioni che siano anatomicamente connesse. Le caratteristiche del connettoma sono state valutate sia a livello globale che a livello dei singoli lobi cerebrali, calcolando le principali metriche di analisi dei grafi: clustering coefficient, path length, nodal strength e local efficiency. Sono stati effettuati confronti tra i gruppi utilizzando il modello statistico ANOVA corretto per età, sesso e tipologia di trattamento, seguito da confronti post-hoc a coppie con correzione di Bonferroni per confronti multipli (p <0.05). Inoltre, le connessioni funzionali sono state studiate utilizzando l’analisi di network-based statistics (NBS) con i seguenti parametri: p <0,05 e 10.000 permutazioni. Tutte i risultati ottenuti sono stati corretti per età, sesso e tipo di trattamento. Risultati. I pazienti del gruppo “early-PD” presentavano un'architettura cerebrale funzionale globale relativamente conservata rispetto al gruppo di controllo, a differenza del gruppo Mild-to-severe PD, che mostrava proprietà topologiche funzionali alterate nelle aree sensomotoria e parietale rispetto ai controlli. Sono state individuate diffuse alterazioni funzionali a livello dei gangli della base, del circuito sensorimotorio, dell’area frontale, parietale e temporale nel gruppo Mild-to-severe PD e “early-diffuse” rispetto ai controlli e, solo nel gruppo Mild-to-severe PD rispetto ai pazienti "early motor-predominant". Discussione. Sono state identificate alterazioni della connettività funzionale sia motoria che extra-motoria nei pazienti con PD rispetto ai controlli sani, progressivamente ingravescenti all’aumentare dello stadio della malattia. I risultati dell’analisi condotta hanno evidenziato un’organizzazione topologica funzionale globale del cervello relativamente conservata in diversi gruppi di PD rispetto ai controlli sani. Tuttavia, a livello dei lobi cerebrali, l’analisi ha rilevato patterns di alterazioni funzionali diversi nei sottogruppi clinici. L'analisi della connettività funzionale ad un livello regionale ha mostrato una diversa distribuzione del deterioramento tra i gruppi di pazienti. Valutando un sottogruppo di pazienti in fase iniziale della patologia, i risultati ottenuti hanno sottolineato che, sebbene la malattia di Parkinson sia nota come disturbo del movimento, alcuni segni/sintomi non motori possono precedere l'apparizione dei sintomi motori, mentre la degenerazione funzionale del circuito motorio si presenta già nelle fasi più precoci della malattia. Conclusioni. Le tecniche avanzate di RS fMRI basate sull’analisi dei networks potrebbero aiutare a comprendere i processi fisiopatologici che sottendono le diverse fasi della malattia di Parkinson e individuare biomarcatori di progressione nel tempo legati alla patologia.Introduction and Objective. Graph analysis and connectomics may be a powerful approach to assess brain network degradation in Parkinson’s disease (PD). In particular, in this study we investigated functional neural pathway organization and changes in large cohort of PD patients using advanced network-based techniques. Materials and Methods. 146 PD patients performed clinical and cognitive evaluations and resting state functional MRI. Cluster analysis using data on demographics, motor symptoms/signs, cognitive testing and other non-motor non-cognitive manifestations identified two PD subtypes: 86 “early” patients and 60 “mild-to-severe” patients. Within the “early” subtype, two clinical groups were also identified: “early motor-predominant” and “early diffuse”, with the “early diffuse” group having greater cognitive deficits and more frequent non-motor manifestations (e.g., urinary dysfunction, rapid eye movement sleep behavior disorder). 60 age- and sex-matched controls performed the assessments as well. Graph analysis and connectomics assessed global and local topological network properties and regional functional connectivity (FC). The human macroscale connectome was constructed from RS fMRI. Preprocessing of RS fMRI images was performed with FSL and consisted of motion correction, removal of nonbrain tissue, spatial smoothing using a 6 mm full width at half maximum Gaussian kernel, and high-pass temporal filtering equivalent to 100s (0.01 Hz). FC matrices were obtained on the basis of correlation analysis. For each brain region i, a mean RS fMRI time-series was obtained by averaging over the time-series of all voxels contained in i. The Pearson correlation coefficient between these mean time-series, indicating the level of FC between regions i and j, entered into cell c(i,j) of the matrix. Negative correlation coefficients, reflecting functional distinct brain regions, were set to 0 to mark these brain regions as unconnected. The resulting functional connectivity matrix was masked with a structural connectivity matrix of an independent healthy control sample, for consideration of functional interactions only where an anatomical connection between two areas occurred in the independent healthy control sample. Global and mean lobar network characteristics were explored, and network metrics, including clustering coefficient, characteristic path length, mean network strength, and local efficiency were assessed and compared between groups using ANOVA models adjusted for age, sex, and treatment, followed by post-hoc pairwise comparisons, Bonferroni-corrected for multiple comparisons (p<0.05). Moreover, affected functional connections were investigated using Network-Based Statistic (NBS) (p<0.05, 10.000 permutations). All the NBS analyses were adjusted for age, sex and treatment. Results. “Early” PD patients showed a relatively preserved global functional brain architecture. “Mild-to-severe” patients showed altered functional topological properties of the sensorimotor and parietal areas relative to controls. A widespread pattern of decreased FC involving the basal ganglia, sensorimotor, frontal, parietal and temporal networks was found in “mild-to-severe” and “early diffuse” patients relative to controls and in “mild-to-severe” relative to “early motor-predominant” cases. Discussion. Motor and extra-motor functional network degeneration was observed in PD patients according to the disease stage. Our results suggest that global topological organization of the functional brain network remains relatively preserved in different PD groups relative to healthy controls, however, lobar network alterations can occur differently in specific clinical subtypes. Regional functional connectivity analysis showed different deterioration patterns among patient clusters. Results of studying a subtype of patients in the early stage of the disease, suggest that although PD is known as a movement disorder, some non-motor signs/symptoms can precede the appearance of motor symptoms, while disruption in the motor network organizations happen from the very early phases of the disease. Conclusions. Network-based advanced MRI analyses, specifically graph analysis and connectomics, might represent a powerful approach in understanding the pathophysiological process across different stages of PD and hold the promise to offer useful markers of disease-related pathological changes

Electromigration in Nano-Interconnects: Determining Reliability Margins in Redundant Mesh Networks Using a Scalable Physical&ndash;Statistical Hybrid Paradigm

This paper presents a hybrid modelling approach that combines physics-based electromigration modelling (PEM) and statistical methods to evaluate the electromigration (EM) limits of nano-interconnects in mesh networks. The approach, which is also compatible with standard Place and Route (P&amp;R) tools and practises, takes into account the positive impact of network redundancy on EM current limits. The numerical simulations conducted in this study show that conventional methods underestimate the EM current limits of a power delivery network (PDN) unit-cell by 80% due to their lack of consideration for redundancy. Additionally, the time-to-failure (TTF) distributions of a PDN unit-cell obtained by the developed modelling framework adhered to a lognormal distribution, where the lognormal sigma, &sigma;logn, exhibits a 55% reduction compared to that of the single constituent interconnects. The study also found the negative voltage (i.e., ground or Vss) grid to be more susceptible to EM than the positive voltage, i.e., Vdd grid. In the examined grid unit-cell design, both the number of interconnect sites prone to voiding and also the magnitude of the peak tensile stress within the nano-interconnects were found to be two times as high in the Vss case compared to Vdd. The lognormal sigma of TFF for the grid unit-cells, &sigma;logn&minus;tile, show a marked reduction compared to the lognormal sigma of the constituent single interconnects, &sigma;logn, with a 50% and 66% decrease compared to single interconnects, for downstream (Vss) and upstream (Vdd), respectively. In addition, &sigma;logn&minus;tile was three times higher for downstream (Vss) compared to upstream (Vdd), whilst, in contrast, this difference was only 2-fold at the single interconnect level. TTF50% was predicted to be 4.13-fold higher at the grid unit-cell level for the upstream compared to downstream operation, which was also more pronounced than in the single interconnect level where the difference was only 2-fold. This research provides valuable insights into the EM ageing of nano-interconnects in mesh networks and could pragmatically enhance the accuracy of EM compliance evaluation methods